Cryptococcosis
A potentially serious fungal infection caused by Cryptococcus species that primarily affects immunocompromised individuals
Quick Facts
- Type: Fungal Infection
- ICD-10: B45
- Organism: Cryptococcus species
- Severity: Can be life-threatening
Overview
Cryptococcosis is a fungal infection caused by encapsulated yeasts of the genus Cryptococcus, primarily Cryptococcus neoformans and Cryptococcus gattii. This opportunistic infection predominantly affects individuals with compromised immune systems, particularly those with HIV/AIDS, organ transplant recipients, and patients on immunosuppressive therapy.
The infection typically begins in the lungs after inhalation of fungal spores from environmental sources such as bird droppings, soil, and decaying organic matter. From the lungs, the infection can disseminate to other organs, most notably the central nervous system, where it can cause life-threatening cryptococcal meningitis. The disease can also affect the skin, bones, and other organs.
Cryptococcosis has emerged as a significant cause of morbidity and mortality worldwide, particularly in regions with high HIV prevalence. Without proper treatment, disseminated cryptococcosis, especially cryptococcal meningitis, has a mortality rate exceeding 70%. However, with appropriate antifungal therapy and immune system support, the prognosis can be significantly improved. Early recognition and treatment are crucial for preventing severe complications and death.
Symptoms
Cryptococcosis symptoms vary depending on the organs affected and the patient's immune status. The infection can present as pulmonary, disseminated, or central nervous system disease, with symptoms ranging from mild to life-threatening.
Neurological Symptoms
Central Nervous System Manifestations
- Headache: Often severe and persistent
- Neck stiffness: Signs of meningeal irritation
- Fever: Low-grade to high fever
- Altered mental status: Confusion, lethargy, or coma
- Nausea and vomiting: Due to increased intracranial pressure
- Photophobia: Sensitivity to light
- Seizures: In severe cases with brain involvement
- Cranial nerve palsies: Affecting vision, hearing, or facial movement
Pulmonary Symptoms
- Cough: Dry or productive cough
- Shortness of breath: Dyspnea on exertion or at rest
- Chest pain: Pleuritic or substernal pain
- Fever: Often accompanied by chills
- Weight loss: Unintentional weight loss
- Night sweats: Profuse sweating at night
- Fatigue: Persistent tiredness and weakness
Cutaneous Manifestations
- Skin lesions: Papules, nodules, or ulcers
- Cellulitis-like lesions: Red, swollen areas of skin
- Molluscum-like lesions: Small, flesh-colored bumps
- Abscesses: Collections of pus in skin and soft tissue
Systemic Symptoms
- Fever: Persistent or intermittent fever
- Malaise: General feeling of discomfort
- Anorexia: Loss of appetite
- Weight loss: Significant unintentional weight loss
- Night sweats: Drenching sweats during sleep
Symptoms by Disease Form
Pulmonary Cryptococcosis
- Often asymptomatic in immunocompetent patients
- Cough and dyspnea in symptomatic cases
- May present as pneumonia or lung masses
Cryptococcal Meningitis
- Severe headache and neck stiffness
- Altered mental status or confusion
- Cranial nerve involvement
- Increased intracranial pressure symptoms
Disseminated Cryptococcosis
- Multiple organ involvement
- Skin lesions with CNS symptoms
- Bone and joint pain
- Prostatic involvement in men
Causes
Cryptococcosis is caused by infection with encapsulated yeasts of the Cryptococcus genus. Understanding the causative organisms and transmission routes is essential for prevention and treatment.
Causative Organisms
Cryptococcus neoformans
- Primary pathogen: Most common cause worldwide
- Varieties: C. neoformans var. grubii and var. neoformans
- Associated with: Bird droppings, especially pigeons
- Geographic distribution: Worldwide
- Host preference: Immunocompromised individuals
Cryptococcus gattii
- Environmental pathogen: Associated with eucalyptus trees
- Geographic distribution: Australia, Pacific Northwest, tropical regions
- Host preference: Can infect immunocompetent individuals
- Clinical presentation: Often causes pulmonary disease
Environmental Sources
- Bird droppings: Especially pigeon excrement
- Soil contamination: Areas with accumulated bird droppings
- Decaying organic matter: Wood, tree hollows
- Eucalyptus trees: Primary source of C. gattii
- Urban environments: Parks, building ledges, air conditioning systems
Transmission Routes
Inhalation (Primary Route)
- Inhalation of aerosolized fungal cells or spores
- Entry through respiratory tract
- Initial pulmonary infection
- Potential dissemination to other organs
Direct Inoculation (Rare)
- Traumatic implantation into skin
- Surgical or medical procedures
- Primary cutaneous infection
Pathogenesis
- Pulmonary entry: Initial infection in lungs
- Immune evasion: Polysaccharide capsule prevents phagocytosis
- Hematogenous spread: Dissemination through bloodstream
- CNS invasion: Crosses blood-brain barrier
- Tissue invasion: Affects multiple organ systems
Virulence Factors
- Polysaccharide capsule: Antiphagocytic properties
- Melanin production: Protects against oxidative stress
- Phospholipase activity: Tissue invasion
- Urease production: Diagnostic marker
- Growth at 37°C: Adaptation to human body temperature
Risk Factors
Cryptococcosis primarily affects individuals with compromised immune systems, though certain factors can increase susceptibility even in immunocompetent individuals.
