1. 1. Prepared by Deepa Devkota Roll no:07 Human Biology 7th batch Aspergillus fumigatus
2. 2. INTRODUCTION Genus Aspergillus include over 185 species,19 species have been listed clinically significant in humans Aspergillus fumigatus :major cause of aspergillosis,other associated with infection are A.niger, A.terres and A.flavus Aspergillosis:oppurtunistic fungal infection caused by Aspergillus species Aspergillous fumigatus Found in >90% of aspergillosis saprophytic; spores are ubiquitous Thermophilic species (growth at 40c and above) angioinvasive
3. 3. Morphology branched,septate hyphae that produces conidial head when exposed to air in culture Conidial head consist of conidiophore with a terminal vesicle on which are phialides Elongated phialide produce columns of spherical conidia :infectious propagule from which mycelial phase of fungus develops
4. 4. EPIDEMIOLOGY bone marrow transplants or solid organ transplants taking high doses of corticosteroids undergoing chemotherapy for cancer chronic granulomateous disease advanced AIDS case,Leukemia patients, cysticercosis Tuberculosis patients
5. 5. PATHOGENESIS Route of infection: Inhalation through respiratory tract Incubation: days to weeks A. fumigatus has about 4 virulence factors alone: 1. Gliotoxin 2. Fumagillin 3. Fumagatin 4. Helvolic acid
6. 6. Clinical manifestations of A.fumigatus 1.Pulmonary disease a. allergic bronchopulmonary aspergillosis b. Aspergilloma(non invasive colonization) c. Dissiminated aspergillosis: CNS aspergillosis PNS aspergillosis 3. Aspergillous endocarditis 4. Cutaneous aspergillosis
7. 7. PULMONARY DISEASES 1)allergic aspergillosis :Inhaled spores provoke a hypersensitive reaction which may be: a. Type I HSR(bronchial asthma) :occur in atopic individuals following sensitization to inhaled aspergillus spores b. Type III HSR(extrinsic alveolitis) c. Combined Type I and Type III HSR(allergic bronchopulmonary aspergillosis-ABPA):asthma with eosinophilia Fungus grows within the lumen of bronchioles, occludes the lumen by fungal plugs Demonstrated in sputum and worsen by development of HSR to fungus
8. 8. Allergic bronchopulmonary aspergillosis(ABPA) Results due to heavy and repeated exposure to spores of Aspergillus species Causes an allergic alveolitis leading to fever,malaise and breathlessness after few hrs of exposure Repeated attack may cause progressive lung damage Fungus grows in longer airways to produce plugs of entangled mycelia and mucus Blockage of segment of lung tissue and even entire lobe Mucous plugs may be coughed out :diagnostic feature
9. 9. Diagnostic features of ABPA Bronchial asthma Pulmonary infiltrates Fleeting shadows Central bronchiectasis Eosinophilia in blood Immune response to A.fumigatus antigen: Type I Type III(Arthus) Total serum IgE(>1000ng/ml) Sputum: eosinophilia(44-100) Culture of A.fumigatus:46-83%(+ve)
10. 10. 2.Aspergilloma Fungus colonize the pre existing cavities often caused by tuberculosis or bronchiectasis or cystic fibrosis Fungus ball: compact mass of fungal mycelia covered by dense fibrous walls(8-10cm in diameter) True aspergilloma surgical removal is necessary as it may cause massive hemoptysis
11. 11. 3.Invasive aspergillosis Growth of fungus in lungs may disseminate mainly to involve kidney and brain Poor prognosis and diagnosed by autopsy Common cause of morbidity and mortality in patients with AIDS, acute leukemia ,bone marrow and solid organ transplantation Scourge of transplantation medicine and surgery Common cause of pneumonic mortality in bone marrow transplantation recipients
12. 12. Case study
