Mycology
1. What this chapter covers, and how NEET PG actually tests it
Mycology is a small subject that carries more marks than its size suggests, because fungal infections cluster in the immunocompromised patients the exam likes to describe.
The organising principle is that the host, not the fungus, decides the disease.
Most pathogenic fungi are environmental organisms of low intrinsic virulence. What determines whether they cause a trivial rash or a fatal invasive infection is which host defence has failed.
| Defect | Characteristic fungal infection |
|---|---|
| Neutropenia | Invasive aspergillosis, candidaemia, mucormycosis |
| T cell deficiency | Cryptococcus, Pneumocystis, endemic mycoses |
| Diabetes with ketoacidosis | Mucormycosis |
| Skin barrier breach | Candida, dermatophytes |
| Indwelling catheter | Candidaemia |
Neutrophils control moulds and T cells control yeasts and intracellular fungi, which is why the pattern in the table is so consistent and why it can be reasoned rather than memorised.
2. Fundamentals
2.1 Structure and classification
Fungi are eukaryotes with a chitin cell wall and an ergosterol-containing membrane, and both are the targets of antifungal drugs.
Ergosterol occupies the place cholesterol holds in human membranes, which is why azoles and amphotericin are selective but not perfectly so, and why their toxicity profiles are what they are.
Yeasts are single cells reproducing by budding; moulds grow as filamentous hyphae; dimorphic fungi are moulds in the environment and yeasts in tissue.
The dimorphic rule is worth stating explicitly: mould at ambient temperature, yeast at body temperature.
Septate hyphae branching at acute angles indicate Aspergillus, while broad aseptate hyphae branching at right angles indicate the Mucorales.
That single morphological distinction separates two invasive mould infections with very different treatments.
2.2 Laboratory identification
Potassium hydroxide mount dissolves keratin and reveals fungal elements in skin, hair and nail samples.
Sabouraud dextrose agar is the standard culture medium, its low pH suppressing bacterial growth.
India ink demonstrates the cryptococcal capsule as a clear halo, though antigen testing has largely replaced it.
Calcofluor white binds chitin and fluoresces, and periodic acid-Schiff and Gomori methenamine silver are the tissue stains.
Galactomannan and beta-D-glucan are circulating fungal cell wall antigens used to detect invasive disease before culture becomes positive.
Beta-D-glucan is present in most fungi but absent from the Mucorales and from Cryptococcus, which is why a negative result does not exclude those two.
3. Superficial and cutaneous mycoses
3.1 Dermatophytes
Three genera cause dermatophytosis: Trichophyton, Microsporum and Epidermophyton.
They digest keratin and are therefore confined to skin, hair and nails, which is why invasive dermatophyte disease essentially does not occur in immunocompetent people.
| Site | Name |
|---|---|
| Scalp | Tinea capitis |
| Body | Tinea corporis |
| Groin | Tinea cruris |
| Foot | Tinea pedis |
| Nail | Tinea unguium or onychomycosis |
Topical treatment suffices for most sites but fails for scalp and nail, because the fungus resides within the hair shaft and nail plate where topical agents cannot penetrate.
Oral terbinafine or itraconazole is therefore required for those two sites, and griseofulvin remains useful in tinea capitis in children.
Recurrent and treatment-resistant dermatophytosis has become a substantial problem in India, associated with over-the-counter topical steroid-antifungal combinations that suppress inflammation while allowing the fungus to spread.
Tinea incognito is the resulting atypical presentation, in which steroid use has removed the characteristic raised active edge.
Trichophyton indotineae has been identified as a distinct terbinafine-resistant species behind much of this, carrying mutations in the squalene epoxidase gene that terbinafine targets.
That is a resistance mechanism of exactly the kind seen in bacteria: alteration of the drug's target, rendering the whole class less effective.
3.2 Other superficial infections
Malassezia furfur causes pityriasis versicolor with hypopigmented or hyperpigmented macules, and shows a spaghetti and meatballs appearance of short hyphae and spores on microscopy.
It is lipophilic, which explains its distribution over sebum-rich areas and its association with the neonatal use of lipid infusions.
Candida causes oral thrush, intertrigo, vulvovaginitis and nappy rash, and is favoured by moisture, antibiotics, diabetes and steroid use.
Oral thrush in an adult with no obvious local cause should prompt consideration of HIV or another immunodeficiency, since it is otherwise unusual outside infancy and denture use.
3.3 Subcutaneous mycoses
These occupy the middle ground: acquired by traumatic inoculation, spreading locally, but not disseminating in immunocompetent hosts.
