Aspergillosis Dr. Ansari Systemic Fungal infections • Primary (endemic, dimorphic) fungal pathogen – Histoplama capsulatum – Coccidioides immitis – Blastomyces dermatitidis – Paracoccidioides Secondary (opportunistic) fungal infections • Aspergillosis • Candidiasis • Cryptococcosis • Mucormycosis • Penicillosis marneffei • Pneumocystis jirovecii pneumonia (PCP) Definition: Aspergillosis: Tissue invasive disease Allergic disease Aspergilloma (fungus ball) Mycotoxicosis: A.flavus and A.parasiticus Otomycosis Onychomycosis Keratitis Mycetoma Animals Agents: Aspergillus Farms Ubiquitous Cellars Exogenous Hay barns Agents: Aspergillus fumigatus (invasive) 90% Fumigatus & Clavatus(allergic) Asp.flavus Asp.terreus Asp.niger A.flavus A.flavus A.niger A.fumigatus Asp.fumigatus Asp.fumigatus Asp.flavus Asp niger Aspergillus terreus Predisposing factors: For invasive aspergillosis neutrophil deficiencies or dysfunction children with chronic granulomatous disease (CGD) Transplant Corticostreoid Pathogenesis: A.fumigatus Fast.dimeter(2-5) Termotolorant hydrophobic Pathogenesis: Aflatoxines Fumagillin Ochratoxine A Gliotoxin Clinical manifestations of Aspergillus: Clinical manifestations: 1-Allergic disease (lung and sinus): Allergic bronchopulmonary aspergillosis(ABPA) Allergic aspergillus sinusitis 2-Aspergilloma (lung and sinus) Clinical manifestations: 3-Invasive disease: Invasive pulmonary aspergillosis (IPA) invasive aspergillus sinusitis Clinical manifestations: 4-Brain 5-Endophthalmitis 6-Cutaneous aspergillosis Allergic disease: 1-Allergic bronchopulmonary aspergillosis (ABPA): Underlying asthma Cystic fibrosis (IgG.IgE) Plug. Charcot-leyden crystals Cortico… Typical sputum plug of allergic bronchopulmonary aspergillosis 2-Allergic aspergillus sinusitis: Black fungi. nasal surgery Aspergilloma (lung): Preexisting pulmonary cavities Cysts or Tuberclosis Pseudoallescheria Mucorales Aspergilloma (lung): Some: Asymptomatic Cough. IgG in serum Difficult to treat Surgery Aspergilloma (Fungus ball) Aspergilloma (sinus): Maxillary and ethmoid sinus cavities Endodontic treatment of the upper jaw Invasive pulmonary aspergillosis (IPA) (80-90%) Most immunocompromised patients: Bone marrow transplant recipients (acute IPA) Less immunocompromised patients: AIDS (chronic IPA) Acute IPA: The earliest symptoms the nodules may cavitate The major problem: Hemoptysis Invasive Pulmonary Aspergillosis — A Nodular Infarct Surrounded by a Hemorrhagic Rim Chronic IPA: Lower incidence of chronic IPA A substantial minority: No immunocompromisig factors Chronic IPA: Symptomatic: for weeks or months Chronic IPA: Cavitation(Chest radiography) Difficulty…lung aspergiloma Definitive diagnosis: biopsy Strongly positive Aspergillus antibodies in serum Culture + Invasive Aspergillus sinusitis: Acute Chronic Granulomatous (Asp.flavus.paranasal) Acute rhinosinusitis: Neutropenic patients Bone marrow transplant recipients Acute rhinosinusitis: Fever Cough Epistaxis Headache Nasal discharge Sinus pain Destructive lesion of the maxillary sinuses, anterior palate, and nasal passages Chronic invasive aspergillus sinusitis: Most patients: No immunocompromising factors A substantial minority: Diabetic. Brain: The worst manifestation Bone marrow transplant (25-50%) Complication of neurosergery Brain: The most immunocompromised patients(attack) Less immunocompromised patients (Headace) Aspergillus meningitis is rare. Disseminated Aspergillosis of a Brain Brain: CT scan: Abscess Definitive dignosis: Biopsy Aspiration of a cerebral lesion Endophthalmitis: Uncommon After penetrating eye surgery or trauma Hematogenous endophthalmitis (endocardit …) Cutaneous: In neutropenic patients In premuture neonates In AIDS patients Primary cutaneous aspergillosis Site of an intravenous catheter Leukemia Cutaneous