Fungal infections
Mycology for FCPS: Candida, Aspergillus, Mucor, Cryptococcus and antifungals
Fungal structure, superficial, subcutaneous, dimorphic and opportunistic fungi, and how antifungal drugs work, for FCPS Part 1. Learn each fungus by its shape in tissue, the host it attacks and the drug that kills it.
Fungal basics
- Fungi are eukaryotes. Their membrane sterol is ergosterol (not cholesterol) and their wall is chitin and β-glucan; both are drug targets.
- Forms: yeasts (budding single cells: *Candida*, *Cryptococcus*), moulds (hyphae: *Aspergillus*, Mucorales, dermatophytes) and dimorphic fungi, which are moulds in the cold (environment, 25 °C) and yeasts in the heat (body, 37 °C): *Histoplasma*, *Blastomyces*, *Coccidioides* (spherules), *Paracoccidioides*, *Sporothrix*, *Talaromyces*.
- Lab: KOH mount, Sabouraud agar, India ink (*Cryptococcus* capsule), silver (Gomori) and PAS stains, germ tube test (*C. albicans*), galactomannan antigen (*Aspergillus*), β-D-glucan (*Candida*, *Pneumocystis*), cryptococcal antigen.
How antifungals work
| Drug | Target | Notes |
|---|---|---|
| Amphotericin B | Binds ergosterol, making pores | Broadest; nephrotoxic, hypokalaemia; liposomal form for mucor and cryptococcus |
| Azoles (fluconazole, itraconazole, voriconazole, posaconazole) | Inhibit lanosterol 14α-demethylase (fungal CYP51), blocking ergosterol synthesis | Also inhibit human CYP450: raise warfarin INR, tacrolimus, ciclosporin levels; voriconazole does not cover Mucorales |
| Echinocandins (caspofungin, micafungin) | Block β-glucan synthesis in the wall | First line for candidaemia and *C. auris* |
| Terbinafine | Inhibits squalene epoxidase | Dermatophytes (nails, scalp); useless for *Malassezia* orally |
| Griseofulvin | Binds microtubules, stops mitosis; deposits in keratin | Tinea capitis in children |
| Flucytosine | Converted to 5-FU in fungal cells | With amphotericin for cryptococcal meningitis |
| Nystatin | Ergosterol pores; not absorbed | Oral and gut candida |
- *Pneumocystis* has little ergosterol, so amphotericin and azoles fail; it is treated with co-trimoxazole.
Superficial and cutaneous mycoses
- Pityriasis versicolor (*Malassezia furfur*): pale or brown fine-scaled macules on the chest and back, obvious after sun exposure because affected skin does not tan; KOH shows "spaghetti and meatballs" (short hyphae and round yeasts). First line is topical ketoconazole shampoo or selenium sulphide; oral terbinafine does not work.
- Dermatophytes (*Trichophyton*, *Microsporum*, *Epidermophyton*) live on keratin: tinea corporis (annular, active scaly edge, central clearing), cruris, pedis, unguium (oral terbinafine), barbae; tinea incognito after topical steroids.
- Tinea capitis needs oral griseofulvin or terbinafine, because the fungus is inside the hair shaft and follicle; some *Microsporum* fluoresce green under Wood's lamp. A kerion is a boggy, pustular, inflammatory tinea capitis that looks like an abscess: do not incise; give oral antifungal.
- Toe-web tinea pedis cracks the skin and lets streptococci in; it is the usual portal for recurrent leg cellulitis and must be treated.
- Otomycosis after antibiotic ear drops: white fluffy debris (*Candida*) or debris with black specks (*Aspergillus niger*); clean, stop the antibiotic drops, use topical antifungal.
Subcutaneous mycoses
- Sporotrichosis (rose gardener's disease): nodules spreading along lymphatics from a thorn prick; itraconazole.
