Opportunistic fungal infections
Opportunistic mycoses occur when fungi that are normally controlled by intact cellular immunity, neutrophils, mucosal barriers or normal flora cause invasive disease. They are major causes of illness in advanced HIV, transplant recipients, cancer chemotherapy, prolonged corticosteroid use, neutropenia, diabetes, severe malnutrition and intensive-care patients. The same organism can produce superficial colonisation in one patient and rapidly fatal disseminated disease in another.
Fever plus a compatible risk state is not enough: define the syndrome, obtain specimens early, start appropriate antifungal therapy promptly when invasive disease is likely, and reverse the immune defect.
Learning objectives
- Recognise Candida, Cryptococcus, Aspergillus, Mucorales, Pneumocystis and other opportunistic fungi.
- Relate each organism to immune defects, route of entry and characteristic organ disease.
- Interpret cultures, microscopy, antigen tests, fungal biomarkers and CT findings.
- Manage life-threatening pulmonary, CNS, bloodstream and disseminated disease.
- Integrate antifungal therapy with ART, neutrophil recovery, surgery, source control and prophylaxis.
Who is at risk?
| Host problem | Fungal syndromes to consider |
|---|---|
| Advanced HIV, low CD4 count | Cryptococcal meningitis, oesophageal candidiasis, disseminated histoplasmosis, recurrent mucosal Candida, Pneumocystis. |
| Neutropenia/chemotherapy | Invasive Candida, Aspergillus, Mucorales and disseminated mould infection. |
| Transplant or prolonged steroids | Aspergillosis, Candida, cryptococcosis, Pneumocystis and endemic mycoses. |
| Diabetes/ketoacidosis | Mucormycosis, invasive Candida and severe dermatophyte infection. |
| ICU, central lines, broad antibiotics | Candidemia, intra-abdominal Candida and catheter-associated infection. |
Major pathogens and pathogenesis
Candida
Candida colonises the mouth, gut and genital tract. Barrier disruption, antibiotics, central lines and neutropenia permit invasion, candidemia and organ seeding. Candida can cause thrush, oesophagitis, vulvovaginitis, candidemia, endocarditis, hepatosplenic disease and endophthalmitis.
Cryptococcus
Cryptococcus neoformans and C. gattii are inhaled and may disseminate to the brain, particularly in advanced HIV. Encapsulated yeast, high organism burden and raised intracranial pressure drive meningitis.
Aspergillus
Inhaled conidia germinate when neutrophil function is impaired. Disease ranges from allergic bronchopulmonary aspergillosis to invasive pulmonary nodules, infarction, haemoptysis, sinus/orbital invasion and CNS dissemination.
Mucorales
Angioinvasive moulds invade vessels, causing thrombosis and tissue necrosis. Diabetic ketoacidosis, iron overload, neutropenia and steroids are key risks. Rh inocerebral, pulmonary, cutaneous and gastrointestinal forms are emergencies.
Pneumocystis jirovecii
This organism causes diffuse interstitial pneumonia in advanced HIV and other T-cell immunodeficiency. It produces profound exertional hypoxaemia and dry cough despite initially modest chest signs.
Clinical syndromes
Mucosal and oesophageal candidiasis
White plaques that scrape off leaving an erythematous base, angular cheilitis, sore mouth, odynophagia or retrosternal pain. Oesophageal disease can occur without visible oral thrush.
Candidemia and invasive candidiasis
Persistent fever or sepsis despite antibacterial therapy, central-line infection, abdominal surgery, pancreatitis, neutropenia, renal replacement therapy or multiple antibiotics. Metastatic endophthalmitis, endocarditis, osteomyelitis and hepatosplenic lesions may follow.
Cryptococcal meningitis
Subacute headache, fever, malaise, visual symptoms, nausea, confusion, cranial-nerve palsy, papilloedema or reduced consciousness. Fever may be mild in advanced HIV. Raised intracranial pressure is a major cause of death.
Invasive pulmonary aspergillosis
Persistent fever, pleuritic chest pain, cough, dyspnoea, haemoptysis and nodular or cavitating CT lesions in neutropenia or transplant. Sinus pain, orbital swelling, focal neurological deficit or skin necrosis suggests dissemination.
Mucormycosis
Rapidly progressive facial pain, orbital swelling, black necrotic nasal/palatal tissue, cranial neuropathy, pulmonary fever/haemoptysis or necrotic skin lesions. Do not wait for culture before surgical consultation.
Pneumocystis pneumonia
Subacute dry cough, fever, progressive exertional dyspnoea, tachypnoea and hypoxaemia. Oxygen saturation may fall dramatically with exertion; auscultation can be deceptively normal.