Immunocompromising Conditions
HIV/AIDS
- Primary risk factor: CD4+ count <100 cells/μL
- Geographic correlation: High prevalence in sub-Saharan Africa
- Clinical presentation: Often disseminated disease
- Prognosis: High mortality without treatment
Organ Transplantation
- Solid organ transplants: Kidney, liver, heart, lung
- Hematopoietic stem cell transplant: Bone marrow transplant
- Immunosuppressive therapy: Anti-rejection medications
- Timing: Risk highest in first year post-transplant
Malignancies
- Hematologic malignancies: Leukemia, lymphoma
- Solid tumors: During chemotherapy
- Bone marrow suppression: Neutropenia
- Corticosteroid therapy: High-dose or prolonged use
Medical Conditions
- Chronic corticosteroid use: Long-term prednisone therapy
- Autoimmune diseases: Systemic lupus erythematosus
- Sarcoidosis: Chronic inflammatory condition
- Diabetes mellitus: Poorly controlled diabetes
- Chronic kidney disease: Advanced stage disease
- Liver cirrhosis: End-stage liver disease
Medications
- Immunosuppressive drugs: Cyclosporine, tacrolimus, mycophenolate
- Biologics: TNF-alpha inhibitors, rituximab
- Chemotherapy agents: Cancer treatment drugs
- High-dose corticosteroids: >20mg prednisone daily
Environmental Risk Factors
- Geographic location: Areas with high Cryptococcus prevalence
- Occupational exposure: Bird handlers, gardeners, construction workers
- Urban environments: Areas with pigeon populations
- Activities: Cave exploration, archaeological excavations
Host Factors
- Age: Extremes of age (very young or elderly)
- Gender: Slight male predominance
- Genetic factors: Inherited immunodeficiencies
- Pregnancy: Altered immune status
- Malnutrition: Protein-energy malnutrition
Special Populations
- Healthcare workers: Potential nosocomial exposure
- Laboratory personnel: Handling clinical specimens
- Travelers: Visiting endemic areas
- Homeless populations: Poor living conditions and healthcare access
Diagnosis
Diagnosing cryptococcosis requires a combination of clinical suspicion, laboratory testing, and imaging studies. Early diagnosis is crucial for appropriate treatment and improved outcomes.
Clinical Assessment
- Medical history: Immunocompromising conditions, travel history
- Physical examination: Neurological assessment, skin lesions
- Risk factor evaluation: HIV status, immunosuppressive medications
- Symptom assessment: Duration and progression of symptoms
Laboratory Tests
Cerebrospinal Fluid (CSF) Analysis
- Lumbar puncture: Essential for suspected meningitis
- Opening pressure: Often elevated (>250 mm H2O)
- Cell count: Lymphocytic pleocytosis
- Chemistry: Low glucose, elevated protein
- India ink stain: Direct visualization of encapsulated yeasts
Antigen Detection
- Cryptococcal antigen (CrAg): Highly sensitive and specific
- Serum testing: Useful for screening and monitoring
- CSF testing: Diagnostic for CNS involvement
- Urine testing: Alternative specimen for antigen detection
- Lateral flow assay: Point-of-care testing option
Microscopy and Culture
- Direct microscopy: KOH preparation, calcofluor white
- Fungal culture: Sabouraud dextrose agar
- Identification: Urease test, phenol oxidase
- Susceptibility testing: Antifungal sensitivity patterns
Imaging Studies
Chest Imaging
- Chest X-ray: Pulmonary infiltrates, nodules, masses
- CT chest: Better characterization of lung lesions
- Patterns: Consolidation, cavitation, pleural effusion
Neuroimaging
- CT brain: Rule out mass lesions, hydrocephalus
- MRI brain: More sensitive for cryptococcomas
- Findings: Gelatinous pseudocysts, enhancement patterns
Specialized Testing
- Histopathology: Tissue biopsy with special stains
- Molecular diagnostics: PCR for species identification
- MALDI-TOF: Mass spectrometry identification
- Antifungal susceptibility: MIC testing for treatment guidance
Screening Recommendations
- HIV patients: CD4+ count <100 cells/μL
- Transplant recipients: Pre-transplant screening
- High-risk areas: Routine screening in endemic regions
- Symptomatic patients: Rapid antigen testing
Differential Diagnosis
- Bacterial meningitis
- Tuberculous meningitis
- Other fungal infections (histoplasmosis, coccidioidomycosis)
- Brain tumors or metastases
- Viral encephalitis
Treatment Options
Treatment of cryptococcosis depends on the site of infection, severity of disease, and patient's immune status. The approach typically involves induction, consolidation, and maintenance phases of antifungal therapy.
