Fungal infections

ALMA E. MALILONG, MD, FPSP

Fungal infections
Infections termed mycoses Eukaryotes that grow by budding (yeasts) or filamentous extensions (hyphae) Dimorphic fungiyeast at human body temperature mold form at room temp

Yeasts CANDIDIASIS
Normal flora of skin, mouth, GIT, vagina Versatile commensals Superficial lesions in healthy persons Disseminated infections in immunocompromised hosts C. albicans grows best on warm, moist surfaces oral thrush, diaper rash, vaginitis Diabetics & burn patients susceptible

Yeasts CANDIDIASIS
Introduced via IV lines, catheters Associated with neutropenia due to leukemia or anticancer therapy Course of sepsis less rampant than that of bacterial etiology leads to shock, DIC

pathogenesis
Phenotypic switching to adapt to changes in host environment Adhesins for adherece, morphogenesis, signalling Candida yeast- bind to mannose receptors Candida hyphae- bind to complement receptor 3 (CR3) and Fc receptor Complex immune response

pathogenesis
Innate immunity, T-cells- vs cutaneous & mucosal infection Neutrophils & MN phagocytes- vs systemic infections Dendritic cells Hyphae escape from phagosomes & enter cytoplasm Enzymes for invasiveness: 9 aspartyl proteinases, adenosine

morphology
Blastoconidia, pseudohyphae, true hyphae (with septae)
*pseudohyphae- budding yeast cells joined end-to-end at constrictions, thus simulating true hyphae

Special fungal stains: Gomori methenamine Ag periodic acid-Schiff

morphology
Most common- superficial infection of oral cavity (thrush) gray-white, dirty-looking pseudomembranes composed of matted organisms & inflammatory debris --mucosal hyperemia deep to the surface -children, debilitated & immunocompromised patients

morphology
Candida esophagitis AIDS, hematolymphoid malignancies Endoscopy: white plaques Candida vaginitis Common vaginal infection Diabetic, pregnant, OCPs Intense itch, thick curdlike discharge

morphology
Cutaneous candidiasis Onychomycosis- nail proper Paronychia- nail folds Folliculitis- hair follicles Intertrigo- intertriginous skin Balanitis- penile skin Diaper rash

morphology
Chronic mucocutaneous candidiasis Chronic, refractory Skin, hair, nails Underlying T-cell defects Endocrinopathies, hypoparathyroidism, Addisons disease Dissemination is rare

morphology
Invasive candidiasis Blood-borne dissemination to various organs Renal abscesses Myocardial abscesses, endocarditis Brain Endophthalmitis Hepatic abscesses Candida pneumonia

Yeasts CRYPTOCOCCOSIS
Cryptococcus neoformans Encapsulated yeast Meningoencephalitis in normal individuals Opportunistic infection- more frequent High-dose corticosteroids a major risk factor Soil & bird droppings inhaled

Yeasts CRYPTOCOCCOSIS
Virulence factors: Polysaccharide capsule Melanin production Enzymes- laccase

Granulomatous reaction- yeast cells persist within macrophages

morphology
Only yeast forms (no hyphal or pseudohyphal forms) 5-10 m, thick gelatinous capsule (stains an intense red with PAS & mucicarmine) Detected by Ab-coated beads, India ink

India ink preparation of CSF showing a typical yeast cell of C. neoformans surrounded by a characteristic wide gelatinous capsule.

Cryptococcosis of lung in patient with AIDS. Mucicarmine stain. Histopathology of lung shows widened alveolar septum containing a few inflammatory cells and numerous yeasts of Cryptococcus neoformans. The inner layer of the yeast capsule stains red.

morphology
Lung is the primary site of localization- solitary pulmonary granuloma Major lesions are in CNS meninges, gray matter, basal nuclei Variable response Immunocompromised- may have no inflammatory reaction Healthy patients- granulomatous reaction May disseminate to other organs

X-ray showing pulmonary cryptococcal infection [right upper lobe].

MRI scan showing multiple cryptococcomas [white masses] in the brain.

Molds ASPERGILLOSIS
Allergies (brewers lung) Sinusitis, oneumonia, fungemia in immunocompromised patients Neutropenia, corticosteroids Saprophytic sporulates to produce conidia (asexual spores)aerosolized Immune status of host more important than fungal pathogenicity Aspergillus fumigatus- most common species to cause disease

Conidia of Aspergillus

pathogenesis
Transmitted by airborne conidia Major portal of entry: LUNG Small spores (2-3m) reach alveoli Killed by alveolar macrophages Virulence factors: adhesins antioxidants- melanin, superoxide dismutase enzymes toxins

pathogenesis
Aflatoxin- carcinogen made by aspergillus on surface of peanutsliver CA TH2 reaction- alveolitis Allergic bronchopulmonary aspergillosisasthmatic patients results in COPD

morphology
Colonizing aspergillosis (aspergilloma) Growth in pulmonary cavities with tissue invasion (including nose) Pre-existing Tb, abscesses, bronchiectasis, old infarcts Fungus balls (masses of hyphae) lying free within cavities Sparse inflammation, or chronic inflammation with fibrosis Recurrent hemoptysis

This chest radiograph shows probable aspergillosis with an aspergilloma, or fungus ball in the upper lobe of the right lung. Lung diseases that damage a lung can cause cavities that can leave a person more susceptible to developing an aspergilloma, or fungus ball. The fungus can then begin secreting toxic and allergic products.

Aspergillosis, nasal cavity of deer

Aspergillus pneumonia in lung

Aspergillosis. Human mouth. Gomori's silver methenamine stain

Lung: Aspergillus hyphae in fungal pneumonia

morphology
Invasive aspergillosis Opportunistic infection, immunosuppressed & debilitated hosts Widespread hematogenous spread Heart valves, brain, kidneys common Lung: necrotizing pneumonia with sharply delineated, rounded gray foci with hemorrhagic borders (target lesions)

morphology
Forms fruiting bodies & septate filaments, 510m, branching at acute angles (400) Invade blood vessels hemorrhage & infarction superimposed on necrotizing tissue reaction Rhinocerebral infection similar to that of mucormycosis

Molds ZYMYCOSIS (mucormycosis)

Opportunistic infection bread mold fungi, class Zygomycetes Rhizopus, Absidia, Cunninghamella, Mucor Widely distributed in nature Infected immunosuppressed hosts Neutropenia, DM, corticosteroids, breakdown of cutaneous barrier (wounds)

pathogenesis
Transmitted by airborne asexual spores Infection in sinuses, lungs Infection following percutaneous exposure or ingestion Initial defense: macrophages Neutrophils have a key role in killing during established infection Proteolytic and lipolytic enzymes Thermotolerant spores

morphology
Nonseptate, irregularly wide (6-50m) fungal hyphae, frequent right angle branching 10 sites of invasion: lungs, sinuses, GIT Rhinocerebral mucormycosis spread from nasal sinuses to orbit to brain Local tissue necrosis, arterial wall invasion, penetration of periorbital tissues and cranial vault followed by meningoencephalitis, sometime cerebral infarction

morphology
Lung involvement may be 20 to rhinocerebral disease or primary in immunocompromised hosts Hemorrhagic pneumonia, vascular thrombi, distal infarctions

Lung parenchyma with hyphae

Involvement of nose, sinuses and orbit

Endarteritis caused by mucormycosis