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Chapter 3Infectious Diseases Related To Travel
Histoplasmosis
Monika Roy, Tom M. Chiller
INFECTIOUS AGENT
Histoplasma capsulatum is a dimorphic fungus that grows as a mold in soil and as a yeast in animal and human hosts, as an intracellular pathogen.
MODE OF TRANSMISSION
Histoplasma is acquired via inhalation of spores (conidia) from soil contaminated with bat guano or bird droppings. Histoplasmosis is not transmitted directly from person to person.
EPIDEMIOLOGY
In the United States, H. capsulatum var. capsulatum is primarily found along the Ohio and Mississippi River Valleys, mostly in the central and southeastern states. Its occurrence has been described on every continent except Antarctica. Indigenous human cases have been reported throughout North, Central, and South America; the Caribbean; parts of the Middle East (Iran and Turkey); parts of Asia (Pakistan, India, China, Thailand, Indonesia, Vietnam, Malaysia, Philippines, Burma, and Japan); parts of Europe (northern Italy, Bulgaria, Spain, Hungary, Austria, France, Portugal, Romania, the countries of the former Soviet Union, Great Britain, Ireland, and Norway); parts of Africa; and Australia. H. capsulatum var. duboisii, also known as African Histoplasma, is found in central and western Africa.
Overall, histoplasmosis is rare among returning travelers. GeoSentinel surveillance data on illness in returning travelers showed that <0.5% of travelers presenting ill to clinics were diagnosed with histoplasmosis. However, exposures that lead to clusters of cases with attack rates of >50% are reported yearly.
People of all ages who visit endemic areas and are exposed to accumulations of bat guano or bird droppings are at increased risk for infection. Not all sources of exposure are obvious when visiting endemic areas; however, activities such as spelunking, mining, construction, excavation, demolition, roofing, chimney cleaning, farming, gardening, and installing heating and air-conditioning systems are associated with histoplasmosis. While in caves or mines, spending time close to the ground or kicking up dirt infested with bat guano containing H. capsulatum can increase the risk of infection. Other risk-prone activities may become better recognized as ecotourism and adventure tourism become more common in endemic areas of Central and South America.
CLINICAL PRESENTATION
The incubation period is typically 3–17 days. Ninety percent of infections are asymptomatic or result in a mild influenzalike illness. Some infections may cause acute pulmonary histoplasmosis, manifested by high fever, headache, nonproductive cough, chills, weakness, pleuritic chest pain, and fatigue. In general, severity of illness depends on the number of conidia inhaled, as well as the immune status of the host. Most people spontaneously recover 2–3 weeks after onset of symptoms, although fatigue may persist longer.
Dissemination, especially to the gastrointestinal tract and central nervous system, can occur in people who are immunocompromised (including patients with HIV/AIDS, hematologic malignancies, solid organ transplants, and tumor necrosis factor antagonist use). Dissemination may occur acutely or chronically as part of a clinical pattern known as progressive disseminated histoplasmosis. Other less common, chronic clinical patterns include chronic pulmonary histoplasmosis and mediastinitis. Reinfection can occur with sufficient exposure, and in these people, the incubation period can be shorter.
DIAGNOSIS
Culture of H. capsulatum from bone marrow, blood, sputum, and tissue specimens is the definitive method of diagnosis. Blood should be cultured by using a lysis-centrifugation method. Yield for this diagnostic is highest for patients with acute pulmonary, chronic pulmonary, and disseminated histoplasmosis.
Demonstration of the typical intracellular yeast forms by microscopic examination strongly supports the diagnosis of histoplasmosis when clinical, epidemiologic, and other laboratory studies are compatible. Yield for this method is highest for patients with acute pulmonary and disseminated histoplasmosis.
An EIA antigen detection test on urine, serum, plasma, bronchoalveolar lavage, or cerebrospinal fluid is a rapid, commercially available diagnostic test. The yield for an EIA antigen detection test is highest for severe, acute pulmonary infections and for progressive disseminated infections. It often is transiently positive early in the course of acute, self-limited pulmonary infections. A negative test does not exclude infection.
Serologic testing for antibodies is also available; however, these tests should be interpreted by an expert. Yield for serologic tests is highest for patients with subacute or chronic pulmonary infections. They are not useful for acute cases or patients with HIV.
TREATMENT
Antifungal treatment is not usually indicated for healthy, immunocompetent people with acute, localized pulmonary infection, because this form of the disease is self-limited, often resolving within 3 weeks. People with persistent symptoms beyond 1 month can be treated with itraconazole for mild to moderate illness or amphotericin B for severe infection. All people with more extensive disease, including diffuse pulmonary and disseminated histoplasmosis, should be treated with either itraconazole or amphotericin B based on illness severity. People with immunocompromising conditions and other chronic disease may require prolonged treatment. Consultation with an infectious disease specialist is advised.
PREVENTIVE MEASURES FOR TRAVELERS
No vaccine is available. People at increased risk for severe disease should be advised to avoid high-risk areas, such as bat-inhabited caves. If exposure cannot be avoided, travelers should be advised to decrease dust generation in infested areas by watering the areas and to wear masks and special protective equipment.
After engaging in high-risk activities, hosing off footwear, and placing clothing in airtight plastic bags to be laundered could also decrease the potential for exposure. Further detail about protective equipment can be obtained from www.cdc.gov/niosh/docs/2005-109. Soil, guano, and other potential fomites should not be transported.
BIBLIOGRAPHY
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- Cano MV, Hajjeh RA. The epidemiology of histoplasmosis: a review. Semin Respir Infect. 2001 Jun;16(2):109–18.
- CDC. Cave-associated histoplasmosis—Costa Rica. MMWR Morb Mortal Wkly Rep. 1988 May 27;37(20):312–3.
- CDC. Outbreak of histoplasmosis among travelers returning from El Salvador—Pennsylvania and Virginia, 2008. MMWR Morb Mortal Wkly Rep. 2008 Dec 19;57(50):1349–53.
- Freedman DO, Weld LH, Kozarsky PE, Fisk T, Robins R, von Sonnenburg F, et al. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med. 2006 Jan 12;354(2):119–30.
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- Morgan J, Cano MV, Feikin DR, Phelan M, Monroy OV, Morales PK, et al. A large outbreak of histoplasmosis among American travelers associated with a hotel in Acapulco, Mexico, spring 2001. Am J Trop Med Hyg. 2003 Dec;69(6):663–9.
- Nasta P, Donisi A, Cattane A, Chiodera A, Casari S. Acute histoplasmosis in spelunkers returning from Mato Grosso, Peru. J Travel Med. 1997 Dec 1;4(4):176–8.
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- Valdez H, Salata RA. Bat-associated histoplasmosis in returning travelers: case presentation and description of a cluster. J Travel Med. 1999 Dec;6(4):258–60.
- Weinberg M, Weeks J, Lance-Parker S, Traeger M, Wiersma S, Phan Q, et al. Severe histoplasmosis in travelers to Nicaragua. Emerg Infect Dis. 2003 Oct;9(10):1322–5.
- Wheat LJ. Histoplasmosis: a review for clinicians from non-endemic areas. Mycoses. 2006 Jul;49(4):274–82.
- Wheat LJ. Improvements in diagnosis of histoplasmosis. Expert Opin Biol Ther. 2006 Nov;6(11):1207–21.
- Wheat LJ. Laboratory diagnosis of histoplasmosis: update 2000. Semin Respir Infect. 2001 Jun;16(2):131–40.
- Wheat LJ, Freifeld AG, Kleiman MB, Baddley JW, McKinsey DS, Loyd JE, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807–25.
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