Cryptococcal Meningitis Treatment
Induction Phase (2 weeks)
- Amphotericin B deoxycholate: 0.7-1.0 mg/kg/day IV
- Plus 5-flucytosine: 25 mg/kg PO every 6 hours
- Alternative: Liposomal amphotericin B 3-4 mg/kg/day
- Monitoring: Renal function, electrolytes, blood counts
Consolidation Phase (8 weeks)
- Fluconazole: 400 mg (6 mg/kg) daily PO/IV
- Duration: 8 weeks after induction
- Monitoring: Clinical response, CSF sterilization
Maintenance Phase
- Fluconazole: 200 mg daily PO
- Duration: HIV patients - until CD4+ >100 cells/μL for 6 months
- Non-HIV patients: 6-12 months
Pulmonary Cryptococcosis
Immunocompetent Patients
- Asymptomatic: May observe without treatment
- Symptomatic: Fluconazole 400 mg daily for 6-12 months
- Severe disease: Amphotericin B plus flucytosine
Immunocompromised Patients
- All cases: Require antifungal treatment
- Mild-moderate: Fluconazole 400 mg daily
- Severe: Amphotericin B-based therapy
Alternative Antifungal Agents
- Voriconazole: 6 mg/kg IV q12h x 2 doses, then 4 mg/kg q12h
- Posaconazole: 300 mg PO twice daily
- Isavuconazole: 200 mg PO/IV daily
- Itraconazole: 200 mg PO twice daily (limited use)
Management of Complications
Increased Intracranial Pressure
- Serial lumbar punctures: Remove 10-30 mL CSF
- Ventricular drainage: For severe cases
- Corticosteroids: Generally avoided
- Mannitol: Temporary measure
Immune Reconstitution Inflammatory Syndrome (IRIS)
- Recognition: Worsening symptoms with immune recovery
- Management: Continue antifungal therapy
- Corticosteroids: Consider for severe cases
- ART timing: Delay in HIV patients with CNS disease
Supportive Care
- Fluid management: Maintain euvolemia
- Electrolyte monitoring: Correct imbalances
- Seizure management: Anticonvulsants if needed
- Pain control: Adequate analgesia
- Nutritional support: Ensure adequate nutrition
Monitoring Treatment Response
- Clinical improvement: Symptom resolution
- CSF analysis: Sterilization, pressure normalization
- Antigen levels: Declining cryptococcal antigen titers
- Imaging studies: Resolution of lesions
- Drug levels: Therapeutic monitoring for some agents
Special Populations
- Pregnancy: Amphotericin B preferred
- Pediatric: Weight-based dosing
- Renal impairment: Dose adjustments for azoles
- Liver disease: Monitor hepatotoxicity
Prevention
Prevention strategies for cryptococcosis focus on reducing exposure to environmental sources and implementing prophylaxis in high-risk populations.
Environmental Prevention
- Avoid high-risk areas: Areas with heavy pigeon droppings
- Protective equipment: Masks when cleaning contaminated areas
- Proper ventilation: Ensure good air circulation
- Building maintenance: Regular cleaning of air conditioning systems
- Urban planning: Control pigeon populations in public areas
High-Risk Population Strategies
HIV/AIDS Patients
- Routine screening: CrAg testing when CD4+ <100 cells/μL
- Pre-emptive therapy: Fluconazole for positive CrAg, asymptomatic
- ART adherence: Maintain suppressed viral load
- Immune recovery: Goal CD4+ >200 cells/μL
Transplant Recipients
- Pre-transplant screening: CrAg testing
- Environmental counseling: Avoid high-risk exposures
- Monitoring: Regular assessment for signs of infection
- Prophylaxis: Consider in very high-risk patients
Primary Prophylaxis
- Fluconazole: 200 mg daily for very high-risk patients
- Indications: CD4+ <50 cells/μL in endemic areas
- Duration: Until immune reconstitution
- Monitoring: Drug interactions, resistance
Secondary Prophylaxis
- Maintenance therapy: Fluconazole 200 mg daily
- Duration: Until immune recovery in HIV patients
- Discontinuation criteria: CD4+ >100 cells/μL for 6 months
- Monitoring: No evidence of active disease
Occupational Safety
- Healthcare workers: Proper handling of specimens
- Laboratory safety: BSL-2 procedures for cultures
- Construction workers: Respiratory protection in dust areas
- Bird handlers: Use protective equipment
Travel Recommendations
- Endemic area travel: Avoid high-risk activities
- Immunocompromised travelers: Medical consultation
- Prophylaxis consideration: For very high-risk travelers
- Post-travel monitoring: Symptom awareness
Public Health Measures
- Surveillance: Monitoring disease trends
- Education: Healthcare provider awareness
- Screening programs: Routine CrAg testing
- Research: Vaccine development efforts
When to See a Doctor
Cryptococcosis can be a life-threatening infection, particularly in immunocompromised individuals. Early recognition and treatment are crucial for preventing serious complications and death.