13. 13. CNS aspergillosis Hematogenous dissemination from pulmonary and gastrointestinal focus Accounts for 5% of CNS fungal infection Common cause: A.fumigatus while other include A.flavus , A.vesicolor Clinical manifestations:ranges from Abscesses to granuloma Rhinocerebral form to meningitis Intracranial mass(solitary or multiple):followed by granuloma,meningitis and ventriculitis Clinical syndrome: encephalitis,meningoencephalitis,stroke like syndrome Diagnosis:computed tomogram and magnetic resonance
14. 14. Aspergillous endocarditis Common in immunocompromised and those who had prior cardiac surgery Most common fungal species after candida species implicated to endocarditis following cardiothoracic surgery Lesion characterized by large fungal vegetation on heart valves having high frequency of embolism Risk factors: hyperalimentation,antibiotic therapy, iv drug abuse,concomitant bacterial endocarditis Diagnosis: Echocardiography
15. 15. Superficial infections A.flavus and A.fumigatus colonization a)Paranasal sinus:sinusitis b)External ear: otomycosis c)eye: mycotic keratitis
16. 16. Laboratory diagnosis Sample: Sputum, bronchoalveolar lavage fluid,transbronchial biopsy wet mounts:10% KOH & Parker ink or Gram stained smears Tissue sections should be stained with H&E, GMS and PAS digest:stain magenta of cell wall of fungi Demonstration of hyaline septate hyphae(3-6 m in diameter) with dichotomous branching hyphae which arises at acute angles
17. 17. 2.culture Inoculating media: Sabouraud's dextrose agar Colonies are fast growing,may be white, yellow, yellow- brown, brown to black or green in colour
18. 18. Species characteristics A.flavus A.fumigatus A.niger A.terres colony Valvety,yellow to green or brown Reverse is golden to red brown Valvety or powdery at first,turning to smoky green Woolly at first white to yellow then turning dark brown Reverse is white to yellow Valvety cinnamon brown Reverse is white to brown conidiophore Variable length,rough pitted and spiny smooth Variable length Short and smooth phialides Uniseriate covering entire vesicle,point out all directions uniseriate,usual ly cover upper half vesicle,parallel to axix of stalk Biseriate,coveri ng entire vesicle form radiate head Biseriate and compactly columnar
19. 19. Laboratory diagnosis 3)Skin test (intra-dermal) For suspected allergic bronchopulmonary aspergillosis and atopic dermatitis or allergic asthma Type I HSR (erythema and wheal):within 1hrs Type III HSR(arthus reaction):within 4-10hrs Type IV HSR: induration of >5mm diameter after 24hrs 4)serology: Immunodiffusion tests and precipitation tests for the detection of antibodies to Aspergillus species (aspergillus galactomannan antigen) diagnosis of allergic aspergilloma and invasive aspergillosis
20. 20. Radiodiagnosis Computed tomography or magnetic resonance imaging Radiodense shadows are due to calcium and magnesium salts inside fungal granuloma ultrasonography and CT scan can be done for hypodense lesions Transthoracic needle aspiration can also be done
21. 21. Differential diagnosis From deep mycotic infections Includes ecthyma gangrenosum caused by pseudomonas or candida species, herpes simplex virus infection ,zygomycosis, cryptococcus and phaeohyphphomycosis Aspergillus granuloma should be differentiated from other granulomatous disease as well as neoplasia
22. 22. TREATMENT Invasive aspergillosis are almost difficult to treat Cutaneous infection:clotrimazole or nystatin Prophylaxix:posaconazole(oral:200mg every 8hrs) Treatment :itraconazole(200mg BD),amphotericin B To this date there is development of vaccines Concomitant effort to decrease immunosupression and reconstitute host immune defense
23. 23. REFERENCES 1. Chander Jagdish,textbook of medical mycology,3rd edition 2. Patrick R.Murray,Ken S.Rosenthal,medical microbiology,6th edition 3. Anantanarayan and paniker,textbook of microbiology,9th edition 4. medscape.org/viewarticle/555993(retrieved on 26th december 2014) 5. mycology.adelaide.edu.au/virtual/guidelines(retrieved in 27th december 2014)