Page 1 of 113

Disease: Anthrax

Classification: ICD-9 022; ICD-10 A22

Syndromes and synonyms: Charbon, malignant pustule,

malignant edema, woolsorter disease, tanner disease.

Agent: Spores of Bacillus anthracis, a Gram-positive, encapsu- lated, non-motile rod. The spores are resistant to desiccation,

extremes of temperature and pH, ultraviolet radiation and

many disinfectants, and can remain viable for 60 years. It is

considered a biological warfare agent.

Reservoir: Soil, animal hair, wool or hides, particularly goat

skins contaminated with soil. Spores can germinate outside an

animal under appropriate conditions.

Vector: Tabanid and Stomoxys flies and mosquitoes can

transmit, but are not epizootic vectors. Blow-flies can also

spread the bacteria.

Transmission: Contact with infected animal tissue. Cutaneous

anthrax: direct skin inoculation during processing of contami- nated animal hides, hair, wool, or animal hide products.

Gastro-intestinal (GI) anthrax: consuming meat from infected

livestock. Inhalation anthrax: inhalation of anthrax spores by

tanning/shearing sheep or processing contaminated hair/

wool or intentional during a bioterrorist attack. Rare in

IVDU from contaminated heroin. There is no direct person- to-person transmission.

Cycle: Herbivores become infected when they ingest spores

during grazing on contaminated soil. When the animal dies,

the soil under the carcase is contaminated. Omnivores and

carnivores are infected by feeding on infected prey or carcases.

Carnivores and humans are incidental hosts.

Incubation period: 1–7 days; up to 60 days in case of low

inhaled dose.

Clinical findings: Depends on portal of entry. The skin lesion

is a characteristic black eschar surrounded by edema, usually

on the head, forearms or hands, accompanied by malaise and

fever, in 80% of cases resolving spontaneously after 7–10 days,

but if left untreated it may evolve into fatal septicemia. GI

anthrax produces nausea, vomiting, abdominal pain,

fever, hematemesis, occasionally bloody diarrhea and often

fatal septicemia and shock. Inhalation anthrax is rapidly pro- gressive and starts with fever, malaise and mild cough and

chest pain, evolving to acute respiratory distress, diagnostic

mediastinal widening, cyanosis and shock. Untreated cutane- ous anthrax has a CFR of 5–20% (<1% with treatment), GI

anthrax 25–60%, and inhalation anthrax 100% (75% with

treatment).

Diagnostic tests: Microscopy (M’Fadyan stain) of lesion;

bacterial culture of lesion, blood, or respiratory specimen;

PCR; ELISA.

Therapy: Cutaneous anthrax: penicillin, ciprofloxacin or

doxycycline po; severe anthrax (GI or inhalation): ciprofloxa- cin iv preferred. Clindamycin can inhibit toxin production.

Prevention: Vaccination of livestock and humans with occu- pational risk in endemic areas. Antibiotic prophylaxis when

exposed and vaccination in case of inhalation anthrax. Infected

animal carcases should be burned or deeply buried, preferably

at the site of death.

Epidemiology: Anthrax has a worldwide distribution. Live- stock vaccination, antibiotic treatment, and quarantaine regu- lations lead to a strong decline in anthraxinfections in domestic

lifestock. Anthrax occurs mainly in rural areas in countries

where there is no livestock vaccination and no veterinary

control of slaughtered animals.There is a seasonal variation

in animal disease with an increase in cases during hot dry

weather. Anthrax is an occupational hazard for people who

process contaminated animal tissues. GI anthrax occurs when

infected tissue is ingested. Of note is the terrorist distribution of

anthrax powder by mail in the USA in 2001, which killed 5

people and produced sickness in 17.

Map sources: Modified from WHO World Anthrax Data

Site, available at: www.vetmed.lsu.edu tropics (accessed

Jan. 2011).

Key references

Dixon TC, et al. (1999) Anthrax. N Engl J Med 341(11):815–826.

Hugh-Jones ME, et al. (2009) The ecology of Bacillus anthracis. Mol Aspects Med 30(6):356–367.

Swartz MN (2001) Recognition and management of anthrax – An update. N Engl J Med 345:1621–1626.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

43

Page 2 of 113

Disease: Bartonellosis, Bartonella bacilliformis

Classification: ICD-9 088.0; ICD-10 A44

Syndromes and synonyms: Oroya fever, Carrión disease,

verruga peruana (Peruvian wart).

Agent: Bartonella bacilliformis, a fastidious intracellular Gram- negative bacterium.

Reservoir: Humans are the only known reservoir host.

Vector: The sandfly Lutzomyia verrucarum. Preferred habitat:

narrow river gorges at elevations between 500 and 3,200

meters.

Transmission: By bite of the female sandfly (usually at dusk

and at sundown, often indoors); rarely by blood transfusion or

transplacental. There is no direct person-to-person

transmission.

Cycle: Human–sandfly–human. Humans can be bacteremic

for many months. Period of infectivity in the sandfly is

unknown.

Incubation period: 16–22 days, occasionally up to 7 months.

Clinical findings: There are two phases, divided into an acute

phase (Oroya fever) followed after at least 2 weeks by a chronic

phase (verruga peruana). Verruga peruana may occur without

an evident acute phase. Oroya fever: fever,myalgia, arthralgia,

headache, evolving to severe hemolytic anemia, generalized

lymphadenopathy and hepatosplenomegaly; milder symp- toms in children. The CFR for untreated Oroya fever is

40–88% and for treated disease is 1–9%. Survivors are immune.

Mortality is associated with secondary infections (e.g. Salmo- nella andToxoplasma). Verruga peruana: painless nodular rash,

appearing as ‘bleeding warts,’ mainly on extensor surfaces of

the limbs, face, trunk and mucous membranes; may last 3–6

months and is rarely fatal; relapses occur. Differences in

clinical presentation and mortality may be due to strain

heterogeneity.

Diagnostic tests: Giemsa stain of red blood cells or dermal

biopsy; blood culture on special media (results take 3–6

weeks); PCR; serology.

Therapy: Oroya fever: penicillin, streptomycin, chloram- phenicol and tetracyclines are all effective, with ampicillin

for secondary infections, but the case may still evolve to

verruga peruana, which is treatable with streptomycin or

rifampicin. Severe cases: ceftriaxone iv is used and blood

transfusion in case of severe anemia. Verruga peruana: rifam- picin or streptomycin. B. bacilliformis is intrinsically resistant

to quinolones.

Prevention: Sandfly control with residual insecticide; avoid

endemic areas after sunset; use insect repellents and covering

clothes; insecticide-treated bednets. Active case finding in

households where cases occur. Vector-control efforts

should target the homes of incident case patients. Patients

should be kept in sandfly-proof wards.

Epidemiology: Bartonellosis due to B. bacilliformis was origi- nally restricted to high, dry mountain valleys from 600 to 3,200

meters in the Andes of Colombia, Ecuador and Peru. Since

1997 it has expanded geographically to the Utcubamba river

valley, Cusco, La Libertad and the low-lying hills below 600

meters in coastal Ecuador. The cause for this expansion is

unknown. The disease incidence is increasing in Peru, partic- ularly in children. In endemic areas attack rates of 12.7/100

person-years are found, with highest rates in children under 5.

There is a decreasing incidence with increasing age due to

acquired immunity. For each year of age, the risk of infection

diminishes by 4%. Most cases cluster, with 70% occurring in

only 18% of households in the community where the outbreak

happens.

Map source: The Bartonella bacilliformis map was made by

geocoding reported cases in the medical literature up to 2010.

Elevation, rivers and lakes are also shown.

Key references

Chamberlin J, et al. (2002) Epidemiology of endemic Bartonella

bacilliformis: a prospective cohort study in a Peruvian moun- tain valley community. J Infect Dis 186(7):983–990.

Del Valle LJ, et al. (2010) Bartonella bacilliformis, endemic

pathogen of the Andean region, is intrinsically resistant to

quinolones. Int J Infect Dis 14(6):e506–10.

Maguiña C, et al. (2009) Bartonellosis. Clin Dermatol

27:271–280.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

45

Page 3 of 113

Disease: Bartonellosis, Bartonella quintana

Classification: ICD-9 083.1; ICD-10 A79.0

Synonyms: Trench fever, quintana fever, quintan fever, shin- bone fever, shank fever, His-Werner disease, and Wolhynia

fever.

Agent: Bartonella quintana (formerly Rochalimaea quintana and

Rickettsia quintana), a fastidious intracellular Gram-negative

bacterium.

Reservoir: Humans and possibly cats.

Vector: The principle vector is the human body louse

(Pediculus humanus corporis), which lives in clothes. B. quintana

has also been detected in cat and monkey fleas. Transmission: Transmission to humans occurs by rubbing

infected louse feces into abraded skin or into the conjunctivae.

Cycle: B. quintana multiplies in the louse’s intestine and is

excreted in the feces. Body lice feed several times per day that

leads to itchiness and scratching, by which the skin is inocu- lated with louses’ contaminated feces. Chronic B. quintana

bacteremia facilitates infection in lice and further spread.

Incubation period: 5–20 days, with a median of 8 days.

Clinical findings: ‘Classic’ trench fever is characterized by

febrile attacks that last 1 to 3 days, with headache, shin pain,

and dizziness. The attacks recur every 4 to 6 days, with

succeeding attacks being less severe; no deaths have been

reported. ‘Urban’ trench fever generally occurs generally in

homeless people and clincal features are highly variable,

including severe disease with endocarditis, non-specific symp- toms with or without fever, and chronic asymptomatic bacter- emia. Infection with B. quintana (or B. henselae) may also cause

bacillary angiomatosis, usually in patients with HIV.

Diagnostic tests: Blood culture with prolonged incubation

(42 days); lysis centrifugation blood culture systems or sub- culture of blood culture bottles onto fresh chocolate agar

enhances sensitivity. Several serological assays are available

(CFT, ELISA, IFA), but cross-reactivity occurs; PCR on

blood and tissue.

Therapy: Treatment of uncomplicated B. quintana bacteremia

is with a macrolide (erythromycin, azithromycin) or

doxycyclin. In case of endocarditis 4–6 months of therapy is

recommended in combination with a third-generation cepha- losporin or gentamicin for the first 2–3 weeks. Heart valve

replacement may be needed.

Prevention: Lice infestation (pediculosis) can be controlled by

treating clothes and bedding with insecticides or boiling (bed- ding at shelters is a major source of lice infestation). The body

does not need to be deloused as the lice live and lay their eggs

in clothes or bedding. Oral ivermectin has been effective in

delousing homeless people.

Epidemiology: Trench fever is named afterinfected soldiers in

the trenches during World War I. Little data exist on the

incidence and distribution of B. quintana infections. Infections

have been reported from every continent. Trench fever is a sign

of social turmoil and personal hardship. For instance, an

epidemic of trench fever erupted in a refugee camp in Burundi.

In Europe and North America, B. quintana infections are

associated with poverty, alcoholism, and homelessness,

known as urban trench fever. Crowded and unhygienic living

conditions facilitate exposure of B. quintana infected indivi- duals to lice that subsequently pass on the infection to others.

Trench fever is a re-emerging disease due to the increase in

homeless people and HIV-infected individuals.

Map sources: The Bartonella quintana map was made by

geolocating reported cases (1990–2010) in the medical

literature.

Key references

Foucault C, et al. (2006) Bartonella quintana characteristics and

clinical management. Emerg Infect Dis 12(2):217–223.

Maguina C, et al. (2009) Bartonellosis. Clin Dermatol

27:271–280.

Ohl ME, et al. (2000)Bartonella quintana and urban trench fever.

Clin Infect Dis 31:131–135.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

47

Page 4 of 113

Disease: Botulism

Classification: ICD-9 005.1; ICD-10 A05.1

Syndromes and synonyms: None.

Agent: Botulinum toxin, produced by the anerobic spore- forming bacterium Clostridium botulinum types A, B, E and

rarely F. Type E and F neurotoxins have been recovered from

infants with botulism due to C. butyricum and C. barati. C.

botulinum is considered a biological warfare agent.

Reservoir: C. botulinum spores are found in soil, dust, honey,

marine sediments, and in intestines of fish and land animals.

Vector: None.

Transmission: By ingestion of contaminated food (honey

in infant botulism), injection of contaminated drugs, or

contamination of wounds by soil, dust or gravel. There is

no human-to-human transmission.

Incubation period: Usually 12–36 hours; sometimes several

days; up to 2 weeks for wound botulism.

Clinical findings: Descending flaccid skeletal muscle paraly- sis beginning at the shoulders in the absence of fever; fatigue,

weakness, vertigo, blurred vision, dry mouth, difficulty in

speaking and swallowing, progressing to an inability to

breathe without assistance. Vomiting, diarrhea or constipation

may occur. The CFR in the USA after treatment is 5–10%;

recovery may take months. Infants present with constipation,

anorexia, weakness, an altered cry, difficulty sucking, and

swallowing. Muscle weakness progresses in a symmetric

descending fashion over hours to a few days. The prognosis

is excellent when treated timely.

Diagnostic tests: Detection of toxin in serum, stool or wound

by mouse inoculation or ELISA; culture of the bacterium from

stool or wound; electromyography.

Therapy: Food-borne botulism: intensive supportive care

and polyvalent botulinum antitoxin iv. Wound botulism:

wound debridement, antibiotics (penicillin) and polyvalent

botulinum antitoxin iv. Equine botulinum antitoxin can

prevent progression of illness and shorten symptoms in

food-borne and wound botulism if administered early.

Avoid aminoglycoside antibiotics as these may potentiate

the toxin and result in a complete neuromuscular blockade

and resultant paralysis.

Prevention: Food for canning or bottling should be thor- oughly cooked; consumption of inadequately smoked or

salted food and uneviscerated fish should be avoided. Also

avoid honey and dusty excavation sites with infants.

A pentavalent botulinum toxoid (PBT) vaccine is available

from the CDC.

Epidemiology: Rare, but good disease burden data are lack- ing. Underdiagnosis is common. There are four main types of

botulism: intestinal/infant, food-borne, wound and inadver- tent. Infant botulism is the most common form of botulism in

the USA and is caused by growth of spores germinating the

immature gut of infants and releasing the toxin, or rarely in

adults with abnormal intestinal tracts. Honey is a common

source, but in 85% of infants, the source is unknown.

Infant cases occur from 6 days to 12 months of age and affect

equally both sexes. Food-borne botulism is the result of

eating fermented, salted, or smoked fish, seafood or meat

that has not been cured for long enough to eliminate contam- ination. It is also due to incorrect home canning or bottling

of vegetables or fruit. Botulism usually occurs in outbreaks

in those exposed to the same food. The largest numer of

reported cases per country over the decade 2000–2009 in

ProMED mail have occurred in Thailand (83 cases from

deer meat, 163 from bamboo shoots), Poland (276 from

preserved food), and Georgia (217 from home-preserved – vegetables). Food-borne botulism outbreaks occur in indige- nous tribes in Alaska and Canada by consuming improperly

preserved fish products (seal, salmon, salmon eggs). Wound

botulism results from failure to remove contaminated soil

completely from wounds and sealing them, permitting anaer- obic growth of the bacteria. Inadvertent botulism is a recent

phenomenon resulting from the use of diluted Botulinum

toxin to treat patients for several disorders and for cosmetic

reasons. Map sources: Reported human botulism outbreaks in

ProMED-mail between 2000 and 2009, available at: www.

promedmail.org.

Key references

Brook I (2006) Botulism: the challenge of diagnosis and treat- ment. Rev Neurol Dis 3(4):182–189.

Brook I (2007) Infant botulism. J Perinat 27:175–180.

Smith LA (2009) Botulism and vaccines for its prevention.

Vaccine 27(4):33–39.

Sobel J (2005) Botulism. Clin Infect Dis 41(8):1167–1173.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

49

Page 5 of 113

Disease: Brucellosis

Classification: ICD-9 023; ICD-10 A23.1

Syndromes and synonyms: Undulant fever, malta fever,

Mediterranean fever.

Agent: Brucella melitensis, B. abortus, B. suis, and B. canis, intracellular Gram-negative bacilli.

Reservoir: Cattle, swine, goats, sheep, and various wildlife

species. B. canis in dogs and coyottes.

Transmission: Enteric by ingestion of unpasteurized milk or

milk products (soft cheese, yoghurt) from infected animals;

direct inoculation of mucosa or skin with infected animal

tissue (usually occupational in farmers or butchers); inhalation

in housing of infected animals. Brucellosis is an occupational

disease in shepherds, abattoir workers, veterinarians, dairy

industry workers, and microbiology laboratory staff. No per- son-to-person transmission apart from isolated case reports of

sexual transmission.

Cycle: Brucella spp. is introduced into animals via inhalation,

broken skin, or mucosa and invades local lymph nodes where

it propagates and enters the bloodstream and disseminates to

mainly the reticulo-endothelial system (bone marrow, spleen,

liver, lymph nodes), kidneys and placenta in pregnant ani- mals. From infected organs, like mammary glands, kidneys,

and placenta, viable bacteria are shedded into the environment

by milk, urine, and uterine discharge, leading to new infections

in exposed animals and humans.

Incubation period: Usually 14–21 days, up to several months.

Clinical findings: Acute irregular fever, chills, sweating,

arthralgia, headache, and depression. Evidence of localized

suppurative infections may be found in liver, spleen, genito- urinary tract, and osteo-articular (joints and sacrum). Symp- toms may last for months and vary from mild to severe and

even fatal (CFR: <2%).

Diagnostic tests: Blood or bone marrow culture and other

infected bodily tissues (urine, CSF); serology; PCR.

Therapy: Doxycycline for 6 weeks, in combination with either

rifampicin for 6 weeks, or streptomycin for 2–3 weeks, or

gentamicin for 1–2 weeks.

Prevention: Pasteurize milk; do not eat unpasteurized dairy

products, especially in endemic areas; brucellosis control in

domestic animals; hygienic measures in farms and slaughter

houses; screening of livestock. Laboratory infections occur

where biosafety measures are not adequate.

Epidemiology: Brucellosis is a common zoonosis with

approximately 500,000 new cases per year world wide. The

disease occurs mostly in areas where it is common to consume

unpasteurized dairy products (soft cheese) and where poor

veterinary health systems exist. The main Brucella infecting

species vary by region. Incidence is highest in males with

occupational exposure. The highest incidences are recorded in

Mediterranean countries, Middle East, Central America, and

Central Asia. Five of 10 countries with highest incidences are in

the Middle East, with Syria leading. Many of the high-inci- dence countries were formerly part of the Soviet Union. Since

their independence the veterinary health system has deterio- rated, leading to an increase in brucellosis cases. In the USA it is

mainly reported in Hispanics eating imported infected food.

The disease is not considered highly endemic in South Amer- ica. Data from Brazil is lacking, despite high cattle densities in

this country (see Livestock map). Many western European

countries have brucellosis-free status. Mediterannean Euro- pean countries implemented eradication campaigns, but still a

high prevalence exists, especially in the Balkan peninsula. In

eastern Europe the disease is limited to veterinarians.

Map sources: The Brucellosis map is a modified version

from Pappas et al. (2006).

Key references

Akhvlediani T, et al. (2010) The changing pattern of human

brucellosis: clinical manifestations, epidemiology, and treat- ment outcomes over three decades in Georgia. BMC Infect

Dis 10:346.

Pappas G, et al. (2006) The new global map of human brucel- losis. Lancet Infect Dis 6:91–99.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

51

Page 6 of 113

Disease: Buruli Ulcer

Classification: ICD-9 031.1; ICD-10 A31.1

Syndromes and synonyms: Bairnsdale ulcer (southern

Australia), Daintree ulcer (northern Australia) Kumusi ulcer

(Papua New Guinea), Searl ulcer.

Agent: Mycobacterium ulcerans, an acid-fast, slow-growing

bacillus. There are at least four geographically distinct

strains: African, American, Asian, and Australian. They all

produce mycolactone, which destroys tissue and suppresses

the immune system. Variations in the structure of mycolactone

may correlate with disease severity in different regions.

Reservoir: This is unknown at present. M. ulcerans has been

found in biofilms on vegetation in swamps and other perma- nent wetlands, aquatic insects, snails, and fish. In Australia,

some land animals, particularly native possums, have been

found to carry M. ulcerans in their gastrointestinal tracts.

Vector: Aquatic insects; in southern Australia mosquitoes; not

yet fully understood.

Transmission: Contamination of a break in the skin by bacilli

in the environment, or by the bite of an infected aquatic insect

or mosquito. Person-to-person transmission is rare.

Cycle: The disease ecology is not completely understood.

Humans are likely dead end hosts.

Incubation period: From 2–3 months to several years. Most

infections do not progress to disease.

Clinical findings: Chronic, painless skin nodule that pro- gresses to a severe,deforming ulcer. One-third of early nodules

heal spontaneously. Most nodules appear on limbs, but also

face and breast; skin lesions may also appear as plaques or

indurated edematous lesions; osteomyelitis. Typical charac- teristic is the presence of deeply undermined ulcers. Sequelae

include contracture, deformity, and permanent disability.

Diagnostic tests: Ziehl–Neelsen stain on smears or biopsies,

culture (takes 6–12 weeks), PCR, histopathology.

Therapy: In early and limited disease: 4 weeks of streptomycin

and rifampicin followed by 4 weeks of rifampicin and clari- thromycin. For more extensive disease: rifampicin plus strep- tomycin for 8 weeks; extensive lesions may require

reconstructive surgery and physiotherapy. Lesions < 5cm

can be excised under local anesthetic.

Prevention: Wear clothes that cover extremities; cover skin

lesions; insect repellent; cover water supply.

Epidemiology: Buruli ulcer is named after Buruli county

in Uganda, where the disease was common in the 1960s.

The disease is reported in 30 countries with tropical

climates, but it may occur in some temperate regions. West

Africa is the most affected region. Typical Buruli endemic

regions are areas with slow-flowing or stagnant water. Flood- ing due to deforestation or the construction of dams,

and irrigation systems such as rice fields, can lead to out- breaks. Outbreaks have also been associated with mining

activities in Africa, due to creation of pits with stagnant

water. In southern Australia several coastal towns have

reported local outbreaks. It is unclear what triggered these

outbreaks. World wide, mainly children are susceptible to

Buruli ulcer disease.

Map sources: The Buruli ulcer map was made by geolocating

confirmed cases reported in the medical literature up to 2010.

As Buruli ulcer is associated with water, the humidity index is

also shown.

Key references

Johnson PDR, et al. (2005) Buruli ulcer (M. ulcerans infection):

New insights, new hope for disease control. PLoS Med

2(4):e108.

Fyfe JAM, et al. (2010) A major role for mammals in the ecology

of Mycobacterium ulcerans. PLoS Negl Trop Dis 4(8):e791.

Nienhuis WA, et al. (2010) Antimicrobial treatment for early,

limited Mycobacterium ulcerans infection: a randomised con- trolled trial. Lancet 375(9715):664–672.

Portaels F, et al. (2008) First cultivation and characterization of

Mycobacterium ulcerans from the cnvironment. PLoS Negl

Trop Dis 2(3):e178.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

53

Page 7 of 113

Disease: Cholera

Classification: ICD-9 001; ICD-10 A00

Syndromes and synonyms: Summer diarrhea, acute

diarrhea.

Agent: Enterotoxin-producing Vibrio cholerae 01 and 0139 Ben- gal. Serogroup 01 has two biotypes, classical and El Tor, each

with three serotypes: Inaba, Ogawa, and the rarer Hikojima.

Reservoir: Principally humans; also warm-water marine and

estuarine copepods, other zooplankton. Crabs, shrimps, and

shellfish carry the vibrio on their carapaces and shells.

Vector: Main transmission is fecal–oral, but houseflies act as

supplementary vectors by contaminating food after feeding on

exposed human feces.

Transmission: Consuming fecally contaminated food or water,

raw or undercooked contaminated shellfish. Person-to- person transmission through indirect fecal–oral transmission

occurs. The role of bacteriophages needs further elucidation.

Cycle: Two interacting cycles can be distinguished: (1) a persis- tent cycle in the aquatic reservoir, and (2) in the human

host, leading to amplification through fecal–oral spread.

Incubation period: A few hours to 5 days; usually 2–3 days.

Clinical findings: Among those infected, about 20% develop

acute watery diarrhea, of which 10–20% develop severe

watery diarrhea with vomiting, leading to severe dehydration

which may be lethal if not treated. The CFR is typically below

5%, but in crowded refugee camps it can run as high as 50%.

Diagnostic tests: Dipstick test, dark-field or phase micros- copy on fecal or rectal swab smear; bacterial culture.

Therapy: Oral rehydration therapy (ORT) using reduced

osmolarity ORS; intravenous rehydration in severe cases.

Antibiotics are only useful to prevent spread, as they do not

affect the already released toxin.

Prevention: Hygiene, access to clean water and sanitation. An

oral cholera vaccine is available which is safe and provides

sustained protection of > 50% that lasts for 2 years in endemic

populations. The vaccine does not protect against infections

with O139 strains. Chemoprophylaxis for contacts may consist

of tetracycline or doxycycline. Breast-feeding protects infants.

Quarantine is ineffective. Infection results in limited protection

against homologous strains, but there is no cross-protection.

Cholera must be reported to national health authorities as small

local outbreaks may become large epidemics.

Epidemiology: Cholera is a common cause of epidemic diar- rhea throughout the developing world. There are an estimated

3 to 5million cholera cases and 100,000 to 130,000 deaths due to

cholera each year. The disease is endemic on the Indian

subcontinent, Southeast Asia and Sub-Saharan Africa. It has

a seasonal pattern with one or two peaks corresponding to the

warm season. Areas with overcrowding and poor sanitation

such as slums, refugee camps, and regions with political conflicts are at high risk for cholera outbreaks. Natural dis- asters (e.g. flooding) can be followed by cholera outbreaks due

to disruption of the sanitation system (see Natural Disasters

map). In 2010, a severe cholera epidemic was introduced into

Haiti by human activity from a distant geographic source.

Cholera was absent from Haiti for at least 100 years. Cases

have also been detected in Florida and the Dominican

Republic.

Current-circulating V. cholerae strains are of the O1 and O139

serotype. Cholera caused by O1 strains of the El Tor biotype

occurs world wide. The O1 classical biotype is confined to

Bangladesh. In India, some recently isolated strains display

characteristics of both the classical and El Tor biotype. Since

1992, the O139 serotype has caused cholera in Bangladesh and

India. Other serotypes of toxin-producing Vibrio cholerae (e.g.

O141 and O75) have caused severe diarrhea in patients who

consumed seafood from the Gulf Coast of the USA.

Map sources: The Cholera map was made with data

obtained from WHO and the medical literature from 2004

to 2010. The Haiti cholera outbreak was reported at the end of

2010.

Key references

Chin CS, et al. (2011) The origin of the Haitian cholera outbreak

strain. N Engl J Med 364(1):33–42.

Emch M, et al. (2008) Seasonality of cholera from 1974 to 2005: a

review of global patterns. Int J Health Geogr 7:31.

Nelson EJ, et al. (2009) Cholera transmission: the host,

pathogen and bacteriophage dynamic. Nat Rev Microbiol 7

(10):693–702.

Reidl J, et al. (2002) Vibrio cholerae and cholera: out of the

water and into the host. FEMS Microbiol Rev 26(2):125–139.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

55

Page 8 of 113

Disease: Diphtheria

Classification: ICD-9 032; ICD-10 A36

Syndromes and synonyms: Veldt sore (cutaneous

diphtheria).

Agent: Corynebacterium diphtheriae is a Gram-positive, aerobic

rod that is classified into three potentially toxigenic biotypes,

intermedius, mitis, and gravis. Toxin producing strains of

C. diphtheriae carry a bacteriophage-derived tox gene. Toxin- producing strains of C. ulcerans may also cause respiratory

diphtheria.

Reservoir: Humans. Cattle and other livestock may harbor

C. ulcerans. Transmission: Respiratory droplets from people with respi- ratory diphtheria, or from asymptomatic throat or nasal car- riers. Direct contact with discharge from the skin of cutaneous

diphtheria cases. People recovering from diphtheria may carry

the organism in the nasopharynx for weeks. Rarely from

contaminated items. In the past, outbreaks have been linked

to consumption of contaminated raw milk.

Incubation period: Usually 2–5 days (range 1–10 days).

Clinical findings: Respiratory diphtheria is classically associ- ated with fever, inflammation of the pharynx or larynx, pseu- domembrane formation, lymphadenopathy and edema of the

soft tissues of the neck. However, most cases are mild and may

resemble streptococcal pharyngitis and the pseudomembrane

may be absent. The exotoxin of C. diphtheriae can cause poly- neuritis and myocarditis. Nasal diphtheria is usually mild and

chronic with nasal discharge and ulceration. Cutaneous diph- theria is characterized by chronic, sharply demarcated ulcers

with an adherent gray pseudomembrane. It is usually associ- ated with skin infections caused by Staphylococcus aureus and

group A streptococci.

Diagnostic tests: Isolation of C. diphtheriae and C. ulcerans by

culture and toxigenicity testing of strains at reference labs.

Therapy: Therapy is aimed at neutralizing the potent exo- toxin, eradicating the organism, and providing supportive

care. Immediate treatment with diphtheria antitoxin and iv

antibiotics (penicillin or macrolide).

Prevention: Immunization with diphtheria toxoid, usually

formulated in a multivalent vaccine (see DTP3 map).

Recommended schedule is a primary course of three

doses in the first 4 months of life and one or two boosters

between 18 months and 5 years. Treatment of cases and

carriers with antibiotics to eradicate the organism and pre- vent further transmission.

Epidemiology: In the early 20th century diphtheria was the

leading cause of death in children aged 4–10 years in Europe,

and many countries experienced large diphtheria outbreaks

during World War II. Childhood vaccination has now virtu- ally eliminated diphtheria as a public health problem in most

developed countries, and diphtheria cases reported to WHO

have fallen by almost 93% between 1980 and 2008. The

WHO has estimated that around 5,000 deaths from diphthe- ria occurred in 2004, with 4,000 of these in children under 5

years of age. However, a steady decline in the global number

of reported diphtheria cases from 1980 was interrupted by a

large recrudescence in the early to mid-1990s in the former

Soviet Union. Since 1990, diphtheria outbreaks have also

occurred in Africa, the Middle East, Asia, and South America.

Without periodic immunological boosting through vaccina- tion or natural exposure to toxigenic strains of C. diphtheriae, adults may become susceptible to infection. Epidemics may

then occur, exacerbated by poor living conditions or the

emergence of new toxigenic variants. This has led to the

introduction of booster doses of toxoid in adolescents in

some non-endemic countries.

Map sources: The Diphtheria map was made with data

obtained from WHO, available at: http://www.who.int/

immunization_monitoring/en/.

Key references

Galazka A (2000) The changing epidemiology of diphtheria

in the vaccine era. JID 181(Suppl 1):S2–9.

World Health Organization (2009) State of the World’s Vaccines

and Immunization, 3rd edn. Geneva, WHO, UNICEF, World

Bank Report.

World Health Organization (2009) WHO Vaccine-Preventable

Diseases: Monitoring System. 2009 Global Summary: Immu- nization, Vaccines, and Biologicals.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Page 9 of 113

Disease: Donovanosis

Classification: ICD-9 99.2; ICD-10 A58

Syndromes and synonyms: Granuloma inguinale, granu- loma venereum.

Agent: Klebsiella granulomatis, formerly Calymmatobacter- ium granulomatis, a Gram-negative facultative aerobic

coccobacillus.

Reservoir: Human.

Vector: None.

Transmission: By sexual contact. In children with no history

of abuse, the route of transmission is unclear. Several reported

pediatric cases have been in contact with infected adults, but

without evidence of sexual contact.

Incubation period: Approximately 50 days, but varies.

Clinical findings: A progressive chronic illness of the skin and

mucous membranes in the genital and perigenital regions with

painless granulomatous ulcers and regional lymphadenopa- thy. Nodular skin lesions can appear as lymphadenopathy,

known as ‘pseudobulbar.’ The painless lesions are often found

in warm moist body regions and bleed easily. Lesions can be

progressive and cause local tissue destruction. Systemic

spread is rare but bones and internal organs may eventually

be infected.

Diagnostic tests: Detection of Donovan bodies in cytodiag- nostic or histopathologic examination (may be absent when

pretreated with antibiotics); histology is similar to that of

rhinoscleroma; PCR.

Therapy: Doxycycline; erythromycin for pregnant women;

alternatives are ceftriaxone, norfloxacin and trovofloxacin;

in cases of no response: gentamicin; surgery in advanced

cases. Prevention: Early diagnosis and treatment; safe sexual prac- tices (condom use). Proper bodily hygiene.

Epidemiology: It is endemic in tropical and subtropical cli- mates, such as Papua New Guinea, South Africa, parts of

India and Indonesia, and among the aborigines of Australia.

Some cases have been reported in the countries of Central

and South America and the Caribbean. The disease may be

related more to socioeconomic conditions than to racial or

geographical factors. In some settings it is a common cause

of chronic genital ulcers in HIV patients. In the USA, it is

more common in African-Americans, of people in lower

socioeconomic status, and those with poor hygiene. It has

been hypothesized that the natural habitat of K. granulomatis

is the intestine and that the skin is affected by direct contact

during anal coitus, or indirectly through contamination of

the genitals by fecal material. There is no gender difference

in incidence; most cases occur in adults between the ages of

20 and 40 years. There are no reports of congenital infec- tions, but cases have been reported in newborn and nursing

babies; the course of the disease is more aggressive during

gestation. Donovanosis increases the risk of subsequent HIV

infection.

Map sources: The Donovanosis map was made by geolocat- ing reported cases in the medical literature from 1990 to 2009.

Countries considered hotspots (relative high number of cases)

by experts are visualized.

Key references

O’Farrell N (2002) Donovanosis. Sex Transm Inf 78(6):452–457.

Velho P, et al. (2008) Donovanosis. Braz J Infect Dis

12(6):521–525.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

59

Page 10 of 113

Disease: Ehrlichioses

Classification: ICD-9 083.8; ICD-10 A77.4

Syndromes and synonyms: Human monocytic ehrlichioses

(HME), human granulocytic anaplasmosis (HGA), Sennetsu

fever.

Agent: Obligate intracellular, pleomorphic bacteria of the

family Anaplasmataceae, which invade host leukocytes. Ehrli- chia chaffeensis infects mononuclear phagocytes; E. ewingii

and Anaplasma phagocytophilum infects neutrophils. E. canis

may cause human disease in Venezuela. In 2009 an E. muris- like organism was discovered in USA. Neorickettsia sennetsu

causes Sennetsu fever.

Reservoir: Deer and dogs (E. chaffeensis, E. ewingii). The white- tailed deer is a complete host for maintaining the transmission

cycle of E. chaffeensis. Deer, ruminants, and field rodents (A.

phagocytophilum); unknown for N. sennetsu; other members of

the genus parasitize the trematode worms of aquatic verte- brates and invertebrates.

Vector: Ticks of the genera Amblyomma and Ixodes. Transmission: By tick bites, except for N. sennetsu, which is

probably transmitted through ingestion of uncooked, parasit- ized aquatic hosts. No person-to-person spread except by

blood transfusion.

Cycle: Tick to mammalian host to tick for Ehrlichia and

Anaplasma; trematode to aquatic host to trematode for

Neorickettsia. Human is a dead-end host for all. During the

eclipse phase of both HME and HGA infection, the blood

remains potentially infectious by blood transfusion.

Incubation period: 7–10 days for HME, 7–14 days for HGA,

14 days for Sennetsu fever.

Clinical findings: HME, HGA: fever, headache, anorexia,

myalgia, nausea, and vomiting; occasionally a rash. Leucope- nia and thrombopenia are common and thrombopenia may be

life-threatening. HME cases may progress to meningoenceph- alitis. Sennetsu fever: sudden onset fever, chills, malaise,

headache, muscle and joint pain, sore throat; generalized

lymphadenopathy. Reinfection can occur. CFR is 2.7% for

HME, <1% for HGA, and absent for E. ewingii infection.

Diagnostic tests: Serology (IFA on acute and convalescent

serum); cross-reactivity occurs. Microscopy of blood or bone

marrow smears is insensitive; PCR on acute phase whole

blood; isolation by cell culture in reference labs.

Therapy: Doxycycline for all patients. Rifampicin may be

useful for HGA in younger children and pregnant patients.

Prevention: Standard antitick precautions; avoidance of raw

aquatic food from N. sennetsu endemic regions.

Epidemiology: Ehrlichiosis occurs worldwide, principally

following the distribution of the transmitting tick vectors

and reservoir species. Less is known of the epidemiology

and ecology ofE. chaffeensis as compared to A. phagocytophilum. Most HME cases are reported in the south-central and -

eastern USA, where A. americanum reaches high population

densities. Approximately 70% of HME cases occur from May

to July in the USA, corresponding to the peak feeding activity

period of the ticks. HME is most commonly diagnosed in

adults, with a male-to-female ratio of > 2:1. Most HME

cases are single and not clustered. Recreational or occupational

activities in rural tick-infested habitats are at risk. Majority of

the cases have a history of a tick bite. Ehrlichiosis is often not

recognized in Africa, where the primary diagnostic focus is

malaria and typhoid fever. Sennetsu fever occurs in Asian

regions where the eating of raw fish is common, such as in

Japan. N. sennetsu has been detected in the climbing perch

in Laos, a fish common throughout the Mekong River, Basin.

Climbing perch is widely distributed and eaten in Asia.

Map sources: The Ehrlichioses map was made with the

following data and updates from medical literature: • Average annual incidence of ehrlichiosis and anaplasmosis

reported to CDC (2001–2002), available at: www.cdc.gov

• Vector distributions from Fauna of Ixodid Ticks of theWorld, at:

www.kolonin.org.

Key references

Ganguly S, et al. (2008) Tick-borne ehrlichiosis infection in

human beings. J Vector Borne Dis 45:273–280.

Ndip LM, et al. (2009) Molecular and clinical evidence of

Ehrlichia chaffeensis infection in Cameroonian patients

with undifferentiated febrile illness. Ann Trop Med Parasitol

103(8):719–725.

Newton P, et al. (2009) Sennetsu neorickettsiosis: a probable

fish-borne cause of fever rediscovered in Laos. Am J Trop

Med Hyg 81(2):190–194.

Paddock CD, et al. (2003) Ehrlichia chaffeensis: a prototypical

emerging pathogen. Clin Microbiol Rev 16(1):37–64.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Page 11 of 113

Disease: Endemic Treponematosis

Classification: ICD-9 102.0 (yaws), 103.0 (pinta), 104.0

(endemic syphilis); ICD-10 A65 (endemic syphilis), A66

(yaws), A67 (pinta).

Syndromes and synonyms: Endemic syphilis (bejel, non- venereal) syphilis, pinta (carate), yaws (frambesia), non- venereal treponematosis.

Agent: Treponema pallidum ssp. endemicum (bejel), T. pallidum

ssp. pertenue (yaws), and T. carateum (pinta), spirochetes that

are morphologically and serologically similar to T. pallidum

ssp. pallidum, the agent of syphilis.

Reservoir: Mainly humans; yaws is also found in non-human

primates (baboons, chimpanzees, and gorillas).

Vector: Possibly mechanic transmission by non-biting flies

(Hippelates pallipes) in the transmission of yaws.

Transmission: Direct transmission via skin to skin or oral

contact (also via sharing drinking and eating utensils). Sharing

of drinking vessels plays an important role in transmission of

endemic syphilis in arid regions. There is little or no mother-to- child transmission during pregnancy.

Incubation period: Endemic syphilis and yaws: 2 weeks to

3 months; pinta: 18 weeks.

Clinical findings: Similar to syphilis, the clinical manifesta- tions can be classified into early and late stages. Early-stage

lesions are generally infectious and may last up to 5 years,

with periods of latency. The disease has a relapsing clinical

course with mainly skin manifestations, which is the only

finding in pinta. In yaws and endemic syphilis there is also

involvement of the mucous membranes and the bones.

Cardiovascular and neurological lesions are extremely rare.

Diagnostic tests: Serology; there is no serological test that can

distinguish between T. pallidum and the non-venereal

T. pallidum subspecies. Definitively diagnosis by PCR and

sequencing.

Therapy: Single im injection with benzathine penicillin G.

Prevention: Prevent intimate contact with cases and contam- ination of environment from lesions. Lesions or discharge from

the lesions are infectious. Treat close contacts. There has been a

drastic decline in global disease prevalence since mass treat- ment campaigns with penicillin under the technical guidance

ofWHO and with material support from UNICEF in the 1950s

and 1960s.

Epidemiology: Endemic treponematoses is now rarely

reported since the eradication campaign. Complete eradica- tion may have been achieved if surveillance was continued and

rural healthcare services improved. Disease foci still exist, but

reports are lacking. Several nations fail to report to avoid the

stigma of ‘being backward.’ The WHO has estimated that 2.5

million people are still infected with endemic treponemes, and

about 460,000 are actively infectious. The disease primarily

afflicts children in tropical and subtropical areas. The distri- bution of endemic treponematoses is patchy and associated

with poverty and poor access to social and healthcare services;

it thus affects mainly rural communities in developing coun- tries (see Human Development map). Endemic syphilis gen- erally affects individuals in hot, arid climates, and yaws affects

those in hot and humid areas. Pinta is found only in Central

and South America, but has not been reported for over 40

years. No endemic syphilis cases have been reported since the

1980s. Yaws is also rare and currentlyis only reported from foci

in West Africa and Indonesia. Also, no new yaws cases have

been reported in India since 2004. It has been suggested that

the presence of non-venereal treponematoses indicates that the

country or region has a poor-quality healthcare system.

Map sources: The Endemic Treponematosis map was made

by combining data from Farnsworth et al. (2006) and WHO.

Key references

Antal GM, et al. (2002) The endemic treponematoses. Microbes

Infect 4(1):8394.

Asiedu K, et al. (2008) Yaws eradication: past efforts and future

perspectives. WHO Bulletin 86(7):499.

Farnsworth N, et al. (2006) Endemic treponematosis: review

and update. Clin Dermatol. Harper KN, et al. (2008) On the origin of the treponematoses:

a phylogenetic approach. PLoS Negl Trop Dis 2(1):e148.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

63

Page 12 of 113

Disease: Haemophilus influenzae Type b

Classification: ICD-9 320.0; ICD-10 G00.0

Syndromes and synonyms: None.

Agent: Haemophilus influenzae, a Gram-negative bacterium

that can be uncapsulated or capsulated. Capsulated strains

are classified into serotypes a–f. H. influenzaetype b (Hib) is the

most pathogenic serotype.

Reservoir: Humans.

Transmission: Hib is transmitted from person to person via

airborne droplets or direct contact with respiratory secretions.

Incubation period: Approximately 2–4 days.

Clinical findings: Hib is a common invasive bacterial infec- tion that primarily causes pneumonia, meningitis, and

bacteremia. Pneumonia due to Hib is clinically indistinguish- able from other causes of bacterial pneumonia. Hib meningitis

may present acutely or subacutely with fever, vomiting, leth- argy, irritability, and a bulging fontanelle in infants or a stiff

neck in older children. Bacteremia may be present with men- ingitis or pneumonia but may also occur without an obvious

focus of infection. Hib may also cause epiglottitis, which

presents with fever, sore throat, and difficulty swallowing,

talking and breathing. Infections of soft tissue, bones, and

joints with H. influenzae may occur.

Diagnostic tests: Gram stain and culture of CSF, blood, or

synovial fluid. Capsular polysaccharide antigen detection by

latex agglutination or other techniques. PCR from normally

sterile site.

Therapy: Third generation cephalosporins (e.g. ceftriaxone or

cefotaxime). Other beta-lactam antibiotics may be used in case

the organism is susceptible, like amoxicillin. Alternative

agents are: fluoroquinolones, macrolides, and tetracyclines.

Prevention: Vaccination of children with three doses of Hib

conjugate vaccine from the age of 2 months, with a booster dose

aged 12–15 months. Since household contacts of confirmed

cases of invasive Hib disease are at increased risk of disease,

rifampicin prophylaxis is recommended for all household

members if the household contains an infant or inadequately

immunized children under the age of 3 years.

Epidemiology: In the absence of vaccination, Hib is com- monly carried in the nose and throats of healthy individuals

and almost all children are exposed to Hib by the age of 5. In

developed countries (prior to immunization), Hib was the

commonest cause of bacterial meningitis in young children,

but in countries with high vaccination coverage Hib is now

almost eliminated as a public health problem. In developing

countries Hib meningitis is common but Hib pneumonia

appears to be even more common, with pneumonia

morbidity and mortality exceeding that of meningitis. In

2000 Hib is estimated to have caused around 8 million cases

of severe invasive disease and 360,000 deaths in children under

5 years of age. Ten countries, all in Africa and Asia, accounted

for an estimated 61% of all these Hib deaths. Hib pneumonia is

estimated to be responsible for around 16% of pneumonia

deaths in HIV-negative children, therefore Hib makes an

important contribution to the high childhood mortality rates

and low life expectancy of Sub-Saharan Africa. Global cover- age with three doses of Hib vaccine was estimated at 28% in

2008, with overall coverage of around 90% in the Americas,

65% in Europe, 40% in Africa, and less than 5% in Asia and the

Pacific. The introduction of Hib vaccination has however been

accelerating and by the end of 2009, in 83% of WHO Member

States (160/193), Hib is included in the national immunization

schedule.

Map sources: Data for the Haemophilus influenzae map were

obtained from WHO, available at: http://apps.who.int/

immunization_monitoring/en/globalsummary/timeseries/

tscoveragehib3.htm (vaccination coverage) and http://www.

who.int/nuvi/hib/db_hib1.jpg (incidence).

Key references

Levine OS, et al. (2010) Global status of Haemophilus influ- enzae type b and pneumococcal conjugate vaccines: evi- dence, policies, and introductions. Curr Opin Infect Dis 23

(3):236–241.

Watt J.P, et al. (2009) Burden of disease caused by Haemophi- lus influenzae type b in children younger than 5 years: global

estimates. Lancet 374(9693):903–911.

WHO, UNICEF, World Bank (2009) State of theWorld’s Vaccines

and Immunization, 3rd edn. Geneva, World Health Organi- zation, Report.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

65

Page 13 of 113

Disease: Leprosy

Classification: ICD-9 030; ICD-10 A30

Syndromes and synonyms: Hansen disease, multibacillary

leprosy (ML), paucibacillary leprosy (PL), lepromatous lep- rosy, tuberculoid leprosy.

Agent: Mycobacterium leprae, a slow-growing, acid-fast, intra- cellular bacterium. It grows best at 27–30 C, which explains

the main target organs of M. leprae: skin, peripheral nerves,

nasal mucosa, upper respiratory tract, and eyes.

Reservoir: Humans are the main reservoir. Subclinical infec- tion is likely common in endemic areas, as M. leprae DNA

can be found in nasal swabs in up to 5% of healthy individuals

in Asian endemic regions. Subclinical infection generally does

not develop into clinical disease. Natural infection occurs in

armadillos and several primates.

Transmission:The precise mechanism is unclear: probably by

aerosol spread of nasal secretions from a case to respiratory

mucosa of close contacts.M. leprae cannot cross intact skin. The

relative risk for leprosy disease in household contacts is 8 to 10

for multibacillary (lepromatous) leprosy and 2 to 4 for pauci- bacillary (tuberculoid) leprosy.

Incubation period: 3 to 5 years (range 9months to > 20 years);

shorter for PL than for ML.

Clinical findings: The disease mainly affects the skin, periph- eral nerves, mucosa of the upper respiratory tract and the eyes,

shown by patches of pigmented or reddish skin with loss of

sensation, peripheral nerve enlargement with loss of sensation,

sometimes paralysis, muscle wasting and trophic ulcers.

Patients are classified as having either PL or ML. PL

is milder and characterized by < 5 skin patches or lesions.

ML is defined as 5 skin patches or lesions. Skin lesions are

often symmetric. Involvement of the nasal mucosa results in

nasal congestion and epistaxis. Reduced sensation of digits

may lead to their loss due to trauma. Up to 10% of cases with

early lesions may resolve spontaneously.

Diagnostic tests: According to the WHO leprosy case defi- nition, at least one of the following: (1) hypopigmented or

reddish skin lesion(s) with loss of sensation, (2) thickening of

the peripheral nerves with loss of sensation, and (3) acid-fast

bacilli in skin smear (often negative). Histology is the gold

standard. M. leprae cannot be cultured in vitro.

Therapy: PL: dapsone and rifampicin for 6 months. ML:

dapsone, rifampicin, amd clofazimine for 24 months. Relapses

may occur in up to 2.5% of treated cases.

