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This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
Key points
- Superficial: oral/vaginal candidiasis (fluconazole), dermatophyte infections — tinea (topical terbinafine/clotrimazole)
- Invasive candidiasis: candidaemia in ICU/surgical patients, central lines, TPN. Treat with echinocandin (caspofungin) or fluconazole
- Invasive aspergillosis: immunocompromised (neutropenic, transplant) — fever not responding to antibiotics, CXR/CT halo sign. Treat with voriconazole (first-line) or liposomal amphotericin B
- Cryptococcal meningitis: HIV with CD4 <100 — headache, raised ICP, India ink stain CSF. Treat with liposomal amphotericin B + flucytosine induction, then fluconazole maintenance
- Pneumocystis jirovecii pneumonia (PCP): HIV with CD4 <200 — dry cough, exertional desaturation, bilateral perihilar ground-glass on CXR, raised LDH. Treat with high-dose co-trimoxazole + steroids if hypoxic
Overview
Fungal infections range from common superficial mucocutaneous disease to life-threatening invasive infections in immunocompromised patients. Superficial infections (Candida, dermatophytes) are extremely common and readily treated. Invasive fungal infections (IFI) — including invasive aspergillosis, invasive candidiasis, cryptococcal meningitis, and Pneumocystis jirovecii pneumonia (PCP) — are major causes of morbidity and mortality in immunocompromised patients (HIV/AIDS, transplant recipients, neutropenic patients, ICU patients). Early diagnosis is challenging and often relies on clinical suspicion combined with biomarkers and imaging.
Epidemiology
Superficial candidiasis affects most people at some point (oral thrush, vaginal candidiasis). Invasive aspergillosis is the most common invasive mould infection in immunocompromised patients — mortality 30-50% even with treatment. Candidaemia is the fourth most common bloodstream infection in ICU patients. Cryptococcal meningitis is a leading cause of death in HIV/AIDS globally (>100,000 deaths/year), primarily in sub-Saharan Africa. PCP has declined dramatically in HIV patients since ART and co-trimoxazole prophylaxis but remains common in non-HIV immunosuppressed patients.
Clinical Features
Symptoms
Oral candidiasis: white plaques on oral mucosa (removable, leaving erythematous base)
Vaginal candidiasis: vulval itching, thick white "cottage cheese" discharge, dysuria
Invasive aspergillosis: persistent fever despite broad-spectrum antibiotics in neutropenic patient, cough, pleuritic pain, haemoptysis
Cryptococcal meningitis: headache (progressive, severe), fever, photophobia — insidious onset over days-weeks in HIV patient with low CD4
PCP: progressive dyspnoea (especially exertional), dry cough, fever — subacute onset over days-weeks in HIV or immunosuppressed
Signs
Oral thrush: white pseudomembranous plaques on buccal mucosa, tongue, palate
Dermatophyte infection: annular, scaly, erythematous plaque with raised leading edge and central clearing (tinea corporis/ringworm)
Invasive aspergillosis: fever, tachypnoea, chest signs may be minimal despite significant CT changes
Raised intracranial pressure signs in cryptococcal meningitis (papilloedema, VI nerve palsy)
PCP: bilateral fine crackles. Desaturation on exertion (exercise SpO2 test)
Investigations
First-line
Clinical assessment and risk factor identificationImmunocompromised status, CD4 count (HIV), neutrophil count, transplant status, ICU stay, central lines
CXRPCP: bilateral perihilar ground-glass opacities. Aspergillosis: nodules, cavitation. May be normal early
CT chest (HRCT)Aspergillosis: halo sign (ground-glass halo around nodule — early), air-crescent sign (later). PCP: ground-glass opacities, interstitial pattern
Second-line
Serum galactomannanBiomarker for invasive aspergillosis — serial monitoring in high-risk neutropenic patients