They matter disproportionately in India because they follow barefoot agricultural work and thorn injuries.
Mycetoma presents as a chronic swelling with multiple discharging sinuses containing visible grains, and the grain colour narrows the cause.
Eumycetoma is fungal with black grains typically, while actinomycetoma is bacterial with pale or red grains, and the distinction matters because actinomycetoma responds to antibiotics while eumycetoma often needs surgery.
That is a rare instance where a clinical appearance decides between antibacterial and antifungal therapy.
Sporotrichosis follows a thorn prick, classically from rose gardening, and spreads along lymphatics producing a chain of nodules.
That linear lymphocutaneous pattern is characteristic enough to be called sporotrichoid spread, and potassium iodide or itraconazole is used.
Chromoblastomycosis produces verrucous plaques with sclerotic bodies visible on histology, and rhinosporidiosis produces friable nasal polyps and is associated with pond bathing.
4. Systemic and opportunistic mycoses
4.1 The endemic dimorphic fungi
| Fungus | Geography | Feature |
|---|---|---|
| Histoplasma capsulatum | Ohio and Mississippi valleys, also India | Intracellular in macrophages, bird and bat droppings |
| Blastomyces | North America | Broad-based budding |
| Coccidioides | Southwestern United States | Spherules with endospores |
| Paracoccidioides | Latin America | Pilot-wheel budding |
| Talaromyces marneffei | Southeast Asia | HIV-associated, bamboo rat reservoir |
These fungi cause self-limiting pulmonary disease in healthy people and disseminated disease in the immunosuppressed, which is the host principle again.
Histoplasmosis is endemic in parts of India, particularly the Gangetic plain, and disseminated disease presents with fever, hepatosplenomegaly and pancytopenia.
Histoplasma survives inside macrophages rather than being killed by them, which is why it behaves like an intracellular pathogen and why intact cell-mediated immunity is what controls it.
The consequence is that disseminated histoplasmosis clusters in advanced HIV and in patients on anti-TNF therapy, and that it can reactivate years after the original exposure.
Coccidioidomycosis is notable for producing erythema nodosum, sometimes called desert rheumatism, which represents a vigorous immune response and paradoxically indicates a good prognosis.
Talaromyces marneffei is the one dimorphic fungus that causes disease chiefly in HIV, and it is essentially confined to Southeast Asia and adjacent parts of northeast India.
4.2 Cryptococcus
Cryptococcus neoformans is an encapsulated yeast acquired by inhalation, with pigeon droppings as the classical source.
Its polysaccharide capsule is the principal virulence factor, inhibiting phagocytosis.
Cryptococcal meningitis is the archetypal T cell deficiency infection, occurring almost exclusively at CD4 counts below one hundred.
Cryptococcal antigen testing on serum or cerebrospinal fluid is more sensitive than India ink and is the preferred diagnostic method.
Raised intracranial pressure is a major cause of death and requires repeated therapeutic lumbar puncture, which is as important as the antifungal therapy itself.
Treatment is amphotericin B with flucytosine for induction, followed by fluconazole.
4.3 The invasive moulds
Aspergillus produces a spectrum determined entirely by host immunity.
Allergic bronchopulmonary aspergillosis occurs in asthma and cystic fibrosis with raised IgE and eosinophilia; aspergilloma colonises an existing cavity; invasive aspergillosis occurs in neutropenia.
The same organism therefore produces an allergic disease, a colonising mass and a fatal invasive infection, depending only on the host.
Mucormycosis is caused by the Mucorales and is characteristically angioinvasive, producing tissue infarction and the black necrotic eschar of rhino-orbital-cerebral disease.
Diabetic ketoacidosis is the classic predisposing state, because acidosis releases iron from transferrin and the organism requires free iron to grow.
Treatment demands urgent surgical debridement alongside amphotericin B, since dead infarcted tissue cannot be reached by any drug.
Deferoxamine therapy paradoxically worsens mucormycosis, because the organism uses the iron-chelator complex as a siderophore and takes up the iron it delivers.
That observation is what established the central role of iron availability in the disease, and it is why iron chelation is avoided in patients at risk.
India saw a sharp rise in mucormycosis during the COVID-19 pandemic, driven by the combination of corticosteroid therapy, uncontrolled diabetes and the illness itself.
That surge illustrates the chapter's principle exactly: the organism had not changed, but a large population suddenly acquired the specific host defect it exploits.
