African Histoplasmosis
Also known as: Histoplasma duboisii Infection, Histoplasmosis duboisii
African histoplasmosis is caused by Histoplasma capsulatum variety duboisii, which is endemic in tropical Africa. It differs from classic histoplasmosis in its large yeast form and in its predominantly cutaneous, subcutaneous, lymph node, and bone disease with relatively little lung involvement.
It occurs in immunocompetent people, and also in the immunosuppressed, in whom disseminated disease resembles that of the classic form. Histoplasma capsulatum variety capsulatum also occurs in Africa, so both varieties cause disease on the continent, and their separation is based on yeast morphology and molecular typing.
| Feature | Description |
|---|---|
| Dimorphism | Mould at 25 to 30 degrees Celsius, and yeast at 37 degrees Celsius |
| Yeast in tissue | Large (8 to 15 micrometres), oval to lemon shaped, thick walled yeasts with a broad based bud, in macrophages and giant cells, often extracellular, and often in clusters; arranged in chains and as "figure of eight" forms |
| Mould phase | Indistinguishable from variety capsulatum, with tuberculate macroconidia; it grows more slowly |
| Taxonomy | An African clade within the species complex, with genetic separation from the other clades |
| Culture | 2 to 6 weeks on Sabouraud dextrose agar and enriched media, with biosafety precautions |
The disease is reported mainly in West and Central Africa (Nigeria, Cameroon, Senegal, Mali, Democratic Republic of the Congo, Uganda, and Zimbabwe), East Africa, and Madagascar, and the risk map is poorly defined. The reservoir is thought to be soil, bat guano, and bird droppings, although the ecology of the duboisii variety is less studied. Disease affects children and adults, with a male predominance in some series, and cases are seen in HIV, though less often than classic histoplasmosis. Imported cases occur in returned travellers and migrants.
| Form | Features |
|---|---|
| Cutaneous | The commonest; papules, nodules, pustules, ulcers, and plaques, often resembling molluscum contagiosum, with umbilication and crusting; lesions are on the face, trunk, and limbs, and heal with scarring |
| Subcutaneous | Cold abscesses, painless and fluctuant, that drain through sinuses |
| Osteoarticular | About 30 to 50 percent; lytic lesions of the skull, ribs, vertebrae, sternum, and long bones, often with adjacent cold abscesses and draining sinuses, and joint involvement; a radiographic picture similar to tuberculosis and tumour |
| Lymph node | Painless regional or generalised lymphadenopathy, with suppuration |
| Pulmonary | Uncommon; nodules, infiltrates, and cavities |
| Disseminated | Fever, weight loss, hepatosplenomegaly, lymphadenopathy, pancytopenia, and widespread skin and bone lesions; mortality of 50 percent or higher when untreated |
| Other | Gastrointestinal, adrenal, oral and genital ulcers, and rarely central nervous system disease |
| Condition | Points that separate it |
|---|---|
| Cryptococcosis | Capsule on India ink, mucicarmine positive, antigen positive |
| Blastomycosis | Broad based bud 8 to 15 micrometres, thick double contoured wall, mostly extracellular |
| Paracoccidioidomycosis | Multiple budding "ship wheel" yeasts |
| Talaromycosis | Yeasts with a central septum (fission) in cells; red pigment in culture |
| Emergomycosis | Small yeasts with narrow based budding; culture and sequencing |
| Tuberculosis (lupus vulgaris, scrofuloderma, bone disease) | Acid fast bacilli |
| Molluscum contagiosum | Inclusion bodies |
| Leishmaniasis | Amastigotes |
| Yaws, sporotrichosis, leprosy, and tumour | Biopsy |
| Osteomyelitis from bacteria | Culture |
| Test | Details |
|---|---|
| Microscopy | Pus, aspirates, scrapings, and biopsy with Giemsa, methenamine silver, and periodic acid Schiff show large yeasts of 8 to 15 micrometres with broad based budding |
| Histology | Granulomas with many multinucleate giant cells that contain yeasts, with necrosis and neutrophils |
| Culture | Slow; confirmation of the mould and conversion; sequencing |
| Antigen | The enzyme immunoassay for Histoplasma antigen may give lower sensitivity than for classic disease, and a negative test does not exclude disease in localised forms; a positive test supports the diagnosis |
| Serology | Variable sensitivity and cross reactivity |
| Molecular tests | Polymerase chain reaction and sequencing for confirmation |
| Imaging | Radiographs and computed tomography for bone lesions and chest involvement; abdominal ultrasound |
| HIV test | Required in all patients |
| Form | Regimen |
|---|---|
| Severe or disseminated disease, and progressive disease in HIV | Liposomal amphotericin B 3 mg per kg intravenously once daily (or deoxycholate 0.7 to 1 mg per kg once daily where liposomal is not available) for 1 to 2 weeks or until clinical improvement, then itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily |
| Localised cutaneous, lymph node, and mild disease | Itraconazole 200 mg twice daily after a 3 day loading period of 200 mg three times daily, for 6 to 12 months |
| Osteoarticular disease | Itraconazole for 12 months or longer, and surgery (drainage or curettage) for abscesses and sequestra |
| Alternatives | Fluconazole 400 to 800 mg daily is less effective and is used when itraconazole is not available, with relapse risk; voriconazole and posaconazole as salvage |
| HIV | Antiretroviral therapy within 2 weeks of the start of antifungal therapy, and maintenance itraconazole 200 mg daily until immune recovery |
| Monitoring | Clinical response, itraconazole levels (at least 1 microgram per mL), liver tests, and follow up for at least 12 months for relapse |
Most data come from case series and the experience with the classic form, so the regimens are extrapolated from that disease, and the duration of treatment is empirical.
Localised cutaneous and bone disease has a good response, with relapse after short courses. Disseminated disease is lethal without therapy and has a high mortality where amphotericin B and itraconazole are not available. No effective preventive measure is established beyond avoidance of caves and guano. Improvement in access to antifungal drugs and diagnostics is the key public health need.