Prevention: Leprosy control is achieved by timely detection

and treatment of new cases. BCG vaccination provides vari- able protection: from 34% to 80%. Chemoprophylaxis and

quarantine are not recommended. M. leprae bacilli remain

viable for 9 days in dried nasal secretions and about 6

weeks in moist soil.

Epidemiology: The disease is thought to have originated in

the tropics and subtropics of Africa and Asia. WHO reported

213,036 leprosy cases at the beginning of 2009. Although the

worldwide prevalence has declined in the last two decades, the

incidence has remained the same. India had the most new

cases in 2008 (134,000), followed by Brazil (39,000), and Indo- nesia (17,000). Males are affected more than females (2:1);

young children are rarely infected. Epicurves for PL show a

peak at age 15 followed by a trough at age 20. WHO considers

that leprosy has been eliminated as a public health problem in

any country when the prevalence is less than 1 case per 10,000

population. In 2007, the DRC and Mozambique achieved that

status. Also India reported that their national prevalence is

below 1/10,000. However, pockets of high endemicity still

remain in some areas within those countries. Decreased prev- alence without a reduction in incidence maylead to an increase

of cases as countries may be less committed to control them

once they meet elimination status. Foci in Brazil are found in

the Amazonian jungle, but also in arid areas. Poverty and

crowded dwellings are important risk factors. Leprosy in

North America and Europe has declined to zero cases in

line with improvement in living conditions.

Map sources: Data for the Leprosy map were obtained from

WHO: www.who.int/lep/situation/en/. The leprosy clusters

in Brazil were obtained from Penna et al. (2009).

Key references

Britton WJ, et al. (2004) Leprosy. Lancet 363:1209–1219.

Penna MLF, et al. (2009) Spatial distribution of leprosy in the

Amazon region of Brazil. Emerg Infect Dis 15(4):650–652.

Scollard DM, et al. (2008) The continuing challenges of leprosy.

Clin Microbiol Rev 19(2):338–381.

World Health Organization (2009) Global leprosy situation,

2009. Weekly Epidemiol Rec 33(84):333–340.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Page 14 of 113

Disease: Leptospirosis

Classification: ICD-9 100; ICD-10 A27

Syndromes and synonyms: Weil disease, swamp fever, cane

cutters disease, hemorrhagic jaundice, swineherd disease.

Agent: Multiple species of the spirochetal genus, including

Leptospira interrogans, whichis the species associated withmost

severe disease. There are currently 8 species found to be

pathogenic for humans, associated with > 250 serovars

belonging to the pathogenic species. Antigenically related

serovars are grouped into 24 serogroups. A single serovar

may belong to different Leptospira species.

Reservoir: Rats and other rodents, dogs, cattle, and pigs are

the most important zoonotic reservoirs of human infection.

Transmission: Direct contact of abraded skin or conjunctival

mucosa to urine of infected animals or exposure to

environmental sources where urine is deposited. Infection

via ingestion is uncommon.

Cycle: Leptospira chronically colonize the proximal renal

tubules of many animals and are excreted in the urine into

the environment. Animals can shed Leptospira into the envi- ronment for prolonged periods without any signs of disease.

Incubation period: 1–3 weeks.

Clinical findings: From asymptomatic to fatal. Acute febrile

illness with chills, headache, severe myalgia (with mild rhab- domyolysis), conjunctivitis and gastrointestinal symptoms.

Less common findings are hepatomegaly, rash, lymphadenop- athy, jaundice, and aseptic meningo-encephalitis. Pulmonary

symptoms may occur varying from cough, dyspnea, and

hemoptysis, to adult respiratory distress syndrome. Weil

disease is a severe form of leptospirosis and is characterized

by jaundice, renal failure and hemorrhage with a CFR of

5–20%.

Diagnostic tests: Serology (acute and convalescent sera)

using the microscopic agglutination test (MAT). Isolation of

leptospira from blood or CSF during first 10 days of illness and

urine during the 2nd and 3rd weeks; PCR may provide early

diagnosis. Dark-field microscopy is not recommended.

Therapy: Supportive and antibiotics: oral doxycycline,

ampicillin or amoxicillin for mild disease, parenteral penicillin

G, ceftriaxone or cefotaxime for severe disease.

Prevention: Occupational hygiene by the use of protective

clothing and avoiding contaminated surface waters

(difficult in case of flooding in developing countries). Envi- ronmental control measures, like rodent and flood control,

are difficult to implement. Chemoprophylaxis for adventure

travelers, military personnel who visit endemic areas, and

after an accidental lab exposure.

Epidemiology: Leptospirosis has a worldwide distribution, is

more common in tropical regions where it is both an occupa- tional disease and a disease of ‘daily lives,’ mainly during

heavy rainfall. Most foci are found in Latin America and the

Caribbean, India, Southeast Asia, Oceania, and eastern Eur- ope. The agent favors warm, humid environments. The prev- alence of different serovars depends on the reservoir in which

animals are present, local environmental conditions, local

occupation, and agricultural practices. Protective measures

have decreased the occupational risk in high-risk jobs, like

mining, sewermaintenance, farming, veterinary work, and the

military. In the tropics, occupational exposures (rice and sugar

cane farming, fishing) and other agricultural activities remain

an important risk. Leptospirosis is an emerging disease in

slums, especially during rainy seasons. Also large recreational

events with water exposure can be an important source of big

multinational outbreaks.

Map sources: The Leptospirosis map was made by geocoding

reported human leptospirosis outbreaks in ProMED-mail and

the medical literature between 2000 and 2010.

Key references

Adler B, et al. (2010) Leptospira and leptospirosis. Vet Microbiol

140(3–4):287–296.

Bhart AR, et al. (2003) Leptospirosis: a zoonotic disease of

global importance. Lancet Infect Dis 3:757–771.

Pappas G, et al. (2008) The globalization of leptospirosis:

worldwide incidence trends. Int J Infect Dis 12:351–357.

Reis RB, et al. (2008) Impact of environment and social gradient

on leptospira infection in urban slums. PLoS Negl Trop Dis 2

(4):e228.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

69

Page 15 of 113

Disease: Listeriosis

Classification: ICD-9 027.0; ICD-10 A 32.1

Syndromes and synonyms: Listeriasis, listerellosis.

Agent: Listeria monocytogenes, a Gram-positive rod-shaped

intracellular bacterium. There are at least 13 serotypes, with

serotypes 1/2a, 1/2b, and 4b causing most disease. L. ivanovii

is a very rare enteric opportunistic human pathogen.

Reservoir: Soil, (decaying) vegetation, and ruminants.

Humans and ruminants can carry listeria in their intestines.

Transmission: Food-borne and transplacental (mother to

child). Ingestion of L. monocytogenes occurs commonly

world wide. Development of the disease depends on the

host immunity.

Cycle: Listeria bacteria in the environment or food are

ingested by ruminants and humans, colonize the intestine

and shed again into the environment with the feces. L. mono- cytogenes is able to cross the intestinal mucosa under specific

conditions, resulting in systemic disease or hematogeneous

spread to the central nervous system and, in the case of

pregnancy, fetus.

Incubation period: 3 to 70 days, usually about 3 weeks. For

gastroenteritis: hours to 10 days with a mean of 24 hours.

Clinical findings: Non-invasive GI listeriosis: fever, muscle

aches, nausea and diarrhea. Invasive listeriosis: septicemia,

meningoencephalitis, and perinatal listeriosis. Meningoenceph- alitis: headache, stiff neck (often absent), confusion, convulsions

and coma (CFR: 20–30%). Infection during pregnancy can lead to

miscarriage, stillbirth and infection of the newborn. Pregnant

womenmost commonly haveflu-likesymptoms. Focalinfections

in any organ may occur. Focal cutaneous and eye infections can

occur after direct inoculation with contaminated tissue, usually

occupational. Listerial gastroenteritis is uncommon.

Diagnostic tests: L. monocytogenes can be detected from

blood and CSF by microscopy/culture or PCR. MRI is indi- cated for suspected brainstem infection (rhombencephalitis).

Serology is not useful for diagnosis.

Therapy: First choice is ampicillin or penicillin G. Gentamicin

is added in case of immunosuppression, endocarditis, and

meningitis. Alternative: trimethoprim-sulfamethoxazole.

Prevention: Pasteurization. Persons at high risk of infection

should avoid high-risk foods (smoked fish, raw meat sausage,

soft cheeses) and sufficiently heat foods (e.g. left-overs), che- moprophylaxis can be given to susceptible persons at risk after

exposure to contaminated food. The organism can replicate at

refrigerator temperatures.

Epidemiology: The disease is distributed worldwide, with the

majority cases attributed to contaminated processed foods.

Listeriosis is, after salmonellosis, the second most frequent

cause of food-borne infection-related deaths in Europe. The

disease incidence has decreased in the USA, while it increased

in Europe for unknown reasons. The more regular use of

immunosuppressive medications and the increasing size of

the elderly population has increased the population at risk in

both Europe and the USA. The majority of invasive listerial

infections occurs in individuals with predisposing conditions:

pregnancy, corticosteroid use, or other immunosuppressive

conditions. One-third of reported cases occur in pregnant

women. In non-pregnant patients corticosteroid use is the

most important predisposing factor. Clinical data from Asia,

Africa, and South America are lacking. L.monocytogenes has

been found in food products from these regions. Food-borne

outbreaks, many of which are manifested by febrile gastroen- teritis, have been described with a variety of foods. The most

common are processed/delicatessen meats, hot dogs, soft

cheeses, smoked seafood, meat spreads, and pates. Infections

from animal contact are uncommon and generally occur in

veterinarians, abattoir workers, and farmers.

Map sources: The Listeria map was made by geocoding

human listeria outbreaks (at least two related cases) reported

in ProMED-mail and the medical literature between 2000 and

2010.

Key references

Allerberger F, et al. (2010) Listeriosis: a resurgent foodborne

infection. Clin Microbiol Infect 16(1):16–23.

Guillet C, et al. (2010) Human listeriosis caused by Listeria

ivanovii. Emerg Infect Dis 16(1):136–138.

Siegman-Igra Y, et al. (2003) Listeria monocytogenes infection

in Israel and review of cases worldwide. Emerg Infect Dis

8(3):305–310.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

71

Page 16 of 113

Disease: Lyme Disease

Classification: ICD-9 088.81; ICD-10 A69.2

Syndromes and synonyms: Lyme borreliosis, erythema

(chronicum) migrans (EM), tick-borne meningopolyneuritis,

acrodermatitis chronica atrophicans.

Agent: The spirochete Borrelia burgdorferi. Initially identified

as a single species,B. burgdorferi has been separatedinto at least

12 species. Almost all cases of Lyme disease are caused by B.

burgdorferi sensu stricto, B. garinii, and B. afzelii, and very few

by B. spielmanii and B. lusitaniae. Reservoir: Small rodents (mice, voles, rats) and insectivores

(shrews, hedgehogs) are the most common animal reservoirs

of Borrelia, while larger animals (deer, livestock) serve as

hosts for the tick vectors. Hares and birds may also serve as

reservoirs. Ticks by trans-stadial transmission; transovarial

transmission in ticks is limited.

Vector: Hard ticks, principally Ixodes scapularis (formerly

I. dammini) and I. pacificus in North America, I. persulcatus

and I. ricinus in Eurasia. In Russia, the principal vectors are

I. persulcatus in the west and I. ricinus in the east.

Transmission: By tick bite or blood transfusion. Most trans- mission to humans is by the nymphal tick stage.

Cycle: Tick-small mammals and birds-tick; large mammals

are necessary to maintain tick populations. Humans and

lizards are dead-end hosts.

Incubation period: 3–32 days, mean 7–10 days for EM. Since

EM can remain absent, the interval between the tick bite and

disease can be much longer.

Clinical findings: Lyme borreliosis is a multisystem disease

that can affect the skin, heart, nervous system and, less com- monly, the eyes, kidneys, and liver. Often there is an annular

skin rash that develops at the bite site, known as EM. After

several months, approximately 60% of patients with untreated

infection will have intermittent arthritis. Up to 5% of untreated

patients develop chronic neurological complaints months to

years after infection. Re-infection can occur.

Diagnostic tests: Lyme disease is a clinical diagnosis and

laboratory testing is supportive. ELISA or IFA, confirmed by

IgM and IgG Western or striped blot test. PCR on blood, CSF,

urine and tissues, but is not standardized.

Therapy: Early Lyme disease is generally treated for 10–14

days, late Lyme disease for 21–30 days. Oral antibiotics

commonly used are: doxycycline or amoxicillin. Patients

with neurological or cardiac forms of illness may need iv

ceftriaxone or penicillin.

Prevention: Tick bite prevention by avoiding wooded and

bushy areas with high grass and leaf litter, especially in

summer months; insect repellents; minimize bare skin check

for tick bites and remove them within 24 hours.

Epidemiology: Lyme disease is the most commonly reported

vector-borne diseasein bothNorthAmerica and Europe, where

its incidence is increasing. Incidence is seasonal, corresponding

to increased vector activity during summer. The three Borrelia

species differ in geographic location, vectors, and clinical man- ifestations: B. burgdorferi ss is present both in North America

and Europe, but is absent from Asia; B. garinii andB. afzelii occur

in Europe and Asia. A recent study showed that B. garinii is the

main genotype in China. Data of B. burgdorferi presence are

lacking for South America, Sub-Saharan Africa, South and

Southeast Asia. In the USA the disease is focal: most cases

come from limited areas in the northeastern and upper mid- western regions. In the Baltic region, disease rates are several

fold higher than in the USA. Incidences vary, ranging from 0.3/

100,000 in the UK to 130/100,000 in Austria. Climate change,

more housing in wooded areas, and expanding populations of

deer, and small rodents may be responsible for the increase in

Lyme disease cases. None of the mammal species identified as

reservoir hosts and none of the transmitting ticks are present in

Australia.

Map sources: The Lyme disease map was made with data

obtained from the CDC for USA (www.cdc.gov/ncidod/

dvbid/lyme/) and R. Smith et al. (2006) for Europe. Tick

distributions were redrawn from Kolonin’s website on Fauna

of Ixodid Ticks of the World, available at: www.kolonin.org.

Key references

Goodman JL (eds), et al. (2005) Tick-Borne Diseases of Humans. ASM Press.

Gratz N (2004) The Vector-Borne Human Infections of Europe:

Their Distribution and Burden on Public Health. WHO

Regional Office for Europe, pp. 1–144.

Hao Q, et al. (2011) Distribution of Borrelia burgdorferi sensu

lato in China. J Clin Microbiol 49(2):647–650.

Smith R, et al. (2006) Lyme borreliosis: Europe-wide coordi- nated surveillance and action needed? Euro Surveill 11(25).

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

73

Page 17 of 113

Disease: Melioidosis

Classification: ICD-9 025; ICD-10 A24.1-A24.4

Syndromes and synonyms: Whitmore disease.

Agent: Burkholderia pseudomallei, (formerly Pseudomonas

pseudomallei), an aerobic, motile Gram-negative bacillus of

the beta-proteobacteria group. It is oxidase positive, resistant

to a wide range of antibiotics including gentamicin, poly- myxin, and the second-generation cephalosporins. A similar

disease of equines called glanders, now rare (extinct in the

Americas), is caused by the related bacterium B. mallei. Both

B. mallei and B. pseudomallei are listed as potential biological

warfare agents.

Reservoir: B. pseudomallei is a soil and water saprophyte and

can survive for long periods in moist soil and mammalian

tissues. Infection has been found in a wide range of animals,

but none is thought to be a reservoir host.

Transmission:Through breaks in skin, ingestion or aspiration

of contaminated water, inhalation of contaminated dust. There

are rare reports of transmission from human or animal cases to

humans. Laboratory workers have been infected by aerosols.

Incubation period: 1–21 days for most acute cases but acti- vation of latent infection has occurred from 25 to 63 years after

exposure.

Clinical findings: Range from asymptomatic pulmonary con- solidation to mild bronchitis, through acute pneumonic or

rapidly fatal septicemic presentations to chronic suppurative

infection. Pulmonary cavitation, osteomyelitis and empyema

may also be seen. Easily confused clinically with typhoid fever

and tuberculosis, and laboratories may not recognize the

causative organism and report it as a contaminant.

Diagnostic tests: Isolation of agent from blood, urine,

sputum, pus or skin lesions; direct immunofluorescence; serol- ogy. PCR may be of value on samples other than blood.

Therapy: Drain abscesses, iv ceftazidime, meropenem or

imipenem followed by eradication treatment using cotrimox- azole, with or without doxycycline. Amoxicillin-clavulanic

acid is an alternative for those with resistant strains or

where co-trimoxazole is contraindicated. Also usually

sensitive to piperacillin or ticarcillin with clavulanic acid.

There is an up to 10% relapse rate.

Prevention: Avoid contamination of skin by potentially

infected soil or water. There is no vaccine available.

Epidemiology: The true worldwide distribution and inci- dence is unknown. Antibody prevalence in humans and live- stock in countries with sporadic cases suggest that most

human infections are subclinical or benign, or misdiagnosed

and underreported.

Cases are mainly sporadic and have been reported in

humid areas of the tropics and subtropics world wide, mainly

during the rainy season. Cases have been reported in dryer

areas, like northeastern Brazil and north Iran. This is likely

explained by the fact that these two areas have irrigated rice

fields. In Southeast Asia, it is a disease of mainly rice farmers

and others who are occupationally exposed to contaminated

soil or water. In northeast Thailand, 20% of community- acquired septicemic cases are due to melioidosis, which

accounts for 39% of fatal septicemias and 36% of fatal com- munity-acquired pneumonias. Up to 80% of cases occur in

those who are predisposed by underlying immunocompro- mising conditions such as diabetes, chronic renal disease, or

alcoholism, age, chronic infection, or immunosuppressive

therapy. Sporadic human infections with glanders (B. mallei),

occur in equine veterinarians and pathologists, horse butch- ers, and laboratory workers.

Map sources: The Melioidosis map was made by geocoding

confirmed cases reported in the medical literature up to 2010.

Imported cases were excluded. The global precipitation data

are obtained from WorldClim (www.worldclim.org).

References

Cheng AC (2010) Melioidosis: advances in diagnosis and

treatment. Curr Opin Infect Dis 23(6):554–559.

Cheng AC, et al. (2005) Melioidosis: epidemiology, pathophys- iology, and management. Clin Microbiol Rev 18(2):383–416.

Currie BJ (2008) Advances and remaining uncertainties in the

epidemiology of Burkholderia pseudomallei and melioido- sis. Trans R Soc Trop Med Hyg 102(3):225–227.

Peacock SJ (2006) Melioidosis. Curr Opin Infect Dis

19(5):421–428.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

75

Page 18 of 113

Disease: Meningococcal Meningitis

Classification: ICD-9 036.0; ICD-10 A39.0

Syndromes and synonyms: None

Agent: Neisseria meningitidis, a Gram-negative aerobic diplo- coccus. Pathogenic N. meningitidis produce a polysaccharide

capsule, used for serogrouping. Five serogroups are responsi- ble for most cases: A, B, C, W135, and Y.

Reservoir: Humans. Asymptomatic carriage of N.meningitidis

in the oropharynx is common, although carriage rates vary

widely by geographic and epidemiological setting. The carrier

state is immunizing and development of meningococcal dis- ease is associated with recent acquisition.

Route of transmission: N. meningitidis is transmitted from

person to person by respiratory droplets.

Incubation period: 2–10 days, commonly 3–4 days

Clinical findings: Classically meningococcal meningitis pre- sents with fever, headache, neck stiffness, photophobia, nau- sea, and vomiting. In infants and young children the clinical

picture may be non-specific. If the patient also has meningo- coccal bacteremia, a hemorrhagic skin rash may be seen.

Diagnostic tests: Gram stain and microscopy of cerebrospi- nal fluid, and culture. Latex agglutination tests for detection of

group-specific capsular polysaccharide. PCR.

Therapy: Early iv or im antibiotic therapy: iv benzylpenicillin,

third-generation cephalosporin or chloramphenicol.

Prevention: Polysaccharide vaccines against A, C, Y, and

W135 are available. These vaccines are safe and effective in

adults and older children but are poorly immunogenic in

children under the age of 2 and the duration of protection is

limited to 3–5 years. The development of a group C conjugated

meningococcal vaccine that is effective in children under the

age of 2 years has been an important advance, and conjugate

vaccines are now available for A, C, Y, and W135. The devel- opment of a group B vaccine remains a challenge. Chemopro- phylaxis of close contacts eradicates carriage and reduces the

incidence of secondary cases. Vaccination of household con- tacts may also prevent further cases.

Epidemiology: World wide, but the epidemiology of the

meningococcal meningitis is regionally heterogeneous

and dynamic. Group A causes the highest incidence and is

responsible for large epidemics every 5–10 years in a belt

that stretches across the semi-arid regions of Sub-Saharan

Africa: the ‘meningitis belt.’ These epidemics occur in the

dry season and are associated with periods of low absolute

humidity and dusty conditions. The map opposite shows the

probability of meningococcal meningitis epidemics in Africa

based on reported epidemics occurring between 1841 and 1999

and predicted from differences in physical environmental

conditions between the regions where epidemics have ever

and never occurred. The map provides a reasonable descrip- tion of ‘at-risk’ areas and matches well with the WHO defined

‘meningitis belt.’ However, other factors will also influence

the epidemiology, e.g. demographic and social patterns, and

immunological susceptibility. While epidemic meningococcal

disease does occur in Asia (China – serogroups A, C; India –

serogroup A; Philippines – serogroup A) endemic disease

activity appears to be low, for reasons that are unclear.

Group A epidemics used to occur in western countries but

disappeared after World War II and now groups B and C

predominate, tending to cause sporadic cases or small clusters

in temperate climates and in South America. A significant

proportion of disease due to serogroup Y has been reported

from Canada, the USA, Columbia, and South Africa. Group

W135 had been rare until outbreaks were detected in association

with the annual Islamic pilgrimage to Mecca in Saudi Arabia

(The Hajj) in 2000. It has now emerged as a cause of epidemics in

the meningitis belt, South Africa and Argentina.

Map sources: The Meningococal Meningitis map was made

with data from the International Research Institute for Climate

and Society (http://portal.iri.columbia.edu/portal/server.

pt), Harisson et al. (2009), and Savory et al. (2006).

Key references

Harrison LH, et al. (2009) Global epidemiology of meningo- coccal disease. Vaccine 27S:B51–B63.

Molesworth AM, et al. (2003) Environmental risk and meningi- tis epidemics in Africa. Emerg Infect Dis 9(10): 1287–1293.

Savory EC, et al. (2006) Evaluation of the meningitis epidemics

risk model in Africa. Epidemiol Infect 134(5):1047–1051.

Stephens DS, et al. (2007) Epidemic meningitis, meningococ- caemia, and Neisseria meningitidis. Lancet 369:2196–2210.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

77

Page 19 of 113

Disease: Noma

Classification: ICD-9 528.1; ICD-10 A69.0

Syndromes and synonyms: Cancrum oris, gangrenous

stomatitis

Agent: Oral commensal bacteria such as Fusobacterium necro- phorum, F. nucleatum and a spirochete (formerly identified as

Borrelia vincenti) are the suspected etiological agents.

Reservoir: Human buccal flora. Transmission: Noma is an opportunistic infection with

endogenous buccal flora. Incubation period: Days to weeks.

Clinical findings: Noma is an opportunistic infection that

evolves rapidly from a gingival inflammation to severe, muti- lating orofacial gangrene, which is painless and usually uni- lateral. It begins as a small vesicle or ulcer on the gingiva that

rapidly becomes necrotic and spreads to produce extensive

destruction of the buccal and labial mucosa and tissues of the

face, including the bone, which may result in severe disfigure- ment and even death. Noma can also cause tissue damage to

the genitals (noma pudenda).

Diagnostic tests: None. Diagnosis is made by clinical

examination.

Therapy: Penicillin and metronidazole; rehydration; nutri- tional rehabilitation; treatment of predisposing diseases (e.g.

malaria, measles, tuberculosis); wound disinfection; recon- structive surgery.

Prevention: Noma can be prevented through health educa- tion, poverty reduction, improved nutrition, promotion of

breastfeeding, proper prenatal care and immunisations

against childhood diseases.

Epidemiology: The incidence of Noma and the prevalence of

survivors of Noma are not well known. In 1998, WHO esti- mated that 770,000 people had been affected in the past and

survived the affection, and that 140,000 new cases were

reported each year, of which 100,000 were between 1 and

7 years old and living in Sub-Saharan Africa. An estimation of

the global incidence based on epidemiological field work in

north-west Nigeria indicates 30,000 to 40,000 new cases per

year. It occurs predominantly in debilitated and malnourished

children, especially in underdeveloped countries. Peak inci- dence is at age 1–4 years, the period of growth retardation in

deprived children. The etiology is multifactorial: malnutrition,

concurrent infections with malaria or measles, bad oral

hygiene, severe diarrhea and severe necrotic ulcerative gingi- vitis are risk factors. In developed countries sporadic

cases occur in immune-compromised patients, neonates,

HIV-positive and diabetic patients.

Map sources: The Noma map is modified from Enwonwu

et al. (2006) and updated with cases reported in the medical

literature (2000–2009). The Noma belt was drawn based on

expert opinion that stated that African countries directly

under Sahara (Senegal to Ethiopia) are ‘the noma belt of

the world’. Key references

Enwonwu CO, et al. (2006) Noma (cancrum oris). Lancet

368:147–156.

Fieger A, et al. (2003) An estimation of the incidence of noma in

north-west Nigeria. Trop Med Int Health 5:402–407.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

79

Page 20 of 113

Disease: Pertussis

Classification: ICD-9 033.0, 033.9; ICD-10 A37.0, A37.9

Syndromes and synonyms: Whooping cough

Agent : Bordetella pertussis a Gram-negative, fastidious bacte- rium (Bordetella parapertussis causes a milder illness called

parapertussis).

Reservoir: Humans.

Transmission: Direct person-to-person transmission via

respiratory droplets.

Incubation period: Average 7–10 days (range 5–21 days).

Clinical findings: Classical pertussis has a prodromal stage of

1–2 weeks with coryza and a mild, persistent cough that

progresses to paroxysms of violent coughing interspersed

with an inspiratory whoop. Vomiting may follow coughing

bouts. This stage can last 4–6 weeks. Adolescents and adults

often do not have paroxysms and whooping, presenting more

commonly with a prolonged cough. Asymptomatic infection

may also occur. Infants under 6 months may present with

apnea, and deaths occur mostly in this age group. Serious

complications include pneumonia, seizures, cerebral hypoxia,

and encephalopathy.

Diagnostic tests: Culture is the gold standard but is insensi- tive. PCR is more sensitive than culture. Serology may

be helpful in patients presenting 3 weeks or more after

cough onset, when both culture and PCR are likely to be

negative.

Therapy: Antibiotic treatment with a macrolide antibiotic is

mainly indicated to reduce communicability in those present- ing within 3 weeks of onset. Hospitalization may be needed in

severe causes for supportive care.

Prevention: Two or more doses of a pertussis-containing

vaccine are necessary for protection. Global coverage with

three doses of a pertussis-containing vaccine are shown

elsewhere (see DTP3 map). Infants under the age of 3–5

months are, depending on the vaccination schedule, too

young to have received two doses and are also vulnerable

to complications of pertussis. This group therefore suffers the

greatest burden of pertussis mortality. Post-exposure pro- phylaxis with a macrolide antibiotic may be recommended

for contacts in households where there is a susceptible mem- ber (e.g. an infant).

Epidemiology: Pertussis immunization has been successful in

reducing the burden of pertussis disease and deaths, with

around 150,000 cases reported in 2008 compared to almost

2 million cases in 1980. However, these figures must be inter- preted with great caution since reporting is mostly based on

clinical diagnosis, whichis not easyin neonates, older children,

and adults. The WHO estimated that nearly 18 million cases

and 254,000 deaths occurred in 2004, of which 90% were in

developing countries. Although pertussis disease has clearly

been reduced by immunization, it is not clear to what extent

immunization has reduced circulation of B. pertussis. The con- tinued risk of pertussis in unimmunized infants and the per- sistence of epidemic cycles indicate that B. pertussis

transmission continues despite vaccination programs. Several

developed countries with high coverage in children have expe- rienced outbreaks of pertussis in adolescents and adults. Immu- nity following natural pertussis infection or vaccination is not

permanent, therefore high coverage with pertussis vaccines in

children has shifted susceptibility and peak incidence to ado- lescents and young adults; these age groups are then transmit- ting infection to young infants. Since pertussis in adults usually

manifests as only a prolonged cough it is difficult to identify

cases and protect infants.

Map sources: The Pertussis map was made with pertussis

incidence and immunization data obtained from WHO,

available at: http://apps.who.int/immunization_monitoring/

en/.

Key references

Cherry JD (2005) The epidemiology of pertussis: a comparison

of the epidemiology of the disease pertussis with the epide- miology of Bordetella pertussis infection. Pediatrics

15:1422–1427.

Wood N et al. (2008) Pertussis: review of epidemiology,

diagnosis, management and prevention. Pediatric Resp Rev

9:201–212.

World Health Organization (2009) State of the World’s Vaccines

and Immunization, 3rd edn. WHO, UNICEF, World Bank

Geneva.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

81

Page 21 of 113

Disease: Plague

Classification: ICD-9 020; ICD-10 A20

Syndromes and synonyms: Pestis, pest, bubonic plague,

pneumonic plague, black plague, black death.

Agent: Yersinia pestis, a Gram-negative bacillus. Y. pestis is

considered a potential biological warfare agent.

Reservoir: Rodents, principally rats and sylvatic ground

squirrels: marmots, susliks, and prairie dogs. Rabbits, camels,

carnivores, and domestic cats may also be infected. Cats

can also develop pneumonic plague. The desert regions of

Central Asia contain endemic plague foci where the great

gerbil is the main host.

Vector: Fleas, especially the rat flea (Xenopsylla cheopis) and

possibly human flea (Pulex irritans).

Transmission: By flea bite for the bubonic form, by the

respiratory route for the pneumonic form; handling carcasses

or eating meat of infected animals. Person-to-person transmis- sion occurs through the bite of fleas (bubonic form) or respira- tory droplets (pneumonic form).

Cycle: There are different cycles, including a sylvatic rodent– flea cycle, a commensal rodent–flea cycle, and a cycle of

pneumonic transmission in humans. Y. pestis can survive in

the environment, mainly in rodent burrows in a sylvatic cycle.

In case an infected flea feeds on a commensal rodent (rat), a

rodent–flee–rodent cycle starts. When the rodents dies, their

fleas move to alternative hosts, possibly humans. If humans

develop pneumonic plague, the infection can be transmitted

from person to person via respiratory droplets.

Incubation period: 1–4 days for pneumonic, 2–7 days for

bubonic plague.

Clinical findings: Sudden onset of fever, chills, headaches,

body aches, sore throat, vomiting and nausea. Bubonic plague

is most common, producing swollen, painful and eventually

suppurating lymph nodes (buboes) which are usually inguinal.

In the septicemic form, Y. pestis spreads through the blood- stream usually affecting the lungs, ending in fatal endotoxic

shock and DIC. The CFR of the bubonic form is 40–70%; of

pneumonic and septicemic plague in the absence of prompt

treatment, nearly 100%.

Diagnostic tests: Microscopy of stained smear from a bubo,

sputum or CSF shows characteristic ‘safety-pin’ shape; serology

(IFA; ELISA); rapid dipstick test. Culture takes about 4 days.

Therapy: Streptomycin, tetracyclines, and sulfonamides are

standard; alternatives are gentamicin and fluoroquinolones.

Chloramphenicol in cases of plague meningitis. Treatment

should be started within 18 hours of onset. Buboes may

need to be drained.

Prevention: A killed vaccine is available for laboratory work- ers, but is not recommended for use in epidemics. In buildings

or rodent burrows, flea control with insecticide should be

followed by rat destruction (killing rats liberates fleas); rat

control in ports and ships. Chemoprophylaxis of pneumonic

plague contacts. Pneumonic cases should be isolated.

Epidemiology: There are an estimated 1,000–3,000 human

cases per year, but there is considerable underreporting and

underdiagnosis. The last plague pandemic of 1894 started in

Hong Kong establishing many endemic foci world wide. New

foci continue to arise, as was seen in Algiers, in 2003. Warm

springs and wet summers have increased the plague preva- lence in the great gerbil in Kazakhstan. Similar climatic con- ditions may have resulted in past plague pandemics. Infection

control and antibiotics can decrease plague morbidity and

mortality but plague cannot be eradicated as it is widespread

in wild rodents. There has been a large shift in case load from

Asia to Africa, with more than 90% of cases occurring in Africa.

The most common form is bubonic plague, but outbreaks of

pneumonic plague still occur. Plague is possibly more com- mon in Africa as poor rural communities in Africa live in close

proximity to rodents, which are widely hunted and eaten in

plague-endemic areas.

Map sources: The Plague map is modified from the CDC map

‘Distribution of Plague 1998’, available at: www.cdc.gov/

ncidod/dvbid/plague/world98.htm. The map is updated

with recent literature and expert opinion. Africa plague distri- bution data was obtained from S.B. Neerinckx et al. (2008).

Key references

Gratz N. (1999) Plague Manual Epidemiology, Distribution, Sur- veillance and Control. WHO Report, Geneva.

Neerinckx SB, et al. (2008) Geographic distribution and eco- logical niche of plague in sub-Saharan Africa. Int J Health

Geog 7:54.

Stenseth NC, et al. (2008) Plague: past, present and future. PLoS

Med 5(1):e3.

World Health Organization (2005) Plague. Weekly Epidemiol

Rec 80:138–140.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Page 22 of 113

Disease: Pneumococcal Disease

Classification: ICD-9 041.2; ICD-10 A40.3

Syndromes and synonyms: None.

Agent: Streptococcus pneumoniae (pneumococcus), an encap- sulated Gram-positive bacterium, with > 90 serotypes based

on capsular polysaccharide antigens. Approximately 23 ser- otypes are responsible for 90% if the infections in the devel- oped world.

Reservoir: Healthy humans can carry S. pneumoniae in their

upper respiratory tract.

Transmission: Direct person-to-person transmission between

close contacts by droplet spread or direct oral contact; through

objects contaminated with respiratory secretions.

Incubation period: 1 to 3 days.

Clinical findings: Depends on the type of infection and

severity. S. pneumoniae is an important cause of severe pneu- monia, meningitis, and sepsis. It also is a common cause of

otitis media and sinusitis. It can cause deep-seated infections

involving any organ in a disseminated disease.

Diagnostic tests: Recovery of S. pneumoniae from sputum,

blood, CSF or other normally sterile fluids by culture or PCR. S.

pneumoniae antigen test in urine.

Therapy: Depends on disease severity and type of disease. In

areas with high penicillin resistance, ceftriaxone can be used

for severe disease. In case of ceftriaxone resistance, vancomy- cin is used. For meningitis, dexamethasone is added to antibi- otic treatment.

Prevention: Vaccination with vaccines based on capsular

polysaccharides. Both conjugated and non-jugated vaccines

are available. Conjugated vaccines targeting either 7, 9, 10, or

13 capsule types are recommended for children under 5 years

of age and risk groups. The 23-valent non-conjugated vac- cine can only be used in individuals older than 2 years and at

high risk of disease. National surveillance of pneumococcal

disease and infecting serotypes is required to detect vaccine

escapees, requiring vaccine modification. Individuals are not

protected against pneumococcal capsule types not in the

vaccine. Through the GAVI Alliance, low-income countries

can access pneumococcal vaccines with a small contribution.

Rwanda was the first GAVI-eligible country that introduced

the vaccine in 2009.

Epidemiology: S. pneumoniae is an important cause of

severe pneumonia, meningitis, and sepsis in children and

adults. Risk factors for severe disease are: older age ( > 65

years), diabetes, chronic disease (heart, lung, kidney, liver),

alcoholism, cancer, HIV, non-functioning or absent spleen,

and sickle cell disease. A global burden of disease study

estimated that in 2000 about 14.5 million episodes of serious

pneumococcal disease occurred world wide, leading to about

826,000 deaths in children <5 years. The most common

presentation of severe disease is pneumonia. The majority

of deaths (95%) occurred in Africa and Asia. Since 2000 the

pneumococcal vaccine has been introduced, mostly in devel- oped countries,while developing countries need themmost. In

2008, 24 high-income and two middle-income countries had

pneumococcal vaccination in their program, accounting for

less than 0.2% of childhood pneumococcal deaths in 2000.

Many deaths in low-income countries are due to poor health- care infrastructure and inadequate treatment options. Penicil- lin and chloramphenicol are still widely used to treat

meningitis despite high resistance levels against these agents

in some areas. Vaccination and access to proper treatment are

needed in Africa and Asia. Interventions should be targeted on

countries with large populations and moderate incidence, and

countries with high incidence and mortality.

Map sources: The Pneumococcal Disease map is reproduced

from K.L. O’Brien et al. (2009). The Vaccination schedule data

was obtained from WHO (www.who.int).

Key reference

O’Brien KL, et al. (2009) Burden of disease caused by Strepto- coccus pneumoniae in children younger than 5 years: global

estimates. Lancet 374:893–902.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

85

Page 23 of 113

Disease: Q Fever

Classification: ICD-9 083.0; ICD-10 A78.

Syndromes and synonyms: Coxiellosis, Query fever.

Agent: A zoonosis caused by Coxiella burnetii, an intracellular

Gram-negative bacterium, and is closely related to Legionella

spp., Francisella tularensis, and Rickettsia spp. C. burnetii is

classified as a potential biological warfare agent.

Reservoir: Domestic and free living ungulates (cattle, sheep,

and goats). Also found in other livestock, birds, pets (cats and

dogs), and ticks. Infected animals are generally asymptomatic,

but infection may lead to late abortion.

Vector: Rarely by tick bite.

Cycle: Animals inhale C. burnetii aerosols or ingest contami- nated straw or hay. C. burnetii bacteria invade local lymph

nodes, where they complete their life cycle within phago- somes. From the lymph nodes the agent spreads to other

organs via the bloodstream. This bacteremic phase lasts for

one week. From infected organs, like mammary glands, pla- centa, and kidneys, it can be excreted into the environment and

lead to infection in exposed animals and humans.

Transmission:Inhalation of contaminated aerosols generated

from infected animal body fluids (placenta, urine, milk, feces)

or dust contaminated with dried animal excretions. Less

common routes are enterally when consuming contaminated

food products and possibly through skin inoculation. Person- to-person transmission is rare.

Incubation period: About 2–3 weeks for acute Q fever. One to

20 years for chronic Q fever.

Clinical findings: Half of the infected patients are asymptom- atic and those with symptoms usually have mild disease. The

most common presentations of acute Q fever are pneumonia,

hepatitis, and isolated fever. Other symptoms are neurological

(headache, confusion, peripheral neuropathy), sore throat,

chills, sweats, rash, and non-productive cough. Proportion

of people presenting with pneumonia or hepatitis varies by

region and immune status. CFR: 1–2%. Chronic Q fever occurs

1 to 20 years after acute infection and most often presents as

endocarditis in patients with pre-existing heart disease (valve

abnormality).

Diagnostic tests: IgG and IgM antibody detection to phase I

and II antigens by IFA, CFT, or ELISA; immunohistology;

PCR; ultrasound for endocarditis.

Therapy: Doxycycline for acute Q fever. Chronic Q fever

endocarditis: a combination of doxycycline and hydroxychlor- oquine for approximately 18 months.

Prevention: C. burnetii is resistant to many disinfectants and

extreme environmental conditions. The organism can survive

in aerosols for 2 weeks and in soil up to 5 months. Prevention is

targeted to those working with livestock, mainly sheep and

goats; appropriate disposal of birth products; routine testing of

risk animals; restricted movement of animals in infected

regions; culling of infected animals; a human and veterinary

vaccine is available in several countries; pasteurize milk.

Epidemiology: Q fever has been described world wide, with

the exception of New Zealand. Though small outbreaks are

reported from tropical countries, serological studies do show

that the prevalence of disease is higher there than in temperate

regions. Most human outbreaks involve either goats or sheep.

The largest global outbreak ever reported occurred in the

Netherlands between 2007 and 2010, mainly in the southeast

where there is a high density of dairy goat farms. The outbreak

led to a high incidence of infections in people exposed to

aerosols living in the vicinity of infected farms but had no

occupational exposure. People living within 2 km of a farm had

a much higher risk than those living > 5km away. The hospi- talization rate was relatively high, 20% versus around 5%

which is normally reported.

Map sources: The Q-fever map was made by geocoding

reported Q-fever outbreaks in ProMED-mail and the medical

literature between 2000 and 2010. The Netherlands outbreak

map is modified from W. van der Hoek et al. (2010). The sheep

and goat density data was obtained from FAO.

Key references

Angelakis E, et al. (2010) Q fever. Vet Microbiol 140:297–309.

Raoult D, et al. (2005) Natural history and pathophysiology of

Q fever. Lancet Infect Dis 5:219–226.

Van der Hoek W, et al. (2010) Euro Surveill 15(12):19520.

Woldehiwet Z. (2004) Q fever (coxiellosis): epidemiology and

pathogenesis. Vet Sci 77:93–100.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

87

Page 24 of 113

Disease: Rat Bite Fever

Classification: ICD-9 026; ICD-10 A25

Syndromes and synonyms: Streptobacillosis, streptobacil- lary fever, Haverhill fever, epidemic arthritic erythema, spir- illosis, spirillary fever, sodoku.

Agents: Streptobacillosis: Streptobacillus moniliformis (for- merly Actinobacillus muris, Haverhillia multiformis), a Gram- negative, non-motile pleiomorphic rod-like bacterium.

Spirillosis: Spirillum minus (minor), a Gram-negative motile

spiral bacterium.

Reservoir: Rats are the main host species involved in human

rat bite fever for both agents. The main location for

S. moniliformis in rats is the pharynx. S. minusis mainly present

in the blood and tongue of rats and salivary glands of mice.

Other rodent species such as mouse, squirrel, and gerbil – and

non-rodent species – have occasionally been identified as

possible sources of infection. The rat population is estimated

to be 10 billion, which is one-third of the total global mamma- lian population.

Cycle: Rodent to rodent with spill over to humans in case of

adequate exposure.

Transmission: Via a bite or a scratch by an infected host

animal. Human infection via S. moniliformis ingestion (milk,

water, food) is known as Haverhill fever. Some streptobacil- losis cases may occur by close contact with the oral flora of pet

rats through kissing and sharing food. There is no person-to- person transmission.

Incubation period: 3–10 days for streptobacillosis, 1–3 weeks

for spirillosis.

Clinical findings: The most common clinical presentation for

streptobacillosis is a triad of (1) relapsing fever, (2) severe,

migratory polyarthralgias, and (3) a peripheral, hemorrhagic

maculopapular rash. The most prominent symptom is severe

myalgia with prostration. Polyarthralgias occur in two-thirds

of reported cases. In spirillosis, the bite site becomes indurated

and may ulcerate with regional lymphadenopathy; arthritic

symptoms are rare. If untreated, the disease may progress to

bacterial endocarditis, pericarditis, parotitis, tenosynovitis,

and focal abscesses of soft tissues or the brain. CFR in

untreated cases may be as much as 13%. There is a significant

risk of streptobacillary endocarditis with associated CFR

of 50%.

Diagnostic tests: Microscopy, isolation of the agent from

lesion, blood or pus by inoculation into mouse footpad or

guinea pigs, or culture; serum agglutination test; PCR.

Therapy: Penicillin for both forms of rat bite fever. Penicillin

resistance in S. moniliformis is rare. Tetracycline in penicillin- allergic patients.

Prevention: Rodent control; those with occupational expo- sure to rodents (e.g. sewage workers) should wear personal

protective clothing; avoid close contact with reservoir animals,

including pets; prophylaxis with penicillin or doxycycline

following rat bite.

Epidemiology: Rat bite fever is a rare and underreported

disease with a worldwide distribution. S. minus infection is

reported less frequently than S. moniliformis and occurs mainly

in Asia, particularly Japan. World wide, millions of people are

bitten by animals each year and rats are responsible for about

1% of these bites. It is estimated that 2% of rat bites lead to an

infection (all causes). It is unknown what the proportion of rat

bite fever is of these infections. The relation between humans

and animals is changing which may alter the epidemiology of

rat bite fever. Rats have become a pet in several countries, while

it used to be considered a pest. Children handling pet rats may

be a special risk group. More than half of the reported cases of

rat bite fever occur in children.

Map sources: The Rat Bite Fever map was made by geocod- ing reported case in the medical literature between 1950 and

2010.

Key references

Gaastra W, et al. (2009) Rat bite fever. Vet Microbiol

133:211–228.

Elliott SP. (2007) Rat bite fever and Streptobacillus monilifor- mis. Clin Microbiol Rev 20:13–22.

Wullenweber M. (1995) Streptobacillus moniliformis – a zoo- notic pathogen. Taxonomic considerations, host species,

diagnosis, therapy, geographical distribution. Lab Anim

29:1–15.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

89

Page 25 of 113

Disease: Relapsing Fever

Classification: ICD-9 087; ICD-10 A68.0 – A68.1

Syndromes and synonyms: Epidemic or louse-borne relaps- ing fever (LBRF), endemic or tick-borne relapsing fever

(TBRF).

Agent: For LBRF, Borrelia recurrentis, a Gram-negative

spirochete. For TBRF, at least 15 Borrelia species, each

specific to a particular species of tick vector. Since the

1980s, the number of new Borrelia species associated with

relapsing fever has increased, in part due to improved

diagnostics.

Reservoir: For LBRF, humans; for TBRF, wild rodents, bats

and ticks (by trans-stadial and transovarian transmission).

B. duttonii has thus far not been detected in wild animals,

only in humans and tick vector O. moubata. Livestock may also

become infected.

Vector: TBRF is primarily transmitted by Ornithodoros ticks.

LBRF is transmitted by the human body louse (Pediculus

humanus); neither the head louse nor the pubic louse has

been shown to transmit the disease.

Transmission:LBRF is not transmitted by the bite itself but by

feces or louse gut fluid entering broken skin by scratching.

TBRF: by bite or coxal fluid of infected ticks. Transmission may

also occur through blood transfusion or transplacental.

Cycle: Lice become infective 4–5 days after an infectious blood

meal and remain so for life (20–30 days). Infected ticks remain

infective for life (in excess of 10 years).

Incubation period: LBRF: 5–15 days (usually 8); TBRF: 2–18

days (usually 7).

Clinical findings: Characterized by high fever of 2–7 days

alternating with afebrile periods of 4–14 days, relapsing up to

13 times. Initial symptoms include generalized body aches,

myalgias, arthralgias, headache, chills, sweats, and a transi- tory rash. Later symptoms may include nausea, vomiting, dry

cough, photophobia, neck pain, conjunctivitis, jaundice, hepa- tosplenomegaly, confusion; rarely hematuria and epistaxis.

Long-term sequelae of TBRF include cardiac, neurological,

and renal abnormalities, ophthalmia and abortion. LBRF is

generally more severe than TBRF, but associated with fewer

relapses.

Diagnostic tests: Detection of spirochetemia in blood smears

with dark-field or conventional microscopy; blood culture in

special media or mouse inoculation; quantitative buffy coat

(QBC) fluorescence; PCR.

Therapy: Tetracyclines, chloramphenicol, or penicillins for 7

days have all been shown to be effective for treating TBRF.

LBRF can be treated with a single dose of antibiotics. When

initiating antibiotic therapy, watch closely for a Jarisch– Herxheimer reaction.

Prevention: Standard louse control and personal tick protec- tion. Chemoprophylaxis may be used for bite victims.

Epidemiology: The louse-borne agent is responsible for

epidemics, with a CFR of 30–70%; tick-borne agents cause

endemic disease, with a CFR of 2–10%. LBRF has disappeared

from Europe; tick-borne relapsing fever is found world

wide, except in Australia and New Zealand, and is rare in

Europe and North America. Human TBRF is frequent in

endemic areas where people live in close proximity to burrows

of reservoir animals. Otherwise, the disease is sporadic. LBRF

is now found sporadically in epidemics in Africa, and is

associated with refugee camps, natural disasters, and famine.

LBRF used to be common world wide with large epidemics

during the two world wars. It may re-establish anywhere in

louse-infested human populations.

Map sources: The Relapsing Fever map was made with data

from: S. Rebaudet et al. (2006), CIESIN (http://www.ciesin.

org/docs/001-613/map30.gif), and P. Parola et al. (2001).

Key references

Gratz N (2006) The Vector- and Rodent-Borne Diseases of Europe

and North America: Their Distribution and Public Health Bur- den. Cambridge University Press.

