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Deepa Devkota
Roll no:07
Human Biology 7th batch
Aspergillus fumigatus
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
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
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
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
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
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
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
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)
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
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
Case study
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
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
Superficial infections
 A.flavus and A.fumigatus colonization
a)Paranasal sinus:sinusitis
b)External ear: otomycosis
c)eye: mycotic keratitis
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
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
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
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
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
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
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
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)
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Microbiology seminar

  • 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
  • 6.
  • 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
  • 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
  • 18.
  • 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
  • 21.
  • 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)