Seek Emergency Care (Call 911) If You Experience:
- Severe headache with neck stiffness
- Confusion or altered mental status
- Seizures or loss of consciousness
- High fever with neurological symptoms
- Difficulty breathing or severe shortness of breath
- Signs of severe illness in immunocompromised patients
- Vision changes with severe headache
Schedule Urgent Medical Evaluation For:
- Persistent headache lasting more than a few days
- Fever with cough in immunocompromised patients
- New skin lesions in high-risk individuals
- Unexplained weight loss and night sweats
- Persistent cough with chest pain
- New neurological symptoms (vision changes, weakness)
- Worsening symptoms despite treatment
High-Risk Individuals Should See a Doctor For:
- Any new respiratory symptoms
- Persistent fever without obvious cause
- Changes in mental status or mood
- New or worsening headaches
- Skin lesions that don't heal
- Unexplained fatigue or weakness
Routine Screening Recommended For:
- HIV patients with CD4+ count <100 cells/μL
- Organ transplant recipients
- Patients on high-dose immunosuppressive therapy
- Individuals living in or traveling to endemic areas
Special Populations
HIV/AIDS Patients
- Regular cryptococcal antigen screening
- Any new neurological symptoms
- Opportunistic infection evaluation
- Pre-ART screening and monitoring
Transplant Recipients
- Pre-transplant infectious disease evaluation
- Post-transplant monitoring visits
- Any signs of infection
- Travel-related exposures
Cancer Patients
- During chemotherapy or immunosuppression
- Fever and neutropenia
- Respiratory symptoms
- Neurological changes
Before Your Appointment
- Document symptom timeline and progression
- List all medications and supplements
- Prepare medical history including immunocompromising conditions
- Note recent travel or exposure history
- Bring previous test results and imaging studies
Frequently Asked Questions
No, cryptococcosis is not contagious and cannot be spread from person to person. The infection is acquired by inhaling fungal spores from environmental sources such as bird droppings or contaminated soil.
People with compromised immune systems are at highest risk, particularly those with HIV/AIDS (CD4+ count <100), organ transplant recipients, cancer patients receiving chemotherapy, and individuals on long-term corticosteroids or immunosuppressive medications.
Cryptococcal meningitis is a life-threatening condition with mortality rates exceeding 70% without treatment. Even with appropriate antifungal therapy, mortality remains significant. Early diagnosis and immediate treatment are crucial for survival.
Treatment duration varies by site of infection and immune status. Cryptococcal meningitis typically requires 2 weeks of intensive therapy, followed by 8 weeks of consolidation and months of maintenance therapy. Pulmonary disease may require 6-12 months of treatment.
Prevention focuses on avoiding environmental exposures (areas with bird droppings) and screening high-risk patients. HIV patients with low CD4+ counts should receive routine cryptococcal antigen screening. Prophylactic antifungal therapy may be considered in very high-risk individuals.
Prognosis depends on the site of infection, patient's immune status, and promptness of treatment. Pulmonary cryptococcosis in immunocompetent individuals has an excellent prognosis. However, disseminated disease or CNS involvement in immunocompromised patients carries significant mortality risk even with treatment.
References
- Perfect JR, et al. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the IDSA. Clinical Infectious Diseases. 2010.
- World Health Organization. Guidelines for the diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children. WHO. 2018.
- Rajasingham R, et al. Global burden of disease of HIV-associated cryptococcal meningitis. Lancet Infectious Diseases. 2017.
- Williamson PR, et al. Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy. Nature Reviews Neurology. 2017.
- Boulware DR, et al. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. New England Journal of Medicine. 2014.
- Centers for Disease Control and Prevention. Cryptococcosis. CDC. 2024.