Parola P, et al. (2001) Ticks and tickborne bacterial diseases

in humans: an emerging infectious threat. Clin Infect Dis

32(6):897–928.

Rebaudet S, et al. (2006) Epidemiology of relapsing fever

borreliosis in Europe. FEMS Immunol Med Microbiol

48(1):11–15.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

91

Page 26 of 113

Disease: Rickettsioses, Tick-borne, New World

Classification: ICD-9 082.0; ICD-10 A77.0

Syndromes and synonyms: Rocky Mountain spotted fever

(RMSF), North American tick typhus, New World spotted

fever, Tick-borne or tick typhus, Tobia fever (Colombia),

Sao Paulo fever or ‘febre maculosa’ (Brazil), and fiebre

manchada (Mexico).

Agent: Rickettsia rickettsii, R. parkeri and R. africae, Gram- negative intracellular bacilli. R. rickettsii is the agent of

RMSF, R. parkeri causes a RMSF-like illness. R. africae causes African tick bite fever and is rarely found in the new world.

New agents are still being discovered regularly.

Reservoir: Hard ticks (Ixodidae). Depending on the tick species,

they can acquire infection via feeding on animals with rickettse- mia, or via venereal, transovarial, and trans-stadial passage.

Animals preferred for feeding varies by tick species and their

life stage.Rodent hosts include ground squirrels, mice, and voles.

Vector: The Ixodid ticks are both vector and reservoir.

Amblyomma americanum, Dermacentor andersoni and D. variabi- lis (American dog tick) in Canada and the USA, Rhipicephalus

sanguineus in Mexico and Central America, and A. cajennense

from the southern states of the USA southwards as far as

Argentina. D. variabilis is the primary vector for RMSF in the

USA. A. maculatum is the main vector of R. parkeri in North

America and A. triste in South America.

Transmission: By tick bite or crushing an infected tick or its

feces into a break in the skin or mucous membrane. Also by

blood transfusion and, in the laboratory, aerosol.

Cycle: Tick–vertrebrate–tick with humans as accidental host.

Animals preferred for feeding depends on tick species and

their life stage.

Incubation period: 2–14 days (usually 5–7).

Clinical findings: RMSF and R. parkeri rickettsiosis are char- acterized by fever, myalgia, malaise, headache, and a macu- lopapular eruption that can involve the palms or soles. R.

parkeri rickettsiosis is milder than RMSF, and often does not

require hospitalization. RMSF cases may progress and

develop stupor, delirium, ataxia, or coma; RMSF CFR is

about 7%. Untreated RMSF is often progressive with a CFR

of 20%, which is not the case for untreated R. parkeri rick- ettsiosis. Most ( > 90%) R. parkeri cases have an eschar, which is

rare in RMSF. GI symptoms are common in RMSF and rare in

R. parkeri disease.

Diagnostic tests: PCR on blood or skin biopsy, or IFA on the

latter. Serology is unspecific due to cross-reactivity. Until

recently, R. parkeri cases were misdiagnosed as RMSF.

Therapy: Doxycycline is the treatment of choice. Generally,

treatment is continued for at least 3 days after the patient

is afebrile.

Prevention: Search for ticks on the whole body daily and

remove them without crushing. Use tick repellent on skin

and an acaricide on clothing. There is no effective vaccine.

Epidemiology: The distribution of RMSF and R. parkeri rick- ettsiosis is limited by the tick vector distribution. Average annual

RMSF incidence of the disease in the USA was 2.2 cases per

million between 1997 and 2002, and approximately 250–1,200

cases are reported each year. Many cases of RMSF may actually

have been caused by other rickettsial agents, as was seen with R.

parkeri. Many rickettsiae of unknown pathogenicity are present in

ticks and new disease causing agents are still being discovered.

RMSF in the USA follows a seasonal pattern with most cases in

warmer months, when ticks are most active. RMSF cases are

usually found in rural areas, and less commonly in urban areas.

Residing in wooded regions or areas with high grass and expo- sure to dogs increases the risk of RMSF. RMSF is sporadic and

rarely occurs in clusters.

Map sources: The Spotted Fever, New World map was made

with data from: CDC (www.cdc.gov/ticks/geographic_ dis- tribution.html), CIESIN (www.ciesin.org/docs/001-613/001-

613.html), G.V. Kolonin (2009), recent literature and expert

opinion.

Key references

Dantas-Torres F (2007) Rocky Mountain spotted fever. Lancet

Infect Dis 7(11):724–732.

Kolonin GV (2009) Fauna of Ixodid Ticks of the World (Acari,

Ixodidae). Moscow. Website: www.kolonin.org.

Paddock CD, et al. (2008) Rickettsia parkeri rickettsiosis and its

clinical distinction from Rocky Mountain spotted fever. Clin

Infect Dis 47:1188–1196.

Parola P, et al. (2005) Tick-borne rickettsioses around the

world: emerging diseases challenging old concepts. Clin

Microbiol Rev 18(4):719–756.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

93

Page 27 of 113

Disease: Rickettsioses, Tick-borne, Old World

Classification: ICD-9 082; ICD-10 A77

Synonyms: Mediterranean spotted fever (MSF), Israeli spot- ted fever (ISF), Siberian or North Asian tick typhus (STT/

NATT), Queensland tick typhus (QTT), Japanese or Oriental

spotted fever (JSF/OSF), Astrakhan fever (AF), African tick

bite fever (ATBF), Flinders Island spotted fever (FISF), Indian

tick typhus (ITT), Boutonneuse fever.

Agent: Rickettsia aeschlimannii, R. africae (ATBF), R. australis

(QTT), R. conorii caspia (AF), R. conorii conorii (MSF), R. conorii

indica (ITT), R. conorii israelensis (ISF), R. helvetica, R. honei

(FISF), R. japonica (JSF/OSF), R. massiliae, R. sibirica (STT/

NATT), Gram-negative intracellular bacilli. New agents are

still being discovered regularly.

Reservoir: Hard ticks (Ixodidae). Depending on the tick

species, they can acquire infection via feeding on animals

with rickettsemia, or via venereal, transovarial, and trans- stadial passage. Animals preferred for feeding varies by tick

species and their life stage. Hosts include dogs, rodents, and

other animals.

Vector: Hard ticks (Ixodidae). The brown dog tick (Rhipice- phalus sanguineus), the principal vector of MSF, ISF, ITT, and

AF, is most active during spring and summer, has a low

human affinity, and prefers dogs in a peridomestic environ- ment. The southern African bont tick (Amblyomma hebraeum)

and A. africanum are the principal vectors of R. africae in

southern Africa. A. hebraeum is an aggressive, human-biting

tick and has high rates of rickettsia infection, and ATBF cases

therefore often occur in clusters. See key references for further

reading on ticks and tick-borne rickettsioses.

Transmission: By tick bite or crushing an infected tick or its

feces into a break in the skin or mucous membrane. Also by

blood transfusion and, in the laboratory, aerosol.

Cycle: There is a natural cycle between ticks and animals with

humans as accidental host.

Incubation period: Varies by agent but is generally 7 days

with a range from 1 to 15 days.

Clinical findings: Boutonneuse fever (group name for

R.conorii infections: MSF, ISF, ITT), QTT and STT/NATT:

mild febrile illness that may last up to 2 weeks, eschar at bite

site with regional lymphadenopathy (in ISF, eschars are rare),

generalized maculopapular erythematous rash on palms on

soles after 4–5 days. The disease can be severe with a CFR up

to 3%. ATBF is milder than other rickettsioses, fever and rash

are less common, multiple eschars may be present with

regional lymphadenopathy.

Diagnostic tests: PCR on blood or skin biopsy, or IFA on the

latter. Serology is unspecific due to cross-reactivity.

Therapy: Doxycycline is the treatment of choice. Generally,

treatment is continued for at least 3 days after the patient

is afebrile.

Prevention: Search for ticks on the whole body daily and

remove them without crushing. Use tick repellent on skin and

an acaricide on clothing.

Epidemiology: Ecological characteristics of the ticks influence

the epidemiology of tick-borne rickettsioses. In 1910, the first

case of Mediterranean spotted fever (MSF) R. conorii was considered to be the only agent of tick-borne spotted fever

group rickettsioses in Europe and Africa. Similarly, R. sibirica

was thought to be the only agent in Russia and China and R.

australis in Australia. The reason for this was that diagnosis

was made by serologic testing, which cross-reacts with other

rickettsial species. Due to improved diagnostics, particularly

molecular, the understanding of rickettsioses has increased,

and new agents are being found regularly. Multiple distinct

tick-borne spotted fever group rickettsioses are recognized.

The name of the agent informs us where the agent was initially

found, but most agents have a more widespread distribution.

Map sources: The Tick-Borne Rickettioses map (Old World)

was made with data obtained from P. Parola et al. (2005),

www.kolonin.org, and updated with recent publications and

expert opinion.

Key references

Parola P, et al. (2001) Ticks and tickborne bacterial diseases

in humans: an emerging infectious threat. Clin Infect Dis

32:897–928.

Parola P, et al. (2005) Tick-borne rickettsioses around the

world: emerging diseases challenging old concepts. Clin

Microbiol Rev 18(4):719–756.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

95

Page 28 of 113

Disease: Scrub Typhus

Classification: ICD-9 081.2; ICD-10 A75.3

Syndromes and synonyms: Tsutsugamushi disease, mite- borne typhus fever, chigger-borne rickettsioses, coastal fever

(Australia).

Agent: Orientia tsutsugamushi, obligate intracellular bacte- rium, before 1995 known as Rickettsia tsutsugamushi. In

2010, a new species that can cause scrub typhus was discov- ered in Dubai, O. chuto. Reservoir: Larval stage mites, so-called chiggers from the

genus Leptotrombidium. A number of small rodents, particu- larly wild rats, are the natural hosts for scrub typhus without

apparent disease.

Vector: Larval mites. Nymphs and adults do not feed on

vetebrate hosts. The vector has adapted to various ecologies,

including mountainous and tropical regions.

Transmission:Bite of infected larval mites (chiggers). There is

no direct person-to-person transmission.

Cycle: The mites are infected by feeding on reservoir

animals (small rodents), and maintain the infection through- out their life stages. The infection is passed on by transovarial

transmission. O. tsutsugamushi are present in the salivary

glands of the larvae and injected into the host during

feeding.

Incubation period: 10–12 days, range: 6–21 days.

Clinical findings: Typical skin ulcer, eschar, may develop at

the site of the mite’s bite. Several days later fever, headache,

myalgia, and lymphadenopathy may develop. Dry cough with

signs of pneumonitis, jaundice, and meningoencepahlitis may

occur. Scrub typhus severity and clinical presentation is prob- ably strain dependent.

Diagnostic tests: Serology (IF, EIA); PCR; culture in mice or

cell lines.

Therapy: Tetracycline, doxyxyline. Alternative:

chloramphenicol.

Prevention: Avoid areas with mites; mite bite prevention by

impregnating clothes with miticides; mite elimination in high- risk areas; no effective vaccine is available.

Epidemiology: It is estimated that over one million cases of

scrub typhus occur each year. Infections most often occur in

rural areas where diagnostic facilities are limited. Scrub typhus

is thought to occur within the so-called ‘Scrub typhus triangle,’ bounded by Siberia (north), Kamchatka Peninsula (east), Paki- stan (west), and Australia (south). O. tsutsugamushi infection

primarily occurs in tropical climate in Asia, but is also found in

temperate zones and semi-arid climates, including in scrub,

gardens, forests, beach areas, and mountain deserts. In 2010

the western limit of the Orientia genus extended westwards to

Dubai when a patient was diagnosed with a new Orientia

species (O. chuto). In southern China, human infections typi- cally occur in the summer and in northern areas the disease

occurs mainly during autumn and winter. The migration of

infested or infected rodents can lead to the establishment of

new foci of disease.

Map sources: The Scrub Typhus map is modified from D.J.

Kelly et al. (2). Data on vector distribution was obtained from

the WHO report (1989) (see key references below).

Key references

Izzard L, et al. (2010) Isolation of a novel Orientia species

(O. chuto sp. nov.) from a patient infected in Dubai. J Clin

Microbiol 48(12):4404–4409.

Kelly DJ, et al. (2009) Scrub typhus: the geographic distribution

of phenotypic and genotypic variants of Orientia tsutsuga- mushi. Clin Infect Dis 48:S203–S230.

World Health Organization (1989) Areas of endemic chigger- borne rickettsiosis and distribution of the Leptotrombidium vec- tors. Geographical distribution of arthropod-borne diseases and

their principal vectors. Unpublished document WHO/VBC/

89.967. Geneva.

Zhang et al. (2010) Scrub typhus in previously unrecorgnized

areas of endemicity in China. J Clin Microbiol 48:1241–1244.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Page 29 of 113

Disease: Streptococcus suis

Classification: ICD-9 A41.09; ICD-10 A40.8

Syndromes and synonyms: None.

Agent: Streptococcus suis, a Gram-positive alpha-hemolytic

bacterium, with 35 serotypes based on capsular polysaccha- ride antigens. The predominant one causing human disease is

serotype 2.

Reservoir: Pigs; occasionally found in wild boar, horses, dogs,

cats, and birds. Asymptomatic pigs typically carry the bacteria

in their tonsils.

Transmission: Through wounds on the skin, including

minor abrasions. Infection via ingestion of contaminated

improperly cooked pork products. No human-to-human

transmission.

Cycle: Pig-to-pig, with occasional spill-over to humans.

Incubation period: From a few hours up to 3 days.

Clinical findings: Fever and signs of meningitis (headache,

vomiting, neck stiffness, intolerance of light, and decreased

level of consciousness). Hearing loss, generally permanent, in

around 50% of those infected. Arthritis, pneumonia, and fatal

toxic shock syndrome are possible complications.

Diagnostic tests: Recovery of bacteria from the cerebrospinal

fluid, blood or fluid from arthritic joints; culture; PCR. Strep- tococcus suis is often misidentified as another streptococcus

species and therefore underdiagnosed.

Therapy: For meningitis or septicemia, prompt treatmentwith

appropriate antibiotics (penicillin, ceftriaxon) will lead to

recovery. Specific organ involvement like the heart, requires

specialist treatment. Early treatment with dexamethason can

reduce the risk of hearing loss.

Prevention: During outbreaks: strict control on animal

movements and slaughtering; health education of everyone

who butchers, prepares, and cooks pork, including in their

homes; wearing gloves to handle raw or uncooked pork,

careful washing of hands and utensils. Adequate cooking

essential; WHO recommends cooking pork to reach an inter- nal temperature of 70 C, or until the juices are clear rather

than pink.

Epidemiology: Rarely reported in the Americas and Europe,

sporadic in parts of Southeast Asia, especially Thailand,

China, and Vietnam. Most important risk factor is contact

with pigs or uncooked pig products, typically by farmers,

veterinary personnel, abattoir workers, and butchers. Fur- thermore, in several Asian countries it is common to consume

uncooked pork products, like blood, which is a risk for

acquiring the disease. Individuals who are immunosup- pressed, including those who have been splenectomized,

are also at increased risk. Since S. suis is often misidentified,

S. suis may be more common in certain parts of the world with

high pig densities.

Map sources: The Streptococcus suis map was made by

geocoding all reported human cases in the medical literature

up to 2010. The pig density data is obtained from FAO,

available at: www.fao.org/ag/againfo/resources/en/glw/

home.html.

Key references

Gottschalk M, et al. (2007) Streptococcus suis infections in

humans: the Chinese experience and the situation in North

America. Anim Health Res Rev 8(1):29–45.

Lun ZR, et al. (2007) Streptococcus suis, an emerging zoonotic

pathogen. Lancet Infect Dis 7(3):201–209.

Mai NT, et al. (2008) Streptococcus suis meningitis in adults in

Vietnam. Clin Infect Dis 46:659–667.

Wertheim H, et al. (2009) Streptococcus suis: an emerging

pathogen. Clin Infect Dis 48:617–625.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Page 30 of 113

Disease: Tetanus

Classification: ICD-9 037, 771.3; ICD-10 A33–35

Syndromes and synonyms: Lockjaw.

Agent: Clostridium tetani, a Gram-positive, spore-forming

anaerobic bacterium. The spores can remain viable in the

environment for years. C. tetani produces a highly potent

exotoxin, tetanospasmin, which is responsible for the clinical

features of tetanus.

Reservoir: Intestinal tract of animals and humans, and soil.

Route of transmission: Contamination of wounds with soil,

dust or animal feces that contain C. tetani spores. Puncture

wounds are most commonly associated with tetanus but it can

result from even minor abrasions. Through injection of con- taminated street drugs. Neonatal tetanus results from infection

of the umbilical cord, either through the use of unclean instru- ments to cut the cord or through dressing the stump with

contaminated materials.

Cycle: Tetanus spores enter the body through wounds and

under anaerobic conditions, the spores germinate and produce

toxin. The toxins are disseminated via the blood and lymphatic

system and bind to nerve endings, preventing the release of

inhibitory neurotransmitters. This results in unopposed skele- tal muscle contraction.

Incubation period: Most cases occur within 14 days (range:

1 day to months). Shorter incubation periods are associated

with more heavily contaminated wounds and an inoculation

site closer to the central nervous system. Neonatal tetanus has

a shorter incubation period, with an average of around 6 days.

Clinical findings: The principal clinical feature of tetanus is

painful skeletal muscle spasms and rigidity. Three clinical

forms are recognized. The commonest is generalized tetanus,

which usually begins with spasms of the facial muscles and

spreads in a descending pattern. On presentation patients

commonly have ‘lockjaw’ (trismus), neck stiffness, difficulty

swallowing, and abdominal rigidity. Generalized spasms may

result in an arched posture (opisthotonus). Other symptoms

include elevated temperature, blood pressure, and sweating.

Localized tetanus presents as localized spasms of muscles

around the entry wound. Cephalic tetanus is rare

and results from infection in the head and neck, and affects

cranial nerves.

Diagnostic tests: The diagnosis is based on characteristic

clinical features. The bacterium is usually not cultured from

wounds and a positive culture does not confirm the

diagnosis.

Therapy: Clean wounds, perform debridement and remove

foreign objects. A one-off dose of im or iv human tetanus

immunoglobulin removes unbound toxin but does not affect

bound toxin. Metronidazole in large doses for 7–14 days to

eradicateC. tetani infection. Since the effect of bound toxin may

last for 4–6 weeks, prolonged supportive care is required.

Tetanus does not induce immunity. Vaccination with tetanus

toxoid is therefore indicated during treatment.

Prevention: Immunization with tetanus toxoid (inactivated

tetanus toxin). Immunization of pregnant women protects

infants from neonatal tetanus.

Epidemiology: Tetanus is globally distributed but is more

common in highly populated agricultural areas, and in warm

and wet regions. In the late 1980s tetanus was estimated to

cause around 1 million deaths per year, mostly in newborn

infants. The current distribution of cases represents the cov- erage of tetanus immunization in children and adults. In

countries with good vaccine coverage in children, adult

cases may still be common, as natural immunity plays no

role in the epidemiology of tetanus. The DTP3 Vaccination

Coverage map shows coverage with the third dose of a

tetanus-containing vaccine in childhood. The elimination

of neonatal tetanus was set as a goal in 1989 and by mid- 2010 neonatal tetanus had been eliminated in 79% (153/193)

of WHO Member States. However, since C. tetani will always

remain present in nature, tetanus will always remain a threat,

and high levels of immunization must be maintained

indefinitely.

Map sources: Data for the Tetanus map was obtained from

WHO http://apps.who.int/immunization_monitoring/en/.

Key references

Thwaites CL, et al. (2003) Preventing and treating tetanus. Br

Med J 326(7381):117–118.

Roper MH, et al. (2007) Maternal and neonatal tetanus. Lancet

370(9603):1947–1959.

World Health Organization (2009) State of the World’s Vaccines

and Immunization, 3rd edn. Geneva. WHO, UNICEF, World

Bank.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Page 31 of 113

Disease: Trachoma

Classification: ICD-9 076.1; ICD-10 A71

Syndromes and synonyms: Chronic follicular conjunctivitis.

Agent: Repeated re-infection with Chlamydia trachomatis ser- ovars A, B, Ba, and C, an obligate intracellular bacterium.

The genital serovars D to K can infect the conjunctiva, but

generally do not lead to blindness as they cause self-limited

infections that typically do not recur.

Reservoir: Humans.

Vector: Flies contribute to the spread of ocular serovars of

C. trachomatis. Transmission: Repeated direct contact with infected secre- tions from infected individual (mainly from eye or nose); also

by hands and fomites (shared clothes, towels or bedlinen).

Flies also play a role in the transmission. High risk of infection

in close contacts of infected individuals.

Incubation Period: 5 to 12 days for conjunctivitis; years to

decades for trichiasis and eventually corneal damage and

blindness. Repeated re-infection over many years is required

for deposition of sufficient conjunctival scar to lead to the

blinding complications; host genetic factors are probably also

important.

Clinical findings: Self-limiting conjunctivitis, including

watery or mucopurulent discharge. Typical findings are lym- phoid follicles and papillary hypertrophy. Repeated infections

lead to scarring of the conjunctiva and trichiasis. Trichiasis

damages the corneal surface, resulting in keratitis, vasculari- zation of the cornea, and impaired defence against secondary

bacterial and fungal infection. Corneal damage produces cor- neal scar, leading to blindness.

Diagnostic tests: Clinical diagnosis of active disease by

presence of follicles and papillae on the conjunctival epithe- lium of the upper eyelid. Trichiasis and corneal opacity are also

diagnosed clinically. Presence or absence of infecting agent (by

any method, including PCR) has poor correlation with pres- ence or absence of disease or its severity; serology has no

diagnostic value.

Therapy: Individuals with trichiasis require eyelid surgery.

Active disease requires antibiotics: azithromycin or tetracy- cline eye ointment are recommended. Treatment of individual

cases has little impact, because of rapid reinfection. Commu- nity management using the SAFE strategy (Surgery for trichi- asis, Antibiotics to clear infection, Facial cleanliness and

Environmental improvement [water and sanitation] to reduce

transmission) is the recommended means for control in

endemic areas; this strategy includes both treatment and

prevention.

Prevention: Community management by SAFE strategy (see

above). The WHO Alliance for the Global Elimination of

Trachoma (GET 2020) seeks to eliminate trachoma as a public

health problem by 2020.

Epidemiology: Trachoma is the leading infectious cause of

blindness world wide and is generally a disease of poor rural

communities. These communities are often in hot and dry

regions. It is estimated that there are about 41 million people

with active trachoma and 8 million with trichiasis. Highest

prevalences are found in Sub-Saharan Africa. There is a high

burden in Ethiopia and Sudan, where active trachoma in some

communities can be found in > 50% of 1–9-year-old children

and trichiasis in > 19% of adults. In Asia and Central and South

America, the distribution ismore focal. Overall the incidence of

trachoma is declining and the disease has disappeared from

Europe and North America due to improved living conditions.

Map sources: Data for the Active Trachoma map (all ages) is

obtained from WHO, available at: www.who.int/blindness/

data_maps/en/. More detailed maps are available from the

International Center of Eye Health, available at: https://

www.iceh.org.uk/display/WEB/Global distribution of

trachoma maps.

Key references

Burton MJ, et al. (2010) The global burden of trachoma: a

review. PLoS Negl Trop Dis 3(10):e46.

Hu VH, et al. (2010) Epidemiology and control of trachoma:

systematic review. Trop Med Int Health 15(6):673–691.

Polack S, et al. (2005) Mapping the global distribution of

trachoma. WHO Bull 83:913–919.

Wright HR, et al. (2007) Trachoma. Lancet 371:1945–1954.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Page 32 of 113

Disease: Tuberculosis

Classification: ICD-9 010-018; ICD-10 A15–A19

Syndromes and synonyms: Consumption, white plague,

TB.

Agent: Mycobacterium tuberculosis complex, including M.

tuberculosis, M. africanum, M. canetti, and M. bovis, slow grow- ing acid-fast rods. M. bovis is not discussed further.

Reservoir: Mainly humans; rarely non-human primates and

other mammals.

Transmission: Person-to-person via inhalation of infectious

aerosols from cases with pulmonary TB, particularly after

prolonged exposure over time. Extrapulmonary tuberculosis

is generally not communicable. HIV-infected individuals are

more likely to develop TB.

Incubation period: 2–10 weeks to primary lesion or tubercu- lin-positive skin test; around 10% progresses to active disease

annually, but it may remain latent for decades to lifelong,. This

percentage is higher in children and in HIV-infected or other- wise immune-suppressed individuals.

Clinical findings: TB is a chronic disease with a gradual

onset. Pulmonary lesions occur in 70% of cases, extrapul- monary (meningitis, skeletal, any other organ, disseminated)

in 30%. Extrapulmonary TB is more common in children <5

years. Early symptoms of pulmonary TB are weight loss,

fever, and night sweats, progressing to cough, chest pain, and

hemoptysis. Findings of extrapulmonary TB depends

on infected organ(s), and may present together with pulmo- nary TB.

Diagnostic tests: Direct: acid fast smear/culture and PCR of

sputum and other body fluids, depending on clinical presen- tation; serological: tuberculin skin test (Mantoux); interferon

gamma release assays (IGRAs). Culture in liquid media is gold

standard and allows for antibiotic susceptibility testing but

takes weeks to months; PCR allows for early detection, and

recent assays include detection of resistance-associated

mutations.

Therapy: WHO recommended regimen (Directly Observed

Treatment Short-course or DOTS) is 2 months of rifampicin,

isoniazid, pyrazinamide, and ethambutol, followed by

4 months of rifampicin plus isoniazid. If resistance to rifampi- cin or isoniazid is suspected, treatment must continue with

second-line drugs for at least 18 months. Drug-resistant tuber- culosis (MDR and XDR-TB) require special regimens.

MDR-TB is defined as resistance to two main first-line TB

drugs: isoniazid and rifampicin. XDR-TB (Extensive Drug

Resistant TB) is defined as MDR-TB with resistance to fluor- oquinolones and one second-line injectable drug.

Prevention: Primary: BCG vaccination of children protects

against disseminated disease. Secondary: intensive search for

and treatment of source cases; contact investigation and treat- ment of positive cases with chemoprophylaxis. WHO has

established a ‘Stop TB Partnership’ program to control

TB world wide.

Epidemiology: TB is a major cause of death and disability

world wide, especially in developing countries. Morbidity

and mortality rates increase with age, and are higher in males.

In regions of high incidence, morbidity peaks in adults of

working age. Morbidity is higher in urban populations,

among the poor, and in closed institutions such as prisons

and military barracks. There were an estimated 9.27 million

incident cases of TB in the world in 2007 (14% HIV positive),

an almost 50% increase from 1990, and an estimated one- third of the world’s population is either latently or actively

infected with TB. Most of the cases in 2007 were in Asia (55%)

and Africa (31%).

MDR-TB is a serious problem in Russia, former Russian

republics, India and China. In 2007 there were an estimated 0.5

million MDR-TB cases. By 2008, 55 countries reported at least

one XDR-TB case.

Map sources: The Tuberculosis map was made with

incidence and resistance data from WHO, available at www.

who.int/tb/country/global_tb_database/en/ and WHO

report No. 4 (2008).

Key references

Dye C, et al. (2008)Measuring tuberculosis burden, trends, and

the impact of control programmes. Lancet Infect Dis

8:233–423.

World Health Organization (2008) Anti-Tuberculous Drug

Resistance in the World. WHO Report No. 4, Geneva.

Wright A, et al. (2009) Epidemiology of antituberculosis drug

resistance 2002–07. Lancet 373:1861–1873.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

105

Page 33 of 113

Disease: Tularemia

Classification: ICD-9 021; ICD-10 A21

Syndromes and synonyms: Rabbit fever, deerfly fever, hare

fever, lemming fever, Ohara fever, Francis disease.

Agent: Francisella tularensis tularensis (Type A), F. tularensis

holarctica (Type B), F. tularensis mediasiatica, Gram-negative

non-motile intracellular coccobacilli that infect macrophages.

Type A is highly virulent and divided into two clades: A.I

and A.II. F. tularensis is considered a potential biological

warfare agent. F. novicida is rarely virulent.

Reservoir: Lagomorphs and rodents (ground squirrels) for

F. tularensis (Types A and B) in North America. Aquatic

rodents (beavers, muskrats) in North America, hares and

small rodents in northern Eurasia, for F. holarctica (Type B).

The bacterium can persist in water.

Vector: The primary vectors are ticks and biting flies (deer

flies, tabanids). In central Europe: Dermacentor reticulatus and

Ixodes ricinus are important vectors. In eastern USA, D.

variabilis is the most important vector. In western USA, biting

flies are the predominant vectors in arid regions. In Russia,

transmission is both by ticks (Ixodes) and mosquitoes.

Transmission: By arthropod bite handling or processing of

infected animal carcasses or tissues, by ingestion of contami- nated water, soil or food, or by inhalation of contaminated dust

or aerosols.

Cycle: Generally enzootic cycles of F. tularensis are unnoticed,

humans are accidental hosts.

Incubation period: 1–14 days; most commonly 3–5 days.

Clinical findings: Tularemia has six characteristic clinical

syndromes, depending on the site of infection: ulcerogland- ular (commonest), glandular, oropharyngeal, pneumonic,

oculoglandular, and typhoidal. Clinical signs include sudden

onset of high fever, chills, generalized aches, and chronic ulcer

at the bite site (ulceroglandular). From the primary site,

lymphatic spread to regional lymphnodes. Further hemato- geneous dissemination to other organs. CFR for Type A

(ulcero) glandular disease is < 2% if treated promptly (5 to

30% if not treated). In the acute septic form (typhoidal) of

the disease, lymphadenopathy and ulcer are absent, and the

CFR is high (30–60%). Oculoglandular disease is rare. Inges- tion of infected material may result in oropharyngeal or GI

tularemia. In the oropharyngeal form signs are: throat pain,

large tonsils, pseudomembrane, and enlarged cervical lymph

nodes. Symptoms in GI tularemia range from mild persistent

diarrhea to extensive intestinal ulcers and death. Pneumonic

tularemia occurs after inhalation of bacteria, or secondary

from other entry sites and may progress to severe pneumonia,

respiratory failure, and death.

Diagnostic tests: Culture (cysteine-enriched media) or PCR

on specimens of affected tissues. Blood cultures are often

negative. Testing should be done in a BSL-3 facility. Serology

on acute and convalescent sera.

Therapy: Streptomycin is recommended, with gentamicin as

an alternative. Tetracyclines may be used for less severe cases.

Prevention: Wear impermeable gloves when handling or

skinning rodents or lagomorphs; cook wild game well; avoid

drinking water from untreated sources; wear long-sleeved

clothes and use repellent to protect against arthropod bites.

Epidemiology: F. tularensis tularensis Type A is found in North

America and the distributionis associatedwith wild rabbits, ticks,

and tabanid flies. Type B is found throughout the northern

hemisphere, mainly in Eurasia and is associated with multiple

rodent species, hares, ticks, blood-feeding mosquitoes, and taba- nid flies. There is also an association with water bodies (streams)

and flooding. In the USA, around 200 human tularemia cases are

reported each year,mostly in rural areas during summer months.

In Europe, most cases are reported from Sweden, Finland, and

Russia, and is recently emerging in Spain. Rural populations are

most at risk (e.g. farmers, hunters). Human outbreaks often

coincide with wild animal outbreaks.

Map sources: The Tularemia map was modified from P. Keim

et al. (2007) with a US map inset with data from CDC, available

at: www.cdc.gov/tularemia/.

Key references

Dennis DT, et al. (2001) Tularemia as a biological weapon:

medical and public health management. JAMA 285(21):

2763–2773.

Ellis J, et al. (2002) Tularemia. Clin Microb Rev 15(4):631–646.

Keim P, et al. (2007) Molecular epidemiology, evolution, and

ecology of Francisella. Ann NY Acad Sci 1105:30–66.

Vogler AJ, et al. (2009) Phylogeography of Francisella tular- ensis: global expansion of a highly fit clone. J Bacteriol

191(8):2474–2484.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

107

Page 34 of 113

Disease: Typhoid Fever

Classification: ICD-9 002.0; ICD-10 A01

Syndromes and synonyms: Enteric fever, typhus

abdominalis.

Agent: Salmonella enterica enterica serovar Typhi (S. Typhi), a

Gram-negative bacillus. S. Typhi belongs to Salmonella ser- ogroup D and possesses somatic antigen O9, a single flagellar

antigen Hd, and virulence antigen Vi. S. Paratyphi A can cause

similar disease.

Reservoir: Mainly humans; rarely domestic animals. Humans

can be short-term carriers after an infection (10%) or become

chronic carriers in the biliary tract (1–5%), shedding viable

bacteria in the stool. Chronic carriers are mainly adults with

pre-existingbiliary tractpathology.Urinary carriagemay occur

in areas where Schistosoma haematobium is endemic.

Vector: Flies can contaminate foods.

Transmission: Via fecal contaminated water, drinks or food

from infected individuals or carriers; transmission may also

occur in men who have sex with men.

Cycle: Infected individuals shed bacteria into environment,

contaminating water and food products that are subsequently

ingested by other humans.

Incubation period: 7–14 days, may be up to 2 months.

Clinical findings: Common presenting symptoms are: influ- enza-like symptoms (fever, dry cough, chills, myalgia), head- ache, malaise, anorexia, nausea, abdominal discomfort with

abdominal tenderness, coated tongue, and hepatosplenome- galy. Adults may have constipation, while young children and

HIV patients more often have diarrhea. In 5–30% a rash is

present on the abdomen and chest. Children <5 years regularly

have unspecific symptoms and remain undiagnosed. Compli- cations occur in 10–15%, including GI bleeding (most com- mon), intestinal perforation, and typhoid encephalopathy.

CFR is approximately 2% (range: 0–18%).

Diagnostic tests: Bone marrow culture is the gold standard;

blood culture; stool culture; serology; Widal test performance

is poor and should not be used.

Therapy: Fluorquinolones are recommended in the absence of

resistance. Resistance to ampicillin, chloramphenicol, and

cotrimoxazole is widespread and resistance to older genera- tion quinolones and third-generation cephalosporins is rising.

Both gatifloxacin and azithromycin can be recommended for

the treatment of uncomplicated cases in areas with MDR or

nalidixic acid resistance. Third-generation cephalosporins is

used for severe cases. Surgery for abdominal complications

(e.g. perforation). Dexamethason is recommended for severe

cases. Prevention: Vaccination of risk groups; eradicating carriage;

hygiene; sanitation; access to clean water; pasteurization of

dairy products; quality control and hygiene procedures

for the food industry; exclude typhoid carriers from food

handling.

Epidemiology: In 2000 it was estimated there were approx- imately 21,650,000 new S. Typhi cases and 216,500 deaths,

with large regional variability. These estimates are based

on limited data from mainly countries with a high inci- dence of disease. Typhoid fever incidence is highest among

infants and children living in South Central and Southeast

Asia and South Africa. Two seasonality patterns are

observed: (1) higher incidence in warmer dry months

leading to higher bacterial loads in the water, and (2)

higher incidence in the rainy season, due to spillover

from sewage to drinking water. Declines are seen in

regions were living conditions have improved, mainly

due to access to clean water and sanitation (see Water

and Sanitation map).

Map sources: The Typhoid Fever map is modified from JA

Crump (2004).

Key references

Crump JA (2004) The global burden of typhoid fever. Bull

World Health Org 82:346–353.

Crump JA (2010) Global trends in typhoid and paratyphoid

fever. Clin Infect Dis 50:241–246.

Ochiai RL (2008) A study of typhoid fever in five Asian

countries: disease burden and implications for controls.

Bull World Health Org 86:260–268.

Parry CM, et al. (2002) Typhoid fever. N Engl J Med 347(22):

1770–1782.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Page 35 of 113

Disease: Blastomycosis

Classification: ICD-9 116.0; ICD-10 B40

Synonyms: North American blastomycosis, Gilchrist disease

Agent: Blastomyces dermatitidis (teleomorph Ajellomyces

dermatitidis), a dimorphic fungus: grows as a pathogenic

yeast at body temperature and as a mold in the environment.

Reservoir: Not completely understood: moist environments

close to waterways, in forest or under flooring, also sandy and

acidic soil and rotten vegetation. Bird excreta have also been

implicated as a potential reservoir. Dogs are more commonly

infected than humans but do not transmit disease.

Transmission:Inhalation of spores from disturbed soil. There

is no person-to-person transmission.

Cycle: Environment (soil) to human. Fungal spores are

inhaled and convert to the pathogenic yeast form in the

lung from where they can disseminate to other organs.

Incubation period: Weeks to months; median 45 days.

Clinical findings: A granulomatous fungal infection of the

lung, skin, bone or genitourinary tract. Pulmonary infection

may be acute or chronic. Acute: fever, cough and pulmonary

infiltrate, resolving in 1–3 weeks. Chronic infection is more

common and characterized by erythematous papules on the

face and extremities, low-grade fever, and weight loss; pulmo- nary infection may cavitate. Occasionally bone, prostate, epi- didymis and central nervous system may be affected.

Untreated disseminated or chronic pulmonary disease is gen- erally fatal. The main differential diagnosis is tuberculosis.

Diagnostic tests: Microscopy of sputum smear or material

from lesions can show characteristic budding forms of the

fungus; culture; serology is not routinely used.

Therapy: Amphotericin B is recommended for severe cases.

Itraconazole for milder cases.

Prevention: None.

Epidemiology: Blastomycosis is a sporadic disease with a

worldwide distribution, though most cases are reported from

North America. It is endemic in the Mississippi and Ohio river

basins and around the Great Lakes. In endemic areas blasto- mycosis is frequent in dogs but rare in cats and other animals.

The annual incidence of blastomycosis in northern Wisconsin

is estimated to be 40–100 per 100,000 in humans and 1,400 per

100,000 in dogs. In the USA outbreaks are usually seen in

the spring and fall, indicating infection 1–3 months earlier.

Cases are commoner in males and the disease is rare in

children. Blastomycosis occurs close to rivers and lakes with

changing water levels. Activities involving shores or water- ways, like fishing and canoeing, are identified as risk factors

for infection.

Map sources: The Blastomycosis map was made by geocod- ing human blastomycosis cases in the medical literature. The

distribution of Blastomycosis in Canada and USA was

obtained from KD Reed et al. (2008).

Key references

Pfaller MA, et al. (2010) Epidemiology of invasive mycoses in

North America. Crit Rev Microb 36(1):1–53.

Reed KD, et al. (2008) Ecologic niche modeling of Blastomyces

dermatitidis in Wisconsin. PLoS ONE 3(4):e2034.

Saccente M (2010) Clinical and laboratory update on blasto- mycosis. Clin Microb Rev 23(2):367–381.

Watts B, et al. (2007) Clinical problem-solving: building a

diagnosis from the ground up; a 49-year-old man came to

the clinic with a 1-week history of suprapubic pain and

fever. N Engl J Med 356:1456–1462.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

113

Page 36 of 113

Disease: Coccidioidomycosis

Classification: ICD-9 114; ICD-10 B38

Synonyms: Valley fever, San Joaquin fever, Desert fever,

Desert rheumatism, California disease.

Agent: Coccidioides immitis (Californian) and C. posadasii (non- Californian), dimorphic, soil-borne, ascomycete fungi unique

to the western hemisphere.

Reservoir: Dry, sandy alkaline soil in the semi-arid zones of

the USA–Mexico border and parts of Central and South

America. In North America, the fungus is mainly found in

the Lower Sonoran Life Zone with low rainfall and high

temperatures C. immitis is present in California, and probably

northern Mexico and Arizona, and C. posadasii is present in the

remaining areas.

Transmission: Inhalation of arthroconidia (reproductive

spores) from the environment or dusty fomites. Sometimes

through direct inoculation or transplantation. Person-to-per- son transmission is extremely rare.

Cycle: The fungal agent reproduces asexually; the mold

forms arthroconidia that are aerosolized and can germinate

into new mycelia under appropriate conditions. Arthroconi- dia are infectious when inhaled by an animal or human

(accidental hosts). In the lung the arthroconidia convert to

spherules in which endospores can develop untill the spher- ule ruptures and the endospores are released, forming new

spherules.

Incubation period: Primary infection: 1–4 weeks; chronic/

disseminated form of disease may be months to years.

Clinical findings: About 60% of exposures result in asymp- tomatic infection. Symptoms range from benign pulmonary

infection (fever, chills, cough, chest pain, dyspnea), night

sweats, anorexia and weight loss to progressive pulmonary

or extrapulmonary disease involving skin, bones and/or

joints, the central nervous system, and other organ systems.

Most patients with primary disease recover spontaneously

and have life-long immunity to re-infection. Chronic and

disseminated disease is estimated to occur in up to 5% of

cases. Meningeal infection occurs in less than 1% of extrapul- monary cases and requires life-long treatment.

Diagnostic tests: Microscopy of respiratory secretions,

pleural fluid, tissue or exudate in which detection of spherules

containing endospores is diagnostic (double-walled struc- tures, size 20–100 mm) fungal culture of sputum, blood, pus,

and urine; coccidioidal serologic tests; cocciodin or spherulin

skin test (not available in USA). Serology on CSF to diagnose

meningitis.

Therapy: Amphotericin B desoxycholate and/or azole anti- fungals; surgery to remove foci.

Prevention: It is an occupational risk for those working in

the environment in endemic regions (e.g. farmers, soldiers).

Dust control where feasible (e.g. paving roads). Arthroconidia

are resistant to extreme environmental conditions and can

survive for many years in dust. Screening of organ donors

for coccidioidomycosis in endemic areas. As the fungus is

easily aerosolized it is a laboratory hazard.

Epidemiology: Infections are most frequent in a period of

drought and winds (dust storms) after heavy rains that

advance mold growth, usually late summer or early fall. It is

estimated that more than 150,000 primary infections occur

annually in the USA. Incidence in California and Arizona

appears to have increased since 1991 and again since 2001,

probably driven by immigration of non-immunes andwheather

conditions that favor dissemination of the fungus. Prevalence of

infection in northern Mexico is reported to be 10–40%. Male

gender, African-American and Filipino race/ethnicity, immu- nosuppression, diabetes, older age and pregnancy are risk

factors for chronic and disseminated disease. Infections outside

the western hemisphere are extremely rare and primarily

imported.

Map sources: The Coccidioidomycosis map is modified from

RF Hector et al. (2005) and combined with aridity index data

from FAO, at: www.fao.org/geonetwork/srv/en/.

Key references

Ampel NM (2010) New perspectives on coccidioidomycosis.

Proc Am Thorac Soc 7(3):181–185.

Center for Food Security and Public Health (2010) Coccidioi- domycosis. Factsheet. At www.cfsph.iastate.edu.

Hector RF, et al. (2005) Coccidioidomycosis – a fungal disease

of the Americas. PLoS Med 2(1):e2.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

115

Page 37 of 113

Disease: Histoplasmosis

Classification: ICD-9 115; ICD-10 B39.0-B39.4, B39.9

Synonyms: Cave disease, Ohio valley disease, reticuloen- dotheliosis, African histoplasmosis.

Agent: The dimorphic fungi: Histoplasma capsulatum (world- wide) and H. capsulatum var. duboisii (Africa). The fungi grow

as a mycelium in the soil at ambient temperatures and convert

to the yeast form in the lung at body temperature.

Reservoir: Soil with high nitrogen content, particularly areas

with a lot of bird or bat guano, like barns and caves. Blackbird

roosts can also be heavily contaminated. Unlike bats, birds are

not infected by H. capsulatum and do not excrete the fungus in

their droppings. Bird droppings are considered a nutrient

source for fungal growth in the already contaminated soil.

Transmission: Through inhalation of aerosolized microconi- dia from disturbed soil or guano. Also by inoculation and

organ transplantation.

Cycle: The fungus grows as a mycelium in the environment

and in human or animal tissue it converts into a budding

yeast.

Incubation period: 3 to 17 days; average 10 days.

Clinical findings: Histoplasmosis may be divided into the

following four types: (1) pulmonary histoplasmosis, (2) dis- seminated histoplasmosis, (3) cutaneous histoplasmosis, and

(4) African histoplasmosis. Most infections are asymptomatic

or mild and resolve without treatment. The acute phase begins

with fever, malaise, chest pains and a dry cough. Chest X-ray

findings are normal in 40–70% of cases. Severe infections result

in mediastinitis, hepatosplenomegaly, lymphadenopathy and

adrenal enlargement. Osteomyelitis is rare. Disseminated dis- ease occurs in patients with altered cellular immunity such as

individuals with AIDS and those receiving immunosuppres- sive medications. It presents with systemic complaints and

multiple organ involvement: lung, spleen, bone marrow,

adrenals, CNS and GI tract being the most affected. Dissemi- nated histoplasmosis is fatal unless treated. Past infection

results in partial protection. Reactivation is uncommon but

may occur.

Diagnostic tests: Serology is mainly used (immunodiffusion

and CF tests). Detection of antigen in blood, CSF, urine or

bronchoalveolar lavage fluid by radioimmunoassay. Micros- copy on Giemsa stained bone-marrow or blood smear. His- toplasma skin tests indicate whether a person has been

exposed. PCR-based tests are available. Fungal culture is

generally slow.

Therapy: For mild cases, an oral triazole; for severe cases,

amphotericin B followed by an oral triazole for at least a year.

Prevention: Avoid accumulations of bird or bat droppings

such as are found in caves. The USA government provides a

document, ‘Histoplasmosis: Protecting Workers at Risk’, with

information on work practices and personal protective

equipment.

Epidemiology: H. capsulatum grows in soil and material

contaminated with bird or guano. The fungus has been

found in poultry house litter, caves, areas harboring bats

and in bird roosts. Histoplasma capsulatum is found throughout

the world excluding areas of very low and very high rainfall. It

is endemic in certain areas of the United States, particularly in

states bordering the Ohio river valley and the lower Missis- sippi river, where 90% of the population have positive histo- plasmin skin tests, indicating a large amount of asymptomatic

infection. H. capsulatum var. duboisii is common in caves in

southern and East Africa. Infection can occur outside the cave

entrance without entering. Infants, young children, and older

persons, in particular those with chronic lung disease, are at

increased risk for severe disease. Disseminated disease is more

frequently seen in people with cancer, AIDS or other forms of

immunosuppression.

Map sources: The Histoplasmosis map was made by geocod- ing reported human Histoplasmosis cases in the medical

literature up to 2010, and showing annual precipation

obtained from WorldClim – Global Climate Data, available

at: www.worldclim.org.

Key references

Ashbee HR, et al. (2008) Histoplasmosis in Europe. Med Mycol

46(1):57–65.

Lenhart SW, et al. (2004) Histoplasmosis: Protecting Workers

at Risk. DHHS (NIOSH) Publication No. 2005–109.

Gugnani HC, et al. (1997). African histoplasmosis: a review.

Rev Iberoam Micol 14(4):155–159.

Knox KS, et al. (2010) Histoplasmosis. Proc Am Thorac Soc

7(3):169–172.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

117

Page 38 of 113

Disease: Mycetoma

Classification: ICD-9 039; ICD-10 B47

Synonyms: Maduromycosis, Madura foot

Agent: There are two different groups of etiologic agents:

fungi and bacteria. Fungal mycetoma is called eumycetoma,

and at least 34 fungal species have been implicated. The fungi

Madurella mycetomatis and Pseudallescheria boydii are the most

common fungal causative agents of eumycetoma. Bacterial

mycetoma is called actinomycetoma and at least 14 actinomy- cetes have been implicated, of which the bacterial species of

Nocardia, Streptomyces and Actinomadura are the most common

causative agents of actinomycetoma.

Reservoir: Soil, decaying vegetation.

Transmission: Through contamination of penetrating

wounds (e.g. by thorns, splinters). There is no person- to-person transmission.

Cycle: Environment with occasional spillover to humans.

Incubation period: Months to years.

Clinical findings: A chronic inflammatory process of soft

tissue, with generally painless swelling and suppuration,

developing sinus tracts from which pus-containing granules

drains. Lesions on foot or leg below the knee, sometimes hand,

shoulder, back or elsewhere. The periosteum and bones may

be attacked.

Diagnostic tests: Pus contains visible granules, histopathol- ogy of biopsy, culture (slow).

Therapy: For bacteria, clindamycin, trimethoprim-sulfameth- oxazole, long-acting sulfonamides; for fungi, itraconazole, keta- conazole, or voriconazole. Resection of small lesions; advanced

lesions may require amputation of the hand or leg.

Prevention: Use closed footwear; thoroughly clean penetrat- ing wounds in endemic areas.

