Opportunistic mycosis Dr.Huda Ibrahim Mycology Lec,7 Opportunistic mycosis Dr.Huda Ibrahim

Oppurtunistic mycosis Ordinary fungi causing extraordinary disease Infections due to fungi of low virulence in patients who are immunologically compromised

Opportunistic fungi 1. Saprophytic - from the environment e.g.,Cryptococcus sp. , Aspergillus, Zycomycetes. 2. Endogenous – a commensal organism e.g., Candida sp. Include many species from: A (Aspergillus) To Z (Zygomyces)

Predisposing Factors: Providing a Route/ Source Antibiotics Burns and other skin problems Catheter- related problems Devices (prosthetic) Effects on mucosal integrity Fungus isolated previously

Inducing Immunosuppression AIDS Bone marrow/ organ transplantation Cancer: Leukemia, lymphoma etc Drugs: Cytotoxic drugs,steroids etc Endocrine related: Diabetes Failure of organs: multi-organ

Candida albicans and other Candida species Harmless inhabitants of the skin and mucous membranes of all humans Normal immune system keeps candida on body surfaces As Candida is present in practically all humans, it has many opportunities to cause endogenous infections in compromised host - so, Candida infections are the most frequent opportunistic fungal infections. Other Candida species are: C.tropicalis, C.krusei, C.parapsilosis, C.glabrata,

THE MOST IMPORTANT RISK FACTORS 1. Neutropenia(less than 100 N/L) 2. Diabetes mellitus 3. AIDS 5. Myeloperoxidase defects 6. Broad-spectrum antibiotics In diabetic patients, fusion of lysosome in phagocytes is greatly impaired.

THE MOST IMPORTANT RISK FACTORS 7. Indwelling catethers 8. Major surgery 9. Organ transplantation 10. Neonates 11. Severity of any illness 12. Intravenous drug addicts

INVASIVE CANDIDIASIS If phagocytic system is compromised, infection spreads to many organs and causes focal infection in these organs (kidney ,eye ,heart , liver , meninges) mortality of candidemia is 30-40% Prophylactic antifungal drugs during cytotoxic course of therapy

DIAGNOSIS OF INVASIVE CANDIDIASIS Gram stain and isolation from blood, CSF , urine ,sputum or peritoneal fluid Serology PCR (promising) isolation and/or pathology positive of organ involved

EPIDEMIOLOGY Although candidiasis is endogenous in most cases, cross infections are described, especially in intensive care unit patients. Account for 80% of nosocomial fungal infections Account for 30% of deaths from nosocomial infections Handwashing is the most important activity to prevent spread of many hospital pathogens, and of Candida too.

Cryptococcosis and Cryptococcus neoformans Cryptococcus neoformans causes cryptococcosis. A widespread encapsulated yeast that inhabits soil around pigeon roosts Common infection of AIDS, cancer or diabetes patients Infection of lungs leads to cough, fever, and lung nodules Dissemination to meninges and brain can cause severe neurological disturbance and death.

Pulmonary Cryptococcus

Diagnosis Microscopic Culture India Ink for capsule stain (50-80% + CSF) Gram Calcoflur white Silver stain Culture Bird seed agar Routine blood culture

Diagnosis Serology Radiology Latex agglutination, EIA, 90% sensitive & specific Radiology CXR – infiltrates, nodules, lymphadenopathy, cavitation, effusion CT/MRI – 50% normal, hydrocephalus

Therapy – Cryptococcal meningitis Amphotericin B +/- flucytosine Fluconazole Amphotercin x 2 wk then fluconazole 400-800 mg/d x 8-10 wk Chronic suppression fluconazole 200 mg/d

Aspergillosis: Diseases of the Genus Aspergillus Very common airborne soil fungus 600 species, 8 involved in human disease; A. fumigatus most commonly Serious opportunistic threat to AIDS, leukemia, and transplant patients Infection usually occurs in lungs – spores germinate in lungs and form fungal balls; can colonize sinuses, ear canals, eyelids, and conjunctiva Invasive aspergillosis can produce necrotic pneumonia, and infection of brain, heart, and other organs. Amphotericin B and nystatin

Zygomycosis Zygomycota are extremely abundant saprophytic fungi found in soil, water, organic debris, and food. Genera most often involved are Rhizopus, Absidia, and Mucor. Usually harmless air contaminants invade the membranes of the nose, eyes, heart, and brain of people (Rhinocerebral mucormycosis) with diabetes and malnutrition, with severe consequences. main host defense is phagocytosis

Control Diabetes ,surgery & amphotericin B Prognosis: very poor Diagnosis is made by direct smear and by isolation of molds from respiratory secretions or biopsy specimens. Treatment: Control Diabetes ,surgery & amphotericin B Prognosis: very poor Pulmonary infection can also occur, with very high mortality rate. Diagnosis is made by direct smear and by isolation of molds from respiratory secretions or biopsy specimens. 20

Diagnosis of opportunistic infections requires a high index of suspicion Atypical signs or symptoms Unusual organ affinity Outside the endemic area Unusual Histopathology Etiologic agent may be a “saprophyte” Serological response may be suppressed

A typical sign & symptoms Malasezzia furfur Tinea versicolor (mild disease in normal person) can cause disseminated infection--------Particularly in patients receiving hyperalimentation (compromsed pt..

Unusual organ affinity Immunocompromised patients can develop hepatic candidiasis Liver infected with Candida albicans

Outside Endemic Area Disseminated coccidioidomycosis, Histoplasmosis (not pulmonary)

Unusual Histopathology NORMAL HOST PYOGENIC GRANULOMATOUS IMMUNODEFICIENT HOST NECROTIC

Unusual pathogen Penicillium marneffei Usually not a pathogen The only dimorphic penicillium Produces a red pigment Endemic in the Far East

IMPROVING TREATMENT New Drugs New therapeutic regimen Aggressive therapy Conjunctive therapy

IMPROVING TREATMENT New Drugs Lipid Amphotericin B Third generation azoles (Posaconazole, Voriconazole) New classes of antifungal agents (Echinocandins)

New Therapeutic Regimen IMPROVING TREATMENT New Therapeutic Regimen Combination Therapy Simultaneously administering two drugs Sequential Tx with two or more drugs Alternate Administration of two or more

FOR IMMUNOCOMPROMISED PATIENTS IMPROVING TREATMENT AGGRESSIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTS Prophylactic – Anti-fungal agents at, or near, the time of chemotherapy Fluconazole , Posaconazole now approved.

IMPROVING TREATMENT CONJUNJUNCTIVE THERAPY FOR IMMUNOCOMPROMISED PATIENTS The use of anti-fungal agents with immunotherapy: *Interferons Colony stimulating factors Interleukins

OPPORTUNISTIC FUNGAL INFECTIONS ARE: difficult to diagnose difficult to treat difficult to prevent more and more frequent a great challenge for a future work in all fields 36

“Only the prepared mind can help the impaired host” Libero Ajello, Chief Mycology Division, CDC 1972

MYCOLGISTS have more FUNGI