Microscopy — bone marrow/blood/tissue biopsy showing small, oval, intracellular yeast forms within macrophages (Giemsa/Wright stain).
Culture — on Sabouraud dextrose agar; slow-growing mould at 25°C with characteristic tuberculate macroconidia, converting to yeast at 37°C (demonstrating thermal dimorphism).
Urine/serum antigen detection (Histoplasma polysaccharide antigen) — a rapid, sensitive test particularly useful in disseminated disease.
Serology (complement fixation, immunodiffusion) — for less severe/localized disease.
Treatment: itraconazole for mild-moderate disease; amphotericin B for severe/disseminated disease, particularly in immunocompromised (AIDS-defining opportunistic infection in endemic areas).