Epidemiology: Common in tropical and subtropical areas

world wide among people who go barefoot, endemic

between 30 N and 15 S of the equator. Mycetoma is endemic

in areas with a short rainy season of relatively low rainfall and

a temperature range of 30–37 C, followed by a long dry

season with low relative humidity temperatures ranging

from a night-time low of as little as 15 C to a daytime

maximum of up to 60 C. This extreme alteration in weather

conditions might be necessary to the survival of the causative

organism in its natural niche in soil or plant material. Cases

have been exported from the endemic region to many non- endemic countries. World wide, about 60% of cases are

caused by actinomycetes; the rest are caused by fungi. In

Africa, eumycetomas are more frequently observed than

actinomycetomas; in India, actinomycetes are found in

more than half of the cases reported. In South America,

90% of the cases are caused by actinomycetes. Infection is

most often seen in herdsmen, farmers, and other field

laborers. Males are 4–5 times more often affected than

females, even in areas where both sexes spend a lot of time

in the fields. Mycetoma is seen in all age groups, but usuallyin

adults 20–40 years old. The disease progresses faster in HIV- positive and other immunocompromised patients.

Map sources: The Mycetoma map is modified from the thesis

of W. van de Sande (2007), with permission.

Key references

Lopez Martinez LJ, et al. (1992) Epidemiology of mycetoma in

Mexico: study of 2105 cases. Gac Med Mex 128:477–481.

Van de Sande W (2007) Genetic variability, antigenicity, and

antifungal susceptibility of Madurella mycetomatis. Thesis,

Erasmus University, Rotterdam.

Welsh O, et al. (2007) Mycetoma. Clin Dermatol 25(2):195–202.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

119

Page 39 of 113

Disease: Paracoccidioidomycosis

Classification: ICD-9 116.1; ICD-10 B41

Synonyms: South American blastomycosis, Brazilian blasto- mycosis, Lutz–Splendore–Almeida disease.

Agent: Paracoccidioides brasiliensis, a dimorphic fungus. At

room temperature, P. brasiliensis is a mold and at body tem- perature (37 C) a yeast.

Reservoir: The natural reservoir is unclear. The fungus

can be isolated from nine-banded armadillos (Dasypus novem- cinctus). The disease has also been reported in dogs and other

animals. Culturing the fungus from soil is difficult and

regularly negative. As armadillos have close contact with

soil, it is expected that soil is a reservoir. By using nine- banded armadillos as sentinel animals, it has been shown that

the habitat of P. brasiliensis is likely humid vegetation close to

water sources.

Transmission: Not completely understood. Possibly in the

soil the fungus produces infective propagula that can become

airborne, inhaled, and lead to respiratory infection. Infections

may also occur through traumatic lesions, but this has not been

demonstrated.

Cycle: Unknown.

Incubation period: Months to years.

Clinical findings: Paracoccidioidomycosis is a chronic pro- gressive systemic mycosis. There are two disease forms:

(1) an acute/subacute form in children that mainly involves

the reticulo-endothelial system, and (2) a chronic or adult

form with a long latent period, that mainly affects men and

generally is a pulmonary infection. The disease can dissemi- nate to mucous membranes, skin, and lymph nodes. Relapses

occur in immune-compromised patients and in those with

disseminated disease. CFR can be up to 10%, highest in

children with underlying conditions, and lowest in adults.

Diagnostic tests: Demonstration of multiple-budding cells in

body fluid aspirates or tissue biopsy specimens by microscopy.

Isolation of the fungus. Serology and histopathology.

Therapy: Mild disease: oral itraconazole or trimethoprim- sulfamethoxazole. For severe cases: iv amphotericin B or

trimethoprim-sulfamethoxazole. Treatment is long and is

monitored by clinical and radiological signs.

Prevention: Avoid contact with armadillos or their habitat.

Epidemiology: Most South and several Central American

countries between 23 N and 34 S have paracoccidioido- mycosis endemic regions, particularly Brazil, Colombia,

Venezuela, and Argentina. The prevalence of paracoccidioi- domycosis in endemic areas can be up to 75% in adults, with

active disease developing in approximately 2% of infected

individuals. The endemic areas are generally forest areas

with many water streams, mild temperatures, a short winter,

and a summer with moderate rain. The disease mainly affects

active rural workers (coffee, cotton, and tobacco farmers),

probably due to environmental exposure. This explains why

the disease is more common in men aged 30 to 60 years.

Postpubertal women are partially protected by estrogen that

prevents the fungus from transitioning to the yeast form.

Contact with nine-banded armadillos has also been shown

to be a risk factor for paracoccidioidomycosis.

Map sources: The Paracoccidioidomycosis map was made by

mapping endemic regions stated in the medical literature. We

used climate data from www.worldclim.org to show regions

suitable for paracoccidioidomycosis: mild temperature (17 to

24 C) and rainfall between 900 and 1,500 mm/year. The 23 N

and 34 S lines indicate the geographic limits of the disease.

Key references

Bagagli E, et al. (2006) Phylogenetic and evolutionary aspects

of Paracoccidioides brasiliensis reveal a long coexistence with

animal hosts that explain several biological features of the

pathogen. Infect Genet Evol 6(5):344–351.

Blotta MHSL, et al. (1999) Endemic regions of paracoccidioi- domycosis in Brazil: A clinical and epidemiologic study of

584 cases in the southeeast region. Am J Trop Med Hyg

61(3):390–394.

Nucci M, et al. (2009) Paracoccidioidomycosis. Curr Fung Infect

Rep 3(1):15–20.

Restrepo A, et al. (2001) The habitat of Paracoccidioides brasi- liensis: how far from solving the riddle? Med Mycol

39:233–241.

Travassos LR, et al. (2008) Treatment options for paracocci- dioidomycosis and new strategies investigated. Expert Rev

Anti Infect Ther 6(2):251–262.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

121

Page 40 of 113

Disease: Penicilliosis

Classification: ICD-9 117.3; ICD-10 B48.4

Synonyms: None.

Agent: Penicillium marneffei, a dimorphic fungus. It is the only

Penicillium species that is dimorphic: at body temperature or

37 C it is a yeast form and at cooler temperature it grows as

a mold.

Reservoir: Unclear. Bamboo rats (Rhizomys sinensis, R. pruino- sus, R. sumatrensis, and Cannomys badius) are natural hosts and

the fungus is detected in the soil of their burrows. P. marneffei

can survive in sterile soil for several weeks and only a few days

in non-sterile soil. P. marneffei has not been recovered from

environments not associated with bamboo rats. Bamboo rats

(except C. badius) eat principally bamboo.

Transmission: Unclear, but likely through inhalation of

P. marneffei conidia from the environment; cutaneous inocula- tion may also occur. There is no human-to-human

transmission.

Cycle: Unknown. It has been proposed that bamboo rats may

amplify infectious dispersal stages for human infections.

Incubation period: Few weeks to months.

Clinical findings: Clinical presentation depends on level of

immune suppression. P. marneffei is most often an opportunis- tic infection in HIV patients with low CD4 counts (<100 cells/m

L). Most present with fever and typical skin lesions. Other

findings are anemia, generalized lymphadenopathy, weight

loss, and hepatosplenomegaly. Respiratory signs can also be

observed. Skin lesions are often papules with central necrosis

on the face and neck, but other body sites can also have lesions.

Other opportunistic infections also need to be excluded in

these patients.

Diagnostic tests: Microscopy of infected tissue in which

typical intracellular yeast cells are found; culture of blood,

bone marrow, skin lesion, or lymph node.

Therapy: Amphotericin B iv or itraconazole. Long-term azole

maintenance treatment is required in HIV patients to prevent

relapses.

Prevention: Secondary prophylaxis with itraconazole.

HIV patients with low CD4 counts should avoid endemic areas. Epidemiology: Together with tuberculosis and crypto- coccosis, penicilliosis is a common opportunistic infection

in HIV patients in Southeast Asia. Though we could not find a

report from Myanmar, it is expected to be present there. In

northern Thailand it causes 15% of the HIV-related diseases.

Before the HIV epidemic it was a rare disease in immuno- compromised patients residing in endemic areas in Asia.

Cases of penicilliosis have been described world wide,

mainly in HIV patients with a travel history to endemic

regions. A single case has been described from Ghana

where there was no clear travel history to Southeast Asia.

The association between bamboo rats and human infection is

unclear. There is an association between infection risk and

doing agricultural work, suggesting that soil exposure is a

risk factor. The disease has a seasonal pattern with more cases

during the rainy season.

Map sources: The Penicilliosis map was made by geocoding

reported human cases in the medical literature up to 2010.

Bamboo richness data is obtained from N. Bystriakova

et al. (2010), with permission. Bamboo richness serves as a

proxy for the distribution of the bamboo rat for whichwe could

not find data.

Key references

Bystriakova N, et al. (2003) Distribution and conservation

status of forest bamboo biodiversity in the Asia-Pacific Region. Biodiv Conserv 12:1833–1841.

Cao C, et al. (2011) Common reservoirs for Penicillium marneffei

infection in humans and rodents, China. Emerg Infect Dis 17

(2):209–214.

Pryce-Miller E, et al. (2008) Environmental detection of

Penicillium marneffei and growth in soil microcosms in com- petition with Talaromyces stipitatus. Fungal Ecol 1:49–56.

Ustianowski AP, et al. (2008) Penicillium marneffei infection in

HIV. Curr Opin Infect Dis 21(1):31–36.

Vanittanakom N, et al. (2006) Penicillium marneffei infection

and recent advances in the epidemiology and molecular

biology aspects. Clin Microbiol Rev 19(1):95–110.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

123

Page 41 of 113

Disease: Amebiasis, Entamoeba histolytica

Classification: ICD-9 006; ICD-10 A06

Synonyms: Amebiasis, amebic dysentery, amebic liver

abscess, ameboma, amoebiasis.

Agent: A protozoan parasite, Entamoeba histolytica, that

exists in two forms: non-motile cyst and motile tropho- zoite. E. histolytica needs to be distinguished from the non- pathogenic E. dispar. E. moshkovskii is a common cause of

non-invasive diarrhea.

Reservoir: Humans; the parasite has also been detected in

non-human primates (cynomolgus monkeys, macaques). E.

moshkovskii can be found in varying wet environments: clean

river sediments, sewage, and brackish coastal pools.

Transmission: Fecal–oral route, mainly exposure to food or

water contaminated with infectious cysts. Direct human-to- human transmission occurs via oral and anal sexual activities.

Cycle:IngestedE. histolytica non-motile cysts will excyst in the

gastrointestinal tract and develop to motile trophozoites that

can penetrate the gut mucosa. In the colon, the trophozoites

encyst and the cysts are excreted with the feces.

Incubation period: Days to months.

Clinical findings: 90% of the cases will be self-limited and

asymptomatic; 10% develop invasiveintestinal disease (colitis),

and <1% extra-intestinal disease (liver abscess). Amebic colitis

presents with abdominal cramps, weight loss, and watery or

sometimes bloody diarrhea; most patients are afebrile. Amebic

colitis rarely progresses to necrotizing colitis, ameboma, and

toxic megacolon. Amebic colitis affects children and adults

equally, but mainly males. Amebic liver-abscess mainly occurs

in men aged 18 to 50 years, for unknown reasons. E. moshkovskii

can cause non-invasive diarrhea.

Diagnostic tests: Microscopy of stool specimens cannot

distinguish between E. histolytica, E. moshkovskii, and E. dispar;

PCR is able to distinguish between these species; stool antigen

tests can identify E. histolytica. Therapy: Invasive disease: tinidazole or metronidazole. For

severe amebic colitis antibiotics are added to prevent and

treat bacterial peritonitis. Surgery for intra-abdominal

complications (e.g. bleeding, perforation). Aspiration for

liver abscesses. Intraluminal parasites and asymptomatic

infection are treated with paromomycin.

Prevention: Sanitation and access to clean water. Personal

hygiene during food preparation and sexual activities. Screen- ing and treatment of close contacts.

Epidemiology: E. histolytica is distributed world wide, espe- cially in countries with poor sanitation and little access to clean

water (see Water and Sanitation maps). It is estimated that E.

histolytica is responsible for 40,000 to 100,000 deaths per year.

Most prevalence studies in the past did not distinguish

between E. histolytica and the non-pathogenic E. dispar, and

therefore little is known of the current disease prevalence of the

pathogenic E. histolytica. E. histolytica infection is endemic in

Mexico, India, South Africa, some Central and South American

countries, and Asian Pacific countries. Community-based

studies in urban slums in Bangladesh showed that: 9% of

preschool children suffer from amebic diarrhea each year,

with 2% requiring a hospital visit. In developed countries,

amebiasis is seen in travelers and immigrants from developing

countries, and cases may also be found in closed psychiatric

institutions. MSM are also a risk group, since they are more

exposed.

Map sources: The Amebiasis map was made with data from

C. Ximenez et al. (2009) and shows data from prevalence

surveys of various populations. There is a lack of data on

the amebiasis disease burden since the discovery of E. dispar. Global burden data is urgently needed.

Key references

Ali IKM, et al. (2003) Entamoeba moshkovskii infections in

children in Bangladesh. Emerg Infect Dis 9(5):580–584.

Haque R, et al. (2003) Amebiasis. N Engl J Med 348:1565–1573.

Haque R, et al. (2009) Association of common enteric

protozoan parasites with severe diarrhea in Bangladesh.

Clin Infect Dis 48:1191–1197.

Stanley Jr, SL (2003) Amoebiasis. Lancet 361:1025–1034.

Ximenez C, et al. (2009) Reassessment of the epidemio- logy of amebiasis: state of the art. Infect Genet Evol

9:1023–1032.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

127

Page 42 of 113

Disease: Anisakidosis

Classification: ICD-9 127.1; ICD-10 B81.0

Synonyms: Anisakiasis, pseudaterranovosis, Cod worm

disease, Herring worm disease, Whaleworm disease, and

Sealworm disease.

Agent: The nematodes: Anisakis simplex, A. physeteris, Pseudoterranova decipiens, and Contracaecum spp. A. simplex

and P. decipiens are the most important species for human

disease. Anisakis larvae are whitish, tightly coiled, 1.5–2 cm

in length, and difficult to see in fish flesh. Pseudoterranova

larvae are 2–3 cm in length and red to brown in color.

Reservoir: Marine mammals (definitive host), marine inver- tebrates (intermediate host), and fish (intermediate host). Fish

are frequently infected: tuna, cod, mackerel, herring, red

snapper, pike, sardines, salmon. A. simplex and A. physeteris

are parasites of whales, seals, walruses, sea lions, and related

mammals. P. decipiens is found in Pinnipeds (seals, sea lions,

walruses). Contracaecum spp. are parasites of sea eels and

whiting, and have been associated with human anisakiasis.

Transmission: Ingestion of raw or undercooked fish. There is

no person-to-person transmission.

Cycle: Ova are excreted with the feces of infected animals, and

develop into larvae which are ingested by squid and

other invertebrates – these in turn are ingested by fish which

may be eaten raw by humans. Humans are accidental hosts.

Incubation period: Few hours for gastric anisakiasis, several

weeks for intestinal anisakiasis. Immediate for anisakis- associated hypersensitivity after eating (either raw or cooked)

food containing the allergen.

Clinical findings: Gastric anisakidosis: findings depend on

where in the gastrointestinal tract the ingested larvae embed.

Gastric anisakidosis is the predominant form with acute severe

gastric pain, nausea, and vomiting and sometimes hematemesis.

Intestinal anisakiasis can cause abdominal pain, obstruction,

peritonitis, ulceration, and bleeding. Anisakis-associated hyper- sensitivity is increasingly being reported and varies from acute

urticaria to anaphylaxis. Pharyngeal anisakiasis is rare with

pharyngeal irritation as the main symptom.

Diagnostic tests: Endoscopic identification of larvae.

Eggs and larvae are not found in the feces. Specific antibody

tests are available for anisakis-associated hypersensitivity.

Therapy: Endoscopic removal of larvae; albendazole; surgery

for complications. Allergic patients: symptomatic treatment.

Prevention: Avoid consumption of inadequately cooked

marine fish. Clean the fish early after they are caught as larvae

migrate from viscera into fish flesh after death. Freezing

at 20 C for at least 7 days kills larvae. Larvae can survive

50 days in vinegar. For allergic patients: avoid food that may

contain allergen.

Epidemiology: Anisakidosis occurs world wide, mainly in

coastal regions, and in cultures where consumption of raw fish

occurs. Risky fish dishes are sushi, sashimi, Filipino bagoong,

salted or smoked herring, gravlax, Hawaiian lomi-lomi and

palu, South American ceviche, and Spanish pickled anchovies.

Anisakidosis is increasingly common in western European

countries and the USA due to the increasing popularity of

eating raw fish (usually Sashimi). In the USA most cases are

related to Pacific salmon consumption and in Europe to

herring consumption. It is unclear why anisakidosis is com- mon in Japan, but rarely reported in Taiwan or coastal China

where similar fish products are eaten. Overall there is under- diagnosis of the disease due to the physicians’ inexperience of

the disease. Pseudoterranovosis (codworm) is relatively more

common in North America than in Europe or Japan. Most

allergic cases are reported from Mediterranean Europe. In

Spain it is mainly related to the consumption of cooked

hake and anchovies.

Map sources: The Anisakidosis map was made by geocoding

reported cases in the medical literature up to 2009.

Key references

Audicana MT, et al. (2008) Anisakis simplex: from obscure

infectious worm to inducer of immune hypersensitivity.

Clin Microbiol Rev 21(2):360–379.

Huss HH, et al. (2003) Assesment and Management of Seafood

Safety and Quality. FAO Fisheries Technical Paper 444.

Sakanari JA, et al. (1989) Anisakiasis. Clin Microbiol Rev

2(3):278–284.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

129

Page 43 of 113

Disease: Babesiosis

Classification: ICD-9 088.8; ICD-10 B60.0

Synonyms: Nantucket fever, Piroplasmosis.

Agent: Intraerythrocytic, protozoan parasites, Babesia spp.:

B. microti in North America, B. duncani on the west coast of the

USA and B. divergens-like in four states; B. divergens in Cape

Verde, western Europe, and Finland; B. venatorum in Switzer- land, Italy, and Austria; B. microti-like in Taiwan and Japan;

Babesia strain KO1 in South Korea. Species are uncertain in

China, Egypt, India, and South Africa.

Reservoir: Rodents, voles (B. microti), cattle (B. divergens),

lagomorphs (B.divergens-like), possibly horses (B. duncani,

formerly type WA1), or sheep (Babesia type KO1).

Vector: Minute hard ticks: Ixodes ricinus in Eurasia, possibly

Hemaphysalis longicornisin Korea, I. ovatusin Japan. I. scapularis

(formerly I. dammini) in eastern North America, possibly I.

dentatus in the central USA, I. pacificus in California and

Washington state, USA.

Transmission: By tick bite; rarely by blood transfusion and

transplacental/perinatal. Ticks must feed for more than 24

hours for transmission to occur.

Cycle: Ticks introduce Babesia spp. sporozoites from the

ticks’ salivary glands into small mammals/humans during

feeding. The sporozoites infect erythrocytes in which they

asexually reproduce by budding and develop through various

stages into gametocytes. Ticks can take up circulating game- tocytes during feeding on an infected animal. The gametocytes

fertilize in the tick gut and develop into sporozoites in their

salivary glands.

Incubation period: 1–9 weeks; relapses up to more than a

year.

Clinical findings: Often asymptomatic in healthy individuals.

Symptomatic cases: fever, chills, myalgia, fatigue, and jaundice,

hemolytic anemia; severe cases: retinal infarctions, ecchymoses

and petechiae, acute respiratory failure, congestive heart fail- ure, DIC, liver and renal failure, and splenic rupture, with a

mortality rate of 5–9%, higher in immunocompromised

patients. The differential diagnosis is chloroquine-resistant

malaria, Lyme disease, or human granulocytic anaplasmosis.

Diagnostic tests: Microscopy on Giemsa-stained thick or thin

film blood smear; PCR; isolation in hamsters (2–4 weeks for

result); serology (IFA) on paired acute and convalescent sera.

Therapy: Combination of atovaquone and azithromycin for

mild-to-moderate illness, clindamycin and quinine for severe

disease. Exchange transfusion for life-threatening infection,

dialysis in case of renal failure. Chloroquine is ineffective.

Prevention: Control deer population; avoid areas with ticks;

tick bite precautions: cover skin, repellent on skin and clothing

(permethrin, DEET), check daily for attached ticks and remove.

Epidemiology: Immunocompromised, asplenic, and elderly

people are at higher risk of symptomatic disease. The number

of cases diagnosed in the USA has increased markedly since

1975 due to an increase in the white-tailed deer population,

hosts of the adult vector ticks. Nearly all patients with Babesia

divergens infection in Europe had been splenectomized and

exposed to cattle. TheB. divergens-like parasite in the USA has a

reservoir in cottontail rabbits, and is not infectious for cattle; it

has been found in only 3 patients. All 3 patients with

B. venatorum (EU1) infection had also been splenectomized.

Cape Verdean, Egyptian, and Asian cases lie outside the range

of Ixodes ricinus; B. duncani and B. divergens-like cases in west

coast states of USA lie outside the range of I. scapularis. Possible

vectors for these cases are I. dentatus in the central USA, and I.

pacificus on the west coast. Infection is seasonal (summer),

coinciding with abundance of nymphal ticks in warmer

months.

Map sources: The Babesiosis map was made by geocoding

reported cases in the medical literature up to 2010. The tick

distributions are obtained from G.V. Kolonin (2009).

Key references

Kolonin GV (2009) Fauna of Ixodid Ticks of theWorld; available at

www.kolonin.org.

Saito-Ito A, et al. (2000) Transfusion-acquired, autochthonous

human babesiosis in Japan: isolation of Babesia microti-like

parasites with hu-RBC-SCID mice. J Clin Microbiol

38:4511–4516.

Vannier E, et al. (2008) Human babesiosis. Infect Dis Clin N

Am 22:469–488.

Vannier E, et al. (2009) Update on babesiosis. Interdisc Persp

Infect Dis 984568.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

131

Page 44 of 113

Disease: Capillariasis, Intestinal

Classification: ICD-9 127.5; ICD-10 B81.1.

Syndromes and synonyms: Intestinal capillariasis, Pudoc

mystery disease, wasting disease.

Agent: The agent of intestinal capillariasis is Capillaria philip- pinensis (or Paracapillaria philippinensis), a small nematode

roundworm (males 2.3 to 3.2mm; females 2.5 to 4.3 mm).

Two other Capillaria species that can cause rare human infec- tions: hepatic (C. hepatica or Calodium hepaticum) and pulmo- nary capillariasis (C. aerophila). The map only shows intestinal

capillariasis.

Reservoir: For C. philippinensis: fish-eating birds. Freshwater

fish are intermediate hosts.

Transmission: Consumption of raw or undercooked unevis- cerated fish that have ingested infected feces of humans or

waterfowl. There is no person-to-person transmission.

Cycle: For C. philippinensis: eggs are passed in the stools of

humans and fish-eating birds; after ingestion by freshwater

fish, larvae hatch, penetrate the intestinal wall and migrate to

the tissues. Ingestion of raw or undercooked fish results in

infection of the human and bird host. The adults of C. philip- pinensis reside in the mucosa of the human small intestine,

where the females lay eggs. Released larvae can cause autoin- fection, which may progress to hyperinfection.

Incubation period: At least 2 weeks.

Clinical findings: Intestinal capillariasis starts with mild

abdominal pain, borborygmus, and diarrhea, that develops

to profuse watery diarrhea. If untreated: chronic diarrhea,

vomiting, malabsorption, leading to weight loss, muscle wast- ing, cachexia, and eventually death. Hepatic capillariasis (C.

hepatica) is a (sub)acute hepatitis with eosinophilia, that may

disseminate to other organs and can be fatal. Pulmonary

capillariasis (C. aerophila) may present with fever, cough,

asthma, and pneumonia and may also be fatal.

Diagnostic tests: Microscopy for eggs, larvae and/or adult

worms in the stool, or in intestinal biopsies for C. philippinensis

(eggs resemble those of Trichuris trichiura).

Therapy: Albendazole or mebendazole.

Prevention: For C. philippinensis: sanitation and avoid con- sumption of raw or improperly cooked fish.

Epidemiology: Intestinal capillariasis is generally found in

countries where raw freshwater fish is eaten. The parasite was first reported in 1963 in the northern Philippines. C. philip- pinensisis endemic in the Philippines, Laos, and Thailand. Rare

cases have been reported from other Asian countries and the

Middle East. A single case has been reported in Spain imported

from Colombia, but there are no other reports of cases in the

Americas. Rare cases of human infection with C. hepatica and

C. aerophila have been reportedworldwide. Infected fishmay be

exported from endemic areas to non-endemic countries.

Map sources: The Capillariasis map was made by geocoding

reported human cases infected with Capillaria philippinensis up

to 2010. There is no detailed information on where the human

cases occurred in Indonesia.

Key references

Cross J (1992) Intestinal capillariasis. Clin Microb Rev 5

(2):120–129.

Belizario VJ Jr, et al. (2010) Intestinal capillariasis, western

Mindanao, the Philippines. Emerg Infect Dis 16(4):736.

Dronda F, et al. (1993) Human intestinal capillariasis in an area

of nonendemicity: case report and review. Clin Infect Dis 17

(5):909–912.

Saichua P, et al. (2008) Human intestinal capillariasis in Thai- land. World J Gastroent 14(4):506–510.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

133

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Disease: Clonorchiasis

Classification: ICD-9 121.1; ICD-10 B66.1

Syndromes and synonyms: Chinese liver fluke, Oriental

liver fluke.

Agent: Clonorchis sinensis, a trematode (fluke) 10–25 mm long

and 3–5 mm wide.

Reservoir: Piscivorous (fish-eating) mammals, including:

humans, dogs, cats, pigs, rats, and several species of wild

animals. Humans can remain infected for several decades.

Vector: Freshwater operculate snails (mainly Parafossarulus

sp. and Bithynia sp.).

Transmission: Consumption of raw or undercooked infected

freshwater fish, mainly Cyprinidae (carp and minnows) or

shrimp.

Communicability: None.

Cycle: Fish-eating mammals (including humans) shed C.

sinensis eggs into the environment that are ingested by snails,

where they develop into cercariae. The motile cercariae are

released into water and infect freshwater fish and encyst in

meat and skin as metacercariae. When ingested by mammals,

the metacercariae migrate into the bile ducts where they

develop into adult flukes that produce and excrete eggs into

feces. The cycle takes approximately 3 months.

Incubation period: Depends on infecting dose. Larvae reach

adult fluke stage in less than one month.

Clinical findings: Loss of appetite, epigastric discomfort,

rarely jaundice due to bile duct obstruction, cirrhosis, liver

enlargement, ascites and edema. After years of chronic infec- tion there is a risk of cholangiocarcinoma.

Diagnostic tests: Visualizing characteristic eggs in feces or

duodenal fluid by microscopy.

Therapy: Praziquantel; surgery in case of biliary obstruction.

Prevention: Proper cooking, or freezing of fish at 20 C for

7 days destroys the parasite. Abandon use of human feces to

fertilize fish ponds.

Epidemiology: Clonorchiasis is the most common liver fluke

in humans. Estimates show that approximately 35 million

people are infected world wide, of which 15 million are in

China. In endemic areas, the highest prevalence is in adults

over 30 years of age. The intensity of human infection depends

on the eating habits of the population. In Asia, eating raw fish

is common together with alcohol consumption and, therefore,

men are more often infected than women. The incidence is low

in children. In China the prevalence in some regions is increas- ing, probably due to increased consumption of raw freshwater

fish. The geographical extent of the disease is determined by

snail distribution, the eating habits of the local population, and

contamination of freshwater with egg-containing feces. In

southern China the disease is maintained by the practice of

using human feces in carp raising ponds to promote plankton

growth, on which the fish feed. In non-endemic areas it

appears in Asian immigrants, and in people who consume

raw, dried, smoked or pickled fish imported from endemic areas. Map sources: The Clonorchiasis map was made by geocod- ing human cases reported in the medical literature up

to 2010.

Key references

Lun ZR, et al. (2005) Clonorchiasis: a key foodborne zoonosis

in China. Lancet Infect Dis 5(1):31–41.

Marcos LA, et al. (2008) Update on hepatobiliary flukes:

fascioliasis, opisthorchiasis and clonorchiasis. Current Opin- ion Infect Dis 21(5):523–530.

Rim HJ (2005) Clonorchiasis, an update. J Helminth

79:269–281.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

135

Page 46 of 113

Disease: Cysticercosis

Classification: ICD-9 123.1; ICD-10 B 69.0

Syndromes and synonyms: Taenia solium infection, neuro- cysticercosis, cerebral cysticercosis, taeniosis, taeniasis.

Agent: Larval stage of the pork tapeworm T. solium. Adult

T. solium can be 2–5 meters in length and lives in the small

intestine of human host.

Reservoir: Humans are the definitive host; pigs are an inter- mediate host.

Transmission: Cysticercosis develops after ingesting

T. solium eggs; Taeniasis (tapeworm carriage) occurs after

ingestion of raw or undercooked pork meat with cysticerci;

human to human transmission is by the feco–oral route.

Cycle: Pigs or humans ingest eggs from contaminated envi- ronment. Adult tapeworms will only develop in humans

after eating raw or undercooked pork containing cysticerci.

It takes 2 months for larvae to become an adult worm and

produce eggs (up to 300,000 eggs per day). In pigs, eggs invade

the general circulation via the intestinal wall and migrate to

skeletal and heart muscles where they form cysticerci.

Incubation period: It takes 2 months (range: 5–12 weeks) to

mature to an adult worm in the intestine. The incubation

period of neurocysticercosis (time from infection to first symp- tom) is extremely variable from months to several years.

Clinical findings: Taeniosis is T. solium infection of the small

intestine and varies from asymptomatic (the most frequent) to

weight loss, anorexia and abdominal pain. Cysticercosis is a

tissue infection with T. solium larvae with findings depending

on where cysticerci develop (subcutaneous, eye, heart, CNS).

Its localization in the CNS, causing neurocysticercosis, is the

most severe form of the disease: seizures, headache, focal

neurologic signs, epilepsy, and hydrocephalus may develop.

The CFR is low.

Diagnostic tests: Taeniosis: detection of eggs in stool by

microscopy; T. solium eggs can not be distinguished from

T. saginata eggs; serology; Neurocysticercosis: histology; CT

or MRI scan brain; serology is not sensitive or specific for

neurocysticercosis.

Therapy: Taeniosis: praziquantel. Neurocysticercosis: Treat- ment must be individualized case by case but could include

cestocidal drugs (albendazole or praziquantel), symptomatic

measures (antiepileptic drugs, oedema reducing drugs,

ventriculoperitoneal shunt) and removal by neurosurgery

(limited indications).

Prevention: Sanitation (particularly use of latrine and main- taining pigs enclosed); hygiene; meat inspection; thorough

cooking of pig meat before consumption; treatment of tape- worm carriers. A vaccine has been developed for cattle.

Epidemiology: Cysticerosis has a worldwide distribution,

mainly where pigs are consumed and sanitation is substan- dard (see Streptococcus suis map for pig density and Sanitation

map). In endemic countries it is an important cause of epi- lepsy, causing a high disease burden in mainly poor families.

In several countries neurocysticercosis is the cause of 10–50%

of seizures. Neurocysticercosis is common in Latin America

and non-Muslim African and Asian countries where pig is

eaten and traditional pig rearing is practiced. Regions with the

habit of eating raw or undercooked pig meat are at increased

risk. In Europe, cysticercosis has largely disappeared due to

strong health system and good sanitation. In several devel- oped nations, like the USA and Spain, there is an increase in

certain regions where lots of migrants live who have come

from high endemic countries. Tapeworm carriers can cause

small outbreaks, as was observed in a Jewish community in

New York that employed cooks from Latin America.

Map sources: The Cysticercosis map is modified from G.

Roman et al. (2000) and WHO (2009) at: http://gamapserver

.who.int/mapLibrary/Files/Maps/Global_cysticercosis

_2009.png.

Key references

Carpio A (2002) Neurocysticercosis: an update. Lancet Infect

Dis 2:751–762.

Carpio A, et al. (2008) Effects of albendazole treatment on

neurocysticercosis: a randomised controlled trial. J Neurol

Neurosurg Psychiat 79(9):1050–1055.

Dixon HB, et al. (1961) Cysticercosis: an analysis and follow-up

of 450 cases. Spec Rep Ser Med Res Coun 299:1–58.

Engels D, et al. (2003) The control of human (neuro)cysticer- cosis: which way forward? Acta Trop 87:177–182.

Roman G, et al. (2000) A proposal to declare neurocysticercosis

an international reportable disease. Bull World Health Organ

78(3):399–406.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

137

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Disease: Diphyllobothriasis

Classification: ICD-9 123.4; ICD-10 B70.0

Syndromes and synonyms: Diphyllobothriosis, Dibothrio- cephaliasis, broad or fish tapeworm infection

Agent: The cestode Diphyllobothrium latum (fish or broad

tapeworm), the largest human tapeworm (up to 25 meters

long). In Japan and eastern Russia D. nihonkaiense is common.

At least 13 other Diphyllobothrium species have been reported

to infect humans, but less frequently.

Reservoir: In addition to humans, dogs and fish-eating ter- restrial and marine mammals can also serve as definitive hosts

for D. latum. Transmission: Consumption of raw or undercooked fresh- water fish containing infectious larvae. There is no direct

person-to-person transmission.

Cycle: Eggs are passed in feces into freshwater bodies, mature

in about 2 to 3 weeks, depending on water temperature, and

hatch ciliated larvae (coracidia). Coracidia develop into procer- coid larvae after ingestion by freshwater crustaceans (cope- pods). The copepods are eaten by a second intermediate host,

typically small fish. The larvae migrate into the musculature

where they develop into the human infectious plerocercoid

larvae. Larger predator fish (e.g. pike, burbot, perch) ingest

the smaller infected fish upon which the plerocercoid larvae

migrate to the flesh of these larger fish that serve as third

intermediate hosts harboring larvae. Humans and larger mam- mals acquire the disease by eating these larger fish raw or

undercooked. The larvae mature into adult tapeworms that

attach to the small intestinal wall by scolex and develop egg- filled proglottids that detach. Up to 1 million eggs per day per

worm are passed in the feces, 2–6 weeks after infection.

Prepatent period: 2–6 weeks.

Clinical findings: Most infections are asymptomatic or mild.

Symptoms are: abdominal discomfort, diarrhea, vomiting and

weight loss, rarely anemia. Massive infections may result in

intestinal obstruction. Migration of proglottids can cause cho- lecystitis or cholangitis. Proglottids can be seen in the stool.

Diagnostic tests: Microscopic identification of eggs in the

stool, visualization of proglottids passed in the stool.

Therapy: Praziquantel and niclosamide are the drugs of

choice. In untreated cases the worms can live up to 25 years

and produce eggs.

Prevention: Avoid ingesting raw freshwater fish. Adequate

cooking, freezing at 20 C for at least 7 days, or irradiation of

fish or meat will kill encysted larvae. Sanitation.

Epidemiology: Human infection is associated with cold

waters in the northern hemisphere. A 2005 estimate stated

that 20 million people were infected world wide. It is

common in communities, as in Japan, that have a habit of

eating raw or undercooked fish. Risky fish dishes are sushi,

sashimi, South American ceviche, fish carpaccio, salmon

tartare, and salted or marinated fillets in Scandinavia or

Baltic region. Historically, Finland and Alaska had a high

disease prevalence, but this has decreased due to preventive

measures. Women seem more at risk, probably due to being

involved in meal preparation. The disease incidence is

increasing in some countries such as Russia, South Korea,

Japan, and Brazil. Cases are also reported from regions

where diphyllobothriasis was expected to have been elimi- nated, such as Alpine lakes in Switzerland, northern Italy,

and eastern France. It is not clear whether the cases reported

in Hawaii and Brazil are autochthonous or from imported

fish. D. nihonkaiense, present in Japan and far eastern Russia,

has been reported from a patient who ate raw Pacific sock- eye salmon (Oncorhynchus nerka) from British Columbia,

Canada. D. pacificum (formerly D. arctocephalinum) is increas- ingly reported as a human parasite along the coast of South

America. Infected fish can be transported to any part of the

world for consumption.

Map sources: The Diphyllobothriasis map was made by

visualizing regions or countries were cases have been reported

in the medical literature up to 2010.

Key references

Rausch RL, et al. (2010) Identity of Diphyllobothrium spp.

(Cestoda: Diphyllobothriidae) from sea lions and people

along the Pacific Coast of South America. J Parasit

96(2):359–365.

Scholz T, et al. (2009) Update on the human broad tapeworm

(genus Diphyllobothrium), including clinical relevance. Clin

Microbiol Rev 22(1):146–160.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

139

Page 48 of 113

Disease: Dracunculiasis

Classification: ICD-9 125.7; ICD-10 B72

Syndromes and synonyms: Guinea worm disease, Medina

worm disease, Pharaoh worm disease, serpent worm disease,

dracontiasis.

Agent: Dracunculus medinensis, a nematode roundworm. The

longest adult female recorded is 80 cm, and adult male 40 cm.

Reservoir: Humans.

Vector: Cyclops spp., microscopic copepods (crustaceans)

commonly known as water fleas. Transmission: By ingestion of infected copepods, usually

with drinking water.

Cycle: Human–copepod–human. Adult female worm expels

larvae through a hole in the skin of the leg or foot of an infected

person into stagnant water where they are ingested by the

vectors. The larvae become infectious in 2 weeks and when the

vectors are ingested and digested, the larvae are freed and

migrate into the subcutaneous tissue of the abdomen and

thorax. There they mature into adults. Larvae are shed for

2–3 weeks, are viable in water for up to 5 days, and develop in

the copepod for 2 weeks.

Incubation period: About 12 months (10 to 18 months).

Clinical findings: Blister,usually onthelegor foot,which burns

or itches, fever, nausea, vomiting, diarrhea, dyspnea, dizziness

and generalized urticaria. Multiple and repeat infections occur,

there is no protective immunity. Painful and infected ulcers can

incapacitate patients for months. Secondary bacterial infection

can lead to abscesses, synovitis, ankylosis andlimbcontractures,

septic arthritis, and life-threatening sepsis.

Diagnostic tests: Visual inspection for adult worm protrud- ing from the skin lesion; microscopic identification of larvae

released when lesion is immersed in water.

Therapy: Adult worm can be extracted by carefully and

slowly winding the worm around a stick over a period of

days. Metronidazole or thiabendazole can facilitate the extrac- tion process, but should be used with caution.

Prevention: Use of safe water by filtering or boiling or

disinfection with temephos (insecticide). Avoid wading in

contaminated water, especially people with an apparent

worm. There is no vaccine, but tetanus toxoid may be

given to prevent tetanus. The Global Guinea Worm Eradi- cation Programme is led by the Carter Center, CDC, WHO,

UN Children’s Fund and the individual efforts of endemic

nations.

Epidemiology: Historically, dracunculiasis was endemic in 20

countries in Sub-Saharan Africa and Asia, with an incidence of

3.5 million cases per year (1986). An international control effort

reduced that to just over 1,785 cases detected in five African

countries by 2010: Mali, Ghana, South Sudan, Chad, and

Ethiopia. Nearly 95% of the cases are reported from South

Sudan. Additionally, Niger reported 3 imported cases from

Mali. Chad did not report cases for more than 10 years when an

outbreak occurred with 10 cases in 2010. In Mali and Southern

Sudan, violence has interfered with the eradication campaign,

but Ghana and Ethiopia are close to eradication. Ghana diag- nosed their last indigenous case in May 2010. Dracunculiasis

mainly affects poor communities without a safe portable water

supply and is mainly limited to remote nomadic communities.

There is a marked increase in infection in the dry season when

stagnant pools are the only source of water. Most cases are

young (working) adults who may be exposed to contaminated

water sources more frequently. There is no particular age or sex

predilection. Countries free of transmission neighboring

endemic countries should remain alert for imported cases

and take adequate preventive measures.

Map sources: The Dracunculiasis map was made with data

obtained from WHO (http://apps.who.int/dracunculiasis

/dradata/) and the CDC’s Guinea Worm Wrap Up Nr. 202

(2011).

Key references

Centers for Disease Control and Prevention (2010) Progress

toward global eradication of dracunculiasis, January

2009–June 2010. Morb Mortal Wkly Rep 59(38):1239–1242.

Centers for Disease Control and Prevention (2011) Guinea

Worm Wrap Up nr 202. Memorandum. Glenshaw MT, et al. (2009) Guinea worm disease outcomes in

Ghana: determinants of broken worms. Am J Trop Med Hyg

81(2):305–312.

Iriemenam NC, et al. (2008) Dracunculiasis – the saddle is

virtually ended. Parasitol Res 102(3):343–347.

Lodge M (2010) And then there were four: more countries beat

guinea worm disease. Brit Med J 340:c496.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

141

Page 49 of 113

Disease: Echinococcosis, Echinococcus

multilocularis

Classification: ICD-9 122.7; ICD-10 B67.5–B67.7

Syndromes and synonyms: Alveolar or multilocular

echinococcosis.

Agent: Echinococcus multilocularis, a small (3–6 mm long)

cyclophyllid cestode (tapeworm).

Reservoir: Foxes (including urban foxes) are the definitive

hosts, wild rodents (mainly Arvicolidae), voles and lemmings

are intermediate hosts. Foxes have extended their distribution

into urban areas, partly due to a decrease in rabies deaths in

foxes since rabies vaccination.

Transmission: Ingestion of tapeworm eggs from feces of

foxes, dogs, and cats or contaminated fomites. There is no

person-to-person transmission.

Cycle: Fox–rodent–fox (sylvatic cycle). Foxes are the defini- tive hosts of the adult worm. Eggs are excreted with the feces

and ingested by humans or the intermediate rodent host,

where they hatch. The larvae penetrate the intestinal wall and

via the blood they reach the liver, lungs, brain, and heart.

There they form metacestodes in which protoscolices

develop. When the rodent is eaten by the definitive host,

these attach to the small intestine and grow into adult worms.

Occasionally wild carnivores (e.g. coyotes or wolves) can be

definitive hosts. In some rural areas there is a synanthropic

cycle in which dogs or cats are definitive hosts, acquiring the

parasite from wild rodents.

Incubation period: 5–15 years in humans (5–7 weeks in dogs).

Clinical findings: Headache, nausea, vomiting, abdominal

pain, and hepatomegaly. In the later stage of the disease, the

metacestode may grow into neighboring organs (e.g. through

the diaphragm into the lungs), and metastases can form

anywhere. The differential diagnosis is hepatic cirrhosis or

carcinoma. The disease can be fatal.

Diagnostic tests: Histopathology; imaging tests; serodiag- nosis with purified E. multilocularis antigen; PCR.

Therapy: Mebendazole or albendazole; radical surgical

excision.

Prevention: Avoid exposure to feces of reservoir species wash

hands, fruit and vegetables, periodically treat high-risk dogs,

eliminate ownerless dogs. Praziquantel-containing baits have

reduced infection in urban foxes and water voles in Switzer- land and Germany. Eggs are highly sensitive to elevated

temperatures and desiccation, but survive for months at freez- ing temperatures and are not affected by common disinfec- tants or ethanol.

Epidemiology: Echinococcosis is restricted to the northern

hemisphere, and is most commonly found in adults. The distri- bution of infected foxes is highly uneven; sandy soils, dry

habitats and large forests are unfavorable for the parasite. In

Europe, foxes have adapted well to urban life and urban fox

densities now can exceed rural fox densities. However, there is

no clear correlation between fox densities and cases of human

alveolar echinococcosis. In some areas there is a shift from a

sylvatic to a synantropic cycle, including domestic dogs, as

was seen in China and Alaska. Such a shift leads to a higher

risk of infection in humans. The prevalence in dogs and cats

is still very low in Europe, even in areas highly endemic for

infection in foxes.

Map sources: The Echinococcosis (E. multilocularis) map was

modified from a map provided by Peter Deplazes, University

of Zurich, Switzerland. The map shows areas where there is

convincing parasite detection in intermediate or definitive

hosts, including humans.

Key references

Deplazes P, et al. (2004)Wilderness in the city: the urbanization

of Echinococcus multilocularis. Trends Parasit 20(2):77–84.

Hegglin D, et al. (2003) Anthelmintic baiting of foxes against

urban contamination with Echinococcus multilocularis. Emerg

Infect Dis 9(10):1266–1272.

Romig T, et al. (2006) The present situation of echinococcosis in

Europe. Parasit Int 55:S187–S191.

Tackmann T, et al. (1998) Spatial distribution patterns of

Echinococcus multilocularis (Leuckart 1863) (Cestoda:

Cyclophyllidea: Taeniidae) among red foxes in an ende- mic focus in Brandenburg, Germany. Epidemiol Infect

120:101–109.

Veit P, et al. (1995) Influence of environmental factors on the

infectivity of Echinococcus multilocularis eggs. Parasitology

110:79–86.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

143

Page 50 of 113

Disease: Eosinophilic Meningitis,

Angiostrongylus cantonensis

Classification: ICD-9 128.8; ICD-10 B83.2

Syndromes and synonyms: Eosinophilic meningoenceph- alitis, angiostrongyliasis

Agent: Angiostrongylus cantonensis, a nematode lungworm of

rats. Adult worms are 17 to 25 mm long. Angiostrongylus

costaricensis is the causal agent of abdominal, or intestinal,

angiostrongyliasis and is not shown on the map. Other patho- gens, like Gnathostoma spinigerum, are able to cause eosino- philic meningitis, but are not shown on the map.

Reservoir: Rats (Rattus, particularly R. norvegicus and Bandi- cotta spp.). Infected dogs, wild mammals, and marsupials have

been found, but do not contribute to the spread of the disease.

Vector: Snails, slugs, and land planarians. The giant African

snail, Achatina fulica, is the major source of infection world

wide; but has been replaced by the imported South American

golden apple snail, Pomacea canaliculata, in Taiwan and main- land China.

Transmission: Consumption of raw or undercooked vector

molluscs, infested vegetables or vegetable juice, or other fresh

water related food.

Cycle: Rat–mollusc–rat; humans are incidental dead-end hosts.

Larvae are excreted with rat feces, ingested by vectormolluscs, in

which they develop into the infecting third stage larvae in about

12 days. When ingested by a rat, the larvae enter the brain,

mature into adults, and migrate through the bloodstream to the

lungs. There, female worms lay eggs (about 15,000 per day) that

hatch into larvae, which in 6–8 weeks migrate through the

bronchial system up the trachea to the pharynx, are swallowed

and excreted. When ingested by a human, the third stage larvae

also migrate to the CNS, but the worm does not mature.

Incubation period: 1 day to several months, depending on

parasite load; usually 1–3 weeks.

Clinical findings: Cough, rhinorrhea, sore throat, malaise,

and fever can develop when the worms move through the

lungs. In about 5 to 14 days the larvae reach the central nervous

system, leading to subacute meningitis. Eosinophilic meningi- tisis defined asmeningitiswith > 10 eosinophils/mLin CSFor

at least 10% eosinophils in the total CSF leukocyte count. Some

caseshavelow-grade fever and temporary facial paralysis. Signs

of raised intracranial pressure, like diplopia. Worms occasion- allyenter theeye.Thecourse of theillnessranges from a fewdays

to several months. Death is rare.

Diagnostic tests: Mainly a clinical diagnosis: subacute eosin- ophilic meningitis in an endemic area. Most common test is

serology, but there are often false-positives due to cross-reac- tivity with other parasites. Worms are rarely seen in CSF by

microscopy. MRI or CT scan of the brain is not diagnostic.

Therapy: Mebendazole or albendazole with adjunctive corti- costeroids. Lumbar puncture relieves the headache. Ocular

infection requires surgery.

Prevention: Avoid eating raw slugs, snails, other molluscs,

freshwater prawns, land crabs, and uncooked vegetables

grown in ponds (e.g. watercress) from endemic areas.Washing

of vegetables does not guarantee absence from larval contam- ination. Boil snails and crustaceans for 5 minutes or freeze at

15 C for 24 hours.

Epidemiology: An estimated 650 million people are at risk in

10 provinces of China. The distribution is closely correlated

with the habit of consuming raw terrestrial molluscs, reptiles,

or amphibians. The majority of cases are in adults, except in

Taiwan where most cases are in children. Pomacea canaliculata, a snail native to South America, was imported into Taiwan in

1981 as a food source and then into mainland China. It has

replaced A. fulica as the main intermediate host of A. canto- nensis and has become the main source of human infection in

Taiwan and mainland China. Depending on the region, up to

70% of P. canaliculata can be infected.

