Tom Chiller

Infectious Agent

Histoplasma capsulatum is a dimorphic fungus growing 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.

Occurrence

• In the United States, H. capsulatum is 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.
• Histoplasmosis is not transmitted directly from person to person.

Risk for Travelers

• Overall, histoplasmosis is rare among returning travelers.
• GeoSentinel surveillance data on illness in returning travelers showed that fewer than 0.5% of travelers presenting ill to clinics were diagnosed with histoplasmosis.
• Persons 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, high-risk activities such as spelunking, mining, construction, excavating, demolishing, roofing, chimney cleaning, farming, gardening, and installing heating and air-conditioning systems are known to be 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 understood as ecotourism and adventure tourism become more common in endemic areas of Central and South America.

Clinical Presentation

• Incubation period is typically 3–17 days.
• Ninety percent of infections are asymptomatic or result in a mild influenza-like illness.
• Some infections may cause acute pulmonary histoplasmosis, manifested by high fever, headache, nonproductive cough, chills, weakness, pleuritic chest pain, and fatigue.
• Most persons 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 persons with severe immunocompromising conditions (e.g., HIV infection). Reinfection can occur with sufficient exposure, and in these individuals, the incubation period can be shorter.

Diagnosis

• Culture of Histoplasma capsulatum from bone marrow, blood, sputum, and tissue specimens is the definitive method of diagnosis.
• 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.
• An antigen detection test used on urine and serum is a rapid, commercially available diagnostic test. Antigen detection is most sensitive 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; these tests should be interpreted by an expert.

Treatment

• Antifungal treatment is not usually indicated for healthy, immunocompetant persons with acute, localized pulmonary infection, because this form of the disease is self-limited, often resolving within 3 weeks.
• Persons with persistent symptoms beyond 1 month can be treated with itraconazole or Amphotericin B.
• All persons with severe disease, including diffuse pulmonary and disseminated histoplasmosis, should be treated with either itraconazole or Amphotericin B.
• Persons with immunocompromised conditions and other chronic diseases may require prolonged treatment.
• Consultation with an infectious disease specialist is advised.

Preventive Measures for Travelers

• No vaccine is available.
• Persons at increased risk for severe disease should be advised to avoid high-risk areas, such as bat-inhabited caves.
• If exposure cannot be avoided, persons should be advised to decrease dust generation in infested areas by watering the areas before engaging in dust-generating activities 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 details about protective equipment can be obtained from www.cdc.gov/niosh/docs/2005-109/.
• Transportation of soil, guano, and other potential fomites should be avoided.

References

1. Buxton JA, Dawar M, Wheat LJ, et al. Outbreak of histoplasmosis in a school party that visited a cave in Belize: role of antigen testing in diagnosis. J Travel Med. 2002;9(1):48–50.
2. Cano MVC, Hajjeh RA. The epidemiology of histoplasmosis: a review. Semin Respir Infect. 2001;16(2):109–18.
3. CDC. Cave-associated histoplasmosis—Costa Rica. MMWR Morb Mortal Wkly Rep. 1988;37(20):312–3.
4. Freedman DO, Weld LH, Kozarsky PE, et al; GeoSentinel Surveillance Network. Spectrum of disease and relation to place of exposure among ill returned travelers. N Engl J Med. 2006;354(2):119–30.
5. Morgan J, Cano MV, Feikin DR, et al.; Acapulco Histoplasmosis Working Group. A large outbreak of histoplasmosis among American travelers associated with a hotel in Acapulco, Mexico, spring 2001. Am J Trop Med Hyg. 2003;69(6):663–9.
6. Nasta P, Donisi A, Cattane A, et al. Acute histoplasmosis in spelunkers returning from Mato Grosso, Peru. J Travel Med. 1997;4(4):176–8.
7. Panackal AA, Hajjeh RA, Cetron MS, et al. Fungal infections among returning travelers. Clin Infect Dis. 2002;35(9):1088–95.
8. Valdez H, Salata RA. Bat-associated histoplasmosis in returning travelers: case presentation and description of a cluster. J Travel Med. 1999;6(4):258–60.
9. Weinberg M, Weeks J, Lance-Parker S, et al. Severe histoplasmosis in travelers to Nicaragua. Emerg Infect Dis. 2003;9(10):1322–5.
10. Wheat LJ. Laboratory diagnosis of histoplasmosis: update 2000. Semin Respir Infect. 2001;16(2):131–40.
11. Wheat LJ. Histoplasmosis: a review for clinicians from non-endemic areas. Mycoses. 2006;49(4):274–82.
12. Wheat J, Freifeld AG, Kleiman MB, 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;45(7):807–25.