Aspergillous Fumigatus

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 40ºc 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

7. 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

8. 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

9. 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

10. 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)

11. 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

12. 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

13. Case study

14. 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

15. 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. Superficial infections
 A.flavus and A.fumigatus colonization
a)Paranasal sinus:sinusitis
b)External ear: otomycosis
c)eye: mycotic keratitis

17. 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 µm in diameter)
with dichotomous branching hyphae which arises at acute
angles

19. 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

20. 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

22. 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

23. 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

24. 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

25. 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

26. 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)