Eating raw frogs also lead to human infections in China, and

the USA. Consumption of lizards caused several cases in

Thailand, Sri Lanka, and India. Cases have been seen in at

least five countries in Europe and New Zealand in travelers

returning from endemic regions. Malnutrition and debilitating

diseases can exacerbate the infection.

Map sources: The Eosinophilic meningoencephalitis map

was made by geocoding reported cases in the medical

literature. The inset map with A. cantonensis prevalence in

snails is obtained from S. Lv et al. (2009).

Key references

Wang Q-P, et al. (2008) Human angiostrongyliasis. Lancet Infect

Dis 8(10):621–630.

Lv S, et al. (2009) Invasive snails and an emerging infectious

disease. PLoS Negl Trop Dis 3(2):e368.

Ramirez-Avila L, et al. (2009) Eosinophilic meningitis due to

Angiostrongylus and Gnathostoma species. Clin Infect Dis

48(3):322–327.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

145

Page 51 of 113

Disease: Fascioliasis

Classification: ICD-9 121.3; ICD-10 B66.3

Syndromes and synonyms: Sheep liver fluke disease, pha- ryngeal fascioliasis.

Agent: Large trematode liver flukes living in blile ducts:

Fasciola hepatica and Fasciola gigantica. F. hepatica is 20 to

30 mm long and F. gigantica can be up to 75 mm long.

Reservoir: Sheep, cattle, water buffalo, and other large herbi- vores. Occasionally humans.

Vector: Freshwater (pond) snails (Lymnaeidae).

Transmission: Accidental ingestion of metacercariae via con- taminated water, watercress, or other contaminated plants

(lettuce, alfalfa juice, etc.). Rarely via consumption of raw

sheep or goat liver (pharyngeal fascioliasis). There is no per- son-to-person transmission.

Cycle: Eggs hatch in water and release miracidia larvae that

penetrate the snail, where they develop to cercariae that encyst

on aquatic plants (e.g. watercress) and become desiccation- resistant metacercariae. After the plants are eaten by herbi- vores (e.g. sheep, cattle), or water containing metacercariae is

drunk, the larvae pass through the intestinal wall into the

peritoneal cavity, enter the liver, and lay eggs in the bile duct,

which are then excreted in the feces. The whole cycle takes 3 to

4 months.

Incubation period: 3 to 4 months, but is highly variable.

Clinical findings: Acute: hepatomegaly, prolonged fever,

anorexia, weight loss, nausea, vomiting, cough, diarrhea,

urticaria, lymphadenopathies, and arthralgias. Significant

clinical improvement 3–5 days after specific treatment is

diagnostic. Chronic (which may be asymptomatic and last

for more than 10 years): biliary obstruction with upper

abdominal pain, cholecystitis, cholangitis, and extrahepatic

cholestasis. Liver fibrosis may be a complication of the

infection.

Diagnostic tests: Microscopy for eggs on stool samples by

the Kato–Katz or rapid sedimentation techniques (RSTs) are

diagnostic for the chronic infection. Serological tests (Fas2-

ELISA) is recommended for acute infection. The intradermal

test is rapid and sensitive, but as it is not sufficiently specific it

is no longer used. Radiology, such as computed tomography,

can demonstrate liver lesions (only in acute infection) similar

to metatastic lesions. For chronic infections, a cholangiogram

can detect bile duct pathology caused by the adult parasites.

Therapy: Above 95% cure rate with a single dose triclaben- dazole. Albendazole or praziquantel are not effective.

Prevention: Sanitation to avoid contamination of vector snail

habitat with human or animal feces. Improve water drainage,

use molluscicides and avoid eating uncooked aquatic plants in

endemic areas and drinking untreated water.

Epidemiology: It is estimated that 17 million people are

infected world wide and 91 million are at risk of infection.

F. hepatica is endemic on all continents but is of particular

public health importance in the Andean countries (especially

Peru and Bolivia), Ecuador, Chile, Argentina, Brazil, Vene- zuela, Cuba, Mexico, the Islamic Republic of Iran, Egypt,

Philippines, and western Europe (e.g. France, Portugal, and

Spain). Infections with F. gigantica are restricted to Africa

and Asia. Both species of fluke overlap in many areas of Africa

and Asia, whereas F. hepatica is the major concern in the

Americas, Europe, and Oceania. The rural areas of the Andean

region of Peru and Bolivia have prevalence rates of up to 68%.

Women are affected more than men, with higher prevalence

rates, more severe infections, and more reported liver or biliary

complications; children are affected more than adults. The

main source of infection is the consumption of raw vegetables

contaminated with metacercariae, such as watercress, salads,

and contaminated water from irrigation channels. Pharyngeal

fascioliasis may occur after ingestion of raw goat or sheep liver – a dish in some Middle Eastern countries.

Map sources: The Fascioliasis map was made by geocoding

reported human cases in the medical literature up to 2009.

F. gigantica could be more widespread than shown, because it

could be the species reported as unspecified Fasciola. We were

only able to find a few reports of human cases with F. gigantica

in Africa, but it is probably underreported.

Key references

Keiser J, et al. (2009) Food-borne trematodiasis. Clin Microbiol

Rev 22(3):466–483.

Marcos LA, et al. (2008) Update on hepatobiliary flukes:

fascioliasis, opisthorchiasis and clonorchiasis. Curr Opin

Infect Dis 21(5):523–530.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

147

Page 52 of 113

Disease: Fasciolopsiasis

Classification: ICD-9 121.4; ICD-10 B66.5

Syndromes and synonyms: Giant intestinal fluke infection.

Agent: Fasciolopsis buski, a large trematode worm that can be

up to 75 mm long.

Reservoir: Pigs and humans are definitive hosts; less often

dogs.

Transmission: Eating contaminated water plants. There is no

person-to-person transmission.

Cycle: Eggs develop in water in 3–7 weeks, hatch producing

miracidia which enter the intermediate snail hosts, in which

they develop into cercariae. The cercariae encyst on water

plants and develop to metacercariae. When ingested, the

metacercariae excyst in the duodenum, where theflukes attach

to the mucosa of the small intestine, mature, and start egg

production in 2 to 3 months.

Incubation period: Varies from 1 to 3 months.

Clinical findings: Usually asymptomatic or mild. Diarrhea

alternating with constipation, vomiting and anorexia, edema

of the face, abdominal wall and legs, ascites. Heavy worm

loads may cause bowel obstruction. Eosinophilia, vitamin B12

deficiency, and secondary anemia may occur.

Diagnostic tests: Detection of eggs in feces (eggs resemble

those of Fasciola hepatica). Adult flukes may be seen in the stools

or vomit.

Therapy: Praziquantel or niclosamide.

Prevention: Sanitation. Avoid eating uncooked water plants

in endemic areas. Do not fertilize water plants for consumption

with human or pig feces. Abandon practice of feeding water

plants to pigs. Health education. The eggs can resist low

temperatures and can be maintained at 4 C for 3 to 4 months;

they are killed at 50 C in 4 hours. Water can be chemically

treated to kill the flukes.

Epidemiology: Especially prevalent in pig-rearing regions of

Southeast Asia, where it is estimated that 10 million people are

infected. The disease is most common in lowlands where the

snail host is present and it is common practice to fertilize water

plants with pig or human feces. Disease spread is facilitated by

heavy rainfall and extensive flooding, leading to fecal contam- ination of the water. Highest incidence and intensity of infec- tion is found in 10 to14 year old children (no sex difference),

probably because they pick and consume water plants when

they play. In foci of parasite transmission, the prevalence of

infection in children ranges from 57% in mainland China to

25% in Taiwan, and from 50% in Bangladesh and 60% in India

to 10% in Thailand. Water morning glory (Ipomoea aquatica),

water caltrop (Trapa bicornis), lotus (Nymphaea lotus), water cress

(Neptunia oleracea), and water hyacinth (Eichhornia speciosa) are

most responsible for human infection, but cysts also float on the

surface and may be drunk.

Map sources: The Fasciolopsiasis map is made by showing

the countries that have reported human fasciolopsiasis cases,

as reported in the medical literature up to 2010. We also show

pig density data as the disease is endemic in pig-rearing

regions in Asia. The pig density data is obtained from FAO

available at: www.fao.org/ag/againfo/resources/en/glw/

home.html.

Key references

Graczyk TK, et al. (2001) Fasciolopsiasis: is it a controllable

food-borne disease? Parasitol Res 87(1):80–83.

Keiser J, et al. (2009) Food-borne trematodiases. Clin Microbiol

Rev 22(3):466–483.

Sripa B, et al. (2010) Food-borne trematodiases in Southeast

Asia epidemiology, pathology, clinical manifestation and

control. Adv Parasitol 72:305–350.

Yoshihara S, et al. (1999) Helminths and helminthiosis of pigs

in the Mekong Delta Vietnam with special reference to

ascariosis and Fasciolopsis buski infection. Jap Agric Res

Qtly 33(3):193–199.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

149

Page 53 of 113

Disease: Filariasis

Classification:ICD-9 125.0, 125.1, 125.6; ICD-10 B74.0, B74.1,

B74.2

Syndromes and synonyms: Bancroftian filariasis, Brugian

filariasis, lymphatic filariasis, Malayan filariasis, Timorean

filariasis.

Agent: Wuchereria bancrofti, Brugia malayi, and B. timori, threadlike nematode worms 80 to 100 mm long (W. bancrofti),

or 43 to 55 mm long (B. malayi).

Reservoir: Mainly humans. In Southeast Asia, monkeys, wild

carnivores, dogs, and cats may also be infected with B. malayi. W. bancrofti has no known reservoir host.

Vector: For W. bancrofti: Culex quinquefasciatus, Anopheles spp.,

and Aedes spp. in the Pacific Islands; for B. malayi: Mansonia, Anopheles, and Aedes; for B. timori, An. barbirostris. Anopheles

spp. transmit parasites less efficiently than Culex spp., and

Culex spp. are more abundant in urban settings.

Transmission: A large number of infective mosquito bites are

necessary to establish infection.

Cycle: Microfilariae in human blood are ingested by a vector

mosquito, and develop in 2 weeks into larvae that enter the

mouth-parts. Larvae are deposited onto the skin and invade

through the wound made at the next mosquito feed. In humans,

they travel via thelymphatics, when adults they form ‘nests’ and

produce microfilariae, which migrate to the blood and display

periodicity coinciding with the peak vector biting times.

Incubation period: 3–6 months for B. malayi worms to mature

and produce microfilariae that appear in the blood; 6–12

months for W. bancrofti and B. timori. Clinical findings: Infection is often asymptomatic but as the

adult worms live for 5–10 years, some will develop painful

swelling (sometimes enormous) of legs or arms, and, in cases

of Bancroftian filariasis, the breasts or scrotum (hydrocele).

Up to 40% have renal involvement. Acute cases may have

high fever, recurrent lymphadenitis, and retrograde

lymphangitis.

Diagnostic tests: Microscopy to detect microfilariae in

finger-prick blood smears; immunochromatic test cards; ultra- sound to locate ‘nests.’

Therapy: For interrupting transmission: mass treatment with a

single dose of albendazole or ivermectin combined with diethyl- carbamazine citrate (DEC) once a year for at least 5 years; or the

regularintakeofDEC-fortifiedsaltforatleastone year;individual

treatment: DEC can worsen onchocercal eye disease and cause

serious adversereactionsinpatientswithloiasis.Pathogenicityof

filarial nematodes is largely due to the immune response to their

endosymbioticWolbachiabacteria, therefore doxycycline may be

used. The treatment for hydrocele is surgery.

Prevention: In 2000, WHO started the Global Programme to

Eliminate Lymphatic Filariasis that aims to interrupt trans- mission and reduce morbidity. Endemic areas are mapped

with subsequent mass treatment for the population at-risk (see

Therapy) for 5 years. Care needs to be taken in loiasis endemic

areas to prevent adverse events (see Loiasis map); vector

control (e.g. bed nets, repellent).

Epidemiology: WHO (2010) estimates that there are over 120

million infections world wide, with 40 million patients incapaci- tated or disfigured by the disease, principally in India and Sub- Saharan Africa. 90% of the infections are due to W. bancrofti.

Chronicmanifestationsmainly occurin the elderly.About 27 mil- lion have hydrocele (men) and 16 million have lymphedema or

elephantiasis of theleg (mostly women). Asia and South America

havelowerBancroftianfilariasisprevalences(below8%)thanSub- SaharanAfrica (up to 37%) and Pacific Island (up to 48%) regions.

Within areas of low prevalence, pockets of high prevalence may

exist (e.g. Reciffe, Brazil). In the Americas there is only active

transmission in four countries and mainly affects the poor and

slum inhabitants. China has been declared non-endemic for lym- phatic filariasis since 2007 and Korea in 2008, achieved by exten- sive controlefforts.Thevectors are stillpresentand therefore there

remains a risk of re-emergence.

Map sources: The Lymphatic filariasis map was made

with information obtained from WHO, CIESIN, and medical

literature. Useful distribution data are available at: www.

filariasis.org.

Key references

Addiss DG (2010) Global elimination of lymphatic filariasis.

PloS Negl Trop Dis 4(6):e471.

Taylor MJ, et al. (2010) Lymphatic filariasis and onchocerciasis.

Lancet 376(9747):1175–1185.

World Health Organization (2010) Lymphatic Filariasis.

Progress Report 2000–2009 and Strategic Plan 2010–2020. Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

151

Page 54 of 113

Disease: Hookworm

Classification: ICD-9 126; ICD-10 B76

Syndromes and synonyms: Ancylostomiasis, Necatoriasis,

Uncinariasis, ground itch.

Agent: The blood-feeding nematodes Ancylostoma duodenale

and Necator americanus, also known as soil-transmitted hel- minths (STHs). A. ceylanicum has a limited distribution. The

adult nematodes are up to 10mm long.

Reservoir: Humans.

Transmission: Infective larvae in soil invade the skin; A.

duodenale larvae can also infect via oral ingestion.

Cycle: Hookworm eggs hatch in the soil and develop to

infective larvae (L3) that can penetrate the skin. After entering

the host, the larvae migrate to the lungs, move up the trachea

and swallowed. In the gastrointestinal tract the larvae mature

to adult worms (both sexes). After mating, the female hook- worms produce up to 30,000 eggs per day that are shedded

with the stools into the environment.

Incubation period: Varies from weeks to several months,

depending on infection intensity.

Clinical findings: Hookworm morbidity is higher in patients

infected with large numbers of adult parasites. Attachment of

the hookworm to the intestinal mucosa results in loss of blood,

eventually resulting in anemia and malnutrition in chronic

cases. Chronic hookworm infection can impair cognitive and

growth development in children.

Diagnostic tests: Microscopy (Kato-Katz method). Quanti- tative fecal egg counts are a marker for worm burden: 2,000 to

4,000 eggs per gram of feces is considered to be moderate

infection, and 4,000 eggs is heavy infection.

Therapy: Deworming with mebendazole or albendazole;

repeat treatment in case eggs are still detected in feces. Iron

supplementation to correct anemia.

Prevention: The impact of sanitation, footwear, and health

education is minimal. To reduce the disease burden of STHs,

mass treatment campaigns with benzimidazoles and prazi- quantel are undertaken, and sanitation and access to clean

water improved. As most STHs occur in children, control

efforts are targeted at schools. Infective larvae can survive

in soil for several months.

Epidemiology: The global number of hookworm disease

cases is estimated to be 740 million individuals, with the

highest prevalence in Sub-Saharan Africa and eastern Asia.

The majority (85%) of the hookworm infections are caused

by Necator americanus, which is the predominant hookworm

of Latin America, the Caribbean, Sub-Saharan Africa, and

Southeast Asia. There is strong association between hook- worm prevalence and poverty (see Human Development

map). The remaining 15% infections by Ancylostoma duode- nale are in focal pockets in India, especially around Uttar

Pradesh and West Bengal, and in China north of the Yangtze

river. Mixed infections may also occur. Hookworm disease

prevalence rises with age and plateaus in adults. Disease is

more prevalent where individuals walk barefoot in regions

lacking sanitation (see Sanitation map). Hookworm larvae

prefer sandy soil in mild humid climates, resulting that

individuals living in coastal areas have the highest infection

intensity.

Map sources: The Hookworm map is modified from P.J.

Hotez et al. (2005). For more detailed information on the

distribution of STHs, see www.thiswormyworld.org.

Key references

Hotez PJ, et al. (2005) Hookworm: ‘the great infection of

mankind.’ PLoS Med 2(3):e67.

Hotez PJ, et al. (2004) Current concepts: Hookworm infection.

N Engl J Med 351:799–807.

De Silva NR, et al. (2003) Soil-transmitted helminth infections:

updating the global picture. Trends Parasitol 19:547–551.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

153

Page 55 of 113

Disease: Leishmaniasis, Cutaneous

and Mucosal, New World

Classification: ICD-9 085; ICD-10 B55

Syndromes and synonyms: Cutaneous and mucosal leish- maniasis (CL): Espundia, Uta, Chiclero ulcer, forest yaws.

Agent: Leishmania species, protozoa, members of the Trypa- nosomatidae family, order Kinetoplastida. Based on develop- ment characteristics in the sandfly, Leishmania species

are classified into the subgenera Viannia and Leishmania, within which there are various species complexes. Leishmania

species causing (muco)cutaneous disease in the Americas are: L. (Viannia) braziliensis (espundia), L. (Viannia) colombiensis, L. (Leishmania) mexicana (chiclero ulcer), L. (Leishmania) pifanoi, L. (Viannia) liansoni, L. (Leishmania) garnhami, L. (Leishmania)

amazonensis, L. (Viannia) panamensis, L. (Viannia) guyanensis

(forest yaws), and L. (Viannia) peruviana (Uta). L. infantum/

chagasi can cause both visceral and cutaneous leishmaniasis. L.

chagasi is considered to be the same species as L. infantum, and

will be referred to as L. infantum/chagasi. Reservoir: Mainly rodents and other sylvatic mammals.

Canines are a reservoir for L. infantum/chagasi and possible

reservoir for L. (Viannia) spp.

Vector: Female phlebotomine sandflies (Lutzomyia spp.).

Transmission: By bite of an infected phlebotomine sandfly.

Cycle: During bloodmeal, the sandfly ingests infected blood

with amastigotes. The amastigotes develop to motile promas- tigotes that multiply in the sandfly gut, and finally motile

promastigotes travel to the mouth parts and are injected into

another host during feeding. In the host cell the promastigotes

develop into amastigotes.

Incubation period: Varies from one week to several months.

Clinical findings: Painless cutaneous lesions appear at the site

of sandfly bite and typically these develop into ulcers with a

raised border. Occasionally nodular and rarely verrucous

lesions. Multiple lesions and regional lymphadenopathy

may be present. Lesions may resolve spontaneously or remain

for several months to years. Rarely dissemination to mucosa

occurs of the upper respiratory tract with local tissue destruc- tion leading to disfigurement (most often by L. braziliensis, known as espundia), with risk of severe and sometimes fatal

secondary infections.

Diagnostic tests: Demonstration of intracellular amastigotes

in Giemsa stained slit skin smear or biopsy specimen by

microscopy; PCR tests have been developed for the different

Leishmania species; culture of promastigotes with special

media is laborious and requires experience. The Montenegro

skin test is simple, sensitive and specific, but does not aid in

differentiating between past and present infections.

Therapy: Systemic treatment to prevent dissemination with

pentavalent antimonials. Depending on the infecting Leish- mania species, alternative systemic treatment can be adminis- tered with: amphotericin B, pentamidine, or miltefosine.

Topical treatment options are: paramomycin, ketoconazole,

and thermotherapy.

Prevention: Personal protection from sandfly bites (e.g. pro- tective clothing, insecticide-treated bednets, residual insecti- ciding of breeding places).

Epidemiology: The highest global burden of CL is in the Old

World. In the Americas, Bolivia, Brazil, and Peru have the

highest burden of CL. In the New World, CL mainly occurs

in forested areas, whereas in the OldWorldit is associated with

semi-arid and desert regions. Transmision can also occur in

deforested areas. Disease mainly occurs in those living or

working in the forests of endemic areas. Outbreaks can

occur during military training in the jungle or infrastructural

projetcs in endemic areas. Also, travelers acquire the disease

during visits to rural or jungle regions. Disease prevalence

increases with age and then plateaus, likely due to acquired

immunity. Clusters of leishmaniasis are seen in households,

which is probably related to the short flight range of sandflies.

Map sources: This map was made by reconciling maps from

WHO: (www.who.int/leishmaniasis/leishmaniasis_maps/en/

index. html) and R. Reithinger et al. (2007).

Key references

Campbell-Lendrum D, et al. (2001) Domestic and peridomestic

transmission of American cutaneous leishmaniasis.

Mem Inst Oswaldo Cruz 96(2):159–162.

Reithinger R, et al. (2007) Cutaneous leishmaniasis. Lancet

Infect Dis 7(9):581–596.

World Health Organization (2010) Control of the Leishmaniases. WHO Expert Technical Report Series, Nr 949.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Disease: Leishmaniasis, Cutaneous

and Mucosal, Old World

Classification: ICD-9 085; ICD-10 B55

Syndromes and synonyms: Cutaneous and mucosal leish- maniasis (CL): Aleppo evil, Baghdad boil, Delhi boil, Oriental

sore, Delhi boil, and others.

Agent: Leishmania species, protozoa, members of the Trypa- nosomatidae family, order Kinetoplastida. Leishmania species

that cause CL in the old world are: Leishmania major, L. tropica, and L. aethiopica. L. killicki is synonymous to L. tropica. L.

infantum/chagasi and L. donovani can cause both visceral and

cutaneous leishmaniasis. L. chagasi is considered the same

species as L. infantum, and are referred to as L. infantum/chagasi. Reservoir: Wild rodents (gerbils) that live in burrows together

with sandfly vector. Hyraxes for L. aethiopica. Vector: Female phlebotomine sandflies (Phlebotomus papatasi, P. sergenti, P.chadaudi, P. longipes, P. pedifer)

Transmission: By bite of an infected phlebotomine sandfly.

Cycle: During bloodmeal, the sandfly ingests infected blood

with amastigotes. The amastigotes develop to motile promas- tigotes that multiply in the sandfly gut, and finally motile

promastigotes travel to the mouth parts and are injected into

another host during feeding. In the host cell the promastigotes

develop into amastigotes.

Incubation period: Varies from a week to several months.

Clinical findings: Mainly presents as a dry skin lesion that is

covered with a crust and is smaller than the classic wet

leishmania skin lesions in the New World. Lesions may persist

for months or years. Diffuse cutaneous leishmaniasis may be

seen with L. aethiopica; leishmaniasis recidivans may be seen

with L. tropica. Mucosal leishmaniasis is rare in the Old World,

and more common in the Americas.

Diagnostic tests: Demonstration of intracellular amastigotes

in Giemsa stained slit skin smear or biopsy specimen by

microscopy; PCR tests have been developed for the different

Leishmania species; culture of promastigotes with special

media is laborious and requires experience. The Montenegro

skin test is simple, sensitive and specific, but does not aid in

differentiating between past and present infections.

Therapy: Intravenous, intramuscular, and intralesional appli- cation of pentavalent antimonials; also miltefosine is being

tested for its efficacy. Topical treatment options are: paramo- mycin, ketoconazole, and thermotherapy.

Prevention: Personal protection from sandfly bites (e.g.

protective clothing, insecticide-treated bednets, residual

insecticide of breeding places). There is no vaccine for

human use.

Epidemiology: World wide there are approximately 1.5 mil- lion new cases of CL per year, with most cases reported from

Afghanistan, Algeria, Pakistan, Saudi Arabia, and Syria in the

Old World. The highest burden of CL in the Old Word is in

rural semi-arid and desert regions, but transmission is being

increasingly seen in peri-urban and urban environments. Dis- ease prevalence increases with age and then plateaus, likely due

to acquired immunity. Clusters of leishmaniasis are seen in

households, which is likely related to the short flight range of

sandflies.

Map Sources: The Cutaneous and Mucosal Leishmaniasis, Old

World, map was made by reconciling maps from WHO (www.

who.int/leishmaniasis/leishmaniasis_maps/en/index

.html), EU (http://bioval.jrc.ec.europa.eu/products/glc2000/

products.php), and R. Reithinger et al. (2007). The map was

updated with medical literature and expert opinion.

Key references

Ready PD (2010) Leishmaniasis emergence in Europe. Euro

Surveill 15(10):19505.

Lukes J. (2007) Evolutionary and geographical history of the

Leishmania donovani complex. PNAS 104(22):9375–9380.

World Health Organization (2010) Control of the Leishmaniases. WHO Expert Technical Report Series, Nr 949.

Pratlong F, et al. (2009) Geographical distribution and epide- miological features of Old World cutaneous leishmaniasis.

Trop Med Int Health 14(9):1071–1085.

Reithinger R (2007) Cutaneous leishmaniasis. Lancet Infect Dis

7(9):581–596.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

157

Page 57 of 113

Disease: Leishmaniasis, Visceral

Classification: ICD-9 085.0; IDC-10 B55.0

Syndromes and synonyms: Kala-azar (Hindi for black

sickness), black disease, dum-dum fever.

Agent: Parasite, kinetoplastida. Leishmania donovani and its

subspecies donovani and infantum. L. chagasi is considered to be

the same species asL.infantum, and are referred to asL.infantum/

chagasi. Occasionally, other Leishmania spp. can cause visceral

disease, usually in immunocompromised individuals.

Reservoir: Humans (mainly L. donovani), wild Canidae (foxes,

raccoon dogs, jackals, wolves), domestic dogs (mainly

L. infantum/chagasi), and rodents.

Vector: Phlebotomine sandfly: Lutzomyia spp. (New World)

and Phlebotomus spp. (Old World).

Transmission: Bite of infective female sandfly. Rare reports

exist of non-vector transmission, including transmission by

blood transfusion, sharing of syringes, venereal contact, and

possibly transplacentally; potential transmission via organ

transplantation.

Cycle: During blood meal, the sandfly ingests infected blood

with amastigotes. The amastigotes develop to motile promas- tigotes that multiply in the sandfly gut, and finally motile

promastigotes travel to the mouth parts and are injected into

another host during feeding. In the host cell the promastigotes

develop into amastigotes.

Incubation period: Usually 2–6 months (range: 10 days to

years).

Clinical findings: Infection may be asymptomatic or progres- sive and fatal, if untreated. Onset is often insidious. Common

symptoms include fever, malaise, weight loss, and sweats.

Cough may be prominent. Symptoms can come and go. Spleno- megaly, hepatomegaly, and lymphadenopathy are common

findings. HIV-infected individuals are at increased risk for

symptomatic infection. Bacterial co-infections, including tuber- culosis, may occur. Anemia, leucopenia, and thrombocytopenia

are common laboratory findings.

Diagnostic tests: Identification of intracellular amastigotes in

stained smears from blood, bone marrow, spleen, liver, lymph

nodes. PCR is sensitive and specific. Serologic tests can be useful,

though they may be negative in HIV-infected patients with

leishmaniasis. Rapid diagnostic tests (rK39) are available.

Therapy: Pentavalent antimonials; pentamidine; amphoteri- cin. Other drugs and regimens are being tested (including

paramomycin, miltefosine).

Prevention: Vector control; personal protection from sandfly

bites (e.g. protective clothing, insecticide-treated bednets,

residual insecticiding of breeding places); use of deltame- thrin-impregnated dog collars and dog vaccination; there is

no vaccine for human use.

Epidemiology: VL is found in 62 countries where an estimated

500,000 cases occur annually and 120 million persons are at risk.

Approximately 90% of VLcases occurin rural and suburban areas

of five countries: Bangladesh, India, Nepal, Sudan, and Brazil.

During epidemics, > 5% of a population may develop symptom- atic infection. Personswho are under age of 5 years,malnourished

and immunocompromised (including HIV-infected individuals)

are more likely to develop symptomatic, often severe, infection.

There are indications that VL is spreading to historically non- endemic areas, like northern parts of Europe and Western Upper

Nile Sudan. Clearly the distribution of VL is dynamic and adapts

to changes in demographics, human behavior, environment

(deforestation, urbanization), and host factors (HIV). VL is

reported in Chad, DRC, and Zambia, but the infectious agent

is unknown.L. donovanishas been foundin Sri Lanka,but only as a

cause of cutaneous leishmaniasis.

Map sources: The Leishmaniasis (visceral) map was made

with multiple sources from the medical literature and WHO.

Key references

Alvar J, et al. (2006) Leishmaniasis and poverty. Trends Parasit

22(12):552–557.

GramicciaM, etal. (2007) Theleishmaniasesin SouthernEurope.

In: Emerging Pests and Vector-Borne Diseases: Ecology and Con- trol of Vector-Borne Diseases, Vol. 1, pp. 75–95 (eds Takken W

and Knols BGJ). Wageningen Academic Publishers.

Guerin P, et al. (2002) Visceral leishmaniasis: current status of

control, diagnosis, and treatment, and a proposed research

and development agenda. Lancet Infect Dis 2:494–501.

Herwaldt BL (1999) Leishmaniasis. Lancet 354:1191–1199.

Ready PD (2010) Leishmaniasis emergence in Europe. Euro

Surveill 15(10):19505.

World Health Organization (2010) Control of the Leishmaniases. WHO Expert Technical Report Series, Nr 949.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

159

Page 58 of 113

Disease: Loiasis

Classification: ICD-125.2; ICD-10 B74.3

Syndromes and synonyms: Loa loa filariasis, loiasis, African

eyeworm, Calabar swelling

Agent: Filarial nematode (roundworm), Loa loa. Adult worms

are nematodes that live freely in subcutaneous tissue. Adult

females are 40–70 mm long and males are 30–34mm long.

Reservoir: Humans. Loa loa also infects some monkeys but

the human and simian cycles seem to be independent.

Vector: Tabanid adult female flies, mainly Chrysops silacea, C. dimidiata, and C. distinctipennis. These day-biting and blood- sucking flies breed in forested and damp environments (e.g.

swamps or rotten vegetation). Other favorable environments

are cocoa plantations. Chrysops are attracted by movement,

dark objects, and smoke. The vector does not enter structures

like homes or barns. Up to 18% of the vector population can be

infected with L. loa in endemic areas.

Transmission: Infective larvae migrate out of the mouth part

of the fly during bite onto the skin and subsequently enter the

wound. The tabanid bite is painful with blood loss.

Cycle: Human-deer fly-human. After infectivelarvae enter the

wound they migrate and develop into adult worms in subcu- taneous tissue. Adult worms produce microfilariae, that cir- culate in the peripheral blood in daytime and can be taken up

by the next fly during feeding. In the fly they develop into

larvae in 10–12 days and enter the proboscis, and the cycle

repeats. An infected human can remain infectious to the vector

for up to 15 years. Transmission is facilitated by the fact that

microfilaremia and the vector-biting activity occur in daytime.

Incubation period: 4 months to several years.

Clinical findings: Loiasis is not as severe as other filarial

diseases. Typical finding is transient subcutaneous swellings

(Calabar swellings) which are angiedemas. These swellings

are itchy and mainly occur on the limbs, especially forearms

and when close to joints may restrict movement. Less fre- quently: giant urticaria, arthritis, and fever. The adult worm

sometimes migrates across the subconjunctiva of the eye.

Encephalopathic reactions may occur during mass ivermectin

treatment campaigns to control onchocerciasis. These SAEs

mainly occur in those with heavy infection ( > 30,000 micro- filariae per ml blood).

Diagnostic tests: Microscopy of stained thick blood smears

taken around noon; membrane filtration; PCR. Eosinophilia

and high IgE levels are indicators of active infection.

Therapy: Surgical extraction of adult worms from the eye.

Diethylcarbamazine (DEC) is filaricidal but can cause SAEs

in patients with heavy infection. SAEs can be reduced by co- administering antihistamines or steroids. Alternative: alben- dazole with a lower risk of SAEs in case of heavy infection.

Prevention: Protection from vector bites by wearing

permethrin-treated light-colored clothes and fly repellent on

exposed skin. DEC can be used as prophylaxis, but should not

be used routinely.

Epidemiology: Loiasis occurs in areas where the Chrysops

vectors breed in the tropical rainforest of Central Africa,

where it is estimated that 12–13 million humans are infected.

The prevalence of microfilaremia increases with age, and is

more common in men as they are more exposed. Loiasis has

gained attention because of the serious adverse events that

can occur during mass ivermectin treatment campaigns for

onchocerciasis control. It has been proposed that areas where

the Loiasis prevalence is > 20%, are at increased risk for

adverse events during mass ivermectin treatment.

Map sources: The Loiasis map was made with data from

Boussinesq et al. (1997) and Thomson et al. (2004) and updated

with medical literature. The distribution of the vectors was

reproduced from WHO (1989).

Key references

Boussinesq M, et al. (1997) Prevalences of Loa loa microfilar- aemia throughout the area endemic for the infection. Ann

Trop Med Parasitol 91(6):573–589.

Boussinesq M. (2006) Loiasis. Ann Trop Med Paras 100(8):

715–731.

Padget JJ, et al. (2008) Loiasis: African eye worm. Trans R Soc

Trop Med Hyg 102:983–989.

World Health Organization (1989) Geographical distribution of

arthropod-borne diseases and their principal vectors. Unpub- lished report.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

161

Page 59 of 113

Disease: Malaria, Plasmodium falciparum

Classification: ICD-9 084; ICD-10 B50

Syndromes and synonyms: Falciparum malaria, malaria

tropica, tropical fever, blackwater fever, paludism, marsh

fever.

Agent: Plasmodium falciparum, an intracellular protozoan par- asite in the Phylum Apicomplexa. Among the malaria para- sites, P. falciparum causes the vast majority of mortality.

Reservoir: Humans.

Vector: Mosquito (Anopheles spp.), mainly bites between dusk

and dawn (see Anopheles map).

Transmission: By mosquito bite (Anopheles spp.). Transmis- sion has been described in needle sharing IVDUs and through

blood transfusion.

Cycle:There is an asexual phase in humans and a sexual phase

in the vector mosquito. The mosquito injects sporozoites that

invade human liver cells where they reproduce and develop to

merozoites, which, after release, infect erythrocytes. The eryth- rocytic stages multiply around 10-fold every 48-hours. Erythro- cytes can release gametocytes which infect mosquitoes during a

blood meal. In the mosquito, gametocytes develop into

sporozoites.

Incubation period: 7 to 15 days, but can be longer.

Clinical findings:Uncomplicated malaria: acute febrile illness

with headache, chills, sweats, nausea, and vomiting; hepatos- plenomegaly. Findings of severe malaria can be: cerebral

malaria (confusion, seizures, impaired consciousness to

coma), hemolysis, severe anemia, hypotension, renal failure,

metabolic acidosis and death. Often high parasite counts

are found in patients with severe malaria ( > 5% infected

erythrocytes).

Diagnostic tests: Light microscopy of Giemsa stained thick

and thin blood smears; rapid diagnostic tests (RDTs) based on

immunochromatography on blood; PCR.

Therapy: Malaria requires urgent treatment and type of treat- ment depends on disease severity and drug resistance in the

region. Artemisinin resistance has been confirmed in the Thai–- Cambodian border region. Uncomplicated P. falciparum

malaria: artemisinin-based combination therapies (ACTs);

the choice of ACTs is based on the resistance levels of the

partner medicine in the combination. Artemisinin and its deri- vatives should not be used as monotherapy. Severe malaria:

artesunate iv or im; complete treatment with an ACT or

artesunate plus doxycycline or clindamycin.

Prevention: Vector control; mosquito repellent; insecticide- treated bed nets; residual spraying of insecticides; treatment of

infected humans. Recently control measures are being

upscaled in a malaria elimination effort. Morocco, United

Arab Emirates, and Turkmenistan have been certified malaria

free by WHO.

Epidemiology: The limits of P. falciparum malaria is deter- mined by the presence of vector species and control measures

within a certain region. P. falciparum malaria causes approxi- mately 500 million cases each year and around one million

deaths in Sub-Saharan Africa. In 2007 almost 60% of the 2.4

billion people at risk of malaria were living in areas with a

stable risk of P. falciparum. High endemicity was most common

and widespread in the African region. In the Americas, those at

risk were all in the low endemicity class. In Asia 88% are in the

low endemicity class, 11% in the intermediate class, and 1% in

the high endemicity class. Recent progress is being made by

the Global Malaria Action Plan to reduce malaria morbidity

and mortality world wide and have a vision for malaria

elimination. Ranking countries on the possibility of elimina- tion shows that it is most feasible in the Americas and several

countries in Asia and the west Pacific. It is least feasible in

Africa, where much of west and central Africa need more than

90% reduction in transmission.

Map sources: The Malaria (Plasmodium falciparum) map is

reproduced with permission from the Malaria Atlas Project, S.

I. Hay et al. (2009). Data on first and second line drugs for

malaria were obtained from WHO’s Global Report on Antima- larial Drug Efficacy and Drug Resistance 2000–2010 (2010).

Key references

Hay SI, et al. (2009) A world malaria map: Plasmodium falci- parum endemicity in 2007. PloS Med 6(3):e1000048.

Lancet Series (2010) Malaria elimination. Lancet 376

(9752):1566–1615.

World Health Organization (2010) Guidelines for the Treatment

of Malaria, 2nd edition. Geneva.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

163

Page 60 of 113

Disease: Malaria, Plasmodium knowlesi

Classification: ICD-9 84.4; IDC-10 B53.1

Synonym: Knowlesi malaria, simian malaria

Agent: Plasmodium knowlesi, an intacellular protozoan para- site in the Phylum Apicomplexa. P. knowlesi is an Old World

simian malaria parasite.

Reservoir: Long-tailed and pigtailed macaques, and banded

leaf monkeys. P. knowlesi can also infect other primates, includ- ing New World marmosets (Callithrix jacchus), African olive

baboons (Papio anubis), Old World macaques, and humans by

blood passage and mosquito bites.

Vector: P. knowlesi transmission is restricted to the Leuco- sphyrus group of anophelines, consisting of 20 species.

Transmission: By mosquito bite. Experiments demonstrated

human to human transmission with the mosquito as vector,

but there is no direct human-to-human transmission.

Cycle: Monkey–mosquito–monkey; P. knowlesi has a short

(24-hour) asexual lifeycle; humans are incidental hosts.

Incubation period: About 12 days.

Clinical findings: Headache, fever, chills. Abdominal pain,

renal impairment, jaundice, and thrombocytopenia may

occur. Coma and death are rare.

Diagnostic tests: Often misidentified as P. malariae, but

skilled microscopists are able to make the distinction. A

relatively severe illness with a microscopic diagnosis of

P. malariae should alert clinicians to the possibility of

P. knowlesi because P. malariae malaria is almost invariably

mild. Species can be confirmed by PCR if needed.

Therapy: Chloroquine is effective; primaquine is likely unnec- essary as a gametocidal drug since gametocytes appear to be

sensitive to chloroquine.

Prevention: Early detection and containment of human-to- human P. knowlesi transmission in the event of a complete

emergence into the human population; vector control; anti- mosquito measures.

Epidemiology: The first human P. knowlesi case acquired in

nature was detected in 1965 in Malaysia. P. knowlesi malaria is

widely distributed across Sarawak and Sabah in Malaysian

Borneo and extends to the state of Pahang in Peninsular

Malaysia. P. knowlesi malaria cases have also been acquired

in Thailand, Myanmar, Singapore, and the Philippines. The

distribution and incidence of P. knowlesi malaria is yet

unknown. Bases on current knowledge on the vector and

reservoir, human knowlesi malaria is likely not rare in areas

inhabited by the natural macaque hosts and the vectors.

Humans working in the vicinity of forests are considered at

risk. Deforestation now also brings humans in semi-urban

areas into contact with reservoir hosts. Interestingly, P. know- lesi has been used in the past as a pyretic agent for the treatment

of patients with neurosyphilis.

Map sources: The Malaria, Plasmodium knowlesi map is modi- fied from in J. Cox-Singh et al. (2008).

Key references

Cox-Singh J, et al. (2008) Knowlesi malaria: newly emergent

and of public health importance? Trends Parasitol 24

(9):406–410.

Daneshvar C, et al. (2010) Clinical and parasitological

response to oral chloroquine and primaquine in uncompli- cated human Plasmodium knowlesi infections. Malar J

9:238.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

165

Page 61 of 113

Disease: Malaria, Plasmodium ovale

Classification: ICD-9 084.3; ICD-10 B53.0

Synonyms: malaria, paludism, tropical fever.

Agent: Plasmodium ovale, an intacellular protozoan parasite in

the Phylum Apicomplexa. Phylogenetically, P. ovale clusters

with other Plasmodium species affecting simian primates.

Reservoir: Humans and possibly other primates (chimpan- zees). Evidence of naturally occurring P. ovale in chimpanzees

has been reported.

Vector: Female mosquito of the genus Anopheles (see Anophe- les map).

Transmission: By mosquito bite (Anopheles spp.).

Cycle: Infective sporozoites are inoculated by the bite of

anopheles mosquitoes and through the bloodstream and lym- phatics reach the liver where they differentiate into tissue

schizonts that release merozoites, or to a dormant stage (hyp- nozoite) that can become active after months or years, causing

relapse. Merozoites released from liver infect erythrocytes that

develop to schizonts, rupture and release merozoites that will

infect new erythrocytes (this cycle takes 48 hours). Some

merozoites develop into gametocytes that are able to infect

mosquitoes during a blood meal.

Incubation period: 12 to 20 days, up to to several months

Clinical findings: Acute febrile illness with chills, sweats,

nausea, headache, and vomiting. Usually does not last longer

than 2 weeks.

Diagnostic tests: Microscopy of Giemsa-stained blood

film; differentiation from P. vivax can be difficult and result

in misidentification; parasite load is generally low and may

be undetectable by light microscopy; in regions where

P. falciparum/P. vivax predominate, P. ovale is

frequently overlooked; parasitemia is present for about

2 weeks; PCR.

Therapy: Need to treat both P. ovale blood and liver stage with

chloroquine (blood stage) and primaquine (liver stage).

Prevention: Vector control; mosquito repellent; insecticide- treated bed nets; treatment of infected humans.

Epidemiology: P. ovale initally was thought to be limited to

Sub-Saharan Africa, Papua New Guinea, eastern Indonesia,

and the Philippines. It is actually more widely distributed, and

is reported in the Middle East, the Indian Subcontinent, and

various parts of Southeast Asia. P. ovale has not yet been

reported in South America. In general, P. ovale is relatively

uncommon, though in West Africa prevalences above 10% are

observed. Also, infections are most common in children <10

years. There is likely underreporting due to underdiagnosis.

Due to the short duration of parasitemia and low parasite loads,

P. ovale is regularly ‘missed’ in cross-sectional surveys.

Map sources: The Malaria (Plasmodium ovale) map ismodified

from A.J. Lysenko et al. (1969) and updated with recent

literature. Interestingly, no global map of the geographical

distribution of P. ovale has been produced since that of Lysenko

et al. in 1969.

Key references

Collins WE (2005) Plasmodium ovale: parasite and disease.

Clin Microbiol Rev 18:570–581.

Duval L, et al. (2009) Chimpanzee malaria parasites related to

Plasmodium ovale in Africa. PLoS ONE 4(5):e5520.

Lysenko AJ, et al. (1969) An analysis of the geographical

distribution of Plasmodium ovale. Bull World Health Org

40:383–394.

Mueller I, et al. (2007) Plasmodium malariae and Plasmodium

ovale – the ‘bashful’ malaria parasites. Trends Parasitol 23

(6):278–283.

WHO (2010) Guidelines for the Treatment of Malaria, 2nd edn.

Geneva.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Page 62 of 113

Disease: Malaria, Plasmodium vivax

Classification: ICD-9 084.1; ICD-10 B51.0–B51.9.

Synonyms: Vivax malaria; recurring malaria; tertian malaria;

paludism; marsh fever; ague.

Agent: Plasmodium vivax, an intacellular protozoan parasite in

the Phylum Apicomplexa.

Reservoir: Humans.

Vector: Female mosquito of the genus Anopheles; mainly bites

between dusk and dawn (see Anopheles map).

Transmission: By mosquito bite (Anopheles spp.); trans- mission has been described in needle sharing IVDUs and

blood transfusion.

Cycle: Infective sporozoites are inoculated by bite from anoph- eles mosquitoes and through the bloodstream and lymphatics

reach the liver where they differentiateinto tissue schizonts that

release merozoites, or to a dormant stage (hypnozoite) that can

become active after months or years, causing relapse. Mero- zoites released from liver mostly infect reticulocytes that

develop to schizonts, rupture and release merozoites that

will infect new reticulocytes (this cycle takes 48 hours). Game- tocytes are able to infect mosquitoes during a blood meal.

Incubation period: 12 days to several months

Clinical findings: Common unspecific symptoms are acute

febrile illness with chills, sweats, nausea, headache, and vomit- ing; high fever with chills is more common in P. vivax than in P.

falciparum malaria. Recent reports provide evidence that vivax

malaria is not as benign as previously thought.P. vivax can lead

to severe anemia, acute respiratory distress, liver failure, renal

failure, and even cerebral malaria.

Diagnostic tests: Microscopy: in Giemsa-stained blood

smears Schüfnner’s dots are seen; rapid diagnostic tests

(RDTs); PCR.

Therapy: Need to treat both P. vivax blood and liver stage.

Uncomplicated P. vivax malaria: Chloroquine combined with

primaquine (liver stage). In case of resistance: ACTs com- bined with primaquine. For severe vivax malaria: prompt

treatment and case management as P. falciparum malaria.

Treatment needs to be modified in case of G6PD deficiency

(see Inheritable Blood Disorder map). P. vivax chloroquine

resistance is established in Papua New Guinea and eastern

Indonesia.

Prevention: Vector control; mosquito repellent; insecticide- treated bed nets; treatment of infected humans.

Epidemiology: Vivax malaria is the second most important

malaria species after P. falciparum and accounts for 25–40% of

the cases world wide with 132–391 million cases per year.

Outside Africa it is the dominant species, mainly in Asia. The

distribution is wider than P. falciparum as it is able to develop at

lower temperatures and can form hypnozoites in human liver.

The high prevalence of Duffy negativity in western Africa has

influenced the epidemiology of P. vivax, as Duffy-negative

people are apparently resistant to vivax malaria, although sev- eral reports suggest that Duffy-negative people can be infected

withP.vivax.The disease burdenis greatestininfants. In 2010, an

autochtonousP.vivax casewas diagnosedin northeastern Spain.

Malariawasdeclarederadicated fromSpainin 1964.P.vivaxmay

have been transmitted by the local vector Anopheles atroparvus, which can transmit Asiatic P. vivax strains.

Map sources: The Malaria (Plasmodium vivax) map is repro- duced with permission from the Malaria Atlas Project, C.A.

Guerra et al. (2010). The P. vivax resistance data was obtained

from N.M. Douglas et al. (2010).

Key references

Douglas NM, et al. (2010) Artemisinin combination therapy for

vivax malaria. Lancet Infect Dis 10:405–416.

Guerra CA, et al. (2010) The international limits and popula- tion at risk of Plasmodium vivax transmission in 2009. PloS

Negl Trop Dis 4(8):e774.

Mueller I, et al. (2009) Key gaps in the knowledge of Plasmo- dium vivax, a neglected human malaria parasite. Lancet Infect

Dis 9:555–566.

Mercereau-Puijalon O, et al. (2010) Plasmodium vivax and the

Duffy antigen: a paradigm revisited. Transf Clin Biol

17:176–183.

Price RN, et al. (2007) Vivax malaria: neglected and not benign.

Am J Trop Med Hyg 77 (6 Suppl):79–87.

Santa-Olalla Peralta P, et al. (2010) First autochthonous malaria

case due to Plasmodium vivax since eradication, Spain, Octo- ber 2010. Euro Surveill 15(41):19684.

World Health Organization (2010) Guidelines for the Treatment

of Malaria, 2nd edition, Geneva.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Disease: Onchocerciasis

Classification: ICD-9 125.3; ICD-B73

Syndromes and synonyms: River blindness, onchoder- matitis.

Agent: Onchocerca volvulus, a filarial nematode (roundworm).

Adult female worm is approximately 50 cm long.

Reservoir: Humans are the only natural host. The parasite can

be experimentally transferred to chimpanzees.

Vector: Female blackflies (Simulium). Transmission by

S. damnosum complex in Africa is responsible for > 95%

onchocerciasis cases. S. neavei complex in East Africa and

S. rasyani in Yemen. In Latin America: S. ochraceum (Mexico

and Guatemala), S. exiguum (Colombia and Ecuador),

S. metallicum (northern Venezuela), and S. guianeense(southern

Venezuela and Brazil). Blackfly larvae develop in fast-flowing

rivers and the adult fly’s flight range is up to 40 miles, explain- ing the patchy distribution of the disease. Aided by wind,

blackflies can fly up to 500 km, explaining reinvasion of

areas under control.

