Mycology Revision: Fungal Infections, OmpathStudy

MYCOLOGY AND VIROLOGY Revision and Must-Know Concepts Author: Daniel Rosasi --- PART ONE: MYCOLOGY 1. True Pathogenic vs Opportunistic Mycoses A comparison of the two categories of fungal disease based on virulence, host response, and organism behavior. Property True Pathogenic Infections Opportunistic Infections --- --- --- Degree of virulence Well developed Limited Host condition Resistance high or low Resistance low Primary portal of entry Respiratory Respiratory, mucocutaneous Nature of infection Usually primary, pulmonary and systemic; usually asymptomatic Varies from superficial skin to pulmonary and systemic; usually symptomatic Nature of immunity Well developed, specific Weak, short-lived Infecting form Primarily conidia Conidia or mycelia Thermal dimorphism Shows strongly Not usually Habitat of fungus Soil Varies from soil to flora of humans and animals Geographical location Restricted to endemic regions Distributed worldwide Example organisms Histoplasma capsulatum , Blastomyces dermatitidis Candida , Aspergillus , Pneumocystis jirovecii --- 2. Common Name vs Clinical Name of Disease Several fungal diseases are better known by informal or regional names than by their clinical terms. Darling's disease → Histoplasmosis Valley fever → Coccidioidomycosis South American/Brazilian blastomycosis → Paracoccidioidomycosis Mycotic mycetoma → Pseudoallescheriasis Balanitis → Candidiasis of the penis --- 3. Histoplasmosis (Darling's Disease) A dimorphic fungal infection named after the physician who first described it. Background First described by Samuel Darling "Histio" = within histiocytes "Plasma" = resembled Plasmodium Causative agent Histoplasma capsulatum Small dimorphic fungus Facultative intracellular yeast Localizes in phagocytic cells, including circulating monocytes Despite the name, it has no capsule Filamentous form found in soil enriched with bat or bird guano Isolated worldwide; endemic in the USA Pathogenesis Microconidia inhaled into lungs Microconidia convert to yeast form Neutrophils, macrophages, lymphocytes, and NK cells respond Organisms confined mainly to macrophages Less commonly seen in tissue spaces Occasionally seen in peripheral WBCs in disseminated infection Clinical manifestations Acute pulmonary — self-limited; dry cough, fever, fatigue Chronic pulmonary — fatigue, fever, night sweats, chronic cough, weight loss Disseminated — common in children under 2 years and adolescents HIV-positive patients — higher risk of lymphadenopathy, hepatosplenomegaly, skin and mucous membrane lesions Laboratory diagnosis Microscopy of thick blood smear, bone marrow, or liver biopsy for intracellular yeast Serology (complement fixation) for antibodies/antigens Skin testing with histoplasmin Blood test for antibodies PCR for antigen detection in blood Bacterial culture to rule out other organisms Chest X-ray CT scan of chest Histopathology and cytology with staining Treatment Oral itraconazole 200 mg/day for 6–12 weeks Amphotericin B 0.7–1.0 mg/kg daily --- 4. Cryptococcosis (Disease Associated with Pigeon Feces) An opportunistic yeast infection strongly linked to bird droppings and immunocompromise. Causative agent Cryptococcus neoformans Occurrence Worldwide fungus, mostly in decaying matter Yeast with an antigenic polysaccharide capsule Isolated from fruits, milk, vegetation, soil, and pigeon feces Opportunistic fungus Pathogenesis Common in AIDS/immunocompromised patients Acquired mainly by inhalation Occasionally acquired through skin or mucosa Most infections asymptomatic Pulmonary form may cause mild pneumonitis Disseminated infection leads to visceral, cutaneous, and meningeal disease Visceral form mimics tuberculosis and cancer Cryptococcal meningitis is the most serious form; can resemble tuberculous meningitis Clinical manifestations Fever and headache Nausea, vomiting, malaise Laboratory diagnosis Cryptococcal antigen latex particle agglutination test on CSF India ink or nigrosine wet mount — shows encapsulated yeast Confirmation by culture of CSF Treatment Fluconazole 400 mg/day for 8–10 weeks Flucytosine 100 mg/kg/day for 2 weeks --- 5. Risk Factors for Fungal Infections Conditions and practices that increase susceptibility to fungal disease. Humidity Immunosuppression Poor hygiene Cytotoxic chemotherapy Organ and bone marrow transplant Indwelling IV catheters Broad-spectrum antimicrobial use --- 6. Virulence Factors Used by Fungi How different structural and physiological traits help fungi establish disease. Virulence Factor Function Associated Pathogens --- --- --- Cell wall glycoproteins Adherence to epithelial surfaces Candida species Melanin pigment Shields against immune cells, hydrolyses tissue Cr. neoformans , W. dermatitidis Capsules, glucans Anti-phagocytic Cr. neoformans Thermotolerance Survive and replicate at 37°C Human pathogens generally Resistance to microbicidal products (e.g. H2O2) Evasion of host defense by tissue phase (yeast/spherule) of virulent dimorphic fungi B