Systemic and Opportunistic fungal infection of the respiratory I B29.pdf

Systemic and Opportunistic fungal infection of the respiratory I MRES Batch 29 1 Objectives The objective of the lecture is to discuss systemic fungal infections, their modes of acquisition, predisposing factors and the...

Systemic and Opportunistic fungal infection of the respiratory I MRES Batch 29 1 Objectives The objective of the lecture is to discuss systemic fungal infections, their modes of acquisition, predisposing factors and the laboratory diagnosis of these mycotic agents. Topic outcomes ❖Discuss the important systemic mycoses – histoplasmosis, blastomycosis, coccidioidomycosis and paracoccidioidomycosis ❖Explain the mode of acquisition and predisposing host factors ❖Discuss the principles involved in the laboratory diagnosis of these causative agents of systemic mycoses What is systemic mycosis? Involve skin and deep viscera May become widely disseminated Predilection for specific organs By inhalation of spores True pathogens can infect healthy host Systemic mycoses are fungal infections affecting internal organs. In the right circumstances the fungi enter the body via the lungs, through the gut, paranasal sinuses or skin. TRUE SYSTEMIC (ENDEMIC) MYCOSES Coccidioidomycosis Histoplasmosis Blastomycosis Paracoccidioidomycosis TRUE SYSTEMIC MYCOSES General features Causative agents: thermally dimorphic fungi that exist in nature, soil Tissue 37°C: Yeast /Spherules filled with endospores 25°C: hyphae, arthroconidia Geographic distribution varies Inhalation →pulmonary inf. → dissemination No evidence of transmission among humans or animals Otherwise healthy individuals are infected Thermal Dimorphism 25 degrees - Hyphal state 37 degrees – Yeast State Thermal dimorphism is a property of true fungal pathogens but is uncommon for opportunistic pathogens 6 Endemic Mycoses Those fungus infections with a limited geographic distribution. They are all caused by dimorphic fungi PATIENT HISTORY Medical Travel Occupation Avocation Predisposing host factors Poor blood circulation Diabetes weakened immune system from: HIV/AIDS. Cancer or cancer treatments Immunosuppressant medications (for autoimmune conditions or organ, stem cell or bone marrow transplants). Pathogenesis of systemic fungi Systemic fungal infections usually originate either in the lungs (Aspergillus, Cryptococcus, Mucorales spp., as a result of inhalation) or from endogenous flora (Candida spp. as a result of infected lines or leakage from the gastrointestinal tract), and may spread to many other organs. Fungi gain access to host tissues by traumatic implantation or inhalation. The severity of disease caused by these organisms depends upon the size of the inoculum, magnitude of tissue destruction, the ability of the fungi to multiply in tissues, and the immunologic status of the host.  COCCIDIOIDOMYCOSIS Clinical findings Coccidioides immitis PRIMARY INF. ✓Asymptomatic in most ✓Fever, chest pain, cough, weight loss ✓Nodular lesions in lungs SECONDARY (DISSEMINATED) INF. (1%) ✓Chronic / fulminant ✓Infection of lungs, meninges, bones and skin Coccidioides immitis COCCIDIOIDOMYCOSIS Diagnosis-I Samples: Sputum, tissue 1. Direct examination (KOH; H&E) Spherule 2. Culture SDA: Mold colonies at 25 °C Spherule production in vitro by incubation in an enriched medium at 40°C, 20% CO2  HISTOPLASMOSIS Causative organism: Histoplasma capsulatum Natural reservoir: soil, bat and avian habitats (cave disease) Location: May be prevalent all over the world, but the incidence varies widely (most endemic in Ohio, Mississipi, Kentucky) Micro. Yeast cell in tissue (37°C) Hyphae, microconidia and macroconidia (tuberculate) at 25 °C HISTOPLASMOSIS Pathogenesis Inhalation of microconidia / primary cutaneous inoculation Conversion to budding yeast cells Phagocytosis by alveolar macrophages Fungus lives intracellular in macrophages – ‘immune-evasion’ Restriction of growth or dissemination by bloodstream Suppression of cell-mediated immunity  Histoplasma capsulatum Areas with large amounts of bird/bat droppings are esp. dangerous 17 18 HISTOPLASMOSIS Clinical findings PULMONARY INF. Asymptomatic (%95) / mild / moderate / severe/ chronic cavitary DISSEMINATED INF. (liver, spleen, lymph nodes, bone marrow), mucocutaneous inf. HISTOPLASMOSIS Diagnosis-I Samples: Sputum, tissue, bone marrow, CSF, blood 1. Direct examination: Giemsa / Wright Intra- and extracellular yeast cells 2. Culture: Mold at 25°C Conversion to yeast on an enriched medium at 37°C  Tuberculate macroconidia have a thick wall with distinctive projections on the surface  BLASTOMYCOSIS Etiological agent: Blastomyces dermatitidis Location: America, Africa, Asia Micro.: Yeasts at 37°C--bud is attached to the parent cell by a broad base Hyphae and conidia at 25 °C BLASTOMYCOSIS Pathogenesis Inhalation of infectious particles Primary cutaneous inoculation Infiltration of macrophages and neutrophils and granuloma formation Oxidative killing mechanisms of neutrophils and fungicidal activity of macrophages  BLASTOMYCOSIS Clinical findings ASYMPTOMATIC INF. PULMONARY INF. CHRONIC CUTANEOUS INF. Subcutaneous nodule, ulceration DISSEMINATED INF. Skin, bone, GUT, CNS, spleen  BLASTOMYCOSIS Diagnosis-I Samples: Sputum, tissue 1. Direct micro. exam: KOH, H&E Yeast cells; bud is attached to the parent cell by a broad base 2. Culture: Mould at 25°C Conversion to yeast on an enriched medium at 37°C Blasto Yeast forms with broad-based budding  PARACOCCIDIOIDOMYCOSIS Etio: Paracoccidioides brasiliensis Location: Central and South America Pathogenesis: Inhalation of conidia Micro: At 37°C (in tissue ): multiple budding yeasts; the buds are attached to the parent cell by a narrow base At 25 °C: hyphae and conidia PARACOCCIDIOIDOMYCOSIS Clinical findings ASYMPTOMATIC INF. LATENT FORM (duration variable) SYMPTOMATIC INF. ✓Noduler lesions in lungs ✓Dissemination to other organs (rare)  PARACOCCIDIOIDOMYCOSIS Diagnosis-I Samples: Sputum, tissue 1. Direct micr.ic exam.: KOH, H&E multiply budding yeasts; the buds are attached to the parent cell by a narrow base 2. Culture: Mold at 25°C Conversion to yeast on an enriched medium at 37°C Multiply budding yeast forms in Paracocci- ”Mariner’s wheel” c9c_paracocci_gms THE CAPTAIN’S WHEEL © Ranjith’s Prepared by: Dr. B. Shandra Devi 33