Pneumocystis jirovecii causes pneumonia at CD4 counts below two hundred, with dry cough, exertional desaturation and diffuse infiltrates, and is treated with co-trimoxazole.
Adjunctive corticosteroids are given when hypoxaemia is significant, because killing the organism releases antigen and transiently worsens inflammation.
Pneumocystis is worth noting as a fungus that behaves like a protozoan, which is why it was classified as one for decades and why it responds to co-trimoxazole rather than to conventional antifungals.
It lacks ergosterol in its membrane, which is precisely why amphotericin and the azoles do not work against it.
Diagnosis rests on induced sputum or bronchoalveolar lavage with silver or immunofluorescent staining, since the organism cannot be cultured.
A raised serum lactate dehydrogenase and beta-D-glucan support the diagnosis, and prophylaxis with co-trimoxazole is given below a CD4 count of two hundred.
4.4 Candida: species matter
Candida albicans remains the commonest species but the non-albicans species now account for a large share of invasive disease, and they differ in susceptibility.
Germ tube formation in serum at 37 degrees identifies Candida albicans, and chlamydospore production on cornmeal agar confirms it.
| Species | Practical significance |
|---|---|
| C. albicans | Germ tube positive, generally azole-sensitive |
| C. glabrata | Reduced azole susceptibility |
| C. krusei | Intrinsically fluconazole-resistant |
| C. parapsilosis | Catheter and prosthetic association, reduced echinocandin susceptibility |
| C. auris | Multidrug-resistant, persists on surfaces, causes outbreaks |
Candida krusei is intrinsically fluconazole-resistant, which is why empirical fluconazole is inappropriate where it is likely.
Candida auris deserves separate mention because it behaves more like a resistant bacterium than a typical fungus: it colonises skin, survives on hospital surfaces, resists routine disinfection, and is frequently resistant to multiple antifungal classes.
It is also frequently misidentified by conventional laboratory methods, which is part of why it spreads before being recognised.
Candidaemia requires removal of any indwelling line, since the organism forms biofilm that no antifungal will penetrate, and ophthalmological assessment because endophthalmitis is a recognised complication.
A positive blood culture for Candida is never treated as a contaminant, unlike coagulase-negative staphylococci, because the mortality of untreated candidaemia is high.
5. Antifungal therapy
5.1 Matching drug to target
| Class | Target | Key point |
|---|---|---|
| Amphotericin B | Binds ergosterol, forms pores | Nephrotoxicity, potassium and magnesium wasting |
| Azoles | Inhibit lanosterol 14-alpha-demethylase | Inhibit human cytochrome P450 |
| Echinocandins | Inhibit beta-glucan synthesis | Target absent in humans, well tolerated |
| Flucytosine | Converted to 5-fluorouracil in fungus | Marrow suppression |
| Terbinafine | Inhibits squalene epoxidase | Oral agent for onychomycosis |
| Griseofulvin | Disrupts microtubules | Tinea capitis in children |
The echinocandins are so well tolerated because beta-glucan has no human counterpart at all, unlike ergosterol which resembles cholesterol.
That structural similarity between ergosterol and cholesterol is also why amphotericin causes the toxicity it does.
Azoles inhibit human cytochrome P450 as a direct consequence of the enzyme they were designed to inhibit, which is why azole interactions are so extensive.
5.2 Why antifungals are harder than antibacterials
Antifungal development is intrinsically more difficult than antibacterial development, and the reason explains the whole shape of the drug list.
Fungi are eukaryotes, so they share most of their cellular machinery with human cells, leaving very few targets that exist in the fungus and not in us.
Bacteria are prokaryotes with a completely different ribosome, a peptidoglycan wall and distinct metabolic pathways, which offers many more points of selective attack.
That is why there are only four main antifungal classes against dozens of antibacterial ones, and why the antifungals that do exist tend to be more toxic.
It also explains why the best-tolerated class, the echinocandins, targets the one structure with no human equivalent at all.
Resistance is a growing problem, driven partly by agricultural azole fungicide use selecting for azole-resistant Aspergillus in the environment.
That environmental route means a patient can acquire an azole-resistant strain without ever having taken an azole, which is a genuine departure from the usual model of resistance.
5.3 Choosing between them
Amphotericin remains first-line for mucormycosis and for cryptococcal induction, and echinocandins do not work against either Cryptococcus or the Mucorales.
Fluconazole penetrates cerebrospinal fluid well and is used for cryptococcal consolidation and maintenance.
Voriconazole is preferred for invasive aspergillosis and characteristically causes transient visual disturbance.
