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Describe the dimorphic fungi and the systemic mycoses with their diagnosis.

Microbiology · 2nd Professional — Para-Clinical

The Concept of Dimorphism

Dimorphic fungi exist in two forms — a mould in the environment and in culture at 25°C, and a yeast (or spherule) in tissue and in culture at 37°C. "Mould in the cold, yeast in the heat."

The mould form is the infectious form, producing spores that are inhaled; the yeast form is the invasive (parasitic) form found in the patient
The switch is triggered by temperature, and is essential to virulence — mutants unable to convert to the yeast form are avirulent
They are true pathogens, able to infect the immunocompetent, unlike the opportunists; but disease is far more severe and disseminated in the immunosuppressed
Cultures are hazardous — the mould form generates infectious spores, so suspected cultures must be handled in a biological safety cabinet at BSL-3; these are among the commonest laboratory-acquired fungal infections

Fungus	Distribution and source	Tissue form and disease
Histoplasma capsulatum	Soil enriched with bird and bat droppings; caves, chicken coops and old buildings. In INDIA it is endemic along the gangetic plain, especially West Bengal and Bihar	Small intracellular yeasts within macrophages. Mostly asymptomatic or a flu-like illness; chronic cavitary lung disease resembling tuberculosis; and disseminated disease in HIV with fever, hepatosplenomegaly, pancytopenia and mucosal ulcers
Blastomyces dermatitidis	Moist soil and decaying wood, North America	Broad-based single budding yeast with a thick refractile wall. Pulmonary disease with characteristic verrucous skin lesions and bone involvement
Coccidioides immitis	Arid desert soil of the south-western United States ("valley fever")	Forms a spherule containing endospores — not a budding yeast, which is the exception in this group. Causes pneumonia with erythema nodosum; dissemination is commoner in pregnancy and in certain ethnic groups
Paracoccidioides brasiliensis	South America	A "pilot wheel" of multiple buds around a central yeast; mucocutaneous and pulmonary disease, chiefly in adult men
Talaromyces (Penicillium) marneffei	South-east Asia and north-east INDIA; bamboo rats	Divides by fission, not budding; an AIDS-defining illness with fever, anaemia and umbilicated skin lesions resembling molluscum
Sporothrix schenckii	Soil, thorns, sphagnum moss — implanted by trauma rather than inhaled	Cigar-shaped yeasts; lymphocutaneous sporotrichosis

CLINICAL PEARL

Histoplasmosis is regularly misdiagnosed and treated as tuberculosis in India. Both cause chronic cough, fever, weight loss, cavitary lung disease and granulomas; both are endemic along the Gangetic plain; and both may present with oral ulcers, hepatosplenomegaly and adrenal involvement in disseminated form. The distinction requires looking for the intracellular yeasts in a bone-marrow or tissue smear, or antigen testing — and it matters, because a patient given antitubercular drugs for histoplasmosis will not improve.

Diagnosis and Treatment

Direct microscopy and histopathology with Giemsa, methenamine silver or PAS, looking for the characteristic tissue form, which is often diagnostic by its morphology alone
Culture at both 25 and 37°C to demonstrate dimorphism; growth is slow, taking up to 4 weeks, and must be handled with containment
Antigen detection — Histoplasma antigen in urine and serum is sensitive in disseminated disease and is the most useful rapid test; serology by immunodiffusion and complement fixation, though it is unreliable in the immunosuppressed
Treatment — mild disease may need none; itraconazole for mild to moderate disease, and liposomal amphotericin B for severe or disseminated disease followed by itraconazole, continued for months and until immune reconstitution in HIV

Applied Aspects

Consider histoplasmosis in "tuberculosis" that fails to respond, particularly in an HIV-positive patient from an endemic area with pancytopenia and hepatosplenomegaly
Take an exposure history — caves, bird roosts, poultry, demolition of old buildings, and travel; the epidemiology often makes the diagnosis before any test
Warn the laboratory when a dimorphic fungus is suspected, so that cultures are handled safely; sniffing a plate has caused infection
Look for adrenal involvement in disseminated histoplasmosis, which may cause Addison disease and is treatable if recognised
Talaromycosis is an AIDS-defining illness in north-east India and south-east Asia, and should be considered in a patient from that region with fever and umbilicated skin lesions
Fungal serology is unreliable in the immunosuppressed, who may not produce antibody; antigen detection and direct demonstration are required instead

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