Systemic fungal infections


Histoplasmosis is caused by Histoplasma capsulatum, a non-encapsulated, dimorphic fungus. Spores can survive in moist soil for several years, particularly when it is enriched by bird and bat droppings. Histoplasmosis occurs worldwide and is commonly seen in Ohio and the Mississippi river valley. Transmission is mainly by inhalation of the spores.


 summarizes the pathogenesis, main clinical forms and sequelae of Histoplasma infection.
PRIMARY PULMONARY HISTOPLASMOSIS is usually asymptomatic. The only evidence of infection is conversion of a histoplasmin skin test from negative to positive, and radiological features similar to those seen with the Ghon primary complex of tuberculosis. Calcification in the lungs, spleen and liver occurs in patients from areas of high endemicity. When symptomatic, primary pulmonary histoplasmosis generally presents as a mild influenza-like illness, with fever, chills, myalgia andcough. The systemic symptoms are pronounced in severe disease. Complications such as atelectasis, secondary bacterial pneumonia, pleural effusions, erythema nodosum and erythema multiforme may also occur.

HRONIC PULMONARY HISTOPLASMOSIS is clinically indistinguishable from pulmonary tuberculosis  . It is usually seen in white males over the age of 50 years. Radiologically, pulmonary cavities, infiltrates and characteristic fibrous streaking from the periphery towards the hilum are seen.

Histoplasma lnfectlon=summary of pathogenesis, main clinical forms and sequelae.
Histoplasma lnfectlon=summary of pathogenesis,
main clinical forms and sequelae.

DISSEMINATED HISTOPLASMOSIS resembles disseminated tuberculosis clinically. Fever,  ymphadenopathy, hepatosplenomegaly, weight loss, leucopenia and thrombocytopenia are common. Rarely, features of meningitis, hepatitis, Addison’s disease, endocarditis and peritonitis
may dominate the clinical picture.


Definitive diagnosis is possible only by culturing the fungi or by demonstrating them on histological sections. The histoplasmin skin test is usually positive. Antibodies usually develop within 3 weeks of the onset of illness and are best detected by the complement-fixation test. Titres above 1 : 32 are suggestive of Histoplasma infection. Agar gel diffusion and latex agglutination antibody tests may also be helpful.


Only severe acute pulmonary histoplasmosis, chronic histoplasmosis and acute disseminated histoplasmosis require therapy. Intravenous amphotericin 0.5- 0.6 mg kg-l daily or 1.0-1.2 mg kg-Ion alternate days for 10 weeks is the mainstay of therapy. The less toxic antifungal agent ketoconazole is effective, as are the newer agents itraconazole and fluconazole. Surgical excision of histoplasmomas (pulmonary granuloma due to H. capsulatum) or chronic cavitatory lung lesions and release of adhesions following mediastinitis is often required.

African histoplasmosis

African histoplasmosis is caused by Histoplasma duboisii, the  pores of which are larger than those of H. capsulatum. Skin lesions, e.g. bscesses, nodules, lymph node involvement and lytic bone lesions are prominent. Pulmonary lesions do not occur. Treatment is  imilar to that for H. capsulatum infection.


Aspergillosis is caused by several species of dimorphic fungi of the genus Aspergillus. Of these, A. fumigatus is the commonest cause of disease in humans, although A. flavus and A. niger have also been implicated as pathogens. These fungi are ubiquitous in the environment and are commonly found on decaying leaves and trees. Humans are infected by inhalation of the spores. Disease manifestation depends on the dose of the spores inhaled as well as the immune response of the host. Three major forms of the disease are recognized:
1 Bronchopulmonary allergic aspergillosis, with symptoms suggestive of bronchial asthma. 2 Aspergilloma, sometimes referred to as a pulmonary mycetoma.
3 Fulminant disease, which occurs in immunosuppressed patients, presenting as acute pneumonia, meningitis or an intracerebral abscess, lytic bone lesions, and granulomatous lesions in the liver; less commonly endocarditis, paranasal Aspergillus granuloma or keratitis may occur. Urgent treatment with intravenous amphotericin is required.


Cryptococcosis is caused by the yeast-like fungus, Cryptococcus neoformans. It has a worldwide distribution and appears to be spread by birds, especially pigeons, in their droppings. The spores gain entry into the body through the respiratory tract, where they elicit a granulomatous reaction. Pulmonary symptoms are, however, uncommon and meningitis, which is clinically indistinguishable from bacterial meningitis, is the usual mode of presentation. Lung cavitation, hilar lymphadenopathy, pleural effusions and occasionally pulmonary fibrosis occur. Less commonly, the skin and bones are involved.


This is established by demonstrating the organisms in appropriately stained tissue sections. A positive latex cryptococcal agglutinin test performed on the CSF is diagnostic of cryptococcosis.


Amphotericin (0.3-0.5 mg kg-l daily i.v.) alone or in combination with flucytosine (100-200 mg kg-l daily) has reduced the mortality of this once always fatal condition. Therapy should be continued for 3 months if meningitis is present. Fluconazole has greater CSF penetration and is likely to become the treatment of choice.


Coccidioidomycosis is caused by the non-budding spherical form (spherule) of Coccidioides immitis. This is a soil saprophyte and is found in the southern USA, Central America and parts of South America. Humans are infected by inhalation of the thick-walled barrel-shaped spores called arthrospores. Occasionally epidemics of coccidioidomycosis have been documented following dust storms.


The majority of patients are asymptomatic. Infection is detected by the conversion of a skin test using either coccidioidin (extract from a culture of mycelial growth of C. immitis) or spherulin (the soluble fraction from a culture of C. immitis spherules) from negative to positive. Acute pulmonary coccidioidomycosis presents, after an incubation period of about 10 days, with fever, malaise, cough and expectoration. Erythema nodosum, erythema multiforme, phlyctenular conjunctivitis and, less commonly, pleural effusions may occur. Complete recovery is usual. Pulmonary cavitation with haemoptysis, pulmonary fibrosis, meningitis, lytic bone lesions, hepatosplenomegaly, and skin ulcers and abscesses may occur in severe disease.


Because of the high infectivity of this fungus, and consequent risk to laboratory personnel, serological tests (rather than culture of the organism) are widely used for diagnosis. These include the highly specific latex agglutination and precipitin tests. A positive complement-fixation test performed on the CSF is diagnostic of coccidioidomycosis meningitis.


Mild pulmonary infections are self-limiting and require no treatment, but progressive and disseminated disease requires urgent therapy. Amphotericin is the drug of choice. Surgical excision of cavitatory pulmonary lesions or localized bone lesions may be necessary. For meningitis, intrathecal amphotericin may be required; the role of steroids remains controversial. Ketoconazole or miconazole can be of value.

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