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Infeksi Jamur pada paru-paru Sistem Respirasi

Rizalinda SjahrilBagian Mikrobiologi Fakultas Kedokteran Unhas2010The following fungi cause a variety of infections, clinical manifestation severity varies.Distinguished from opportunistic infection by the ability to cause infection in an otherwise healthy individuals.These fungi are: CryptococcosisBlastomycosisCoccidioidomycosisOpportunistic deep mycoses:AspergillosisZygomycosisCryptococcosisEtiology : Criptococcus neoformans. Replicate by budding new yeast cells 4-6 m, has large characteristic complex polysacharide capsule (>25 m). Major components of the capsule is glucuronoxylomannan (GXM) Culture appearance in Saboraud Dextrose agar containing no cycloheximide*: smooth, creamy, mucoid white colony in 2-3 daysProduce melanin and urease in culture

Cryptococcosis - pathogenesis

Aerosolized spores in soil reach the lung. In tissue, spores start to produce capsule that enables to evade immune response.GXM binds to complement C3 and interfere with antigen presentation.Lung lesions: intense granulomatous inflammationStaining: methenamin silver or Per acid schiffpredisposing conditions: lymphoma, sarcoidosis or treatment of corticosteroid

Cryptococcosis Clinical ManifestationCauses chronic meningitis and pneumonia.Silent hematogenous spread to the brain clusters of cryptococci in the perivasc areas of the gray matterSymptoms:Headache, nausea, staggering gait, dementia, irritability, confusion, blurred visionFever, nuchal rigidity often mildCriptococcal pneumonia is mostly asymptomatic.Chest pain (40%), cough (20%)

Cryptococcosis - diagnosisCryptococcal meningitis: CSF increased pressure, pleocytosis, glucose depressionIsolation of fungi in CSF requires large volume specimen because.?Capsule in CSF can be stained by China InkHistoplasmaEtiology: Histoplasma capsulatumMultiply by budding (blastoconidia)Dimorphic: yeast form 2-4 m at 37oCMold phase at 22-25oC Growth in culture in weeks timeMycelial produces microconidia and macroconidiaDiagnostic structure: tuberculate macroconidiumHistoplasma Clinical ManifestationMost cases are asymtomatic or with fever and coughX-ray : mediastinal lymphadenopathy, infiltrates.Histoplasmin skin test positive in 3 weeks .Severe cases: chills, malaise, chest pain, extensive infiltrates.Residual nodule may continue to enlarge over a year and mimic pulmonary neoplasma.Progressive pulmonary disease resembles pulmonary tuberculosis Histoplasma - PathogenesisReticuloendothelial system is the focus of infection.Initial infection is by inhaled microconidia that changes to yeast form in the host.Phagocytosed (macrophage and PMNs) and may grow inside macrophages by controlling lysosomal pH (increased to neutral)Further lymphatic spread and development of primary lesion is similar to mycobacteria

Histoplasma diagnosisPulmonary histoplasmosis Direct examination or culture of sputum is lowDisseminated histoplasmosis blood and bone marrow, staining by Wright or Hematoxylin Eosin show intracellular histoplasma, tuberculate macroconidium and dimorphismEIA detects Antigen (immunodifusion)Nucleic acid detection Blastomyces Etiologi: Blastomyces dermatitidisDimorphic fungus that changes to mycelial at 25oC. Produces microconidia, but no macroconidia Blastomyces is similar to histoplasma, but larger yeast cells (8-15 m), and broad base buds and thick wall.

Blastomyces clinical manifestationMost clinical features are similar to histoplasmosis (asymtomatic or cough or mild fever).Disseminated infection: skin lesionsBlastomyces - pathogenesisHas surface glucan and glycoprotein adhesin (BAD1) for binding to host cells.Yeast are large cells, thick double walls, extracellularBlastomyces Clinical manifestationPulmonary infection: cough, sputum production, chest pain, fever.Hilar lymphadenopathy, nodular pulmonary infiltrates with alveolar consolidation resembles pulmonary tumor, tuberculosis, other mycosis.Skin lesions: occur on exposed skinBlastomyces - DiagnosisThe presence of large yeast cells with broad-based buds ( blastoconidia) in KOH preparationBiopsy H & E stainingCulture: grow in weeks, but conidia not distinctiveImmunodiffusion testSerologic tests mostly negativeCoccidioides immitisDimorphic fungi filaments and spherulesSpherule= large (12-100m), round walled invasive, multicompartmental structure. The compartment consists of 200-300 endospores, each is then capable to become another spheruleIn Culture and in soil : grow in 2-5 days in mold form regardless of the temperature. Hyphae are septate and thick walled, barrel shaped arthroconidia

Coccidioides immitisIs restricted to Sonoran DesertArthroconidia (2-6 m) are inhaled, enters the bronchioles.Arthroconidia has antiphagocytic action due to the outer portion of the cell wallAthroconidia convert to large spherule Coccidioides immitis clinical aspectsMore than 50% infection shows no symptoms or very mild disease.Symptomatic: malaise, cough, chest pain, fever, arthralgia 2-6 weeks (Valley Fever)Erythema nodosum is common in womenChronic pulmonary infection forms cavityDisseminated disease is more common in men related with racial orientation and immune status

Coccidioides - DiagnosisDirect examination for spherule by KOH prep or biopsy section.Culture Skin and serologic test: conversion 1-4 weeks post infectionComplement fixing test : to measure the extent of the disease.

Organism

GrowthTissueSourcePrimary DiseaseDisseminated DiseaseCulture 25oCCulture 37oCCryptococcus neoformans

Histoplasma capsulatum

Blastomyces dermatitidis

Coccidioides immitis

Paracoccidioides brasiliensisEncaps.Yeast

Mold,TuberculateMacroconidia

Mold

Mold, arthrocon.

Mold

Encaps. Yeast

Small yeast

Yeast

(spherule)

Yeast, mltiple blastokon.Encaps. Yeast

Small intracell yeast

SpherulesEnvironm, worldwide

Environm, US midwest

Environm, Us midwest

Environm, Sonoran desert

Environm, latin americaPnie

Pnie, hilar adenopath

Pnie

Valley fever

Pnie

Chronic meningitis

RES enlargemnt

Skin and bone lesion

Pnie, meningitis, skin, bone

Mukokutan, RESAspergillusAspergillus spp. are molds with branching septate hyphae and characteristic conidia arrangement on he conidiophore.Fluffy colonies 1-2 days 5 days full pigmented growth covering plateMost frequent spp:Aspergillus fumigatusAspergillus flavusAspergillus niger

AspergilosisOccurs in immunocompromised individuals, rapid progression to death.The only sign and symptom may be fever and dry cough.Conidia is small enough to enter the lung Adherence with fibrinogen and laminin.Extracellular elastase, proteinase, phospholipase more virulent

Invasive aspergillosisOccurs in the presence of preexisting pulmonary disease( bronkhiectasis, bronkhitis, asthma, Tb) or immunosuppression.Aspergillus invade tissues by forming branching septate hyphae fungus ball = aspergilloma within preexisting cavity.Invasion into blood vessels hemopthysisErosion to other organs fistulaAspergillus - DiagnosisIsolation and identificationRapid growth, frequently as contaminationSpecimen: lung aspiration, biopsy and bronkhoalveolar lavage ZygomycosisZygomycosis(mucormycosis) is caused by any of zygomycetes (Absidia, Rhizopus, Mucor).SaprophytsImmunocompromised hosts with diabetes are infectedPulmonary disease is similar to other fungiPathologic finding in tissue: ribbonlike non septate hyphae.