- Mycetoma (Madura foot) in barefoot farmers: painless swelling, sinuses discharging grains.
| Feature | Eumycetoma | Actinomycetoma |
|---|---|---|
| Cause | True fungi (*Madurella*) | Bacteria (*Nocardia*, *Actinomadura*, *Streptomyces*) |
| Grains | Often black | Yellow, white or red |
| Microscopy | Broad hyphae in grains | Fine filaments |
| Treatment | Itraconazole for months, then wide excision (incomplete excision spreads it) | Antibiotics (co-trimoxazole with amikacin); surgery rarely |
- Chromoblastomycosis (sclerotic bodies); rhinosporidiosis (strawberry-like nasal polyps, South Asia; excision).
Systemic dimorphic fungi
- *Histoplasma capsulatum* (a fungus, not a bacterium): bird and bat droppings, caves, pigeon lofts; inhaled spores; small yeasts inside macrophages. The lung is the commonest organ involved (TB-like illness, calcified granulomas); disseminated disease in HIV (hepatosplenomegaly, oral ulcers). Itraconazole or amphotericin.
- *Blastomyces* (broad-based budding), *Coccidioides* (spherules with endospores; erythema nodosum), *Paracoccidioides* (ship's-wheel budding), *Talaromyces marneffei* (South-East Asia, HIV).
Opportunistic fungi
| Organism | In tissue | Disease and host | Treatment |
|---|---|---|---|
| *Candida albicans* | Budding yeast with pseudohyphae; germ tube positive | Thrush; oesophagitis (painful swallowing, white plaques) points to immunosuppression (HIV, steroids, chemotherapy); vulvovaginal candidiasis in pregnancy and diabetes; the commonest non-bacterial infection in burns and after long antibiotics; candidaemia with central lines, TPN, ICU | Topical azoles or nystatin; fluconazole; candidaemia: echinocandin plus removal of the central line and an eye examination |
| *Aspergillus fumigatus* | Narrow septate hyphae branching at acute (45°) angles | ABPA (asthma, eosinophilia, high IgE); aspergilloma in an old TB cavity (air crescent, haemoptysis); invasive aspergillosis in neutropenia (CT halo sign); fungal keratitis; chronic invasive sinusitis with granulomas; *A. flavus* makes aflatoxin | Voriconazole (invasive); surgery for aspergilloma or massive haemoptysis |
| Mucorales (*Rhizopus*, *Mucor*) | Broad, ribbon-like, non-septate hyphae branching at right angles; invade vessels | Rhinocerebral mucormycosis in diabetic ketoacidosis (also iron overload, deferoxamine, steroids): black eschar on nasal turbinate or palate, proptosis, cranial nerve palsies; rapidly fatal | Urgent debridement plus liposomal amphotericin B; correct ketoacidosis; posaconazole or isavuconazole step-down |
| *Cryptococcus neoformans* | Yeast with a thick capsule, seen as a clear halo on India ink | Pigeon droppings; meningitis in HIV (CD4 below 100) and transplant recipients; high opening pressure | Amphotericin B plus flucytosine, then fluconazole; repeated LPs for pressure |
| *Pneumocystis jirovecii* | Cysts on silver stain of BAL or induced sputum | Pneumonia with CD4 below 200, steroids, transplant: dry cough, exertional desaturation, bilateral perihilar ground glass; raised LDH | Co-trimoxazole, plus steroids if PaO₂ below 9.3 kPa; prophylaxis below CD4 200 |
- Why DKA invites mucor: acidosis impairs neutrophils and frees iron from transferrin, and Mucorales thrive on free iron.
- Aspergillus serology: galactomannan antigen for invasive disease; precipitating IgG antibodies for aspergilloma and chronic pulmonary aspergillosis; total and specific IgE for ABPA. A perihilar mass with blood and sputum eosinophilia suggests non-invasive allergic aspergillosis.
- Candida auris resists fluconazole, is misidentified by routine biochemical tests, survives on bed rails and spreads in ICUs: contact precautions and echinocandins. *C. krusei* is intrinsically fluconazole resistant.