Transmission: By bite of the vector.

Cycle: Microfilariae ingested by the fly develop in about

7 days into infective L3 stages and migrate to the head and

escape into the skin during feeding. In the subcutaneous

tissues the L3 larvae moult into L4 stages and produce nodules

within which they develop in 10 months into adult filariae and

can live there for 14–15 years. The female worms can produce

microfilariae for 10 years. Microfilariae are typically found

in the skin, skin lymphatics, and ocular tissues. They have a

lifespan of up to 2 years. Humans remain infectious for about

10 years, the time the female worm remains fertile, bur rein- fection occurs in endemic areas.

Incubation period: It takes about 10 months for L3 to develop

into adults. After 12–18 months microfilariae are found in

the skin.

Clinical findings: Fibrous subcutaneous nodules in the head

and shoulders (Americas), pelvic girdle and legs (Africa), a

pruritic rash, disfiguring skin lesions (chronic papular and

lichenified onchodermatitis), skin depigmentation (leopard

skin), edema and skin atrophy, inflammatory process in the

cornea leading to irreversible blindness, growth arrest, and

epilepsy. The proportion of depigmentation and blindness is

most common in older ( > 40 years) age groups. The disease

may lead to excess mortality.

Diagnostic tests: Microscopy of fresh skin snips to detect

microfilariae. Nodule palpation. Rapid card tests based on

antibody detection have been produced with promising

results (but not yet available commercially). Luciferase immu- noprecipitation system with a mixture of four O. volvulus

antigens. Less-invasive techniques for disease surveillance

are diethylcarbamazine patch tests (may become commer- cially available in near future), which provoke a local Mazzotti

skin reaction.

Therapy: Ivermectin, given as a single, oral dose annually or

every 6 months. There is a risk of SAEs in patients coinfected

with L. loa. Doxycycline gives good results by destroying the

endosymbiotic Wolbachia bacteria and has fewer side effects.

Surgical removal of subcutaneous nodules.

Prevention: Insect repellent, protective clothing, and insecti- ciding of vector-breeding sites. Mass treatment with ivermec- tin (see ‘Therapy’). In case transmission is interrupted with

ivermectin, it can recur if ivermectin mass treatment is stopped

prematurely.

Epidemiology: It is estimated that 37 million people areinfected

worldwide, 97% of them in Africa, and remaining in small foci in

Central and South America and Yemen. Onchocerciasis was

imported into Latin America by the slave trade. Onchocerciasis

prevalence is related to the proximity to riverine breeding sites of

black flies, with the highest disease burden in communities

adjacent to rivers. Prevalence of infection rises with age until

around 20 years, after which infection profiles vary between

geographical region and sex. Higher rates of morbidity are

reported in men. This variation canbe explainedby heterogeneity

in age, gender, and occupational exposure to vectors.

Map sources: The Onchocerciasis map is reproduced with

permission from M.G. Basañez et al. (2006).

Key references

Basañez MG, et al. (2006) River blindness: a success story

under threat? PLoS Med 3(9):e371.

Dadzie Y, et al. (2003) Final report of the conference on the

eradicability of Onchocerciasis. Filaria J 2:2.

Taylor MJ, et al. (2010) Lymphatic filariasis and onchocerciasis.

Lancet 376:1175–1185.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

171

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Disease: Opisthorchiasis

Classification: ICD-9 121.0; ICD-10 B66.0

Syndromes and synonyms: Cat liver fluke disease, food- borne trematodiasis

Agent: Small (6–18 mm long) trematode liver fluke of dogs,

cats, and some other fish-eating mammals:Opisthorchis felineus

in Europe and northern Asia, O. viverrini in Southeast Asia.

Both species live in bile ducts.

Reservoir: Humans and fish-eating mammals.

Vector: Freshwater snails (Bithynia spp.).

Transmission: Consumption of raw, undercooked, dried,

salted, or pickled freshwater fish. There is no direct person- to-person transmission.

Cycle: Eggs excreted by the mammalian host in the feces into

freshwater are ingested by the snail vector. They hatch and in 2

months pass through various stages in the snail to produce

motile cercariae, which leave the snail and penetrate freshwa- ter fish. In 6 weeks the cercariae encyst, and when the fish is

eaten by another mammalian host, they exit the cyst and

penetrate the bile duct, where in a month they mature into

adult worms and start to produce eggs.

Incubation period: Depends on infecting dose. For acute

disease, usually 3 to 4 weeks. For chronic disease, up to several

years.

Clinical findings: O. viverrini: usually asymptomatic. Occa- sionally abdominal pain, flatulence, fatigue, mild hepatomeg- aly, jaundice, and cholangitis. Cholangiocarcinoma is the most

serious complication. O. felineus: fever and hepatitis-like symp- toms in the acute stage (right upper quadrant abdominal pain,

nausea, and emesis). Chronic symptoms: biliary tract obstruc- tion, inflammation and fibrosis of the biliary tract, liver

abscesses, pancreatitis, and suppurative cholangitis.

Diagnostic tests: Microscopy for eggs in stool smear

(Kato–Katz technique) is often inconclusive due to the

similarity to eggs of other trematodes. Intradermal test is

rapid and sensitive, but not specific. Immunodiagnosis is

regarded supportive but not confirmatory. Radiology to

demonstrate bile duct pathology. PCR test for O. viverrini

is available.

Therapy: Praziquantel; the cure rate for O. viverrini is over

90%.

Prevention: Sanitation to reduce contamination of vector

snail habitat, together with mass treatment with praziquantel

and health education.

Epidemiology: Food-borne trematodiasis is focal and occurs

in areas where the snail and freshwater fish – that is consumed

raw or undercooked – coexist. The disease is the leading cause

of cholangiocarcinoma in the world. O. viverrini is common in

Southeast Asia in the Mekong region with 8 million infected in

Thailand and 2 million in Laos. In Thailand about 8.7% of the

population is infected and mainly in the northern provinces.

Control activities in Thailand were able to reduce the preva- lence from 34% to 10% in several areas. No data is available for

Cambodia, China, or Vietnam, although opisthorchiasis is

likely common there. O. felineus is found in Europe and

northern Asia with approximately 5 million infected. Infected

fish can be shipped and consumed in non-endemic areas.

Map sources: The Opistorchiasis map was made by geocod- ing reported cases in the medical literature up to 2009.

Key references

Andrews RH, et al. (2008) Opisthorchis viverrini: an under- estimated parasite in world health. Trends Parasit

24(11):497–501.

Kaewpitoon N, et al. (2008) Opisthorchis viverrini: the carcino- genic human liver fluke. World J Gastroenterol 14(5):666–674.

Keiser J, et al. (2009) Food-borne trematodiasis. Clin Microbiol

Rev 22(3):466–483.

Marcos LA, et al. (2008) Update on hepatobiliary flukes:

fascioliasis, opisthorchiasis and clonorchiasis. Curr Opin

Infect Dis 21(5):523–530.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

173

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Disease: Paragonimiasis

Classification: ICD-121.2; ICD-10 B66.4

Syndromes and synonyms: Pulmonary distomiasis, lung

fluke disease

Agent: Several species of Paragonimus trematode flatworms:

P. westermani, P. heterotremus, P. miyazakii, P. skrjabini, and P. hueitungensis (the last two may be the same) in Asia,

P. africanus and P. uterobilateralis in Africa, P. mexicanus

(P. peruvianus) and P. kellicotti in the Americas.

Reservoir: Humans, dogs, cats, pigs, and wild carnivores.

Vector: Freshwater snails: Semisulcospira, Thiara, Aroapyrgus, and others.

Transmission: By consumption of infected raw, salted,

marinated, pickled or undercooked freshwater crabs and

crayfish. Infected humans can excrete worm eggs in sputum

and feces for up to 20 years. There is no person-to-person

transmission.

Cycle: Crustaceans infected with metacercaria larvae are

ingested by the reservoir host, excyst in the gut and migrate

to the tissues, usually the lungs. There they encapsulate,

mature, and lay eggs. Eggs enter the sputum which is coughed

up and swallowed, then pass out in the feces into water and

hatch in 2–4 weeks into miracidia larvae. These penetrate the

body of the vector snail, where they develop in about 2 months

into cercaria larvae which enter and encyst in freshwater crabs

and crayfish.

Incubation period: Flukes begin to lay eggs 6–10 weeks after

ingestion of larvae. In humans, incubation is long and highly

variable depending on the number of larvae ingested and

organs affected.

Clinical findings: Fever, cough, hemoptysis, and pleuritic

chest pain. Flukes may invade the brain and rarely the spinal

cord, causing meningitis, intracranial hemorrhage, epilepsy,

and paralysis. They may also cause acute and chronic inflam- mation of the pleura, pericardium, and mediastinum. Chest X- ray findings are similar to tuberculosis. Complications include

pleural effusion, pneumothorax, bronchiectasis, and pulmo- nary fibrosis.

Diagnostic tests: Microscopic examination of sputum for

eggs (acid-fast staining destroys eggs), and examination of

feces after using concentration techniques; ELISA for

serology.

Therapy: Praziquantel and triclabendazole. Bithionol is an

alternative treatment but has more side effects. In cerebral

paragonimiasis, steroids are added.

Prevention: Thorough cooking of crustaceans, sanitary dis- posal of sputum and feces and use of molluscicides.

Epidemiology: The major endemic area is China, with an

estimated 20 million people infected, followed by India,

Laos, and Myanmar. In the Americas, Ecuador has an

estimated 1.5 million cases, but up to 2010 only 9 autochtho- nous cases of paragonimiasis have been reported from

North America (excluding 2 outbreaks in 2006 in California

from eating raw freshwater crab imported from Japan).

In 1992, the Chinese mitten crab from Korean and Chinese

waters positive with Paragonimus eggs was found in western

US waters.

Map Sources: The Paragonimiasis map was made with data

from G.W. Procop (2009) and human cases reported in the

medical literature up to 2009.

Key references

Aka NA, et al. (2008) Human paragonimiasis in Africa. Ann

African Med 7(4):153–162.

Liu Q, et al. (2006) Paragonimiasis: an important food-borne

zoonosis in China. Trends in Parastol 24(7):318–323.

Prasad PK, et al. (2009) Phylogenetic reconstruction using

secondary structures and sequence motifs of ITS2 rDNA

of Paragonimus westermani (Kerbert, 1878) Braun, 1899

(Digenea: Paragonimidae) and related species. BMC Geno- mics 10 (Suppl 3):S25.

Procop GW (2009) North American paragonimiasis (caused by

Paragonimus kellicotti) in the context of global paragonimia- sis. Clin Microbiol Rev 22(3):415–446.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Disease: Schistosomiasis, Africa & Americas

Classification: ICD-9 120; ICD-10 B65

Syndromes and synonyms: Bilharziasis, Katayama fever or

syndrome, urogenital and intestinal schistosomiasis.

Agent: Trematode worms Schistosoma mansoni, S. haemato- bium, S. intercalatum, and S. guineensis (formerly known as

S. intercalatum). S. haematobium species group contains 8 species,

of which not all cause human disease.

Reservoir: Humans are the main reservoir. S. haematobium can

infect primates, livestock and rodents. S. mansoni, S. intercala- tum, and S. guineensis can infect rodents.

Vector: Freshwater snails: Biomphalaria spp. for S. mansoni,

Bulinus spp. for S. haematobium, S. intercalatum, and S.

guineensis. Technically, humans are the ‘vector’ as they harbor

the parasite’s sexual stage. Snails are intermediate hosts.

Transmission: Contact with freshwater bodies containing

cercariae that penetrate skin or mucous membranes; drinking

contaminated water (uncommon).

Cycle: Snail–human–snail. Infected humans shed eggs into

the water, which hatch into larvae (miracidia) that enter

snails and develop into motile larvae (cercariae). The cercariae

are shed into the water and penetrate the skin of humans in the

water, enter the bloodstream and settle in the liver. When

matured to adult male and female worms, they migrate to

the abdominal veins (S. mansoni, S. intercalatum, S. guineensis)

or pelvic veins (S. haematobium), mate and produce eggs. Snails

remain infectious for up to 3 months, humans for more than 10

years.

Incubation period: Usually 14–84 days for acute schistoso- miasis (Katayama syndrome); chronic schistosomiasis can be

asymptomatic for a long period, months to years.

Clinical findings: Katayama syndrome is an acute form of

schistosomiasis, caused by the host immune response to devel- oping larvae and early egg production and presents with noc- turnal fever, cough, myalgia, headache, and abdominal pain.

Katayama syndrome is more common among infected non- immune individuals (e.g. travelers) and relatively rare among

local residents with exposure since childhood. S. mansoni

causes intestinal schistosomiasis with: diarrhea, abdominal

pain, blood in the stool, hepatosplenomegaly. S. haematobium

causes urogenital schistosomiasis with dysuria, hematuria,

hemospermia, and dyspareunia. S. intercalatumand S. guineensis:

granulomas, rectal polyps and ulcers. Chronic infection may lead

toliverfibrosis,hepatosplenomegaly, and portal hypertension (S.

mansoni), obstructive uropathy, bacterial infection,infertility, and

bladder cancer (S. haematobium); rectitis, salpingitis, infertility and

abortion (S. intercalatum, S. guineensis); anemia and altered

growth and cognitive development in infected children. Rarely,

CNS disease may follow S. haematobium and S. guineensis

infection.

Diagnostic tests: Microscopy for eggs in stool (S. mansoni)

or urine (S. haematobium) samples; quantification of eggs in

stool by Kato–Katz method and in urine by standardized

filtration techniques; PCR.

Therapy: Praziquantel is recommended; alternative: oxamni- quine for S. mansoni, metrifonate for S. haematobium. Prevention: Access to clean water and sanitation; protective

clothing foroccupational risk; after accidental exposure, dry the

skin and apply 70% alcohol; mollusciciding; avoid contact with

contaminated water bodies.

Epidemiology: It is estimated that more than 207 million

people are infected world wide, with 85% of them in Africa.

Infection does not produce full immunity, so reinfection occurs.

Schistosomiasis is a water-based disease that mainly affects rural

agricultural and fishing communities. Higher disease prevalence

rates in endemic regions are found close to irrigation projects or

dams. Man-made water bodies like dams can lead to changes in

snail habitat and cause a shift from urogenital to intestinal schis- tosomiasis (Egypt) and vice versa (Senegal). S. mansoni was pre- sumably introduced with the slave trade from west Africa into

South America and the Caribbean S. intercalatum and S. guineensis

are geographically restricted to Central Western Africa.

Map sources: The Schistosomiasis map is modified from

WHO (1987) Global Schistosomiasis Atlas at: www.who.

int/wormcontrol/documents/maps/en/.

Key references

Murinello A, et al. (2006) Liver disease due to Schistosoma

guineensis – a review. J Port Gastrenterol 13:97–104.

Ross AGP, et al. (2007) Katayama syndrome. Lancet Infect Dis

7:218–224.

Steinman P, et al. (2006) Schistosomiasis and water

resources development. Lancet Infect Dis 6:411–425.

World Health Organization (2011) Schistosomiasis. Factsheet

Nr 115 (www.who.int).

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

177

Page 67 of 113

Disease: Schistosomiasis, Asia

Classification: ICD-9 120; ICD-10 B65

Synonyms: Bilharziasis, snail fever, Katayama fever or syn- drome, intestinal schistosomiasis.

Agent: Trematodeworms Schistosoma japonicum, S. malayensis,

and S. mekongi. Reservoir: Humans, dogs, cats, pigs, cattle, water buffalo and

wild rodents for S. japonicum, rodents for S. malayensis, pigs

and dogs for S. mekongi. Vector: Freshwater snails: Oncomelania spp. for S. japonicum,

Robertsiella spp. for S. malayensis, Neotricula spp. for S. mekongi. Transmission: Contact with freshwater bodies containing

cercariae that penetrate skin or mucous membranes; drinking

contaminated water (less common).

Cycle: Snail–human–snail. Infected humans shed eggs into

the water, which hatch into larvae (miracidia) that enter snails

and develop into motile larvae (cercariae). The cercariae are

shed into the water and penetrate the skin of humans with

water contact. Cercariae enter the bloodstream and settle in the

liver, where they grow into adult male and female worms that

migrate to the abdominal veins, mate, and produce eggs.

Snails are infectious for up to 3 months, humans for 10

years or more.

Incubation period: Usually 14–84 days for acute schistoso- miasis (Katayama syndrome); chronic schistosomiasis can be

asymptomatic for a long period, months to years.

Clinical findings: Katayama syndrome is an acute form of

schistosomiasis, caused by the host immune response to devel- oping larvae and early egg production and presents with noctur- nal fever, cough, myalgia, headache, and abdominal pain.

Katayama syndrome is more common among infected non- immune individuals (e.g. travelers) and relatively rare among

local residentswith exposure since childhood. S. japonicumcauses

intestinal schistosomiasis with: diarrhea, abdominal pain, blood

in the stool, hepatosplenomegaly. Chronic infection leads to liver

fibrosis and portal hypertension, anemia, and altered growth and

cognitive development in infected children; seizures due to egg

granulomas in brain or spinal cord. Infection does not produce

full immunity, so reinfection occurs. S.mekongi causes similar, but

milder, disease compared to S. japonicum. Diagnostic tests: Microscopy for eggs in stool samples;

quantification of eggs by Kato–Katz method; PCR.

Therapy: Praziquantel is the drug of choice for all.

Prevention: Access to clean water and sanitation; protective

clothing (rubber boots and gloves) for those with occupational

exposure; after accidental exposure, dry the skin and apply

70% alcohol; mollusciciding. Replace water buffaloes by trac- tors, and livestock management like fencing off water

buffaloes.

Epidemiology: Approximately 1 million people are infected

with Schistosoma spp. in Cambodia, China, Lao PDR, and the

Philippines. Schistosomiasis has been eliminated from Japan

and the burden has been greatly reduced in China through

extensive control efforts. Schistosomiasis is a water-based

disease, that mainly affects rural agricultural and fishing

communities. Higher disease prevalence rates in endemic

regions are found close to large irrigation projects or dams.

S. japonicum is found in China, Philippines, and Indonesia. In

Indonesia, schistosomiasis is confined to two endemic areas in

Central Sulawesi. S. mekongi is found in the Mekong River area

of Cambodia and Laos, and has also been detected in Thailand.

S. malayensis has only been reported from Malaysia and is a

rare cause of human disease.

Map sources: The Schistosomiasis map is modified from

WHO (1987) Global Schistosomiasis Atlas, at: www.who.int/

wormcontrol/documents/maps/en/.

Key references

ChitsuloL, et al. (2000) The global status of schistosomiasis and

its control. Acta Trop 77:41–51.

Ross AGP, et al. (2001) Schistosomiasis in the People’s Repub- lic of China. Clin Microbiol Rev 14(2):270–295.

Ross AGP, et al. (2007) Katayama syndrome. Lancet Infect Dis

7:218–224.

Steinman P, et al. (2006) Schistosomiasis and water

resources development. Lancet Infect Dis 6:411–425.

World Health Organization (2011) Schistosomiasis. Factsheet

Nr 115 (www.who.int).

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

179

Page 68 of 113

Disease: Strongyloidiasis

Classification: ICD-9 127.2; ICD-10 B78

Syndromes and synonyms: Larva currens.

Agent: Strongyloides stercoralis, a minute nematode round- worm (up to2.2 mmlong).S.fuelleborni(notshownonthemap)is

a less common agent and can causehuman diseasein Africa and

Papua New Guinea (‘swollen belly syndrome’ in infants).

Reservoir: For S. stercoralis: mainly humans, although infec- tions in non-human primates and dogs have been described. S.

fuelleborni is mainly found in in monkeys, but human-to- human transmission may occur in some geographical regions.

Transmission: Mainly skin contact with fecally contaminated

soil, but oral transmission cannot be excluded.

Cycle: S. stercoralis has a free-living (asexual) and parasitic

(sexual) lifecycle. Free-living filariform (L3) larvae in the soil

penetrate the skin, enter the bloodstream, reach the lungs,

travel up to the throat, and are swallowed. In the duododenal

wall they mature into adult female worms, produce eggs

that hatch immediately, thus only larvae (L1) are excreted.

These non-infectious (L1) larvae develop further in the soil into

either adult worms or infectious (L3) larvae. Some non-infec- tious L1 larvae may develop faster into infectious L3 larvae in

the human intestine and penetrate the perianal skin or colon

wall. This process of auto-infection may lead to hyperinfection

in immunocompromised individuals.

Incubation period: Indefinite and variable; from skin

penetration to larvae in the stool takes 2–4 weeks.

Clinical findings: Most infections with S. stercoralis are asymptomatic. Symptoms may include: upper abdominal

pain; cough; diarrhea; a red and painful, creeping urticarial

eruption on the skin; and vomiting. Pulmonary symptoms

(including Loeffler syndrome) can occur. Disseminated

strongyloidiasis occurs in immunocompromised patients

and presents with abdominal pain, distension, shock, pulmo- nary and neurologic complications, and septicemia. High

mortality rates (15–87%) have been described in patients

with disseminated disease.

Diagnostic tests: Demonstration of Strongyloides larvae on

repeated stool specimens by microscopy after concentration

(coproculture or Baermann). Stool examination has poor

sensitivity, particularly in chronic cases. Serological tests

vary in sensitivity and specificity, and perform better in

chronic cases and are therefore used for screening patients

at risk for hyperinfection. PCR has higher sensitivity than

microscopy. Hyperinfection: larvae or parasite DNA can be

found in sputum and other specimens.

Therapy: Ivermectin; alternative: albendazole or thiabendazole.

Prevention: Access to clean water and sanitation; regular

deworming; use of closed footwear. Infection control in im- munocompromised patients with hyperinfection. Immuno- compromised patients who have been in endemic areas

should be screened and treated if positive.

Epidemiology: The estimated prevalence of strongyloidiasis is

between 30 and 100 million infections in 70 countries world

wide; however, the accuracy of these estimates is uncertain due

to poor performance of screening methods. Most cases are

found in tropical and subtropical areas (warm, moist). Rarely,

it is found in foci in North America and Europe. It is of

significance in developed nations as it can cause hyperinfection

in immunocompromised patients that have been infected years

before in an endemic region. The most important risk factor for

hyperinfection is corticosteroid therapy; other risk factors are:

hematologic malignancies, malnutrition, alcoholism, HTLV-1

infection, and immunosuppressive medication (e.g. for organ

transplantation). Interestingly, hyperinfection is not commonly

seen in HIV-infected individuals in endemic countries.

Map sources: The Strongyloidiasis map is modified from

M. Farthing et al. (2004) and updated with data from the

medical literature.

Key references

Farthing M, et al. (2004)WGO Practice Guideline; Management of

Strongyloidiasis. World Gastroenterology Organization.

Keiser PB, et al. (2004) Strongyloides stercoralis in the immuno- compromised population. Clin Microb Rev 17(1):208–217.

Marcos LA, et al. (2008) Strongyloides hyperinfection syn- drome: an emerging global infectious disease. Trans R Soc

Trop Med Hyg 102:314–318.

Montesa M, Sawhney C, Barrosa N (2010) Strongyloides ster- coralis: there but not seen. Curr Opin Infect Dis 23:500–504.

Olsen A, et al. (2009) Strongyloidiasis – the most neglected of

the neglected tropical diseases? Trans R Soc Trop Med Hyg

103:967–972.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

181

Page 69 of 113

Disease: Trypanosomiasis, African

Classification: ICD-9 086.3-086.4; ICD-10 B56.0, B56.1

Syndromes and synonyms: Sleeping sickness, Gambian

trypanosomiasis, Rhodesian trypanosomiasis, West African

sleeping sickness, East African sleeping sickness.

Agent: Extracellular, unicellular hemoflagellate Trypanosoma

brucei, with two subspecies: T. b. gambiensein West and Central

Africa (tropical forest), T. b. rhodesiense in East and Southern

Africa (savannah).

Reservoir: Humans for T. b. gambiense; livestock and wildlife

for T. b. rhodesiense. Vector: Tsetse fly (Glossina). The main human vectors belong

to the palpalis (riverine flies) and morsitans (forest and

savannah flies) complex. The palpalis complex (G. fuscipes,

G. palpalis, G. tachinoides) mainly transmit T. b. gambiense

and the morsitans complex (G. morsitans, G. pallidipes, G.

swynnertoni) mainly transmit T. b. rhodesiense. G. fuscipes and

G. tachinoides can transmit both subspecies.

Transmission: By tsetse fly bite (day biters); blood transfu- sion, and congenital.

Cycle:The parasite isingested by a tsetse fly during feeding on

an infected host, and enters the salivary glands after 12–30

days, and can be transmitted to new susceptible hosts during

the life of the fly (3 months). There is no vertical transmission in

the fly.

Incubation period: 3 days to a few weeks for T. b. rhodesiense, several months to years for T. b. gambiense. Clinical findings: A papule at the bite site develops into a

painful chancre (mainly T.b. rhodesiense), with fever, severe

headache, lympadenopathy, insomnia and progresses to vari- able neurological symptoms including a disrupted sleep cycle,

confusion, seizures, and, if left untreated, eventually death.

Diagnostic tests: Detection of trypanosomes in blood, lymph,

or CSF after concentration; IgM ELISA, IFA, PCR. A card

agglutination trypanosomiasis test (CATT) is available for T.

b. gambiense but not T. b. rhodesiense. Therapy: Early stage disease: suramin for T. b. rhodesiense, pentamidine forT. b. gambiense; Late stage disease: melarsoprol

for both forms; eflornithine with or without nifurtimox

for gambiense. These drugs can cause SAEs.

Prevention: Treat patients to reduce the T. b. gambiense reser- voir, and cattle to reduce the T. b. rhodesiense reservoir; screen

blood donations; vector control: fly traps, insecticide-treated

screens, ground and aerial spraying, release of sterile male

tsetse flies.

Epidemiology: WHO estimates that 50,000 to 70,000 people

are infected each year, with about 60 million people at risk in

36 countries. The disease distribution is limited by the range

of the tsetse fly vector. Cases outside the tsetse fly distribution

are likely imported. The disease distribution is patchy, with

discrete foci and little to no disease between these foci. It is a

disease of poverty and mainly occurs in remote rural areas.

African trypanosomiasis was close to eradication through a

variety of control programs, a loosening of these control

programs caused the disease to reemerge in the 1980s.

However, recent disease control programs are reversing this

trend. The chronic gambiense form in West and Central Africa

accounts for 95% of cases and is seperated from rhodesiense by

the Great Rift Valley. Uganda is the sole country reporting both

forms, with rhodesiense in the south and gambiense in the

northwest.

Map sources: The African Trypanosomiasis map was made

with data obtained from P.P. Simarro et al. (2010). The tstetse

fly distribution data is based on statistical distribution

models produced by the Environmental Research Group

Oxford, available at: www.fao.org/ag/againfo/programmes/

en/paat/maps.html.

Key references

Aksoy S (2011) Sleeping sickness elimination in sight.PloS Negl

Trop Dis 5(2):e1008.

Food and Agriculture Organization (2000) Consultant’s Report;

Predicted Distributions of Tsetse Fly in Africa. Rome, Italy.

Simarro PP, et al. (2008) Eliminating human African trypano- somiasis: where do we start andwhat comes next?PLoS Med

5(2):e55.

Simarro PP, et al. (2010) The Atlas of Human African Try- panosomiasis. Int J Health Geogr 9:57.

Simarro PP, et al. (2011) The human African trypanosomiasis

control and surveillance program of the World Health

Organization 2000–2009. PLoS Negl Trop Dis 5(2):e1007.

World Health Organization (2011) African trypanoso- miasis (sleeping sickness) fact sheet: www.who.int/

trypanosomiasis_african/en/.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Disease: Trypanosomiasis, American

Classification: ICD-9 086.2; ICD-10 B57

Synonyms: Chagas disease.

Agent: Trypanosoma cruzi, a protozoan, with a flagellate

form in the bloodstream and an intracellular form without

flagellum.

Reservoir: Humans and a wide variety of domestic and wild

mammals, especially dogs, cats, guinea-pigs, rodents, and

opossums.

Vector: Blood feeding reduviid bugs of the genera Triatoma,

Rhodnius, and Panstrongylus. The most common vector in south

America is Triatoma infestans. The vector lives up to 2 years.

Transmission: The vector defecates during feeding, and the

infected feces are rubbed into the bite wound or conjunctivae,

mucousmembranes, or abraded skin; blood transfusion, organ

transplant and shared needles. Congenital infection occurs in

2–8% of infected pregnancies. Oral transmission occurs by

eating or drinking contaminated food or drink.

Cycle: 10–30 days in the vector after first infected meal, then

5–42 days in the reservior host.

Incubation period: 5–14 days after infected bite, 30–40 days

after infected blood transfusion.

Clinical findings: Most infections produce few or no symp- toms. Acute symptoms include variable fever, lymphadeno- pathy,malaise, and hepatosplenomegaly. The entry site may be

inflamed for up to 8 weeks, and a diagnostic unilateral bipal- pebral edema (Romana’s sign) appears in a few cases. After a

latent period which may last 10–30 years, chronic irreversible

sequelae occur in 20–30% of cases: myocardial lesions with

arrhythmia, often fatal, andlesions of the esophagus, colon, and

peripheral nervous system. Variations in clinical presentations

can be related to the strain involved. Group I T. cruzi, rare north

of the Amazon region, produce cardiac but not digestive tract

lesions. Group IIT. cruzi can produce both cardiac and digestive

tract lesions. AIDS patients may develop meningoencephalo- pathy. CFR from encephalomyelitis or cardiac failure among

untreated symptomatic patients is 5–10%.

Diagnostic tests: Direct examination of blood smear (low

sensitivity), PCR, serology (indirect immunofluorescence,

indirect hemagglutination). Serology can give false positive

results. Culture takes weeks.

Therapy: Benznidazole, pentamidine, melarsoprol, eflorni- thine, suramin, and nifurtimox are effective in acute cases;

melarprosol and eflornithine can have SAEs. Patients need to

be followed up for 1–2 years.

Prevention: Application of residual insecticides or insecti- cidal paint inside dwellings, use ofinsecticide-treated bed nets,

screening of blood and organ donors from infected areas.

Application of these methods has eradicated intradomiciliary

transmission from Uruguay (1997), Chile (1999), Guatemala

(2005), Brazil (2006), the eastern region of Paraguay, andfive of

the endemic provinces of Argentina. Honduras and Nicaragua

are awaiting certification of eradication. Only the food-borne

risk remains in those areas.

Epidemiology: An estimated 7.6 million people are

infected with T. cruzi and 75 million are at risk in Mexico,

Central and South America, determined by the range of

the vector. Originally American trypanosomiasis was a

disease of agricultural workers (mainly adult men) living

in rural areas in poor housing conditions. In urban areas

transmission is mainly via blood transfusion, and occa- sionally via ingestion of contaminated sugarcane juice or

palm fruit juice. Control programs between 1990 and

2006 resulted in the estimated annual number of deaths

falling from more than 45,000 to 12,500, and the incidence

of new cases from an estimated 700,000 to 41,200.

Chronic cases are diagnosed in non-endemic countries

in immigrants. In the USA 300,000 immigrants have

Chagas disease, and an estimated 30,000 cases of Chagas

cardiomyopathy annually.

Map sources: The American Trypanosomiasis map was mod- ified from P.D. Marsden (1997) and updated with data from A.

Moncayo et al. (2009) and medical literature.

Key references

Marsden PD (1997) The control of Latin American trypanoso- miasis. Rev Soc Brasil Med Trop 30(6):521–527.

Moncayo A, et al. (2009) Current epidemiological trends for

Chagas disease in Latin America. Mem Inst Oswaldo Cruz 104

(Suppl. I):17–30.

Prata A (2001) Clinical and epidemiological aspects of Chagas

disease. Lancet Inf Dis 1(2):92–100.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

185

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Disease: Avian Influenza (A/H5N1)

Classification: ICD-9 488.01; ICD-10 J09.0

Synonyms: Bird flu, avian influenza, highly pathogenic avian

influenza, H5N1.

Agent: Influenza A subtype H5N1, a RNA virus, family

Orthomyxoviridae. Avian influenza H5N1 occurs in two

forms, a virulent form known as highly pathogenic avian

influenza H5N1 (HPAI H5N1) and a milder form known as

‘low pathogenic’ (LPAI H5N1). H5N1 viruses have diverged

into geographically distinct strains (genetic clades).

Reservoir: LPAI viruses naturally circulate in wild birds,

principally waterfowl and gulls, in which they generally

cause no symptoms. LPAI viruses are transmitted to terrestrial

poultry (chickens, turkeys). LPAI most likely evolved to HPAI

in aquatic birds (ducks and geese). Transmission of HPAI into

migratory birds can result in large die-offs.

Transmission: Direct contact with sick or dead poultry (most

common) infected with HPAI, and possibly via inhalation of

virus-laden particles or contact of contaminated material with

the eyes or respiratory mucosa. Other postulated routes: inges- tion of water contaminated with the feces of infected birds,

consumption of undercooked products from infected birds.

Often, however, the route of exposure is not clear. Limited

person-to-person transmission of HPAI H5N1 is possible fol- lowing prolonged close contact with an infected patient.

Incubation period: 3 days (range 2–9 days).

Clinical findings: Sudden onset fever and cough. Other early

symptoms include: myalgia, headache, vomiting, diarrhea,

nausea, and epigastric pain. The disease rapidly progresses

to severe viral pneumonia. Patients may present with enceph- alitis or gastroenteritis. The CFR is around 60%.

Diagnostic tests: Virus detection by RT-PCR of respiratory

specimens is recommended; virus culture requires a BSL-3

facility. Microneutralization assay is recommended to detect

antibodies to A/H5N1. Rapid antigen tests are not recom- mended due to lack of sensitivity.

Therapy: Oseltamivir may improve survival, if given early

after onset. Otherwise treatment is supportive.

Prevention: Prevention of exposure to the wild aquatic bird

reservoir and domestic poultry (farm biosecurity). Surveil- lance for infected poultry flocks and culling of infected flocks

(stamping out). Poultry workers and cullers must wear pro- tective clothing. Education of poultry farmers and the general

public to reduce high-risk exposures. Human cases must be

isolated, close contacts monitored, and healthcare workers

must wear personal protective equipment.

Epidemiology: Since the end of 2003 the A/H5N1 virus has

spread globally, infecting poultry in over 60 countries and

causing the loss of over 250 million poultry. In 2010 HPAI

H5N1 remained entrenched in poultry in several Asian

countries and Egypt. While migratory waterfowl plays a

role in the long-distance spread of H5N1 (see Bird Migration

map), the intensification of poultry farming and poorly

regulated movement and trade in poultry is probably the

most important factor in sustaining the current epizootic.

HPAI H5N1 is highly contagious between birds and has a

high fatality in most poultry species, making it an economi- cally important disease. However, it is the risk to humans

that has driven most of the control activities. Over

500 human cases have been detected in 15 countries. The

concern remains that H5N1 may evolve or reassort with

another influenza A virus to become either more transmissi- ble from poultry to humans or transmissible from person to

person.

Map sources: The Avian Influenza map was reproduced from

WHO, available at: http://gamapserver.who.int/mapLi- brary/ (accessed dec. 2010).

Key references

Abdel-Ghafar AN, et al. (2008) Virus update on avian influ- enza A (H5N1) virus infection in humans. N Engl J Med

358(3):261–273.

Gambotto A, et al. (2008) Human infection with highly patho- genic H5N1 influenza virus. Lancet 371(9622):1464–1475.

Food and Agriculture Organization (revised in 2007)

The Global Strategy for the Prevention and Control of H5N1

Highly Pathogenic Avian Influenza. FAO/OIE Strategy

document.

Peiris JSM, et al. (2007) Avian influenza võrus (H5N1): a threat

to human health. Clin Microb Rev 20:243–267.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

189

Page 72 of 113

Disease: Barmah Forest & Ross River Virus

Disease

Classification: ICD-9 066.3; ICD-10 R50.9 (Barmah Forest)

and B33.1 (Ross River)

Syndromes and synonyms: Polyarthritis and rash, epidemic

polyarthritis, Barmah Forest virus disease, and Ross River

virus disease, Murweh virus disease.

Agent: Barmah Forest virus (BFV) and Ross River virus (RRV),

enveloped RNA viruses, genus Alphavirus in the family Toga- viridae. An early isolate of BF from Queensland was initially

named Murweh virus. There are two topotypes of Ross River

virus, from eastern and western Australia; a third, in north- eastern Australia, has not been found since the mid-1970s.

Reservoir: Large marsupials, particularly kangaroos and

wallabies.

Vector: Mainly Ochlerotatus vigilax and Culex annulirostris. Aedes camptorhynchus, A. normanensis, A. notoscriptus, and

Coquillettidia linealis are vectors in some circumstances.

Transmission: Mosquito bite; transovarial transmission has

been demonstrated in Aedes vigilax. There is no direct person- to-person transmission.

Cycle: Viremic reservoir host to mosquito during feeding,

then after an extrinsic cycle of a few days, the virus is trans- mitted to a new reservoir host during feeding.

Incubation period: 3–12 days (usually 7–9).

Clinical findings: Self-limiting disease. Sudden onset of joint

pain; fatigue, marked arthralgia and myalgia in more than

40%, stiff and swollen joints in 60–85% of cases; anorexia,

headache, back pain, photophobia, sore throat, lethargy, and

lymphadenopathy also occur, with fever and a maculopapular

rash, usually on the trunk and limbs but also on palms and

soles, in 50% of cases. Relapses occur; joint pains and swelling

may relapse for as long as 6 years. Patients eventually recover

completely.

Diagnostic tests: Viral RNA dection in blood by RT-PCR;

serology (IgM ELISA; four-fold increasein IgG); virus isolation

is insensitive.

Therapy: Supportive, there is no specific treatment

Prevention: Anti-mosquito measures: light-colored cloth- ing with long sleeves mosquito repellents containing DEET

on exposed skin, avoid as much as possible outdoor activi- ties at dawn and dusk, when mosquitoes are most active,

and removal of mosquito-breeding sites from around the

home.

Epidemiology: There are only about 5,000 cases of RRV and

usually only a few hundred cases of BFV annually. Peak

incidence is in the 30–40 year age group, the disease is rare in

children. RRV disease is the most common arboviral disease

in Aus tralia, accounting for about 90% of cases, often occur- ring in mixed epidemics with BFV disease on mainland

Australia (to which BFV is restricted). Most BFV cases

occur in Queensland and are only sporadic. RRV cases

have been reported from the island of New Guinea and

caused epidemics in Pacific islands in 1979–1980. Transmis- sion occurs year-round, especially in coastal northern and

northeastern Australia, but is more intense during the mos- quito season in most of the country. Birds are presumed to be

involved in spread around Australia; a viremic tourist from

Australia is believed to have introduced the eastern topotype

of RRV to the Pacific islands. Detailed epidemiological data

is available on line at: http://www9.health.gov.au/cda/

source/cda-index.cfm.

Map sources: The Barmah Forest and Ross River Virus

disease map was made with data obtained from the Australian

Government, Department of Health and Ageing, available at:

www.health.gov.au/internet/main/publishing.nsf/Con- tent/cdi3202.

Key references

Harley D, et al. (2001) Ross River virus transmission, infection,

and disease: a cross-disciplinary review. Clin Microbiol Rev

14(4):909–932.

Mackenzie JS (2001) in Service MW (ed.) The Encyclopedia

of Arthropod-Transmitted Infections. CAB International,

pp. 67–69.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

191

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Disease: Bunyamwera Viral Fever

Classification: ICD-9 066.3; ICD-10 A92.8

Syndromes and synonyms: Bunyamwera encephalitis,

Bunyamwera viral disease, Cache Valley encephalitis.

Agent: Bunyamwera group viruses are enveloped, single- stranded, RNA viruses genus Orthobunyavirus of the family

Bunyaviridae (see also Bunyavirus Group C map). Bunyam- wera group viruses that can cause human disease in Africa are:

Bunyamwera virus (BUNV), Germiston virus (GERV), Ilesha

virus (ILEV), Ngari virus (NRIV), and Shokwe virus. Cache

Valley complex viruses (CVV) have been isolated from human

cases in North America, but are not shown on this map.

Reservoir: Not completely understood; most Bunyamwera

viruses are likely maintained in nature involving a transmis- sion cycle with various small mammals (mainly wild rodents)

as amplifying hosts and mosquitoes. African rodents replicate

BUNV and develop viremia. Livestock (goats, sheep, cattle),

horses and rodents are hosts for GERV as shown by seroprev- alence studies. Amplifying hosts for CVV are mainly large

mammals (caribou, deer, horses, sheep).

Vector: Many species of mosquitoes of the genera Aedes,

Mansonia, Culex, and Anopheles. Transmission: By mosquito bite.

Cycle: The mosquito becomes infected when feeding on a

viremic vertebrate host. The virus crosses the mosquito gut

wall and replicates in the organs of the mosquito. After several

days, the virus reaches the salivary glands and is injected into

the next host during feeding.

Incubation period: Estimated at less than 2 weeks.

Clinical findings: Sudden onset fever, frontal headache, back- ache, diarrhea and a rash; usually resolves without sequelae;

fatalities are rare and the result of hemorrhage or meningoen- cephalitis. ILEV and NRIV can cause hemorrhagic fever out- breaks. CVV rarely causes encephalitis, with only one fatal

case reported in the USA in 1995.

Diagnostic tests: Several serologic tests are available. Virus

can be isolated or RNA detected in acute blood by RT-PCR.

Therapy: Supportive; there is no specific therapy.

Prevention: Anti-mosquito precautions.

Epidemiology: African Bunyamwera viruses known to cause

human disease circulate in Sub-Saharan Africa. Virus trans- mission peaks in the rainy season when mosquitoes are abun- dant. All age groups can be infected, though BUNV mainly

affects children. BUNV is particularly active in the riverine

forests in Nigeria and CAR. 100% of adults living in tropical

rainforest of the DRC are seropositive. Neutralizing antibody

rates of over 50% for ILEV have been found in people in

savannah areas of Nigeria. Lower seroprevalences of ILEV

are found in rainforests. GERV is endemic in southern African

countries. To date, GERV has not been reported to be respon- sible for any major human disease outbreaks, and is therefore

considered of minor public health importance.

Map source: The Bunyamwera Viral Fever map was made by

geocoding human cases reported in the medical literature

up to 2010 and the CDC Arbovirus Catalog, available at:

http://wwwn.cdc.gov/arbocat/index.asp.

Key references

Bouloy M (2001) Bunyamwera virus. In Service MW (ed.) The

Encyclopedia of Arthropod-transmitted Infections. CAB Inter- national, pp. 94–97.

Gavrilovskaya I (2001) Issyk-Kul virus disease. In Service MW

(ed.) Encyclopedia of Arthropod-Transmitted Infections. CAB

International, pp. 231–234.

Gerrard SR (2004) Ngari virus is a Bunyamwera virus reas- sortant that can be associated with large outbreaks of hem- orrhagic fever in Africa. J Virol 78(16):8922–8926.

Grimstad PR (2001) Cache Valley virus. In Service MW (ed.)

The Encyclopedia of Arthropod-transmitted Infections. CAB

International, pp. 101–104.

Morvan JM (1994) Ilesha virus: a new aetiological agent of

haemorrhagic fever in Madagascar. Trans R Soc Trop Med

Hyg 88:205.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Disease: Bunyavirus Group C Disease

Classification: ICD-9 066.3; ICD-10 A92.8

Synonyms: None.

Agent: Spherical, enveloped orthobunyaviruses with single- stranded, negative-sense, tripartite RNA genomes, with con- siderable recognized reassortment. The name derives from the

original classification of arthropod-borne viruses in to A, B and

C groups. Group C viruses can be divided into four complexes:

(1) Caraparu complex [Apeu virus (APEUV), Bruconha virus

(BRCV), Caraparu virus (CARV), Ossa virus (OSSAV), and

Vinces virus (VINV)]; (2) Madrid virus (MADV); (3) Marituba

complex viruses [Gumbo Limbo virus (GLV), Marituba virus

(MTBV), Murutucu virus (MURV), Nepuyo virus (NEPV),

Restan virus (RESV)], and (4) Oriboca complex viruses [Itaqui

(ITQV), Oriboca viruses (ORIV)].

Reservoir: Forest rodents, marsupials, and bats.

Vector: Mosquitoes (Aedes and Culex spp.).

Transmission: By mosquito bite. There is no direct person-to- person transmission.

Cycle: Mosquito-host-mosquito. The mosquito becomes

infected when feeding on a viremic reservoir host. Depending

on ambient temperature, the virus reaches the salivary glands

and is transmitted by feeding on the next host in several days.

Incubation period: 3–12 days.

Clinical findings: Dengue-like fever with headache, malaise,

arthralgia or myalgia for about 2 to 5 days; occasionally

nausea and vomiting, lower limb weakness, conjunctivitis,

photophobia and a rash. The fever resolves in a few days; the

disease is non-fatal.

Diagnostic tests: IgM capture or IgG ELISAs is most com- monly used on paired acute and convalescent sera. Virus

isolation in suckling mice or cell culture and identified by

RT-PCR.

Therapy: Self-limiting disease.

Prevention: Standard anti-mosquito precautions. There is no

vaccine available.

Epidemiology: There is little known about the epidemiology

of these viruses. Group C viruses are geograpically limited to

the tropical and subtropical areas of the Americas, and were

first described in the Brazilian Amazon in the 1950s. Studies

show that these viruses circulate in a compact ecosystem in

which co-infection with more than one virus is possible in

reservoir hosts, leading to genetic reassortment. Genetic anal- ysis shows evidence of intense traffic of these viruses in the

Americas. Nepuyo virus has the widest distribution reported,

from Mexico to Brazil. There is no sex or age preference for

infection. Inapparent and mild infections are common, overt

disease is mostly seen in children residing in endemic areas.

Map source: The Bunyavirus Group C Disease map was made

by showing which bunyavirus group C virus is reported by

country, according to the medical literature up to 2010.

Key reference

Nunes MRT, et al. (2005) Molecular epidemiology of group C

viruses (Bunyaviridae: Orthobunyavirus) isolated in the

Americas. J Virol 79(16):10561–10570.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Disease: California Group Virus Disease

Classification: ICD-9 062.5; ICD-10 A83.5

Syndromes and synonyms: California encephalitis, James- town Canyon encephalitis, La Crosse encephalitis.

Agents: Spherical, enveloped, negative sense RNA viruses

forming a subgroup of the Bunyaviridae family. In the

Americas, human pathogens belonging to the group are

Guaroa virus (GROV), Jamestown Canyon virus (JCV),

LaCrosse virus (LACV), and snowshoe hare virus (SSHV).

Those reported to cause human disease in Europe or Asia are

Inkoo virus (INKV), Tahyna virus (TAHV), and SSHV.

Reservoir: Small wild mammals such as rodents, snowshoe

hares, deer and vector mosquitoes (venereal and transovarian

transmission occur). Dayfeeding chipmunks and squirrels

are the principal amplifying hosts of LACV, as the main vector

(Aedes triseriatus) only bites in daytime. For this reason, night- feeding small mammals are rarely infected with LACV. The

white-tailed deer is the main amplifying host for JCV (horses

can also be an amplifying host). Snowshoe hares and the arctic

ground squirrel are the amplifying hosts of SSHV.

Vector: Mosquitoes, primarily Aedes and Ochlerotatus spp.,

secondarily Anopheles spp. Ae. triseriatus (eastern treehole

mosquito) is the most important vector of LACV in the

USA. LACV is abundant in forests with oak trees (basal

holes are important breeding sites) and hickory hardwoods

drained by rapid streams. Different species of cold-tolerant

mosquitoes serve as vectors for JCV and SSHV.

Transmission: By mosquito bite.

Cycle: Mosquito–reservoir host–mosquito. The mosquito

becomes infected during feeding on a viremic reservoir

host; once the virus reaches the salivary glands it can be

transmitted during feeding to the next reservoir host.

Incubation period: Usually 5–15 days.

Clinical findings: Fever, headache, vomiting, sometimes

progressing to acute CNS and respiratory involvement,

with recurrent seizures in 25% of CNS cases. INKV is associ- ated with severe illness and chronic neurologic disease in

Russia.

Diagnostic tests: Serology (IgM and IgG ELISA) on acute and

convalescent sera; cross-reactivity exists leading to

misidentification. RT-PCR has been used to test human brain

tissue samples.

