Aspergillus

Aspergillus By Flo1ASPERGILLUSUbiquitous mould that causes allergies (bronchopulmonary aspergillosis) in otherwise healthy people and serious sinusitis, pneumonia, and invasive disease in immunocompromised individuals. Hence called opportunistic fungi.

Aspergillus fumigatus is the most common species to cause disease, and it produces severe invasive infections in immunocompromised individuals

Aspergillus

Microscopy demonstrating Aspergillus hyphae. Note the acute angle of branching.3Department of Pathology4SLIDE 34 Microscopy demonstrating Aspergillus hyphae.

4Aspergillus FumigatusMonomorphic filamentous fungi

Thin, septate hyphae with acute branching angle 45

Habitat is the soil

Transmission inhalation of airborne spores (conidia)

Aspergillus, Acute, Amphotericin B5A. Fumigatus - PathogenesisAspergillus species are transmitted by airborne conidia, and the lung is the major portal of entry. The small size of A. fumigatus ( 2-3m), enables them to reach alveoli. Conidia germinate into hyphae which then invade tissues. Neutrophils and Macrophages are the major host defence against Aspergillus. Alveolar macrophages ingest & kill the conidia, while neutrophils produce reactive oxygen intermediates that kill the hyphaeInvasive aspergilosis is associated with neutropenia and impaired neutrophil defences. Aspergillus produces phospholipases, proteases and toxins.

Deep fungal infections usually heal or remain latent in normal hosts; in immunocompromised hosts, however, they can spread systemically and invade tissues, destroying vital organs. Some species responsible for deep fungal infections are limited to particular geographic regions (e.g., Coccidioides in the American Southwest and Histoplasma in the Ohio River Valley). By contrast, many fungi that cause deep infections in immunocompromised hosts (opportunistic fungi such as Candida, Aspergillus, Mucor, and Cryptococcus) are ubiquitous and colonize normal human epithelia without causing illness. In immunocompromised individuals these opportunistic fungi result in life-threatening infections characterized by tissue necrosis, hemorrhage, and vascular occlusion. AIDS patients in particular are frequent victims of the opportunistic fungus Pneumocystis jiroveci (formerly called P. carinii). 6Diseases A. FumigatusAllergic Bronchopulmonary Aspergillosis

In asthma & CF patients

Farmers inhale the spores from hay

Can have type I hyperensitivity reaction and/or type IV with cell infiltrates in lung

T/t: Systemic corticosteroids

Growing mucus plug in the lungs but not penetrating the tissue

7Diseases A. FumigatusFungal ball (Colonising aspergillosis/Aspergilloma)

In lung cavitations preformed by previous tuberculosis infection

May cause hemoptysis (mimicing TB) halo sign and crescent sign at air-liquid (pus) interphase [seen on x-ray]

T/t: Surgical removal of fungus ball

8Diseases A. FumigatusInvasive AspergillosisMost severe disease of organismIn Immunocompromised patients (severe neutropenia, CGD, CF, or burns)Primary lesion is usually in the lungs but widespread hematogenous dissemination with involvement of the heart valves and brain is common (MI and hemorrhage) The pulomonary lesions take the form of sharply delineated, rounded, gray foci & hemorrhagic borders; they are often referred to as target lesionsCellulitis in burn patients may disseminateNasal colonisation - Pneumonia or meningitisT/: Amphotericin B

Paranasal sinus infectionsassociated with aspergillosis isA. fumigatus.Symptoms; fever, cough, chest pain, or breathlessness, which also occur in many other illnesses. Aspergillus has a tendency to invade blood vessels; therefore, areas of hemoorrhage & infarction are usually superimposed on the necrotizing inflammatory tissue reactions.

9Department of Pathology10SLIDE 33Histological section of the lung in Aspergillus Pneumonia.

10DiagnosisCT scan and x-ray of lungs & sinuses Septate hyphae invading tissue is demonstratedOnmicroscopy,Aspergillusspecies are reliably demonstrated bysilver stains, e.g., Gridley stain orGomori methenamine-silver. These give the fungal walls a gray-black colour.Sabourauds agar: Characteristic mycelium formedSerologic tests: IgG precipitins Aspergilloma; IgE antibodies in patients with Allergic Bronchopulmonary Aspergillosis

Sabourauds agar; xtic mycelium formed; chains of conidia radiating frm central stalk.Sabouraud agar - containingpeptones. Used to cultivatedermatophytesand other types offungi, and can also grow filamentous bacteria such asNocardia. Contains 40g/dl dextrose,10 g/Lpeptone, 20 g/Lagar. A positive CT scan may be the first definitive suggestion of IA. CT scanning is more sensitive than radiography and shows the extent and number of lesions. In the early stages of the infection, CT scans may reveal specific signs of an infection, such as the typical halo resulting from hemorrhagic necrosis surrounding the fungal lesion or pleura-based lesions.11SignificanceAspergillus flavus and other fungi produce toxins (called Mycotoxins) that cause liver damage and liver cancer. Aflatoxin is the toxin produced by Aspergillus flavus. This has worldwide significance since Aspergillus grows ubiquitously, contaminating peanuts, grains, and rice. Half of the cancers south of the Sahara desert in Africa are liver cancers and 40% of screened foods contain aflatoxins.Aspergillus flavus and other fungi produce toxinsthat cause liver damage and liver cancer. These toxinsare called mycotoxins. The toxin produced by Aspergillusflavus is called the aflatoxin. This has worldwidesignificance since Aspergillus grows ubiquitously,contaminating peanuts, grains, and rice. The fact thathalf of the cancers south of the Sahara desert in Africaare liver cancers and 40% of screened foods contain aflatoxinssuggests that this is a real threat.12HintA for AspergillusA for Acute (septate) angleA for Amphotericin B