- Long-term antibiotics predispose to Candida, not *Aspergillus*; neutropenia predisposes to both, and to mucor.
- Oral hairy leukoplakia in HIV is caused by EBV, not a fungus; unlike thrush, it cannot be scraped off.
Risk factors for invasive fungal infection
| Host problem | Typical fungus |
|---|---|
| Neutropenia | Aspergillus, Candida, Mucor |
| Diabetic ketoacidosis, iron overload | Mucorales |
| Low CD4 count | Cryptococcus, Pneumocystis, Candida oesophagitis, Histoplasma |
| Central line, TPN, broad-spectrum antibiotics, burns | Candida |
| Old TB cavity | Aspergilloma |
Remember Septate and 45° is Aspergillus; broad, non-septate and 90° is Mucor; a capsule on India ink is Cryptococcus.
Exam trap Voriconazole does not treat mucormycosis; use debridement and liposomal amphotericin.
Exam trap Kerion looks like an abscess but is fungal: do not incise; give oral antifungal.
How FCPS asks about this
- Oesophageal plaques with yeasts and pseudohyphae: Candida, signalling immunosuppression; commonest fungus in burns.
- Pityriasis versicolor: spaghetti and meatballs; topical ketoconazole or selenium sulphide.
- Death after DKA with black nasal eschar: mucormycosis; right-angle non-septate hyphae.
- Corneal scraping with narrow acute-angle septate hyphae: Aspergillus; galactomannan is its serological test.
- Meningitis in HIV or after transplant with haloed yeasts: Cryptococcus; amphotericin plus flucytosine.
- Histoplasma: lungs most often; bat and bird droppings; yeasts inside macrophages.
- Azoles: inhibit lanosterol 14α-demethylase; raise warfarin INR and tacrolimus levels.
Test yourself on this topic
5 of the 35 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A gardener pricks her finger on a rose thorn. Weeks later a nodule ulcerates and new nodules appear in a line up the forearm. What is the organism?
Answer: Sporothrix schenckii
Sporotrichosis is a subcutaneous mycosis from inoculation of Sporothrix schenckii (a dimorphic fungus in soil and plants) via thorns, splinters or sphagnum moss. It causes a primary nodule or ulcer with secondary nodules along draining lymphatics (lymphocutaneous or 'sporotrichoid' spread). Tissue shows cigar-shaped yeasts and asteroid bodies. Treatment: itraconazole (potassium iodide in resource-limited settings). Other causes of sporotrichoid spread: Mycobacterium marinum (fish tanks), Nocardia, leishmaniasis.
Sporotrichosis
- Rose thorn, plants, moss
- Nodules along lymphatics
- Cigar-shaped yeasts, asteroid bodies
- Treat: itraconazole
Remember Rose gardener, string of nodules.
Why the other options are wrong
- Pasteurella multocida Animal bite cellulitis within hours.
- Staphylococcus aureus Acute cellulitis or abscess.
- Bartonella henselae Cat scratch with lymphadenopathy.
- Candida albicans Not this pattern.
A young man has pale, scaly macules on his chest and back that became obvious after sun exposure. KOH shows 'spaghetti and meatballs'. What is the first-line treatment?
Answer: Topical ketoconazole shampoo
Pityriasis versicolor is caused by Malassezia furfur, a lipophilic yeast; azelaic acid production inhibits melanocytes, so patches look pale on tanned skin. KOH shows short hyphae with spores (spaghetti and meatballs), and lesions may fluoresce yellow-green under Wood's lamp. Topical ketoconazole shampoo or selenium sulfide is first line; oral itraconazole or fluconazole for extensive disease. Pigment takes months to return; recurrence is common.
Pityriasis versicolor
- Malassezia yeast
- Pale patches after tanning
- KOH: spaghetti and meatballs
- Treat: ketoconazole, selenium sulfide
- Recurrence common
Remember Pale spots on a tanned back: Malassezia.
