1. Prepared by Deepa Devkota Roll no:07 Human Biology 7th batch
Aspergillus fumigatus
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. 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. 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. 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. 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. 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. 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. 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. 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. 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. Case study
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. 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
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. 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. 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. 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. 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. 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. 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. 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)