Assessment and investigations
- Stabilise first: oxygen saturation, respiratory effort, shock, mental status and glucose.
- Define the host: HIV test/CD4/viral load where appropriate, neutrophil count, transplant/chemotherapy dates, steroids, diabetes and ART adherence.
- Obtain specimens: two sets of blood cultures, catheter samples, sputum/BAL, CSF, tissue, urine or lesion swabs before therapy when this does not delay emergency treatment.
- Use targeted tests: cryptococcal antigen in blood/CSF, Histoplasma antigen where available, galactomannan and beta-D-glucan in appropriate settings, Pneumocystis PCR or induced sputum/BAL, fungal culture and histopathology.
- Image early: chest X-ray/CT, sinus/orbit CT/MRI, brain imaging before lumbar puncture when raised pressure or focal neurology is suspected, and echocardiography for candidemia with persistent fungemia.
Differential diagnosis
Bacterial sepsis, TB, viral pneumonia, Pneumocystis, nocardiosis, mycobacteria, malignancy, pulmonary embolism, drug toxicity, bacterial meningitis and non-infectious inflammatory disease. Mixed infections are common in advanced HIV.
Management principles
Candidemia
Start an echinocandin or another guideline-recommended initial agent in unstable, azole-exposed or resistant-risk patients; step down to fluconazole when susceptible and clinically stable. Remove/replace a likely infected central line, repeat blood cultures and assess eyes/heart according to protocol.
Cryptococcal meningitis
Use an amphotericin-based induction regimen with flucytosine where available, followed by fluconazole consolidation and maintenance. Manage raised intracranial pressure with therapeutic lumbar punctures; do not rely on mannitol or steroids routinely.
Invasive aspergillosis
Use voriconazole, isavuconazole or liposomal amphotericin B according to species, interactions and local guideline. Reduce immunosuppression where safe, assess for surgery and monitor drug levels/interactions.
Mucormycosis
Immediate liposomal amphotericin B, aggressive surgical debridement and correction of ketoacidosis/neutropenia. Posaconazole or isavuconazole may be used for step-down or salvage under specialist care.
Pneumocystis
High-dose trimethoprim–sulfamethoxazole for the recommended duration, oxygen and corticosteroids when hypoxaemia meets guideline criteria. Start or optimise ART at the appropriate time and provide secondary prophylaxis.
Cryptococcal raised intracranial pressure
Measure opening pressure at lumbar puncture when safe. Headache, vomiting, visual change, papilloedema, sixth-nerve palsy or confusion require urgent pressure management. Therapeutic lumbar puncture is repeated based on symptoms and pressure; antifungals alone may not prevent early death. Avoid routine corticosteroids unless another specific indication exists.
Antifungal stewardship and monitoring
- Check renal function, potassium and magnesium with amphotericin.
- Check liver tests and interactions with azoles; consider therapeutic drug monitoring for voriconazole/itraconazole/posaconazole.
- Review QT prolongation, CYP interactions, anticoagulants, anticonvulsants and antiretrovirals.
- Repeat cultures and imaging to document response; treatment often lasts weeks to months.
- Do not stop therapy solely because fever improves if sterilisation or immune recovery is incomplete.
HIV, ART and immune recovery
Test for HIV where appropriate and link patients to ART. Timing of ART must be coordinated with the infection: cryptococcal meningitis requires a delayed, carefully planned ART start because immune reconstitution inflammatory syndrome can be fatal; other infections often benefit from earlier ART. Monitor for IRIS, adherence, drug interactions and prophylaxis eligibility.
Prevention
- Effective ART and immune recovery are the most important prevention measures in HIV.
- Use Pneumocystis prophylaxis and other prophylaxis according to CD4 count and national guidelines.
- Reduce unnecessary broad-spectrum antibiotics and central-line duration.
- Control diabetes and ketoacidosis; avoid unnecessary steroids.
- Use safe food, avoid high-risk mould exposure during profound neutropenia and follow transplant/oncology environmental precautions.
Exam pearls
- Cryptococcal meningitis may have little fever; ask about headache and measure pressure.
- Aspergillus and Mucorales are angioinvasive; haemoptysis, infarcts and necrosis are warning signs.
- Mucormycosis requires antifungal therapy plus urgent surgery and metabolic correction.
- Positive Candida from sputum is not the same as candidemia.
- Pneumocystis causes severe hypoxaemia with a dry cough and often diffuse interstitial imaging.
References
- SlideShare: Opportunistic fungal infection.
- WHO and national HIV/advanced disease guidance.
- Current Uganda Clinical Guidelines and specialist infectious-disease protocols.
Safety note: Invasive fungal disease is life-threatening. Confirm current induction regimens, dosing, monitoring and ART timing with specialist guidelines.