aspergillosis Laboratory Diagnosis: 1-Collection of samples 2-Direct examination 3-Culture 4-Serology 5-Molecular techniques Direct examination: KOH GMS H & E PAS Dichotomus hyphae 2.5-8 µm Section of plug: GMS Section of invasive aspergillosis: H &E Biopsy of maxillary sinus: PAS Culture: Media: SDA + C (SC) Malt extract agar Czapek’s agar Temprature: 25°- 37° C Aspergillus antibody tests: Poor sensitivity in very immunocompromised patients with invasive aspergillosis ID, CF, CIE Aspergillus detection system: Immunodiffusion & Complement Fixation for Antibody Detection Antigen detection test: Circulating galactomannan antigen (2-3) Sandwich ELISA ( 1-3 D-glucan) Latex aglu… In allergic form: RAST test ( specific IgE) DNA detection: Molecular techniques Treatment: Allergic: Prednisone Itraconazole Prevention: High-dose inhaled steroids Aspergilloma: Surgery Amphotericin B Treatment: Invasive: Surgery Voriconazole Amphotericin B Itraconazole Caspofungin Mucormycosis Definition: Mucormycosis refers to severe opportunistic infection with fungi of the order Mucorales. Hence the name “ mucormycosis. Agents: Worldwide, airborne Bread, fruits, decaying vegetations, soil, animal dung 1-Rhizopus 2-Rhizomucor 3-Mucor ORGANISMS Rhizopus species are the most common causative organisms. Other less frequent species include: Absidia, Cunninghamella, Saksenaea, and Apophysomyces Predisposing factors Pathogenesis: Diabetes mellitus Abraded skin Corticosteroids Transplant Pathogenesis: In AIDS: Importance of the neutrophils Special affinity for blood vessels: Thrombosis and tissue necrosis Clinical manifestations: 1-Rhinocerebral mucormycosis 2-Pulmonary mucormycosis 3-Cutaneous mucormycosis 4-Gastrointestinal mucormycosis 5-CNS mucormycosis Rhinocerebral mucormycosis Predisposing factors: Diabetes mellitus Leukemia Broad-spectrum antibacterial drugs Bone marrow transplantation Mucormycosis Mucormycosis-Diabetes mellitus Mucormycosis of the nasal sinuses in a diabetic Rhinocerebral mucormycosis; ophthalmoplegia, fixatin of pupil, and haziness in the anterior chamber Rhinocerebral mucormycosis; sloughing of nasal area Pulmonary mucormycosis Pulmonary mucormycosis Clinical manifestations: Fever Cough Dyspnea Hemoptysis Cutaneous mucormycosis Primary cutaneous mucornycosis Gastrointestinal mucormycosis: Predisposing factor: Protein-calorie malnutrition Kidney transplant recipients Gastrointestinal mucormycosis Stomach Ileum Colon Initial manifestations: Abdominal pain Nausea and vomiting Fever Intra-abdominal abscess CNS mucormycosis: Rare Severely debilitated patients Mode of entry: nose or paranasal sinuses Decreasing consciousness CNS mucormycosis: Open head trauma After intravenous injection of illicit drugs Laboratory Diagnosis: 1-Collection of samples 2-Direct examnation 3-Culture 4-Serology Collection of samples: Sputum BAL Aspirates and secretions of nose Skin scrapings Paranasal sinus biopsy Gasteric washings Touch slides prepared from the biopsy specimens Direct examination: KOH for touch slides H & E GMS PAS Direct examination: Broad, nonseptate hyphae 10 to 20 µm in diameter At right angle Ribbon-like hyphae Aspergillus, Fusarium, Pseudoallescheria spp. LCB: 10-15 µm H & E Culture: Media: SDA + C (SC) Sterile bread Temprature: 25°- 37° C Serology: Remains investigational Prevention: No methods In patients with severe neutropenia (bone marrow transplant or leukemia): HEPA (High-Efficiency Particulate Air filters) Treatment: Treat of underlying disease Doses of immunosuppressive drugs: Decreased Stopped Treatment: Standard therapy for invasive mucormycosis: Aggressive surgical debridement of necrotic tissue Amphotericin B Posaconazole Isavoconazole (2015) Treatment: Two factors: 1-Early diagnosis 2-Resolution of predisposing problems Overall mortality rate: 50% *** .