Exam trap Oral terbinafine does not work for Malassezia.
Why the other options are wrong
- Oral griseofulvin course Used for tinea capitis.
- Potent topical steroid Worsens fungal infection.
- Oral amoxicillin course Not a bacterial infection.
- Oral terbinafine course Works poorly orally for Malassezia.
Several children at a school develop fever, vomiting and jaundice after a common water source was contaminated. Which test confirms acute hepatitis A?
Answer: IgM anti-HAV antibody
Hepatitis A is a picornavirus (RNA) spread faeco-orally through contaminated food and water; it is very common in childhood in Pakistan, often mild or anicteric in young children and more severe in adults. Faecal shedding peaks before jaundice appears, so infectivity is highest in the incubation period (2–6 weeks). IgM anti-HAV indicates acute infection; IgG anti-HAV indicates past infection or vaccination and lifelong immunity. HAV never causes chronic infection or carrier state, and fulminant failure is rare. Prevention: sanitation, hygiene and the inactivated HAV vaccine; immunoglobulin or vaccine can be used for post-exposure prophylaxis.
Hepatitis A
- Faeco-oral; picornavirus (RNA)
- Most infectious before jaundice
- IgM anti-HAV: acute; IgG: immunity
- Never chronic
- Prevent: sanitation, inactivated vaccine
Remember A is acute, always clears, IgM proves it.
Why the other options are wrong
- IgG anti-HAV antibody Past infection or vaccination.
- HBsAg Hepatitis B.
- Anti-HCV Hepatitis C.
- Liver biopsy Not needed.
A man with advanced HIV has cryptococcal meningitis. Which treatment is used for induction?
Answer: Amphotericin B + flucytosine
Cryptococcus neoformans (encapsulated yeast, India ink positive, cryptococcal antigen positive) causes subacute meningitis in people with low CD4 counts. Induction uses amphotericin B (liposomal where possible) with flucytosine, then consolidation and maintenance with fluconazole. Raised intracranial pressure is managed by repeated lumbar punctures. Antiretroviral therapy is delayed about 4–6 weeks to reduce immune reconstitution syndrome.
Cryptococcal meningitis
- Encapsulated yeast: India ink
- Test: CrAg (antigen)
- Induction: amphotericin + flucytosine
- Then fluconazole
- Repeat LP for high pressure
Remember Ampho plus flucytosine first, fluconazole after.
Exam trap Starting ART too early worsens outcome in cryptococcal meningitis.
Why the other options are wrong
- Oral fluconazole alone Used for consolidation and maintenance.
- IV caspofungin Echinocandins do not work against Cryptococcus.
- Oral griseofulvin Used for dermatophytes.
- Oral nystatin suspension Topical only.
Candida albicans is a harmless commensal in many women but causes symptomatic vaginitis when it invades the epithelium. Which change in the organism allows it to penetrate the vaginal epithelial cells?
Answer: Switching from yeast to hyphal form
Candida albicans is dimorphic. As a budding yeast it usually lives harmlessly on the mucosa. When local conditions favour it, it switches to hyphae, which express adhesins and invasins, secrete proteases and the toxin candidalysin, and penetrate epithelial cells, triggering inflammation and symptoms. Capsules are a feature of Cryptococcus, and Candida does not form spores or enterotoxins.
Candida dimorphism
- Yeast: commensal
- Hyphae: invasive
- Adhesins, proteases, candidalysin
- Germ tube = early hypha
Remember Yeast sits, hypha invades.
Exam trap Finding Candida on a swab without symptoms does not need treatment.
Why the other options are wrong
- Forming a thick polysaccharide capsule A feature of Cryptococcus.
- Producing a heat-stable enterotoxin Not a Candida virulence factor.
- Becoming an obligate intracellular form Candida is extracellular.
- Forming endospores in the vagina Fungi do not form bacterial endospores.
Where this sits in the CPSP syllabus
- Paper 1: Microbiology, Mycology
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