Therapy: Supportive, there is no specific treatment. Ribavirin

may limit the severity and improve the prognosis of LACV

infections. Anticonvulsant medication in those with seizures.

Prevention: As mosquito vectors and wildlife reservoirs are

widespread, control is not feasible; personal anti-mosquito

measures; eliminating potential breeding sites (e.g. old tires)

and filling of basal tree-holes with concrete.

Epidemiology: The California group viruses are widely dis- tributed over all types of terrain. Each has its preferred vector

mosquito species and host, for instance snowshoe hare for

SSHV. LACV is the primary cause of arboviral encephalitis in

children in the USA. Most LACV infections occur in those

residing close to woodland breeding sites of Ae. triseriatusfrom

July to September. Boys are more often affected with LACV, as

they more often play in the woods. JCV is most commonly

found around the Great Lakes in USA and Canada. The JCV

vectors prefer hilly woodlands where they breed in ponds

from April to June. SSHV, has a different ecosystem: (sub)

arctic forests and tundras in Canada and Siberia. SSHV has

been detected in China. SSHV transmission occurs during the

arctic summer from May to August, and mainly affects chil- dren (<10 years), especially boys. Lumbo virus is a strain of

TAHV isolated from mosquitoes in Mozambique (Africa), but

no human cases have been diagnosed there.

Map sources: The California Group Virus Disease map was

made by geolocating human outbreaks reported in the medical

literature up to 2010. La Crosse virus epidemiology data was

obtained from the CDC, available at: www.cdc.gov/lac/tech/

epi.html (accessed Dec 2010).

Key references

Beaty BJ (2001) La Crosse virus. In Service MW (ed.) The

Encyclopedia of Arthropod-transmitted Infections. CAB Inter- national, pp. 261–265.

Grimstad PR (2001) Jamestown Canyon virus. In Service MW

(ed.) The Encyclopedia of Arthropod-transmitted Infections. CAB International, pp. 235–239.

Labuda M (2001) Tahyna virus. In Service MW (ed.) The

Encyclopedia of Arthropod-transmitted Infections. CAB Inter- national, pp. 482–483.

Rust RS, et al. (1999) La Crosse and other forms of California

encephalitis. J Child Neurol 14(1):1–14.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Disease: Chikungunya Fever

Classification: ICD-9 066.3; ICD-10 A92.0

Syndromes and synonyms: Chikungunya means ‘that

which bends up’ in Makonde language, to describe the pain.

Agent: Chikungunya virus (CHIKV), an enveloped RNA

virus, genus Alphavirus in the family Togaviridae. CHIKV

belongs to the same antigenic complex as Mayaro, Ross

River, and o’nyong-nyong viruses. Phylogenetic analysis sug- gests an African origin about 500 years ago, with spread to

Asia within the last century.

Reservoir: Non-human primates in Africa and humansin Asia;

Asianmonkeys can be infected, but do not seem to constitute an

important reservoir. During intra-epidemic periods, several

vertebrates have been implicated as potential reservoirs.

Vector: In Africa, the principal vectors are the sylvan mosqui- toes Ae. furcifer and Ae. africanus, Ae. luteocephalus, and

Ae. taylori; in Asia, urban Ae. aegypti, Ae. albopictus, and various

Culex species.

Transmission: By mosquito bite. Transmission from mother

to neonate can occur in the intrapartum period; blood-borne

transmission is possible.

Cycle: Humans are viremic at a titer high enough to infect

mosquitoes for 3 to 7 days post illness onset. The virus travels

from the mosquito gut to the salivary glands in 5–7 days, after

which it can infect another human by bite.

Incubation period: 3–7 days (range 1–12 days).

Clinical findings: Sudden onset fever, chills, fatigue, transient

maculopapular rash constant polyarthralgia/arthritis of small

joints (hands, wrists, ankles, feet); leucopenia and mild throm- bocytopenia. Neurological, cardiac, and hepatic complications

rare . The acute stage in infants and young children can be

atypical (epidermolysis, myocarditis, or encephalitis), but is

rarely fatal. Infected neonates (mother-to-child transmission)

are at a high risk of severe encephalopathy and death. Chronic

inflammatory joint symptoms were observed in up to 50%

of adult cases, and after 2 years in some outbreaks.

Diagnostic tests: Within 5 days of disease onset: RT-PCR on

whole blood, virus isolation; After 5 days: IgM ELISA on

serum; serological tests can cross-react.

Therapy: Supportive with pain management.

Prevention: Standard anti-mosquito precautions.

Epidemiology: Before 2004, CHIKV was considered a

minor arboviral disease, but since then has spread globally,

infecting millions of people. Most cases are symptomatic.

CHIKV has been endemic in Africa for centuries, typically

causing small epidemics in rural areas. CHIKV spread to

Asia within the last 60 years producing urban outbreaks,

similar to dengue fever, involving Ae. egypti. The global

epidemic started since a mutation in the CHIKV E1 glyco- protein gene (A226V) occurred, that enhanced its infectiv- ity and transmission by Ae. albopictus. The mutated CHIKV

is succesful in spreading in tropical and temperate regions

where Ae. albopictus is present. In 2005–2006 CHIKV spread

from East Africa to virgin soil in the Indian Ocean Islands

to produce epidemics affecting up to three-quarters of the

population. Since 2006, CHIKV outbreaks with are

reported from several (sub)tropical countries in the new

world. CHIKV virus was imported into several European

countries and caused a small outbreak with autochtho- nous transmission in northern Italy. CHIKV-viremic tra- velers can cause autochthonous transmission in previous

CHIKV-free areas if Ae. albopictus or other competent

mosquitoes are present.

Map sources: The Chikungunya Virus Disease map is made

by showing regions with reported outbreaks reported to

WHO, ProMED-mail, and the medical literature up to 2010.

Datawas also used from the CDC, available at: www.cdc.gov/

ncidod/dvbid/Chikungunya/CH_GlobalMap.html, and De

Lamballerie et al. (2008).

Key references

De Lamballerie X, et al. (2008) Chikungunya virus adapts to

tiger mosquito via evolutionary convergence: a sign of

things to come? Virol J 5:33.

Simon F, et al. (2011) Chikungunya virus infection. Curr Infect

Dis Rep. 13(3):218–228.

Volk SM, et al. (2010) Genome-scale phylogenetic analyses

of chikungunya virus reveal independent emergences of

recent epidemics and various evolutionary rates. J Virol 84

(13):6497–6504.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

199

Page 77 of 113

Disease: Colorado Tick Fever

Classification: ICD-9 066.1; ICD-10 A93.2

Syndromes and synonyms: None.

Agent: Colorado Tick Fever Virus (CTFV), a prototype virus

of the genus Coltivirus of the family Reoviridae; a spherical,

enveloped virus with a double-stranded RNA genome of

12 segments.

Reservoir: High altitude rodents, including ground squirrels

and porcupines; ticks by trans-stadial transmission; possibly

transovarial, but this is considered unlikely.

Vector: Ixodid wood tick (Dermacentor andersoni). Transmission: By tick bite, blood transfusion; bone marrow

for transplantation is routinely screened in endemic areas.

Cycle:The tick feeds on an infected host, the virusmultipliesin

the tick’s midgut and spreads to the salivary glands, to be

injected into another host at the next feed, where it infects

erythrocytes. As the virus infects erythrocytes, it is partially

protected from immune clearance, leading to prolonged vire- mia in both humans (up to 4 months) and rodents, favoring

spread.

Incubation period: <1–19 days, average about 3–4 days,

depending on the infecting dose. Viremia in humans may

last for 4 months or more.

Clinical findings: Sudden onset of high fever (biphasic), chills,

myalgia, arthralgia, severe headache, ocular pain, conjuncti- vitis, anorexia, nausea, and sometimes vomiting. Spleen and

liver can be palpable, and pericarditis or myocarditis may be

found. A few cases have a petechial or maculopapular rash.

Prolonged convalescence may follow. Children may have a

more severe syndrome with hemorrhagic manifestations,

including a more pronounced rash, DIC, and GI bleeding;

or CNS involvement including meningitis and encephalitis.

Fatalities are rare.

Diagnostic tests: Serology (IgM ELISA, IFA of erythrocytes).

Diagnosis is confirmed by a significant ( > 4-fold) change in

antibody titer between acute and convalescent sera. Virus

isolation or RNA detection by RT-PCR from the blood or CSF.

Therapy: Supportive.

Prevention: Personal anti-tick precautions (appropriate cloth- ing, acaricide, repellent). Vaccine production ceased in the

1970s and there is no possibility of vector control due to

the habitat. Screening of bone marrow donors in endemic areas. Epidemiology: Colorado tick fever is only present in North

America (USA and Canada). In the USA, besides the states

with human cases shown on the map, the virus has been

isolated from ticks within the range of D. andersoni. The typical

habitat of the tick and its rodent hosts is a south-facing slope

above 1,500 meters with Ponderosa pine and shrubs on dry,

rocky surfaces. Infection is seasonal, coinciding with the

period of greatest tick activity in early summer. Human

cases can be detected from March to September in the

Rocky Mountain region, USA. Most human cases are males,

aged 20–29 years, probably reflecting the frequency of outdoor

activity in the mountains.

Map sources: The Colorado Tick Fever map was made with

geolocating reported cases in the medical literature up to

2010.

Key references

Attoui H, et al. (2005) Coltiviruses and Seadornaviruses in

North America, Europe, and Asia. Emerg Infect Dis

11(11):1673–1679.

Brackney MM, et al. (2010) Epidemiology of Colorado tick

fever in Montana, Utah, and Wyoming, 1995–2003. Vector

Borne Zoonotic Dis 10(4):381–385.

Calisher CH (1994) Medically important arboviruses of the

United States and Canada. Clin Microbiol Rev 7(1):89–116.

Calisher CH (2001) Colorado tick fever. In Service MW (ed.)

The Encyclopedia of Arthropod-Transmitted Infections. CAB

International, pp. 121–126.

Klasco R (2002) Colorado tick fever. Med Clin North Am

86(2):435–440.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

201

Page 78 of 113

Disease: Crimean–Congo Hemorrhagic Fever

Classification: ICD-9 065.0; ICD-10 A98.0

Synonyms: Congo fever, Congo–Crimean hemorrhagic fever,

Central Asian hemorrhagic fever

Agent: Crimean-Congo hemorrhagic fever virus (CCHFV) is

an enveloped, spherical virus with a tripartite, single- stranded, negative sense RNA genome, belonging to the

genus Nairovirusin the family Bunyaviridae. It has 7 genotypes

distinguished by the small (S) segment of the RNA.

Reservoir: Hares, hedgehogs, wild mice, livestock, ostriches.

Since hard ticks overwinter and can pass the virus transova- rially, ticks also serve as reservoirs.

Vector: Hard ticks, principally Hyalomma spp., also Boophilus

spp. and Rhipicephalus spp.

Transmission: By tick bite; larval ticks are carried on migrat- ing birds, which are refractory to the virus. The virus is also

spread among veterinarians, farmers, shepherds, butchers,

and slaughter-house workers by contact with the blood of

infected livestock. Person-to-person spread is by contact with

infectious body fluids of patients.

Cycle: Tick–vertebrate–tick, with humans as incidental hosts.

Incubation period: 1–12 days, usually 3–7.

Clinical findings: Sudden onset of fever (which may be

biphasic), malaise, weakness, irritability, headache, severe

pain in limbs and loins and marked anorexia; occasionally

vomiting, abdominal pain, and diarrhea. Hemorrhage in oro- pharynx, nose, lungs, uterus, intestines; hematomas, echymo- sis, and petechiae; hematuria and albuminuria. In Russia,

estimates are that only 1 in 6 cases is hemorrhagic. The CFR

ranges from 2 to 80% in different countries.

Diagnostic tests: Virus isolation in cell culture; RT-PCR;

antigen detection; serology by IgM ELISA. The virus is a

BSL-4 agent.

Therapy: Supportive; intravenous ribavirin and convalescent

human serum are recommended.

Prevention: Personal anti-tick precautions. An inactivated

mouse-brain vaccine is in use in Russia and eastern Europe.

Healthcare workers caring for CCHF patients are at risk and

need to take proper barrier precautions.

Epidemiology: The disease is limited geographically to the

range of the vector tick. Hyalomma spp. do not occur in the

Americas and Oceania. Historically the tick does not appear

above 50 N latitude, but possibly due to changes in climate

and environment the tick and CCHFV outbreaks have

occurred above this latitude. In the northern hemisphere, H.

marginatum becomes more active by increasing temperatures

during spring (April–May) and immature stages are active

from May to September. The potential roles of migratory birds

and the movement of livestock carrying ticks in the spread of

the virus are unclear. CCHFV outbreaks mainly occur in those

working in agricultural areas. About 90% of the cases in a

recent outbreak in Turkey were farmers. Cases regularly had

skin contact with livestock or other animals. Also outdoor

activities (hiking, camping) in endemic areas are a risk factor.

Countries on the map marked as having no data (western

Sahara, Palestine, parts of the Arabian peninsula, Kashmir) are

within the range of the vector tick and likely at risk for CCHFV

outbreaks. CCHFV genotypes cluster geographically, with

exceptions: the Asia 1 genotype has been found in Madagas- car, where it was possibly introduced by migrating birds, and

Africa 1 in the Middle East, which may have been introduced

with infected livestock.

Map sources: The Crimean–Congo Hemorrhagic Fever map

was made with data on CCHF outbreaks between 1943 and

2010 obtained from ProMED mail, the medical literature and

WHO, available at: www.who.int/csr/disease/.

Key references

Ergonul O, et al. (2006) Crimean–Congo haemorrhagic fever.

Lancet Infect Dis 6:203–214.

Leblebicioglu H, et al. (2010) Crimean–Congo haemorrhagic

fever in Eurasia. Int J Antimicrob Agents 36(Suppl. 1):

S43–S46.

World Health Organization (2004) The Vector-Borne Human

Infections of Europe, their Distribution and Burden on Public

Health. Publication from the WHO Regional Office for

Europe.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

203

Page 79 of 113

Disease: Dengue

Classification: Dengue fever (DF): ICD-9 061, ICD-10 A90;

Dengue hemorrhagic fever/Dengue shock syndrome (DHF/

DSS): ICD-9 065.4; ICD-10 A91.

Synonyms: Breakbone fever.

Agent: Dengue virus (DENV) is an enveloped RNA virus,

genus Flavivirus in the family Flaviviridae. There are four

antigenically related, but distinct, dengue virus serotypes

(DEN-1, DEN-2, DEN-3, and DEN-4), all of which can cause

DF/DHF.

Reservoir: Humans; forest monkeys in West Africa and

Southeast Asia.

Vector: Most commonly, the urban container-breeding, day- bitingmosquitoesAedes aegypti and Ae. albopictus; in Polynesia,

Ae. scutellaris complex spp.; in Malaysia, Ae. nivaeus complex

spp., in West Africa, Ae. furcifer-taylori complex spp., and

recently in Europe by Ae. albopictus (see Aedes map).

Transmission: By mosquito bite.

Cycle: Human–mosquito–human around housing; monkey–- mosquito–monkey and monkey–mosquito–human in the for- ests of West Africa and Malaysia. Human viremia lasts 3–5

days since onset of symptoms; the mosquito can transmit 8–12

days after taking a viremic blood meal, depending on the

ambient temperature.

Incubation period: 3–14 days (usually 4–7 days).

Clinical findings: Sudden onset of fever lasting 2–7 days,

sometimes biphasic, severe headache, myalgia, arthralgia,

retro-orbital pain, anorexia, nausea, vomiting and a maculo- papular rash (not easily seen on dark skin). Most cases recover.

Minor occurrence of petechiae, epistaxis, or gingival bleeding

may be seen. Serious hemorrhagic manifestations, like a severe

drop in blood platelets, indicate dengue hemorrhagic fever

(DHF), that can progress to dengue shock syndrome (DSS) and

death. Infection with any serotype results in lasting homolo- gous immunity, but little cross-immunity to other serotypes.

Cross-immunity may exacerbate, rather than diminish, disease

severity when infected with a new serotype; DHF leading

to DSS can occur as a secondary infection with a different

serotype, but DHF/DSS has also been reported in primary

infections. CFR for DHF is up to 20%, for untreated DSS up to

50%, and 1–2% if correctly treated.

Diagnostic tests: IgM capture ELISA; NS1 antigen test; RT- PCR of blood or tissue; virus isolation in mosquitoes or

mosquito cell culture with identification by IFA.

Therapy: Supportive, including rehydration. Avoid aspirin

because of potential hemorrhage.

Prevention: Removal of breeding sites in any type of con- tainer that holds water (e.g. vase, tire). Larviciding standing

water, adulticiding with non-persistent insecticides. Personal

protection with suitable clothing, mosquito repellents, nets,

and screens.

Epidemiology: The global dengue distribution follows vec- tor presence and introduction of the virus, and occurs basi- cally between the 10 C isotherms. Autochthonous dengue

fever cases appeared in Europe for the first time in 2010, north

of 10 C isotherm and likely transmitted by Ae. albopictus (see

Aedes agypti and Aedes albopictus map). There is strong sea- sonality, correlated with the rainy season, which produces a

marked increase in vectors because more mosquito-breeding

sites become available then. Two, 3 or all 4 serotypes may

occur concurrently. DHF/DSS in many countries is most

often seen in children suffering a secondary infection with

a different serotype. Incidence rates of up to 3% have been

seen in dengue naõve populations such as are found in some

Pacific islands.

Map sources: The Dengue map was reproduced from Sim- mons CP (2012), with permission.

Key references

Guzman A, et al. (2010) Update on the global spread of dengue.

Int J Antimicrob Agents 36(Suppl. 1):S40–S42.

Jelinek T (2009) Trends in the epidemiology of dengue fever

and their relevance for importation to Europe. Euro Surveill

14(25):19250.

Kyle JL, et al. (2008) Global spread and persistence of dengue.

Ann Rev Microbiol 62:71–92.

Simmons CP, et al. (2012) Dengue. N Engl J Med.

366:1423–1432.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

205

Page 80 of 113

Disease: Eastern Equine Encephalitis

Classification: ICD-9 062; ICD-10 A83.2

Synonyms: None.

Agent: Eastern equine encephalitis virus (EEEV) is an envel- oped, single-stranded positive-sense RNA alphavirus, genus

Alphavirus in the family Togaviridae, with four lineages:

Group I is endemic in North America and the Caribbean

and causes most human disease cases; the other three groups

(IIA, IIB, and III) infrequently cause equine or human illness in

Central and South America.

Reservoir: Principally wild birds in North America. Wild

rodents, bats, reptiles, or amphibians may also be involved.

Pheasants may serve as sentinels as they develop fatal disease.

Chickens are more typically used as sentinels by detection of

seroconversion.

Vector: Mosquitoes. In North America,Culiseta melanura bird- to-bird; Aedes or Coquillettidia spp. from bird to other verte- brates (including horses and humans). In South America,Culex

spp.

Transmission: By mosquito bite. There is no direct person-to- person transmission.

Cycle: Culiseta melanura: bird to bird; Aedes or Coquillettidia

spp.: from bird to other vertebrates (including horses and

humans). Viremia lasts 2–5 days in birds, and the extrinsic

cycle in mosquitoes lasts 2–3 days. Horses and humans are

dead-end hosts because their viremia is generally not high

enough to infect mosquitoes.

Incubation period: 4–10 days.

Clinical findings: Sudden onset of high fever, headache,

chills, vomiting, myalgias, photophobia and dysthesias;

50–90% of apparent cases develop encephalitis. In the USA,

one-third of encephalitis cases die and one-third of the survi- vors are moderately to severely disabled.

Diagnostic tests: IgM antibody detection in CSF (in serum

may not be from the current infection), neutralization test on

paired acute and convalescent sera; RT-PCR. Virus isolation

takes time. IFA in necropsy brain tissue is definitive.

Therapy: Supportive, there is no specific treatment.

Prevention: Personal anti-mosquito precautions. Adulticide

spraying is practiced in areas where horse cases appear. A

human vaccine against only the North American strain is

available for laboratory personnel.

Epidemiology: In the USA, an average of only 6 neuroinva- sive cases of EEE are reported annually. The annual number of

cases has declined in recent years. Incidence is similar among

different age groups and ethnicities, but it is twice as high

among men. Persons aged over 50 and under 15 are at greatest

risk for developing severe disease. In North America, out- breaks occur during the mosquito season. In tropical South

America transmission to horses is year-round, but human

cases are rare. Culiseta breeds in swampy areas in woodland,

transmitting the virus from marsh-nesting birds to horses kept

in such areas; unvaccinated horses often die. Outbreaks in

Mexico and islands of the Caribbean have all been due to the

North American subtype, indicating spread by migratory

birds. South American strains are distinct and of three different

lineages, probably determined by the range of different rodent

hosts. Only a single human case has been reported from Brazil,

and none from Guatemala, Belize, Colombia, Ecuador Peru,

Cuba, or Trinidad and Tobago in spite of detection of the virus

in mosquitoes or horses in those countries. The virus has also

been isolated from horses in eastern Canada.

Map sources: The Eastern Equine Encephalitis map was made

with distribution data obtained from themedical literature and

CDC (www.cdc.gov/EasternEquineEncephalitis/tech/epi.

html). The distribution of the vector Culiseta melanura was obtained from CIESIN, available at: www.ciesin.org/

docs/001-613/001-613.html.

Key references

Davis LE, et al. (2008) North American encephalitic arbo- viruses. Neurol Clin 26(3):727–757.

Reimann CA, et al. (2008) Epidemiology of neuroinvasive

arboviral disease in the United States, 1999–2007. Am J

Trop Med Hyg 79:974–979.

Smith DW (2009) Arbovirus infections. Chapter 40 inManson’s Tropical Diseases, 22nd edn.

Weaver SC (2001) Eastern equine encephalitis. In Service MW

(ed.) The Encyclopedia of Arthropod-transmitted Infections. CAB International, pp. 151–159.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

207

Page 81 of 113

Disease: Ebola and Marburg Virus Disease

Classification: ICD-9 065.8 and 078.89; ICD-10 A98.4 and

A98.3

Syndromes and synonyms: Ebola or Marburg hemorrhagic

fever.

Agent: Ebola viruses (genus Ebolavirus), marburg viruses

(genus Marburgvirus), and ‘cueva viruses’, family Filoviridae,

order Mononegavirales; enveloped, single-stranded,

negative-sense RNA viruses. There are five ebola viruses:

Bundibugyo virus (BDBV), Ebola virus (EBOV), Reston

virus (RESTV), Sudan virus (SUDV), and Taõ Forest virus

(TAFV); two marburg viruses: Marburg virus (MARV) and

Ravn virus (RAVV); and one ‘cuevavirus’: Lloviu virus

(LLOV).

Reservoir: Ebola viruses: possibly fruit bats, unknown for

BDBV, SUDV, and TAFV; Marburg viruses: infectious MARV

and RAVV have been isolated from Egyptian fruit bats; ‘Cue- vaviruses’: Schreiber’s long-fingered bats.

Transmission: Ebola viruses: unknown route. Bats have not

yet been implicated in the initiation of ebola outbreaks. How- ever, most outbreaks are associated with the consumption or

contact with diverse non-human primates, suggesting that

transmission could occur from bats to monkeys to humans;

exposure to contaminated body fluids; by direct person-to- person contact; via injection with re-used syringes; preparing

bodies of cases for burial. Marburg viruses: most outbreaks are

associated with index cases visiting caves or working in mines.

As Egyptian fruit bats are cave animals, transmission may

occur directly from bats to humans or via contact with their

excreta and secreta; transmission between humans is similar as

for ebola virus. ‘Cuevaviruses’ are probably apathogenic for

humans.

Cycle: Not completely understood (see ‘Transmission’).

Incubation period: 2–21 days.

Clinical findings: Sudden onset of fever, chills, malaise,

myalgia, and headache, followed by pharyngitis, vomiting,

diarrhea, and a maculopapular rash. Severe cases have internal

and external hemorrhages, CNS involvement and multi-organ

failure leading to terminal shock. The case fatality rate (CFR)

varies, depending on location, virus involved, and clinical

care: 0% for RESTV and TAFV, 34% for BDBV; 78% for

EBOV, 53% for SUDV, 82% for MARV. Recovery may be

prolonged and accompanied by long term sequelae, particu- larly hearing loss. Filoviruses can persist for months and

disease may recur.

Diagnostic Tests: Must be done in BSL-4 facilities if

samples contain infectious virus. IgM ELISA, RT-PCR and

virus isolation can be used on acute specimens; in convales- cence, antibody tests; on autopsy specimens, electron micros- copy and immunohistochemistry.

Therapy: Supportive, there is no specific treatment.

Prevention: Isolation and barrier nursing of cases; discourage

butchering of wildlife that died from unknown causes and

burial practices of cases involving ritual embalming. Avoid

bat-infested caves or mines in endemic areas.

Epidemiology: Ebola viruses, except RESTV, are endemic in

the tropical rain forests of equatorial Africa. Most outbreaks

started from a single case admitted to a hospital that had

inadequate infection control, resulting in rapid nosocomial

transmission. Cases have been imported from endemic coun- tries into South Africa and Switzerland, and laboratory infec- tions have occurred in the UK and Russia.

Marburg viruses are endemic in arid woodlands of equato- rial Africa. Outbreaks are usually limited to a few cases, with

the exception of one outbreak in the DRC and Angola. Cases

have been imported into South Africa, the Netherlands, and

possibly the USA. A laboratory outbreak in 1967 in Germany

and in Yugoslavia, led to the discovery of the disease (not

shown on the map).

Map sources: The Ebola and Marburg Virus Disease map was

made with data obtained from CDC, available at: www.cdc.

gov/ncidod/dvrd/spb/mnpages/disinfo.htm.

Key references

Klenk H-D, Feldmann H (2004) Ebola and Marburg viruses:

Molecular and Cellular Biology. Wymondham, Norfolk, UK:

Horizon Bioscience.

Kuhn JH (2008) Filo viruses – A Compendium of 40 Years of

Epidemiological, Clinical, and Laboratory Studies. Archives of

Virology Supplement, Vol. 20. Vienna, Austria: Springer,

Wien, New York.

Kuhn JH, et al. (2010) Proposal for a revised taxonomy of the

family Filoviridae. Arch. Virol 155(12):2083–2103.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

209

Page 82 of 113

Disease: Hantaviral Disease, New World

Classification: ICD-9 480.8; ICD-10 B33.4

Syndromes and synonyms: Hantavirus pulmonary syn- drome (HPS), Hantavirus cardiopulmonary syndrome, Four

Corners disease.

Agents: Hantaviruses, a large group of different, enveloped,

single-stranded, negative-sense viruses with a tripartite RNA

genome, that belong to the Bunyaviridae family. Hantaviruses

that cause HPS were discovered in 1993; more than 30 new

hantaviruses have been detected since then, but not all cause

HPS.There at least 14 hantaviruses that cause HPS in the

Americas: Sin Nombre virus (SNV), Monongahela virus

(MGLV), New York virus (NYV), Bayou virus (BAYV),

Black Creek Canal virus (BCCV), Choclo virus, Andes virus

(ANDV), Bermejo virus (BMJV), Lechiguanas virus (LECV),

Maciel virus (MCLV), Oran virus (ORNV), Laguna Negra

virus (LANV), Araraquara virus, Hu39694, and Juquitiba

virus. Old World and New World hantaviruses share high

similarity in their genome and have comparable lifecycles.

Currently, there is no consensus on the classification of

hantaviruses.

Reservoir: Each hantavirus has its specific rodent host. HPS is

generally caused by the sigmodontine-borne hantaviruses.

Phylogenetic analysis reveals that hantaviruses have a long

co-evolutionary history with their host.

Transmission: By inhalation of aerosols from dried rodent

excreta (this is unlike other Bunyaviruses that are generally

arthropod-borne). Person-to-person transmission has been

reported for ANDV.

Cycle: Rodent-to-rodent though saliva, excreta and bite, with

humans as an accidental, dead-end host.

Incubation period: Typically 2 weeks (days to 6 weeks).

Clinical findings: Typically a cardiopulmonary infection as

opposed to the primarily renal infection produced by Old

World hantaviruses; renal involvement and hemorrhage are

rare in NewWorld cases. Symptoms are fever, myalgia, and GI

pain, followed by sudden onset of respiratory distress and

hypotension, with rapid progression to respiratory failure and

shock. Convalescence is prolonged. CFR is 35–60%.

Diagnostic tests: Serology (IgM ELISA, Western blot, strip

immunoblot, IFA); RT-PCR of biopsy material.

Therapy: Supportive, there is no specific treatment.

Prevention: Domestic and peridomestic rodent control,

disinfection of rodent-contaminated areas.

Epidemiology: The first hantavirus found in the New World

was Sin Nombre virus in the ‘Four Corners’ area (USA) in 1993,

where an outbreak occurred of severe pulmonary disease in

previously healthy adults. Since then, sporadic outbreaks have

been detected throughout the Americas, with new strains and

reservoir hosts. Approximately 200 cases of HPS per year are

reported in the Americas. There is no HPS in the Caribbean,

probably because the rodent host Sigmodontinae is infrequent

there. The number of cases is much smaller than that of HFRS

in the Old World, but the CFR is higher. Cases confirmed by

serology have been reported in Colombia and Venezuela but

the identity of the hantavirus unknown. Seoul virus (see

Hantavirus Disease, OldWorld map) seropositives in humans

and Rattus norvegicus are found in many port cities in the

Americas, spread by shipping, but without evidence of dis- ease. Risk of exposure to hantavirus is correlated with outdoor

occupations such as agriculture, in which a person might

encounter rodents or their excreta; the greatest risk is entering

rodent-infested closed buildings. Epidemiology differs by

country and virus. In household contacts of index patients

with HPS in Chile, the risk of secondary cases was 17.6%

among sex partners and 1.2% among other household mem- bers. Infection is more common in males, with most cases

occurring within the 20–40 age group.

Map sources: The New World Hantavirus map was made

with various sources:

CDC (www.cdc.gov/ncidod/diseases/hanta/hps/), and

C.B. Jonsson et al. (2010).

Key references

Bi Z, et al. (2008) Hantavirus infection: a review and global

update. J Infect Dev Ctries 2(1):3–23.

Jonsson CB, et al. (2010) A global perspective on hantavirus

ecology, epidemiology, and disease. Clin Microbiol Rev

23(2):412–441.

Padula PJ, et al. (2000) Genetic diversity, distribution, and

serological features of hantavirus infection in five countries

in South America. J Clin Microbiol 38:3029–3035.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

211

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Disease: Hantaviral Disease, Old World

Classification: ICD-9 078.6; ICD-10 A98.5

Syndromes and synonyms: Hemorrhagic fever with renal

syndrome (HFRS), Korean Hemorrhagic Fever, Hemorrhagic

Nephrosonephritis, Nephropathia epidemica

Agent: Hantaviruses, a large group of different, enveloped,

single-stranded, negative-sense viruses with a tripartite

RNA genome, that belong to the Bunyaviridae family. Han- taviruses are named after the Hantan River area in South

Korea, where the first hantavirus (Hantaan) was isolated in

the 1970s. Old World and New World hantaviruses share

high similarity in their genome and have comparable life

cycles. Currently, there is no consensus on the classification

of hantaviruses. Old World hantaviruses shown on the map

are: Dobrava–Belgrade virus (DOBV), Hantaan virus

(HTNV), Puumula virus (PUUV), and Saaremaa virus

(SAAV). Seoul virus (SEOV) is not shown, it is world wide

in major port cities.

Reservoir: HFRS is caused by Myodes-, Rattus-, and Apodemus- borne hantaviruses. Each virus has its particular host: Apode- mus spp. (striped field mouse) for HTNV, DOBV and SAAV

and Myodes ( Clethrionomys) for PUUV. SEOV infects Rattus

norvegicus and can therefore be found world wide.

Transmission: By inhalation of aerosols from dried rodent

excreta. Person-to-person transmission has not been reported.

Cycle: Rodent-to-rodent though saliva, excreta and bite, with

humans as an accidental, dead-end host.

Incubation period: Usually 2–4 weeks (days to 2 months).

Clinical findings: Sudden onset fever, headache, malaise,

anorexia, severe abdominal or lower back pain, often with

nausea and vomiting, followed by hypotension which may

progress to shock, hemorrhages and renal involvement, and

death. Convalescence is prolonged. PUUV virus causes less

severe disease. The CFR is 5–15% for HFRS; for PUUV and

SAAV infection the CFR is 1%; for DOBV the CFR is 9–12%.

The differential diagnosis is leptospirosis or rickettsioses.

Diagnostic tests: Serology (IgM ELISA, IFA); RT-PCR. Virus

isolation is difficult.

Therapy: Supportive; ribavirin is effective if given within the

first 6 days; dialysis if indicated.

Prevention: Domestic and peridomestic rodent control; dis- infection of rodent-contaminated areas; formalin-inactivated

HTNV vaccines are used in Russia, China and Korea.

Epidemiology: Approximately 150,000 to 200,000 patients

with HFRS are hospitalized each year throughout the

world, more than half of them in China. The main agent of

HFRS in Asia is HTNV. SEOV is also an important cause, but

has a wider distribution. The most prevalent hantaviral dis- ease in western and central Europe is caused by PUUV, with

> 9,000 cases per year. DOBV is restricted to the Balkans.

Hantaviral disease is seasonal, linked to the activity of the

rodent host. HFRS epidemics are associated with rodent abun- dance, caused by various seasonal factors. During the agricul- tural season, infection is linked to outdoor activities, and

during the winter, rodents seek shelter in and around build- ings and infection is contracted indoors. There have been

reports of clinical hantaviral infections in the UK and there

is serological evidence of human infection in Israel, Kuwait,

Laos, Malaysia, Philippines, Thailand, and Vietnam and in

several African nations.

Map sources: The Old World Hantavirus map is made

with various sources from the medical literature and

ProMED-mail.

Key references

Bi Z, et al. (2008) Hantavirus infection: a review and global

update. J Infect Dev Ctries 2(1):3–23.

Heyman P, et al. (2009) Hantavirus infections in Europe. Exp

Rev Anti Infec Ther 7(2):205–217.

Jonsson CB, et al. (2010) A global perspective on hantavirus

ecology, epidemiology, and disease. Clin Microbiol Rev

23(2):412–441.

Makary P, et al. (2010) Disease burden of Puumala virus

infections, 1995–2008. Epidemiol Infect 138(10):1484–1492.

Tersago K, et al. (2010) Hantavirus outbreak in Western

Europe. Epidemiol Infect 139(3):381–390.

Vapalahti O, et al. (2003) Hantavirus infections in Europe.

Lancet Infect Dis 3(10):653–661.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Disease: Hendra and Nipah Virus

Classification: ICD-9 078.8; ICD-10 B33.8

Synonyms: Hendra virus disease, Nipah virus disease.

Agent: Hendra virus and Nipah virus are negative-stranded

RNA viruses, and comprise the Henipavirus genus within the

family Paramyxoviridae. Hendra virus was discovered in

horses and stable staff in Australia in 1994, Nipah virus in

pigs and pig farmers in the town Nipah, Malaysia, in 1999.

Reservoir: Primarily Old World fruit-eating bats, mainly in

the family Pteropodidae.

Transmission: Hendra virus: through contact with infectious

body fluids, including urine, saliva, and nasal discharge, or

during autopsy of infected horses. Nipah virus: through con- tact with infectious body fluids, including bat saliva (on fallen

fruit and in date palm sap), or droplets from coughing infected

pigs. In Bangladesh, half of reported cases between 2001 and

2008 were due to human-to-human transmission.

Cycle: Bat to bat via unknown route. Humans and domestic

animals are incidental hosts.

Incubation period: Varying from 4 to 45 days.

Clinical findings: Hendra virus: encephalitis and pneumonia,

with a rapid progression to death (few survive). One case

recovered from encephalitis but relapsed 14 months later and

died with neurologic signs, suggesting latency and recrudes- cence. Nipah virus: encephalitis and pneumonia. There has

been a case of relapse encephalitis more than 4 years after

infection. The CFR can vary from 10 to 75%, but is generally

high.

Diagnostic tests: Virus isolation, RT-PCR, serology. Both

viruses are BSL-4 agents.

Therapy: Supportive measures such as mechanical ventila- tion. There is no specific treatment, but ribavirin may have

some effect. Monoclonal antibodies as post-exposure prophy- laxis before onset of clinical signs.

Prevention: Hendra virus: manage contact between fruit

bats and horse by basic husbandry measures such as placing

food and water points under cover, regulate movement of

horses from areas where the disease is occurring, regulate

import of horses from Australia during outbreaks. Nipah

virus: avoid contact with fruit bats and their discharges;

wash and peel fruit, and wash hands before and after prepar- ing fruit; regulate importation of pigs from outbreak areas.

Epidemiology: Hendra virus: pteropid bats are the primary

reservoir of Hendra virus and are asymptomatic. The viruses

can be isolated from their reproductive tracts and urine. The

epidemiological reasons for the emergence of Hendra virus

infection in horses are not clear. All human cases had close

contact with infected horses.

Nipah virus outbreaks have occurred only in South Asia

and may be associated with the bat-breeding season. In

Malaysia, it was hypothesized that the bats fed on fruit

trees in pig farms, and that fallen fruit contaminated with

bat saliva containing Nipah virus was eaten by pigs, who

became infected. Nipah viruses have been isolated from bats

in Cambodia and Thailand, and a high seroprevalence has

been found in fruit bats in NW India, in the absence of

reported pig or human disease. In Bangladesh, there is

epidemiologic evidence of bat–human transmission without

an intermediate livestock host, and of human–human trans- mission. Young boys who gather fruit from the trees are at

higher risk of disease. Also drinking palm sap from trees is a

potential risk factor. Antibodies to henipaviruses have been

found in fruit bats in Madagascar (Pteropus and Eidolon sp.)

and in Ghana (Eidolon sp.), but in the absence of virus isola- tion or RNA detection, it is not possible to know which virus

is involved. No human or animal cases have been reported in

Madagascar or in Africa.

Map sources: The Hendra and Nipah Virus mapwas made by

geocoding reported human cases or outbreaks in the medical

literature or reported to WHO up to 2011. The fruit bat

distribution was obtained from WHO, available at: http://

www.who.int/csr/disease/nipah/en/index.html.

Key references

Field H, et al. (2001) The natural history of Hendra and Nipah

viruses. Microbes Infect 3(4):307–314.

Hayman D, et al. (2008) Evidence of henipavirus infection in

West African fruit bats. PLoS ONE 3(7):e2739.

Montgomery JM, et al. (2008) Risk factors for Nipah virus

encephalitis in Bangladesh. Emerg Infect Dis doi 10.3201/

eid1410.060507.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

215

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Disease: Hepatitis A

Classification: ICD-9 070.1; ICD-10 B15.

Synonyms: Epidemic hepatitis, infectious hepatitis, infectious

jaundice, catarrhal jaundice.

Agent: Hepatitis A virus (HAV), a single stranded RNA virus,

genus Hepatovirus in the family Picornaviridae.

Reservoir: Humans are the main reservoir; non-human pri- mates can be infected, rarely.

Transmission: Person-to-person transmission via fecal–oral

route (hands, food, water, sexual contact).

Cycle: After ingestion, the virus infects hepatocytes, resulting

in periportal necrosis. The virus is shed via bile into the stool

and contaminates the environment, leading to new infections

in susceptible exposed individuals.

Incubation period: Commonly 28–30 days, ranging from 15

to 50 days.

Clinical findings: Fever, fatigue, anorexia, abdominal dis- comfort, nausea, vomiting, myalgia, jaundice, dark urine, and

light stools. Arthritis and rash may occur. Disease may be mild

and short-lived (several weeks) to severe and prolonged

(months), with a CFR <0.3%.

Diagnostic tests: Serology to detect specific IgM antibodies;

RT-PCR to detect viral RNA in blood or stool.

Therapy: Supportive.

Prevention: Hygiene, access to clean water, and sanitation.

An effective vaccine is available; vaccination should be offered

to high-risk groups (MSM, liver disease, travelers to endemic

areas, IVDUs, outbreaks); passive immunization with immu- noglobulins can be given as PEP within 2 weeks of the expo- sure. The virus remains viable for weeks at room temperature.

Epidemiology: Globally, there exist four patterns of HAV

infection, based on age-specific HAV seroprevalence rates.

High-endemic areas generally have low disease rates as

most infections occur in young children, who are usually

asymptomatic. Adults are immune and epidemics in these

high-endemic areas are uncommon. High-endemic areas is

defined as a region where > 90% of the children <10 years are

already infected and most cases are asymptomatic. The high- endemic areas are generally in poor regions with poor sanita- tion and lack of access to clean water (see Human Develop- ment Index map and Sanitation map). Improving living

conditions leads to intermediate endemicity, which causes

high disease rates because more infections now occur in

older people (as disease averted in children), who are symp- tomatic. HAV epidemiology in high-endemic areas is shifting

to intermediate endemicity, which results in an increase in

disease burden. Large variations exist within countries in HAV

incidence. In (very) low-endemic areas, children will not

acquire the disease and the adult population will remain

susceptible, leading to localized outbreaks. In areas of low

endemicity, the overall prevalence is <25%. In developed

countries with low endemicity, outbreaks are often caused

by contaminated food products, like shellfish, which can

concentrate virus, and other food products that are contami- nated by an infected food handler.

Map sources: The Hepatitis A map is modified from K.H.

Jacobsen et al. (2010).

Key references

Beth BP (2002) Global epidemiology of hepatitis A: implica- tions for control. Proc. 10th International Symposium on Viral

Hepatitis and Liver Disease. Jacobsen KH, et al. (2010) Hepatitis A virus seroprevalence by

age and world region, 1990 and 2005. Vaccine 28:6653–6657.

Melnick JL (1995) History and epidemiology of hepatitis A

virus. J Infect Dis 171:S2–S8.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

217

Page 86 of 113

Disease: Hepatitis B

Classification: ICD-9 070.3; ICD-10 B16 and B18.

Syndromes and synonyms: Type B hepatitis, serum hepati- tis, homologous serum jaundice, long-incubation hepatitis.

Agent: Hepatitis B virus (HBV), a DNA virus belonging to the

family of Hepadnaviridae. There are 8 genotypes (A to H) with

marked differences in disease severity. Genotypes are classi- fied by comparing complete HBV genomes. The map illus- trates the distribution of chronic HBV infection. Co-infection

with hepatitis D virus (HDV) may occur resulting in severe

chronic liver disease. HDV is a defective RNA virus that

requires HBV for replication.

Reservoir: Humans.

Transmission: Percutaneous or mucosal exposure to blood or

body fluids (e.g. semen, vaginal fluid, saliva) of an infected

individual. Person-to-person transmission via sexual contact,

needle sharing in IVDUs, sharing toothbrushes or razors, and

blood transfusion. Transmission does not occur via kissing,

coughing, or sneezing. Mother to child transmission occurs

mainly during birth or transplacentally (not via breast- feeding).

Incubation period: 2–3 months.

Clinical findings: HBV disease has an acute and chronic

form. 10% of children and 30–50% of adults present with

symptoms of acute HBV infection similar to hepatitis A and

last several weeks: fatigue, abdominal pain, nausea, vomit- ing, myalgia, jaundice, dark urine, and light stools. Fever is

often absent and arthritis and rash may be present. Chronic

disease evolves to cirrhosis or hepatocellular carcinoma and

eventually death. 90% of infants who are infected in their first

year develop chronic infection. Only 10% of adults who

acquire infection develop chronic disease, as the majority

is able to clear HBV within 6 months. Differences in disease

severity, risk of liver cirrhosis and development of hepato- cellular carcinoma are seen by age of infection, level of viral

replication, level of inflammation, region and HBV genotype.

Also co-infection with HDV leads to more severe chronic liver

disease.

Diagnostic tests: Serologic tests to assess active infection:

HBsAg, HBeAg; HBV DNA can be detected in blood by PCR;

quantitative PCR to monitor treatment.

Therapy: Supportive for acute hepatitis B. Interferon-alpha

and reverse transcriptase inhibitors for chronic hepatitis B.

Treatment response, particularly interferon treatment, differs

by HBV genotype. Treatment is expensive and often not

available in developing countries. In SoutheastAsia,medicinal

herbs are widely used to treat chronic HBV disease, of which

the efficacy is yet unclear. Liver transplant is possible for

decompensated cirrhosis.

Prevention: WHO recommends vaccination of all newborns.

In countries where prevalence is low: HBV vaccination of risk

groups and those living in endemic communities; safe sexual

practices; screening of blood products; universal precautions

when caring for patients; infection control. Vaccine and immu- noglobulins as PEP within 24 hours of exposure.

Epidemiology: Hepatitis B is a common disease world wide,

despite the existence of a vaccine. The WHO estimates that

globally 2 billion individuals have been infected, of which

about 360 million have chronic disease. Yearly, it is estimated

that there are 500,000 to 700,000 HBV associated deaths world

wide. In high-endemic regions like Southeast Asia, Africa, and

the Amazon basin, most individuals become infected during

childhood (mother-to-child, or child-to-child). In developed

regions, the prevalence is low and important routes of trans- mission are different, consisting mostly of unsafe sexual prac- tices, IVDU, and occupational transmission in healthcare

workers. Chronic HBV associated liver cirrhosis is more com- mon in developed nations than in Southeast Asia, but the

incidence of hepatocellular carcinoma is lower compared to

Southeast Asia. It is not yet fully clear whether this is due to

differences in HBV genotype or age of infection.

Map sources: The Hepatitis B Virus map is redrawn from

World Health Organization report (2001) and A. Kramvis et al

(2005).

Key references

Kramvis A, et al. (2005) Hepatitis B virus genotypes. Vaccine

23:2409–2423.

Liaw YF, et al. (2010) The natural history of chronic HBV

infection and geographical differences. Antivir Ther

15(S3):25–33.

Palumbo E (2007) Hepatitis B genotypes and response to

antiviral therapy: a review. Am J Therap 14:306–309.

World Health Organization (2001) Introduction of Hepatitis B

Vaccine into Childhood Immunization Services. Report WHO/

V&B/01.31. Geneva.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

219

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Disease: Hepatitis C

Classification: ICD-9 070.5; ICD-10 B17.1 and B18.2.

Syndromes and synonyms: Non-A non-B hepatitis, HCV

infection.

Agent: Hepatitis C virus (HCV) is an enveloped RNA virus

(hepacavirus) and belongs to theflaviviruses. The HCV genome

is highly mutable. There are at least six HCV genotypes and

several subtypes with differences in clinical presentation,

geographic distribution and treatment response. HCV was

discovered in 1989 as another cause of transfusion associated

hepatitis (non-A non-B hepatitis).

Reservoir: Humans.

Transmission: Person-to-person transmission occurs paren- tally (blood to blood). Mother to child transmission or trans- mission via sexual contact is rare. Mother to child transmission

increases if the mother is co-infected with HIV.

Incubation period: Usually 6 to 9 weeks; range from 2 weeks

to 6 months.

Clinical findings: Majority will be asymptomatic in the acute

phase, but approximately 80% develops chronic HCV disease.

Acute disease: insidious onset with right upper quadrant pain,

fatigue, nausea, malaise and vomiting; some progress to jaun- dice and dark urine. Most infected cases (approx. 80%) develop

chronic disease with fatigue as main symptom; 20–30% even- tually develop severe liver disease: cirrhosis and liver cancer

(may take 20 years and is dependent on the presence of other

risk factors). HCV infection is an important cause for liver

transplantation in developed countries. There is accelerated

progression of hepatic fibrosis and increased risk of hepato- cellular carcinoma in: men, elderly, obese, alcoholics, those

infected with HIV or hepatitis B virus.

Diagnostic tests: Serology (EIA, recombinant immunoblot

assay (RIBA)); RT-PCR on plasma; quanititative RT-PCR to

monitor treatment; genotyping; liver biopsy for histology to

assess disease stage and activity.

Therapy: Ribavirin in combination with peg-interferon.

Response to interferon differs by HCV genotype: there is a

more sustained virological response in HCV genotype 2 and

3 infections, as compared to HCV genotype1 and 4. The peg- interferon and ribavarin response can be improved by the

combination with oral DNA-polymerase and protease

inhibitors.

Prevention: Infection control hospitals; safe injection prac- tices by healthcare providers; screening of blood products;

clean needle programs. HCV immunoglobulin is not effective.

There is no vaccine.

Epidemiology: HCV infection has a worldwide prevalence of

2% and an estimated 130 to 170 million chronic cases globally.