Serum/CSF cryptococcal antigen (CrAg)Highly sensitive and specific for cryptococcal disease. Latex agglutination or lateral flow assay
India ink stain of CSFClassic for Cryptococcus — shows encapsulated yeast. Less sensitive than CrAg but pathognomonic when positive
Induced sputum / BAL for PCPPCP immunofluorescence or PCR on induced sputum or bronchoalveolar lavage
Blood cultures for CandidaCandidaemia: positive blood cultures with Candida species. Remove central lines
Serum beta-D-glucanPan-fungal biomarker — raised in most invasive fungal infections. Non-specific but useful screening test
LDHRaised in PCP (>500 IU/L typical) — useful screening marker
Specialist
Bronchoscopy with BALFor diagnosis of PCP and invasive pulmonary aspergillosis when non-invasive tests are inconclusive
Lumbar punctureCryptococcal meningitis: raised opening pressure (often very high), lymphocytic pleocytosis, raised protein, low glucose. CrAg positive. India ink positive
Management
NICE + ESCMID/ECMM Guidelines + BHIVA1
Superficial fungal infections
- Oral candidiasis: nystatin oral suspension (swish and swallow) or oral fluconazole 50 mg OD for 7 days
- Vaginal candidiasis: topical clotrimazole pessary or oral fluconazole 150 mg single dose
- Dermatophyte (tinea): topical terbinafine or clotrimazole for skin. Oral terbinafine for nails (6 weeks fingernails, 12 weeks toenails)
2
Invasive aspergillosis
- First-line: voriconazole (IV then oral step-down) — monitor voriconazole levels
- Alternative: liposomal amphotericin B (AmBisome)
- Reduce immunosuppression where possible, support neutrophil recovery with G-CSF
3
Invasive candidiasis/candidaemia
- First-line: echinocandin (caspofungin, anidulafungin, micafungin)
- Step-down to fluconazole once species identified and susceptible
- REMOVE central venous lines (source control)
- Repeat blood cultures until negative — determine duration by last positive culture
4
Cryptococcal meningitis
- Induction: liposomal amphotericin B + flucytosine for 2 weeks
- Consolidation: fluconazole 400 mg OD for 8 weeks
- Maintenance: fluconazole 200 mg OD until CD4 >200 for ≥12 months on ART
- Manage raised ICP: therapeutic lumbar punctures (aim opening pressure <20 cmH2O) — CRITICAL for survival
5
PCP (Pneumocystis jirovecii pneumonia)
- High-dose co-trimoxazole (trimethoprim 15 mg/kg/day + sulfamethoxazole) IV for 21 days
- If PaO2 <9.3 kPa (70 mmHg) or SpO2 <92%: add adjunctive prednisolone 40 mg BD for 5 days, 40 mg OD for 5 days, 20 mg OD for 11 days — reduces mortality in severe PCP
- Prophylaxis (prevention): co-trimoxazole 960 mg OD or 480 mg OD when CD4 <200
Complications
- Invasive aspergillosis: Pulmonary haemorrhage, CNS aspergillosis, disseminated disease. Mortality 30-50%
- Cryptococcal meningitis: Raised ICP is the main cause of death — requires serial LP drainage. IRIS after starting ART
- PCP: ARDS, pneumothorax. Mortality ~10-20% with treatment in HIV, higher in non-HIV immunosuppressed
- Candidaemia: Endophthalmitis (all candidaemia patients need ophthalmology review), endocarditis, bone/joint infection
UKMLA Exam Tips
- 1PCP: bilateral perihilar ground-glass + raised LDH + desaturation on exertion + CD4 <200 = classic exam scenario
- 2Cryptococcal meningitis: India ink (encapsulated yeast), CrAg (best test), VERY HIGH opening pressure — serial LPs save lives
- 3Voriconazole = first-line for invasive aspergillosis. Amphotericin B = backup and first-line for Cryptococcus
- 4Halo sign on CT = early invasive aspergillosis. Air-crescent sign = later (recovering neutrophils)
- 5Echinocandin (caspofungin) = first-line for invasive candidiasis/candidaemia. Always remove the line
- 6Co-trimoxazole prophylaxis at CD4 <200 prevents PCP — one of the most important prophylactic interventions in HIV
- 7Galactomannan = Aspergillus biomarker. CrAg = Cryptococcus. Beta-D-glucan = pan-fungal (non-specific)
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