HIV-associated histoplasmosis — DTM&H MCQ

Correct answer: C — Disseminated histoplasmosis

The correct answer is C, disseminated histoplasmosis. The vignette describes a classic AIDS-defining presentation in Central America (a recognised Histoplasma capsulatum endemic region), with fever, weight loss, hepatosplenomegaly and pancytopenia from bone marrow involvement, and the positive urine Histoplasma antigen is diagnostic. Among people living with HIV, disseminated histoplasmosis should be diagnosed by detecting circulating Histoplasma antigens, and this test has high sensitivity for disseminated disease in advanced immunosuppression. The combination of geography (Guatemala) plus a positive antigen test makes this the only option supported by a specific confirmatory result rather than clinical suspicion alone. Why the other options are wrong: D. Miliary tuberculosis: Can cause a similar febrile wasting syndrome with hepatosplenomegaly and pancytopenia, but there is no antigen or microbiological evidence for TB here, and the urine test performed specifically detects Histoplasma antigen, not TB. B. Visceral leishmaniasis: Also causes fever, hepatosplenomegaly and pancytopenia in advanced HIV, but diagnosis requires demonstration of amastigotes on bone marrow/splenic aspirate or serology/PCR, not a Histoplasma urine antigen, and Leishmania is not the organism detected in this stem. E. Talaromycosis: Talaromyces marneffei infection is endemic to Southeast Asia, southern China and parts of South Asia, not Central America, so geography excludes it, and the antigen test used would differ. A. Brucellosis: Causes fever and hepatosplenomegaly but is acquired from unpasteurised dairy or animal contact, does not typically cause pancytopenia of this severity, and is diagnosed by blood culture or serology, not a fungal urine antigen. Key point: A positive urine Histoplasma antigen in an advanced HIV patient with a compatible travel history and marrow suppression is diagnostic of disseminated histoplasmosis, distinguishing it from TB and leishmaniasis which mimic it clinically but not on this specific test.

Reference: WHO Guidelines for diagnosing and managing disseminated histoplasmosis among people living with HIV (2020), summarised in NCBI Bookshelf: 'Among people living with HIV, disseminated histoplasmosis should be diagnosed by detecting circulating Histoplasma antigens' https://www.ncbi.nlm.nih.gov/books/NBK620075/