Opportunistic Fungi
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Direct answer
Four opportunistic fungi map onto four host defects, and the mapping is the exam. Cryptococcus neoformans, a capsulated budding yeast spread by pigeon droppings, causes meningitis when the CD4 count falls below 100, diagnosed by India ink and cryptococcal antigen on cerebrospinal fluid and treated with liposomal amphotericin B plus flucytosine, then fluconazole. Aspergillus fumigatus, whose septate hyphae branch at acute angles, invades angiotrophically in prolonged neutropenia — halo and air-crescent signs on imaging, galactomannan antigen in serum — and is treated with voriconazole. The Mucorales (Rhizopus, Mucor), broad aseptate ribbons branching at right angles, cause rhino-orbital-cerebral mucormycosis in diabetic ketoacidosis and were the defining complication of India's 2021 COVID-19 second wave, with tens of thousands of reported cases. Pneumocystis jirovecii, now classified among fungi, causes fever and hypoxia with ground-glass infiltrates below a CD4 count of 200, prevented by cotrimoxazole prophylaxis.
What you must remember
- Cryptococcus bench card: capsulated budding yeast (narrow-based buds, unlike the broad-based Blastomyces), India ink halo, mucicarmine-staining capsule, urease positive; cryptococcal antigen testing on cerebrospinal fluid and serum outperforms microscopy; opening pressures are high, glucose low.
- Induction therapy for cryptococcal meningitis: liposomal amphotericin B plus flucytosine for at least two weeks, step-down to high-dose then maintenance fluconazole; manage raised intracranial pressure with therapeutic lumbar punctures.
- Aspergillus spectrum: angioinvasive disease in neutropenia (treat voriconazole first-line); aspergilloma (fungal ball in a old cavity — surgical question); allergic bronchopopulmonary aspergillosis in asthma (steroids with itraconazole, driven by IgE and eosinophilia).
- Septate versus aseptate is the emergency discrimination: Aspergillus — septate, acute-angle branching; Mucorales — broad, ribbon-like, aseptate or pauciseptate, right-angle branching.
- Mucormycosis management bundle: urgent glycaemic control and ketoacidosis reversal, liposomal amphotericin B, aggressive surgical debridement of necrotic tissue, and stopping or reducing immunosuppression; posaconazole or isavuconazole for step-down.
- The Indian COVID-19 lesson: the drivers were uncontrolled diabetes, high-dose corticosteroids and prolonged critical illness; more than 45,000 cases were reported in the May–July 2021 window, with black necrotic nasal turbinates the warning sign.
- Pneumocystis pneumonia: insidious dyspnoea, dry cough, hypoxia out of proportion to examination findings, bilateral perihilar ground-glass on imaging; diagnose by bronchoalveolar lavage with silver or immunofluorescent stain; treat high-dose cotrimoxazole with corticosteroids when hypoxic.
- Prophylaxis thresholds in HIV: cotrimoxazole below a CD4 count of 200 (or oral candidiasis), with cryptococcal antigen screening before antiretroviral initiation where implemented.
Reading a fever in the immunocompromised host
A patient with newly diagnosed leukaemia on broad-spectrum antibiotics spikes a fever during neutropenia. The chest computed tomography shows a nodule with a surrounding halo. The halo narrows to angioinvasive aspergillosis: serum galactomannan sent, voriconazole started, and surgery reserved for a lesion threatening a great vessel or the pericardium. Change the host and the fungus changes: a man in diabetic ketoacidosis arrives with facial pain, proptosis and a black crust inside the nose — an emergency debridement list, liposomal amphotericin B, and histopathology showing broad aseptate right-angle ribbons; every hour of delayed surgery costs vision. In the HIV ward, a two-week headache with a CD4 count of 40 gets a lumbar puncture with India ink and cryptococcal antigen before any steroid is contemplated. Three hosts, three fungi, one principle: identify the immune defect, and the differential writes itself.
Where students slip
Branching-angle trivia decide one-mark questions under time pressure: acute angles with septa mean Aspergillus, right angles with broad aseptate ribbons mean Mucorales — examinees transpose them. Second, therapy-first drugs get shuffled: voriconazole for aspergillosis but liposomal amphotericin B for mucormycosis — posaconazole or isavuconazole step down for both, and fluconazole and voriconazole lack reliable Mucorales activity, which is why the distinction matters at all. Third, Pneumocystis is treated as a protozoan by habit: it stains with silver and methenamine, but it is managed as a fungus (cotrimoxazole) and no longer responds to the "antiprotozoal" mental file. Fourth, the India ink stem: a capsulated narrow-based budding yeast in cerebrospinal fluid is Cryptococcus; the broad-based bud belongs to Blastomyces, a different chapter.
Frequently asked questions
How is cryptococcal meningitis diagnosed and treated?
India ink mount, mucicarmine stain and cryptococcal antigen on cerebrospinal fluid, with pressure measurement; treatment is liposomal amphotericin B plus flucytosine induction, then consolidation and maintenance fluconazole.
How are Aspergillus and Mucorales distinguished histologically?
Aspergillus shows septate hyphae with uniform width branching at acute angles; the Mucorales show broad, ribbon-like, aseptate hyphae branching at right angles — a distinction that changes first-line therapy.
Why did mucormycosis explode in India's 2021 COVID wave?
Uncontrolled diabetes, high-dose corticosteroids and prolonged critical illness created the classic triad; tens of thousands of rhino-orbital-cerebral cases were reported, demanding glycaemic control, liposomal amphotericin B and surgical debridement.
What is allergic bronchopulmonary aspergillosis?
A hypersensitivity disease of asthmatic airways: fleeting infiltrates, brown plugs, high immunoglobulin E and eosinophilia, treated with corticosteroids plus itraconazole.
How is Pneumocystis pneumonia prevented and treated in HIV?
Cotrimoxazole prophylaxis below a CD4 count of 200 (or with oral candidiasis); treatment is high-dose cotrimoxazole with adjunctive corticosteroids when hypoxic — the organism is fungal by classification.