Echinocandins are first-line for candidaemia, particularly where azole resistance is a concern.
They are a poor choice for urinary candidiasis, however, because they achieve very low urinary concentrations, and fluconazole is preferred there.
Flucytosine is never given alone, because resistance emerges rapidly during monotherapy, which is why it always appears in combination with amphotericin.
Liposomal amphotericin reduces nephrotoxicity substantially but does not eliminate the infusion reactions, and it is considerably more expensive.
Pre-medication and saline loading reduce those two problems with conventional amphotericin, which is why they remain routine practice.
6. Worked examples
Example 1
A patient in diabetic ketoacidosis develops facial pain, black nasal discharge and a necrotic palatal eschar.
The combination of ketoacidosis and a black necrotic eschar is close to diagnostic.
Mucorales are angioinvasive, thrombosing vessels and infarcting the tissue they occupy, which is what produces the eschar.
Acidosis releases iron from transferrin, and the organism requires free iron to grow, which is why ketoacidosis specifically rather than diabetes alone is the risk factor.
Management is urgent surgical debridement plus amphotericin B, and debridement is essential because infarcted tissue has no blood supply to deliver the drug.
Example 2
A man with HIV and a CD4 count of 40 has headache and fever. Cerebrospinal fluid opening pressure is markedly raised.
A CD4 count below one hundred with subacute meningitis points strongly to Cryptococcus.
The polysaccharide capsule inhibits phagocytosis, which is why intact T cell function is required to contain the organism.
The raised opening pressure is not incidental and is a major cause of death, requiring repeated therapeutic lumbar puncture alongside antifungal therapy.
Cryptococcal antigen testing is more sensitive than India ink, and induction treatment is amphotericin B with flucytosine.
Example 3
A child with tinea capitis is treated with topical antifungal cream without improvement.
Dermatophytes digest keratin, and in tinea capitis the organism lies within the hair shaft itself.
Topical agents cannot penetrate into the hair shaft, which is why scalp and nail infections both fail topical treatment while body and groin infections respond well.
Systemic therapy is required, with griseofulvin or terbinafine depending on the species and local practice.
The same reasoning explains why onychomycosis requires prolonged oral therapy rather than topical lacquer alone in most cases.
7. Traps the exam sets repeatedly
Treating tinea capitis or onychomycosis topically. The organism sits where topical agents cannot reach.
Using an echinocandin for cryptococcal or mucormycotic infection. Neither organism is susceptible.
Relying on beta-D-glucan to exclude invasive fungal disease. It is negative in Mucorales and Cryptococcus infection.
Treating mucormycosis medically alone. Infarcted tissue receives no drug, so debridement is essential.
Assuming aspergillosis means invasive disease. The same organism causes allergic, colonising and invasive disease depending on the host.
Using an azole or amphotericin for Pneumocystis. It lacks ergosterol, so both are useless; co-trimoxazole is the treatment.
Dismissing a blood culture growing Candida as a contaminant. Candidaemia is never a contaminant and carries high mortality untreated.
Prescribing empirical fluconazole where Candida krusei is likely. It is intrinsically resistant to fluconazole.
Summary
The host rather than the fungus decides the disease, and identifying the failed defence predicts the infection.
Neutrophils control moulds and T cells control yeasts and intracellular fungi.
Ergosterol resembles cholesterol, which explains both the selectivity and the toxicity of the ergosterol-targeting drugs.
Acute-angle septate hyphae indicate Aspergillus; right-angle aseptate hyphae indicate the Mucorales.
Beta-D-glucan is negative in Mucorales and Cryptococcus infection, so it cannot exclude them.
Dermatophytes are confined to keratin, and scalp and nail infections require systemic therapy.
Topical steroid-antifungal combinations have driven resistant dermatophytosis in India and produce tinea incognito.
Cryptococcal meningitis occurs below a CD4 count of one hundred, and raised intracranial pressure must be treated alongside the infection.
Diabetic ketoacidosis predisposes to mucormycosis because acidosis liberates the free iron the organism needs.
Echinocandins are exceptionally well tolerated because beta-glucan has no human counterpart.
Subcutaneous mycoses follow traumatic inoculation, and grain colour in mycetoma decides between antibacterial and antifungal treatment.
Candida species differ in susceptibility, with krusei intrinsically fluconazole-resistant and auris multidrug-resistant.
Pneumocystis lacks ergosterol, which is why it responds to co-trimoxazole rather than to conventional antifungals.
Antifungals are few and relatively toxic because fungi are eukaryotes sharing most cellular machinery with us.