The highest prevalences are found in Africa and Asia. Egypt

has the highest HCV prevalence rate (22%), likely due to a

national schistosomiasis treatment campaign since the 1960s

that re-used needles. In developing countries the high preva- lence is likely due to poor infection control practices in the

healthcare system (therapeutic injections, blood transfusion,

surgery). Also local practices in the community, like acupunc- ture and cutting of the skin with unsterile knives, are other

important routes of transmission. In Asia it is common to

receive injections for various illnesses outside the hospital

setting. In developed countries HCV is mainly transmitted

by IVDU, accounting for 70–80% of HCV infections.

Map sources: The Hepatitis C Virus map was made with data

obtained from WHO: the prevalence map was redrawn from

a map by the World Health Organization (2002); and the

genotype datawas obtained fromWHO (2009) (www.who.int/

vaccine_research/documents/ViralCancer7.pdf)

Key references

Khattab MA, et al. (2010) Management of hepatitis C virus

genotype 4: Recommendations of an international expert

panel. J Hepatol 54(6):1250–1262.

Munir S, et al. (2010) Hepatitis C treatment: current and future

perspectives. Virol J 7:296.

Shepard CW, et al. (2005) Global epidemiology of Hepatitis C

virus infection. Lancet Infect Dis 5:558–567.

World Health Organization (2002) Hepatitis C. Guide WHO/

CDS/CSR/LYO/2003. Geneva.

World Health Organization (2002) Map: Hepatitis C, 2001.

Weekly Epid Rep 6(77):47.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

221

Page 88 of 113

Disease: Hepatitis E

Classification: ICD-9 070.5; ICD-10 B17.2.

Syndromes and synonyms: Epidemic non-A non-B hepatitis,

fecal–oral non-A non-B hepatitis, enterically transmitted non- A non-B hepatitis.

Agent: Hepatitis E virus (HEV), a non-enveloped single- stranded RNA virus, genus Hepevirus, the single member in

the Hepeviridae family. The virus can be classified into four

genotypes (genotype HEV-1 to HEV-4), and > 24 subgeno- types (1a–1e, 2a–2b, 3a–3j, and 4a–4g). Avian isolates of HEV

are now considered to be a separate genus. HEV was discov- ered in the 1980s as a result of a large water-borne non-A non-B

hepatitis outbreak in India between 1978 and 1979.

Reservoir: Humans are the natural host. Numerous mammals

have serologic evidence of HEV disease, including but not

limited to: pigs, cattle, sheep, goats, horses, macaques, cats,

dogs, rabbits, mongoose, deer, wild boar, rats, and mice. HEV

in pigs is asymptomatic, but there is transient viremia and

excretion of virus into the environment.

Transmission: Fecal–oral route, mainly via fecally contami- nated water, but also via: food, materno-fetal, and transfusion

of blood products. Direct person-to-person transmission is uncommon. Cycle: Human to human and occasionally animal to human.

HEV is excreted from the liver into the stool via the bile and

eventually into the environment. The amount of infectious

virus in the stool is relatively low and explains a lower rate of

transmission as compared to hepatitis A (see Hepatitis A

map).

Incubation period: On average 40 days (range: 2 to 10 weeks).

Clinical findings: The disease is self-limiting and acute symp- toms are similar to acute hepatitis A disease. Children are

generally asymptomatic or have mild disease. Clinical evident

disease is more common in age group 15–44 years, with

following symptoms: fatigue, fever, nausea, vomiting, abdom- inal pain, jaundice, dark urine, and light stool. Pregnant

women are at risk for severe disease, including fulminant

hepatitis and death. In immunocompromised persons (e.g.

transplant recipients or users of immune-modulating therapy)

chronic infection has been reported.

Diagnostic tests: Serology (HEV IgM, IgG); HEV RNA

detection in blood and stool by RT-PCR.

Therapy: Supportive.

Prevention: Hygiene; access to clean water; sanitation (see

Water and Sanitation map). A vaccine has been developed and

proven effective, but is not yet available.

Epidemiology: HEV is more prevalent in areas with hot

climates and poor sanitation. Outbreaks are more common

during heavy rainfall and flooding, which leads to fecal con- tamination of the drinking water. Food-borne outbreaks also

occur, especially with contaminated shellfish. HEV genotypes

have their own geographic distribution. HEV-1 is common in

high endemic areas of Asia and Africa. HEV-2 can be found in

Mexico andWest Africa. HEV-3 has been found in rare cases in

the USA and several developed countries in Europe, Japan,

Australia, New Zealand, Korea, and Argentina. HEV-4 causes

sporadic human cases in Southeast Asia and Japan. HEV-3 and

HEV-4 are also reported in pigs on all continents, causing

sporadic disease in humans.

Map sources: The Hepatitis E map is redrawn from R.

Aggarwal et al. (2009). The data on levels of HEV endemic- ity was obtained from CDC (2009), available at: www.cdc.

gov/hepatitis/HEV.

Key references

Aggarwal R, et al. (2009) Epidemiology of Hepatitis E: current

status. J Gastroenterol Hepatol 24(9):1484–1493.

Aggarwal R (2011) Hepatitis E: Historical, contemporary

and future perspective. J Gastroenterol Hepatol 26

(Suppl. 1): 72–82.

Mushahwar IK (2008) Hepatitis E virus: molecular virology,

clinical features, diagnosis, transmission, epidemiology,

and prevention. J Med Virol 80(4):646–658.

World Health Organization (2001) Hepatitis E. Guide WHO/

CDSCSR/EDC/2001.12. Geneva.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

223

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Disease: Human Immunodeficiency Virus

Classification: ICD-9 042-044; ICD-10 B20-24

Syndromes and synonyms: VIH, SIDA, slim disease,

acquired immune deficiency syndrome (AIDS).

Agent: Human Immunodeficiency Virus (HIV), an enveloped

single-stranded RNA virus of the Lentivirus genus and Retro- viridae family, is divided into two main species HIV-1 and

HIV-2. HIV-1 is more infectious and more virulent than HIV-2

and predominates globally, with HIV-2 transmission

restricted to parts of Western and Central Africa.

Reservoir: Humans.

Transmission: HIV is transmitted through contact with HIV- infected body fluids (blood, semen, and vaginal secretions)

and is predominantly a sexually transmitted infection. Other

routes are: sharing contaminated needles; mother-to-child

transmission during pregnancy, childbirth and breastfeeding;

blood or blood product transfusion; and organ or tissue

transplantation.

Incubation period: Around 50–70% of infected individuals

develop a self-limiting ‘primary’ HIV illness 1–12 weeks after

infection. Time from infection to development of clinically

apparent immunodeficiency ranges from less than 1 year to

over 15 years.

Clinical findings: Primary HIV infection is usually a non- specific illness with fever, headache, myalgia, fatigue, and a

sore throat. Generalized lymphadenopathy and a maculopap- ular rash may occur. Following primary infection there is a

prolonged asymptomatic period before the appearance of the

clinical manifestations of a loss of immune control over infec- tious pathogens and cancers. Common presenting AIDS- defining illnesses are tuberculosis, atypical mycobacterial

infections, recurrent bacterial infections, Pneumocystis jirovecii

pneumonia, candidiasis, Kaposi sarcoma, lymphoma, crypto- coccal meningitis, and CMV disease.

Diagnostic tests: Enzyme immunoassay to detect anti- HIV antibodies with confirmation by Western blot. Fourth- generation HIV serology tests that consist of antibody

detection and p24 antigen detection in combination are now

commonly used. Also rapid tests are available for field testing.

Viral load and HIV-1 p24 antigen may be used in some

circumstances. CD4 cell counts and HIV viral load are used

to monitor progression of infection. Genotypic and phenotypic

tests are used for HIVdrug-resistance testing.

Therapy: A combination of several ARVs is recommended,

known as Highly Active Antiretroviral Therapy (HAART).

Additional strategies include prophylaxis and vaccination

against opportunistic infections, general measures to maintain

nutrition and health, and treatment of specific infections or

HIV-associated disorders.

Prevention: Reducing sexual transmission through the pro- motion ofmonogamy, condom use, male circumcision, and the

detection and treatment of STIs; raising awareness of individ- ual HIV status through voluntary counseling and testing;

protecting IVDUs through needle/syringe exchange and

methadone replacement programs; reducing mother to child

transmission through voluntary counseling and testing and

the provision of ARVs.

Epidemiology: HIV was first recognized clinically in 1981. As

of 2009, over 25 million people are estimated to have died from

HIV and around 33 million people are living with HIV.

HIV epidemics are categorized into ‘low-level’ (HIV preva- lence <1% in the general population and <5% in vulnerable

group such as MSM, injecting drug users, sex workers); ‘con- centrated’ (HIV prevalence <1% in the general population but

> 5% in at least one vulnerable group); and ‘generalized’ (HIV

prevalence > 1% in the general population). The greatest

burden of HIV continues to fall on Sub-Saharan Africa, with

68% of all people living with HIV and 72% of all HIV-related

deaths in 2009. The epidemic in Africa is, however, heteroge- neous, with high-prevalence generalized epidemics in South- ern African countries; generalized but moderate prevalence

epidemics in Central, East and West Africa, and low-level

epidemics in North Africa. No countries in Asia have a gener- alized epidemic.

HIV-1 can be divided in four groups (M, O, N, and P). Over

90% of HIV-1 infections are group M and the map opposite

shows the distribution of the 9 subtypes (clades) and recom- binants of the M group HIV-1 viruses.

Map sources: The Human Immunodeficiency Virus preva- lence map was made with UNAIDS (2009) data. The HIV-1

subtypes and recombinants map is reproduced from J. Heme- laar et al. (2006).

Key references

Joint United Nations Programme on HIV/AIDS (UNAIDS).

(2010) UNAIDS Report on the Global AIDS Epidemic 2010. ISBN 978-92-9173-871-7.

Hemelaar J, et al. (2006) Global and regional distribution of

HIV-1 genetic subtypes and recombinants in 2004. AIDS

20(16):W13–W23.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

225

Page 90 of 113

Disease: Human T-Lymphotropic Virus 1

Classification: ICD-9 202; ICD-10 B97.33 (virus), C84.1

Sezary disease, C84.5 Other and unspecified T-cell lympho- mas, C91.4 Hairy cell leukemia, C91.5 ATL.

Syndromes and synonyms: Adult T-cell leukemia/lym- phoma (ATL), T-cell lymphosarcoma, peripheral T-cell lym- phoma (Sezary disease), hairy cell leukemia, HTLV-associated

myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV- associated uveitis and infective dermatitis.

Agent: Human T-lymphotropic virus 1 (HTLV-1), a type C

retrovirus with at least 6 subtypes. The virus was isolated for

the first time in the USA in 1980, before HIV-1 (also a retrovi- rus) was discovered in 1983. Genomically, simian

T-lymphotropic virus (STLV) isolates cluster closely with

HTLV-1 in the same region, suggesting simian-to-human

transmission at multiple occasions.

Reservoir: Human.

Transmission: The virus can be transmitted from mother to

child through breast-milk; also through sexual contact, con- taminated blood products, organ transplants, and shared

syringes during iv drug use.

Incubation period: 20–30 years.

Clinical findings: The most prevalent HTLV-1 clinical man- ifestations can be divided into those associated with ATL

(immunosuppression) or associated with HAM/TSP (immu- noactivation). The HTLV-1-infected individual who immuno- logically tends to immunosuppression can develop

opportunistic infections such as Strongyloides stercoralis hyper- infection, recurrent skin infections and ATL. The HTLV-1-

infected individual who tends to immunoactivation can

develop HTLV-associated uveitis, polymyositis, inclusion

body myositis, arthritis, pulmonary infiltrative pneumonitis,

Sjogren syndrome and HAM/TSP.

Diagnostic tests: Serological tests cross-react with HTLV-2,

requiring positive ELISA to be confirmed by Western blot, IFA,

or radioimmunoprecipitation (RIPA); RT-PCR.

Therapy: Chemotherapy is ineffective for treating aggressive

forms of ATL. There is no satisfactory treatment for HAM/

TSP. Access to adequate counseling and correct information

about HTLV is of fundamental importance for HTLV-1 sero- positive individuals.

Prevention: Screening blood and blood products before use,

bottle-feeding (20% of breast-fed infants of infected mothers

become infected), using condoms. Counseling and education

of IVDUs to implement harm reduction practices.

Epidemiology: Approximately 15 to 20 million people world- wide are believed to be infected. In Africa all HTLV and STLV

subtypes are found, and phylogenetic research suggest that

HTLV-1 originated in Africa about 27,000 years ago. HTLV-1

infection is more common in women and the prevalence

increases with age, with a peak incidence around age 50.

Among HTLV-1 carriers, the lifetime risk of developing

HAM/TSP ranges from between 0.3% and 4%. For ATL,

this risk is estimated to be 1% to 5% and for HTLV-1-associated

diseases in general, including ATL, HAM/TSP, uveitis, poly- myositis and arthropathy, the lifetime risk may be close to 10%.

Japan, Africa, Caribbean islands and South America are the

areas of highest prevalence, but the reasons for this are

unknown. Most infections world wide are due to subtype

HTLV-1a. Distribution of the infection is focal, e.g. Brazil,

Japan, and Iran, where HTLV-1 is limited to certain areas of

each country. On several Japanese islands the prevalence can

reach 37%. Socioeconomic or genetic factors may contribute to

the development of HTLV-associated infective dermatitis,

since the disease has not been reported in HTLV-1 epidemic

Japan. For non-endemic areas such as Europe and North

America, HTLV-1 infection is mainly found in immigrants

from endemic areas, their offspring and sexual contacts,

among sex workers and IVDUs.

Map source(s): The HTLV-1 map was made with data from D.

U. Goncalves et al. (2010), S.A. Cooper et al. (2009), and F.A.

Proietti et al. (2005).

Key references

Cooper SA, et al. (2009) The neurology of HTLV-1 infection.

Pract Neurol 9:16–26.

Goncalves DU, et al. (2010) Epidemiology, treatment, and

prevention of human T-cellleukemia virus type 1-associated

diseases. Clin Microbiol Rev 23(3):577–589.

Proietti FA, et al. (2005) Global epidemiology of HTLV-I

infection and associated diseases. Oncogene 24:6058–6068.

Verdonck K, et al. (2007) Human T-lymphotropic virus 1:

recent knowledge about an ancient infection. Lancet Inf

Dis 7:266–281.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

227

Page 91 of 113

Disease: Japanese Encephalitis

Classification: ICD-9 062.0; ICD-10 A83.0

Syndromes and synonyms: Japanese B encephalitis.

Agent: Japanese encephalitis virus (JEV), an enveloped, sin- gle-stranded, positive sense RNA flavivirus. It is divided into

five antigenic groups and four genotypes, whichmay belinked

to differences in virulence.

Reservoir: Wading birds (Ardeidae) and domestic pigs which

amplify the virus asymptomatically; mosquitoes by transovar- ial transmission and possibly overwintering adults.

Vector: Mosquito species that breedin rice fields and marshes,

principally Culex tritaenorhynchus group; also C. gelidus and C.

vishnui. Transmission: By mosquito bite.

Cycle: Only ardeid birds and pigs have a sufficient viremia

to infect mosquitoes. The mosquito picks up the virus from the

blood of a viremic host. After a few days, the virus reaches the

salivary glands and is injected into the next host when bitten.

Humans are incidental and dead-end hosts as viremia does not

reach sufficient levels to infect mosquitoes.

Incubation period: 6–16 days.

Clinical findings: High fever with headache, chills, neck

stiffness, anorexia, nausea, and vomiting developing into

aseptic meningitis or encephalitis with disorientation, coma,

seizures, spastic paralysis, drowsiness, and stupor. Death

occurs from respiratory complications or seizures. The case

fatality rate is around 20%, but can be as high as 60%; 30% of

those who survive suffer lasting damage to the central nervous

system.

Diagnostic tests: Serology: IgM capture ELISA on serum or

CSF; antibodies can be detected in CSF after 4 days of disease

onset, and in serum after 7 days. Virus isolation or viral RNA

detection by RT-PCR are insensitive.

Therapy: Supportive, there is no specific treatment.

Prevention: Various vaccines are available; personal anti- mosquito precautions; intermittent irrigation of rice fields

disrupts vector breeding; vaccination of pigs reduces

amplification.

Epidemiology: JEV is the leading cause of viral encephalitis in

Asia: 35,000 to 50,000 cases are reported annually but this

believed to be a significant underestimate of the true disease

burden. 20–30% die and 30–50% of survivors have neurologic

or psychiatric sequelae. It is epidemic in temperate parts

of Asia, linked to the seasonal occurrence of mosquitoes,

and endemic in tropical regions of Asia due to the year- round mosquito activity. Intensification and expansion of

irrigated rice production systems in South and Southeast

Asia over the past 20 years have had an important impact

on the disease burden caused by Japanese encephalitis, since

the vectors breed in rice fields. The vectors prefer non-human

hosts, but do feed on humans in periods of peak activity. The

disease is mainly seen in children under the age of 15 and the

elderly, since most adults are immune from earlier infection;

peak age is 3–5 years. The range of JE virus has recently

expanded into the Torres Strait of northern Australia, but

the disease is rare in western Pacific islands.

Map sources: The Japanese Encephalitis map was made with

the following sources: • CDC Approximate geographic range of Japanese encephalitis,

at http://www.cdc.gov/mmwr/preview/mmwrhtml/

rr5901a1.htm#fig2 (accessed on 30/10/2010). • CDC (2010) Risk of Japanese Encephalitis by country, region

and season, at http://www.cdc.gov/ncidod/dvbid/

jencephalitis/risk-table.htm (accessed on 02/1/2010). • WHO at http://gamapserver.who.int/mapLibrary/Files/

Maps/Global_JE_ITHRiskMap.png (accessed on 26/08/

2010).

Key references

Barrett ADT (2001) Japanese encephalitis. In Service MW (ed.),

The Encyclopedia of Arthropod-transmitted Infections, CAB

International, pp. 239–246.

Center for Disease Control and Prevention (2012) Japanese

Encephalitis. Yellow Book. http://wwwnc.cdc.gov/travel/

yellowbook/2012/

Mackenzie JS, et al. (2004) Emerging flaviviruses: the spread

and resurgence of Japanese encephalitis, West Nile and

dengue viruses. Nat Med 10:S98–S109.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

229

Page 92 of 113

Disease: Lassa Fever

Classification: ICD-9 078.8; ICD-10 A96.2

Synonyms: None.

Agent: Lassa fever virus (LFV), a spherical, enveloped, bi- segmented negative strand RNA virus of the genus Arenavirus

in the family Arenaviridae.

Reservoir: The multi-mammate rat (Mastomys natalensis), which lives in houses and surrounding fields. Previous studies

that identified M. erythroleucus and M. huberti as reservoirs

may have confused the species. M. natalensis is generally

absent in coastal West Africa.

Vector: None.

Transmission: By inhalation of aerosolized excreta of the

rodent host, or contact with food or household items contami- nated with rodent excreta. Nosocomial transmission is regular

in resource-constrained settings.

Cycle: Rodent–rodent, with humans as accidental dead-end

hosts. Infected reservoir hosts are asymptomatic and excrete

infectious virus in the urine.

Incubation period: 6–21 days, usually 7–12 days.

Clinical findings: Gradual onset, malaise, fever, headache,

sore throat, cough, nausea, vomiting, diarrhea, myalgia, chest,

and abdominal pain; inflammation and exudation of the

pharynx and conjunctivae are common. Progression to multi- system disease occurs in 20% of infections, with hypotension

or shock, hemorrhage, pleural effusion, seizures, encephalop- athy and edema of the face and neck. Transient alopecia,

ataxia, and eighth cranial nerve deafness may follow; deafness

may be permanent. In third-trimester pregnant patients, 80%

have a fatal outcome and 95% of the fetuses abort. The overall

CFR is 1%, but 15–20% in more severe, hospitalized patients.

Diagnostic tests: IgM ELISA, RT-PCR, virus isolation from

blood, urine, or throat washing, seroconversion to IgG

positive.

Therapy: Supportive care; ribavirin iv is effective if given

within the first 6 days after infection. There is no vaccine.

Prevention: Rodent control in and around dwellings; infec- tion control in hospitals, with barrier nursing and precautions

to avoid contact with body fluids.

Epidemiology: LFV was isolated from a missionary nurse

living in Lassa, Nigeria, in 1969. It is estimated there are

200,000 to 300,000 symptomatic Lassa fever cases in West

Africa each year, with an associated mortality of 5,000 to

10,000. Lassa fever occurs in two geographically distinct

regions: the Mano River region (Guinea, Sierra Leone, Liberia)

in the West, and Nigeria in the East. In the dry season, the

multi-mammate rat gathers in houses, and in the rainy season,

the rat forages in the surrounding fields. Villages with Lassa

fever are all located in rain forest areas or transition zones of

rainforest to savannah, where the mean annual rainfall is

above 1,500 mm and below 3,000 mm. LFV can be transmitted

from rodents to humans both in the rainy and the dry season.

However, in the dry season there may be an increased risk for

humans due to aggregation of the rats in their houses.

Map Source: The Lassa Fever map is modified from Fichet- Calvet and Rogers (2009), with permission. Positive localities

recorded from 1965 to 2007, corresponds to confirmed Lassa

cases or studies demonstrating a seroprevalence superior to

10%.

Key references

Fichet-Calvet E, et al. (2007) Fluctuation of abundance and

Lassa virus prevalence in Mastomys natalensis in Guinea,

West Africa. Vector Borne Zoonotic Dis 7(2):119–128.

Fichet-Calvet E and Rogers D (2009) Risk maps of Lassa fever

in West Africa. PLoS Negl Trop Dis 3(3):e388.

Frame JD, et al. (1970) Lassa fever, a new virus disease of man

from West Africa. Am J Trop Med Hyg 19:670–676.

Gunther S, et al. (2004) Lassa virus. Crit Rev Clin Lab Sci

41:339–390.

Lecompte E, et al. (2006) Mastomys natalensis and Lassa fever,

West Africa. Emerg Infect Dis 12(12):1971–1974.

McCormick JB (1999) Lassa fever. In Saluzzo JF and Dodet B

(eds.), Emergence and Control of Rodent-Borne Viral Diseases. Elsevier, pp. 177–195.

Monath TP, et al. (1974) Lassa virus isolation from Mastomys

natalensis rodents during an epidemic in Sierra Leone.

Science 185:263–265.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

231

Page 93 of 113

Disease: Mayaro Fever

Classification: ICD-9 066.3; ICD-10 A92.8

Syndromes and synonyms: Uruma fever.

Agent: Mayaro virus (MAYV), an enveloped, single-stranded,

positive sense RNA virus, genus Alphavirus in the family

Togaviridae, belonging to the Semliki Forest virus complex.

Reservoir: Probably non-human primates; the virus has been

isolated from monkeys in Panama and French Guiana, also in

the USA from a north-bound migratory bird. Antibody has

been found in domestic animals and other vertebrates.

Vector: Mosquitoes, principally canopy-dwelling Haemago- gus and Sabethes spp. The virus has also been isolated from

Psorophora, Mansonia and Culex spp.

Transmission: By mosquito bite. Airborne transmission has

been reported among laboratory personnel.

Cycle: The mosquito becomes infected with MAYV during

feeding on a viremic host. The virus crosses the gut wall and

multiplies in the organs of the mosquito. After a few days,

depending on the ambient temperature, the virus reaches the

salivary glands and is injected into the next host during

feeding.

Incubation period: Approx. 1 week.

Clinical findings: Dengue-like acute febrile illness with chills,

headache, retro-orbital pain, myalgia and severe arthralgia of

the small joints of the hands and feet, sometimes nausea,

vomiting and diarrhea, painful lymphadenopathies and

often a maculopapular rash. Arthralgias may persist for

months, but no fatalities have been recorded.

Diagnostic tests: IgM ELISA; IgG cross-reacts with other

alphaviruses. Confirmation needed by neutralization test,

virus isolation, or a significant rise in specific antibody

between acute and convalescent serum samples; RT-PCR.

Therapy: Supportive.

Prevention: Since the virus has a jungle cycle, environmental

insecticide spraying is not feasible; routine personal anti-mos- quito measures are indicated.

Epidemiology: MAYV is enzootic in the humid tropical rain- forests of South America. Infections peak in the rainy season

when the mosquito vectors are most abundant. Most human

cases occur sporadically and involve persons who work or

reside in humid tropical forest; several small outbreaks of

Mayaro fever have been described in residents of rural com- munities of the Amazon region of Brazil, Bolivia, and Peru.

Travelers have imported MAYV from Surinam to the Nether- lands and from Brazil into France. The virus has been detected

in migratory birds.

Map sources: The Mayaro Fever map was made with multi- ple sources mentioned under key references.

Key references

Tesh RB, et al. (1999) Mayaro virus disease: an emerging

mosquito-borne zoonosis in tropical South America. Clin

Infect Dis 28(1):67–73.

Powers AM (2006) Genetic relationships among Mayaro and

Una viruses suggest distinct patterns of transmission. Am J

Trop Med Hyg 75(3):461–469.

Torres JR (2004) Family cluster of Mayaro fever, Venezuela.

Emerg Infect Dis 10(7):1304–1306.

Calisher CH (2001) Mayaro virus. In Service MW (ed.) The

Encyclopedia of Arthropod-transmitted Infections, CAB Inter- national, pp. 335–339.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

233

Page 94 of 113

Disease: Measles

Classification: ICD-9 9055.0; ICD-10 B05

Synonyms: Rubeola, morbilli.

Agent: Measles virus, a single-stranded RNA negative-sense

morbillivirus, family Paramyxoviridae.

Reservoir: Humans.

Transmission:By airborne droplets from or contact with nose

and throat secretions of infected persons, very high from 4

days before to 4 days after rash appears, or with fomites

contaminated with those secretions. Droplets remain infec- tious for several hours, longer under conditions of low humid- ity. Measles virus is highly contagious.

Incubation period: Median 12.5 days, range 1–3 weeks.

Clinical findings: High fever, conjunctivitis, coryza, cough,

maculopapular rash beginning on the face, spreading down- wards to reach the hands and feet. Characteristic small white

spots (Koplik spots) on the buccal mucosa. Complications may

consist of otitis media, pneumonia, laryngotracheal bronchitis

(croup), blindness, severe skin infections, severe diarrhea and

encephalitis, sometimes fatal. Complications are more com- mon and more severe in people with malnutrition, vitamin A

deficiency, and chronic diseases. Very rarely, subacute scle- rosing panencephalitis may appear years later.

Diagnostic tests: Detection by RT-PCR on blood or swabs of

nasopharyngeal mucosa; virus isolation from swabs, blood, or

urine; detection of measles specific IgM or significant rise in

antibody titer in paired samples.

Therapy: Supportive; vitamin A supplementation is impor- tant to avoid the complications of vitamin A deficiency result- ing from the infection. Efficacy of ribavirin is unproven.

Prevention: Vaccination with live attenuated virus vaccine

should be routine for children (minimum age: 12 months),

preferably with the combined measles, mumps, and rubella

vaccine (MMR), with a booster at age 4 to 6 years. Infected

children should be kept out of school and away from other

child contacts. Displaced persons (e.g. refugees) should be

vaccinated within a week of their arrival in a camp. For post- exposure prophylaxis, vaccination is recommended within 72

hours of exposure, with a booster in 5–6 weeks; human

immunoglobulin for immunocompromised persons and

those for whom vaccine is contraindicated.

Epidemiology: Measles has a worldwide distribution, but is

eliminated from the western hemisphere through vaccination.

Measles deaths world wide fell by 78% from an estimated

733,000 in 2000 to 164,000 in 2008; all regions but one have

achieved the United Nations goal of reducing measles mortal- ity by 90%, however, it remains the leading cause of vaccine- preventable deaths in children and there are fears of a resur- gence if vaccination falters for lack of resources. WHO figures

for 2008 were 282,000 reported cases, with many thousands

more unreported. Some 58% of countries have 90% or more

vaccine coverage, adequate to stop transmission, but endemic

countries have case fatality rates of up to 30% in places. Most

measles deaths ( > 95%) occur in countries with a per capita

income of <US$ 1,000. Measles-free countries still have

imported cases and limited outbreaks in subpopulations

with low or no vaccination coverage (e.g. religious communi- ties). Measles is being considered for global elimination or

even eradication.

Map sources: The Measles map was made with data obtained

from WHO, available at: www.who.int/immunization_mo- nitoring/en/.

Key references

De Quadros CA (2004) Can measles be eradicated globally?

Bull World Health Organ 82(2):134–138.

Kelly H, et al. (2009) WHO criteria for measles elimination: a

critique with reference to criteria for polio elimination. Euro

Surveill 14(50):19445.

Strebel P, et al. (2003) The unfinished measles immunization

agenda. J Infect Dis 187(Suppl. 1):S1–S7.

World Health Organization (2009) State of the World’s Vaccines

and Immunization, 3rd edn. WHO, UNICEF, World Bank.

Geneva.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

235

Page 95 of 113

Disease: Monkeypox

Classification: ICD-9 051.9; ICD-10 B04

Syndromes and synonyms: Simian variola.

Agent: Monkeypox virus (MPV), a double-stranded DNA

virus of the genus Orthopoxvirus, family Poxviridae. Two

clades of monkeypox viruses are known: the West African

virus and the Congo Basin virus. The Congo Basin strain is

more virulent than the West African strain. The MPV genome

is > 96% identical to the variola virus genome. However, MPV

is not a direct ancestor or descendent of variola virus.

Reservoir: Undetermined. Thought to be forest rodents

(squirrels, rats, mice, dormice), shrews and monkeys in the

rainforests of West and Central Africa.

Vector: None.

Transmission: By bite or direct percutaneous contact, muco- sal or respiratory exposure to blood, tissues, fluids or lesions of

infected animals. In Africa, transmission mainly occurs

through butchering infected wildlife for food. Person-to-per- son transmission probably occurs through direct contact with

infected tissue/fluid, respiratory droplet spread, and indirect

via contaminated objects.

Cycle:Animal to animal, with occasional spill over to humans.

Sustained human-to-human transmission has not been

documented.

Incubation period: 7–21 days (mean 12 days).

Clinical findings: Symptoms are similar to smallpox, but

milder: fever, headache, myalgia, backache, lymphadenopa- thy (not seen in smallpox), malaise, sore throat, cough, short- ness of breath, followed by a vesicular-pustular rash on the

face and body; the lesions eventually crust and fall off. The

outcome can be fatal (CFR: 1–10%).

Diagnostic tests: The detection of virus by culture or PCR in

characteristic skin lesions. Histopathology and immunohis- tochemistry also support the diagnosis. Laboratory testing

should be performed in specialized laboratories.

Therapy: Supportive. Cidofovir has proven anti-monkeypox

viral activity in vitro and in animal studies, but its efficacy in

patients is unknown, neither is any benefit from treatment

with vaccinia immune globulin known.

Prevention: Smallpox vaccine is protective, but not a feasible

solution in the remote forest habitat where monkeypox is

endemic. Hospital personnel should isolate patients and

take infection control precautions.

Epidemiology: MPV is endemic in heavily forested areas of

Africa, primarily of low altitude and high humidity. The

outlier in shrub country in the Sudan is anomalous ecologically

and might have been initiated by an infected traveler from the

Congo Basin region. Males and females are equally affected,

children under 15 more than adults. Comparison of active

surveillance data in one health zone in the Democratic Repub- lic of the Congo from the 1980s (0.72 per 10,000) and 2006–2007

(14.5 per 10,000) suggests a 20-fold increase in human mon- keypox incidence 30 years after mass smallpox vaccination

ceased in that country.

In 2003, multiple cases of monkeypox occurred across the

USA among persons who had contact with the excretions of

sick prairie dogs (native ground squirrels) either at a child-care

center or from pet stores. The animals had been exposed to

imported, infected West African rodents on the premises of a

distributor of exotic pets. There were more than 70 cases but no

fatalities.

Map sources: The Monkeypox map is modified with permis- sion from R.S. Levine et al. (2007) with updates from the

medical literature up to 2010.

Key references

Center for Food Security and Public Health (2009)Monkeypox.

Factsheet MNKY_2009. Damon IK, et al. (2006) Discovery of monkeypox in Sudan.

N Engl J Med 355(9):962–963.

Hutson CL, et al. (2010) Comparison of West African and

Congo Basin monkeypox viruses in BALB/c and C57BL/6

mice. PLoS ONE 5(1):e8912.

Levine RS, et al. (2007). Ecological niche and geographic

distribution of human monkeypox in Africa. PloS ONE

2(1):e176.

Rimoina AW, et al. (2010) Major increase in human monkey- pox incidence 30 years after smallpox vaccination cam- paigns cease in the Democratic Republic of Congo. Proc

Natl Acad Sci 107(37):16262–16267.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

237

Page 96 of 113

Disease: Mumps

Classification: ICD-9 072; ICD-10 B26

Syndromes and synonyms: Infectious parotitis

Agent: Mumps virus, an enveloped RNA virus of the

family Paromyxoviridae. Twelve genotypes are currently

recognized.

Reservoir: Humans

Vector: None

Transmission: Through contact with infectious respiratory

droplets or saliva.

Incubation period: Median 19 days, range 15–24 days.

Clinical findings: Up to one-third of cases are subclinical. The

illness begins with a prodrome of fever, malaise, and headache

followed by unilateral or, more commonly, bilateral tender

swelling of the parotid (parotitis) or other salivary glands.

Parotitis is present in 95% of clinical cases. Infection and

inflammation of the testicles (orchitis) occurs in up to 30%

of adult males but is rare before puberty. Orchitis results in

testicular atrophy in 50% of cases but rarely causes sterility.

Adult women may rarely suffer inflammation of the ovaries

(oophoritis). The commonest nervous system manifestation of

mumps infection is meningitis, which is seen in up to 10% of

cases but is self-limiting and does not result in death of

disability. Other rarer clinical complications include hearing

loss, encephalitis, and pancreatitis. Mumps infection in early

pregnancy may be associated with an increased risk of spon- taneous abortion.

Diagnostic tests: The detection of virus in saliva, cerebrospi- nal fluid, urine, or seminal fluid by culture or RT-PCR. Detec- tion of mumps specific IgM or significant rise in antibody titer

in paired samples.

Therapy: No specific treatment is available.

Prevention: Mumps is preventable by the use of live attenu- ated mumps virus vaccines. Various vaccine strains are avail- able and may vary in immunogenicity and the incidence of

adverse effects, such as fever, rash, parotitis, or meningitis.

Epidemiology: Studies of unvaccinated populations in some

western countries indicate that almost everyone will be

infected with mumps by adulthood; however the epidemiol- ogy of mumps is less well characterized in developing coun- tries. The true number of mumps cases is not known, since it is

often a mild disease and reported cases probably represent

fewer than 10% of all infections. There is geographic variation

in circulating mumps virus genotypes, and there can be several

genotypes circulating simultaneously in one area and shifts

over time in predominant genotypes. Mumps vaccination is

recommended at age 12–18 months and is included in the

standardimmunization program ofmost developed countries,

usually in a trivalent vaccine with measles and rubella (MMR

vaccine). A booster dose in later childhood is also recom- mended for countries with a good immunization program.

Several developed countries with a well-established mumps

vaccination program have experienced significant outbreaks

in young adults, who were too old to be included in the

childhood immunization schedule and had not been exposed

to natural infection due to an overall reduction in the trans- mission of mumps in the population. Other possible reasons

for mumps outbreaks in vaccinated populations include a

waning of vaccine-induced immunity and genotype mismatch

between the vaccine strain and the wild virus. Since the

complications of mumps are more common in affected adults

compared to affected children, a shift in the average age of

infection can lead to an increase in the number of observed

complications. However, despite these issues, it must be

remembered that comprehensive mumps vaccination pro- grams are associated with a massive overall decrease in the

burden of mumps morbidity.

Map sources: The Mumps map was made with data obtained

from WHO, available at: www.who.int/immunization_mo- nitoring/en/.

Key references

Galazka AM, et al. (1999) Mumps and mumps vaccine: a global

review. Bull World Health Org 77:3–14.

Hiivd A, et al. (2008) Mumps. Lancet 371:932–944.

World Health Organization (2009) State of the World’s Vaccines

and Immunization, 3rd edn. WHO, UNICEF, World Bank.

Geneva.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Disease: O’nyong-nyong Virus Disease

Classification: ICD-9 066.3; ICD-10 A92.1

Syndromes and synonyms: The name means ‘joint-breaker’ in the Acholi language of Africa.

Agent: O’nyong-nyong virus (ONNV), an enveloped RNA

virus, genus Alphavirus in the family Togaviridae, closely

related to chikungunya virus (CHIKV, see Chikungunya

Fever map). Strains bear the names Gulu, Igbo-Ora, and

SG650 viruses.

Reservoir: Unknown.

Vector: ONNV is transmitted by the African malaria vectors

Anopheles funestus and An. gambiae, and probably other mem- bers of the complex.

Transmission: By mosquito bite. There is no direct person-to- person transmission documented, and no evidence of congen- ital transmission.

Cycle: Humans are viremic at a titer high enough to infect

mosquitoes for up to 5 days after infection. The virus travels

from the mosquito gut to the salivary glands in 5–7 days,

depending on the ambient temperature (extrinsic incubation

period), after which it can infect another human during

feeding.

Incubation period: Estimated to be at least 8 days.

Clinical findings: Dengue-like acute febrile illness with sud- den onset fever, severe chills, severe headache, eye pain,

symmetrical polyarthralgia of all joints (as opposed to dengue,

which attacks mainly elbows and knees), generalized myalgia,

sometimes dry cough and coryza, leucopenia and often an

itching, descending morbilliform rash. Marked cervical

lymphadenitis distinguishes it from chikungunya infection.

Hemorrhagic signs have not been seen. Recovery is complete,

without sequelae.

Diagnostic tests: RT-PCR on whole blood or serum; virus

isolation; plaque reduction neutralization test (there is cross- reactivity with related viruses, including CHIKV).

Therapy: Supportive, there is no specific treatment.

Prevention: Standard anti-mosquito and anti-malarial pre- cautions. There is no vaccine.

Epidemiology:ONNV is a mutant of CHIKV that appeared in

1959 in Uganda and was spread by anopheline mosquitoes

across the malaria belt of Africa, leading to a large mosquito- borne virus epidemic. This large epidemic was remarkable

because, in spite of the occurrence of millions of cases, no

deaths were reported. It ended without a trace in 1962, reap- pearing as sporadic cases in Africa at rare intervals. In Nigeria

in 1966 and 1969, cases were described as a new virus, Igbo- Ora, later recognized as ONNV. There was a small outbreak in

Côte d’Ivoire in 1984–1985 and again in 2003, also described as

Igbo-Ora virus and a small recurrence in Uganda in 1996.

Serological evidence suggested its presence in humans in

Kenya in 1994–1995 and in horses in Nigeria, but serological

tests are subject to cross-reactions with CHIKV antibody. It is

not known how or where the virus survives between out- breaks, but sequence data show very little variation between

ONNV strains isolated in Uganda in 1959 and 1996–1997,

suggesting that the virus persists, rather than undergoing

repeated mutations from CHIKV (which has a non-human

primate reservoir).

Map sources: The O’nyong-nyong Virus Disease map was

made by visualizing countries with reported human cases

reported in the medical literature up to 2010. In case the

location of human cases is known, this is shown (red dot).

Key references

Lanciotti RS, et al. (1998) Emergence of epidemic O’nyong- nyong fever in Uganda after a 35-year absence: genetic

characterization of the virus. Virology 252:258–226.

Moore DL, et al. (1975) Arthropod-borne viral infections of

man in Nigeria, 1964–1970. Ann Trop Med Parasitol 69:49–64.

Powers AM, et al. (2000) Re-emergence of Chikungunya and

O’nyong-nyong viruses: evidence for distinct geographical

lineages and distant evolutionary relationships. J Gen Virol

81:471–479.

Woodall J (2001) O’nyong-nyong virus. In Service M (ed.) The

Encyclopedia of Arthropod-transmitted Infections. CAB Inter- national, pp. 388–390.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

241

Page 98 of 113

Disease: Oropouche Virus Disease

Classification: ICD-9 065; ICD-10 A93.0

Syndromes and synonyms: Oropouche fever, fevre de

Mojui.

Agent: Oropouche virus (OROV), a spherical enveloped,

single-stranded, negative-sense RNA virus, belonging to the

Orthobunyavirus group of the Bunyaviridae family, with 3

genotypes.

Reservoir: Monkeys, three-toed sloths (Bradypus tridactylus), marsupials, and forest birds.

Vector: During urban epidemics, biting midges (Culicoides

paraensis); also mosquitoes of Aedes and Culex genera.

Transmission: By insect bite.

Cycle: The vector becomes infected with OROV by feeding on

a viremic host. The virus crosses the gut wall and multiplies in

the organs of the insect. After a few days, depending on the

ambient temperature, the virus reaches the salivary glands and

is injected into the next host during feeding. Jungle cycle:

OROV is transmitted among sloths, marsupials, primates,

and birds by the mosquitoes Aedes serratus and Culex quinque- fasciatus. Urban cycle: OROV is transmitted to humans by

midges (Culicoides paraensis).

Incubation period: 2–14 days.

Clinical findings: Sudden onset fever (may be diphasic),

headache, myalgia, arthralgia, anorexia, dizziness, chills,

and photophobia. Also nausea, vomiting, diarrhea, epigastric

and eye pain, conjunctivitis, and meningitis have been

reported. Recently, spontaneous hemorrhagic phenomena

were reported in human cases. The disease is self-limiting,

there are no reports of OROV related deaths.

Diagnostic tests: Serology (IgM ELISA, IFA) or by detection

of OROV RNA in blood by RT-PCR.

Therapy: Supportive, there is no specific treatment.

Prevention: Personal anti-insect measures; there is no vac- cine. Removal of culicoides breeding sites in cacao husks and

felled banana trunks.

Epidemiology: OROV was first isolated in Trinidiad in 1955.

In South America, cases are limited to Trinidad, Panama, and

the Amazon basin. Oropouche fever is, after dengue fever, the

most common arboviral infection in Brazil. The virus has

periodically caused large urban epidemics in Brazil and

Peru, during which up to 60% of the population has been

affected. There also outbreaks in villages and sporadic cases.

Approximately 500,000 cases have occurred in Brazil since the

1960s. There are three OROV genotypes circulating in Brazil:

genotypes I and II in the Amazon Basin and genotype III in the

Southeast Region. Genotype III has been isolated from a

marmoset (Callithrix species) in southeastern Brazil, and

also occurs in Panama. Outbreaks coincide with periods of

highest rainfall, when biting midge density is greatest. OROV

infections are likely underdiagnosed in South America as was

seen during a concurrent outbreak of dengue virus and OROV

in Manus (Brazil), where OROV infections were missed by

physicians and the Public Health Authority.

Map sources: The Oropouche Virus Disease map was made

by geocoding human outbreaks that were reported between

1955 and 2010 in the medical literature and ProMED mail.

Key references

Azevedo RSS, et al. (2007) Reemergence of Oropouche Fever,

Northern Brazil. Emerg Infect Dis 13(6):912–915.

Bernardes-Terzian AC, et al. (2009) Sporadic oropouche virus

infection, acre, Brazil. Emerg Infect Dis 15(2):348–350.

Mellor PS. (2001) Oropouche virus. In Service MW (ed.) The

Encyclopedia of Arthropod-transmitted Infections, CAB Inter- national, pp. 391–399.

Mourao MPG, et al. (2009) Oropouche fever outbreak,

Manaus, Brazil, 2007–2008. Emerg Infect Dis. Available

from: http://www.cdc.gov/EID/content/15/12/2063.htm.

Nunes MR, et al. (2005) Oropouche virus isolation, southeast

Brazil. Emerg Infect Dis 11(10):1610–1613.

Saeed MF (2000) Nucleotide sequences and phylogeny of the

nucleocapsid gene of Oropouche virus. J Gen Virol

81:473–478.

Vasconcelos HB (2009) Oropouche fever epidemic in Northern

Brazil: Epidemiology and molecular characterization of

isolates. J Clin Virol 44:129–133.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

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Disease: Poliomyelitis

Classification: ICD-9 045; ICD-10 A80

Syndromes and synonyms: Polioviral fever, infantile paraly- sis, acute flaccid paralysis (AFP), bulbar polio.

Agent: Poliovirus, an RNA enterovirus with three types; type

1 cases are most common, followed by type 3; wild type 2

disappeared in 1999. Rare cases of all three types occur in

unimmunized contacts of children vaccinated with the Sabin

live attenuated vaccine.

Reservoir: Humans, generally children with inapparent

infections.

Transmission: Oro-fecal. 100% of susceptible contacts

become infected. Virus appears in the throat < 36 hours

after infection, for a week, and in the feces after 72 hours

for 3–6 weeks. Transmission through contaminated water and

food has been reported rarely.

Incubation period: 3–35 days; 6–20 for paralytic cases.

Clinical findings: Less than 1% of infections result in acute

flaccid paralysis, with around 90% of infections being subclin- ical. In 10% symptoms may include fever, malaise, headache,

neck stiffness, pain in the limbs, nausea, and vomiting. Paral- ysis persists in 0.1–1.0% depending on the virulence of the

strain. The flaccid paralysis is usually asymmetric and in one

leg. The risk of paralysis is increased by intramuscular injec- tions, immune-compromised state, trauma or surgery (tonsil- lectomy), and intense physical activity during the incubation

period. Also adults are at greater risk of developing paralysis

than young children. Aseptic meningitis occurs in around 1%

of infections. More severe paralysis with quadriplegia and

breathing problems (bulbar polio) may occur.

Diagnostic tests: Virus isolation from stool, CSF or oropha- ryngeal secretion, followed by typing (to determine if the

virus is ‘wild type’ or a vaccine strain). Alternatively, the

diagnosis can be established by serological testing.

Therapy: Supportive, there is no specific polio treatment.

Prevention: In 1988, the WHO launched the Global Polio

Eradication Initiative (GPEI). The Americas were certified

polio-free in 1994, the WHO Western Pacific Region in 2000

and Europe in 2002 (in 2010, there was importation of polio

into Europe). The GPEI has four main strategies to stop

transmission of the wild poliovirus: (1) high infant immuniza- tion coverage with four doses of oral poliovirus vaccine (OPV)

in the first year of life; (2) supplementary doses of OPV to all

children under 5 years of age during SIAs; (3) surveillance for

wild poliovirus through reporting and laboratory testing of all

acute flaccid paralysis (AFP) cases among children under 15

years of age; (4) targeted campaigns once wild poliovirus

transmission is limited to a specific focal area. To be certified

polio-free, three conditions must be met: (1) there are at least 3

years of zero polio cases due to wild poliovirus; (2) disease

surveillance efforts in countries meet international standards;

and (3) each country must illustrate the capacity to detect,

report, and respond to ‘imported’ polio cases. Oral live atten- uated polio vaccines can give rise to circulation of vaccine- derived polioviruses and rare cases of vaccine-associated

paralytic poliomyelitis. For this reason, efforts are underway

to develop affordable options for inactivated polio

vaccination.

Epidemiology: Since the Global Polio Eradication Initiative,

cases have decreased significantly. There were 1,292 reported

cases in 2010, of which only 232 were in the endemic countries

Afghanistan, India, Nigeria, and Pakistan. In endemic coun- tries most cases are children aged <3 years. In 2009–2010, 23

previously polio-free countries were re-infected due to impor- tation of the virus, notably hundreds of cases in Tajikistan.

Most reported polio cases in 2010 (n 1,060) were in non- endemic countries. Polio transmission seems to have been re- established in Chad, Angola, Sudan, and the DRC. This illus- trates the difficulties of the global polio eradication program.

Risk is seasonal in the temperate climates, with highest risks

during the warmer months.

Map sources: The Poliomyelitis map was made with data

obtained from the Global Polio Eradication Initiative, available

at: www.polioeradication.org.

Key references

World Health Organization (2010) Poliomyelitis. Factsheet

Nr 114 (www.who.int).

Dutta A (2008) Epidemiology of poliomyelitis – options and

update. Vaccine 26(45):5767–5773.

Nathanson N, et al. (2010) From emergence to eradication: the

epidemiology of poliomyelitis deconstructed. Am J Epide- miol 172(11):1213–1229.

Atlas of Human Infectious Diseases, First Edition. Heiman F.L. Wertheim, Peter Horby and John P. Woodall.

2012 Blackwell Publishing Ltd. Published 2012 by Blackwell Publishing Ltd.

245

Page 100 of 113

Disease: Rabies

Classification: ICD-9 071; ICD-10 A82

Syndromes and synonyms: Hydrophobia, furious rabies,

paralytic (dumb) rabies, classic rabies, non-classic rabies