ASPERGILLOSIS

History Aspergillus - named by Pier Antonio Micheli 1729 The molds resembled an aspergillum, a holy water sprinkler (from Latin Spargere-to sprinkle) Fresenius named -A. fumigatus Fumigatus is derived from Latin fumigave which means smoky referring to the smoky blue-gray mycelium 1815 Aspergillus first observed in birds by Mayer 1842 John Hughes Bennett discovered first case of pulmonary aspergillosis in humans

1953 Rankin described the ability of Aspergillus to cause

opportunistic infection in immunocompromised patients

TAXONOMY Kingdom Phylum Order Family Genus

: Fungi : Ascomycota : Eurotiales : Trichocomaceae : Aspergillus

Genus Aspergillus includes over 185 species

 SYNONYMS Pneumonomycosis, Bronchomycosis Etiology A. fumigatus A. nidulans A. niger A. terres A. flavus Aflatoxins A. parasiticus Ubiquitous and distributed worldwide

Occurrence In manUncommon Opportunistic mycosis Nosocomial outbreaks cancer occupational

In animalsDomestic Wild animals Birds young birds Hundreds of conidia inhaled daily

Source of infection - Reservoir soil - Fodder - Bedding materials - Incubators - Hatcheries - Infecting element- conidia (exospore)
Transmission - Airborne - Ingestion aflatoxicosis Not transmitted from one individual to other

 In 4-years- 18,731 samples processed and species identification carried out by standard microbiological methods Four hundred and fifty six samples (2.43%) - Aspergillus species. A.flavus (46.93%) A.fumigatus (37.72%) and A.niger (15.35%) It was observed that A.fumigatus was the predominant species isolated from blood and respiratory specimens, A.flavus was predominantly isolated from nasal polyps A.niger predominated in nail specimens Highest in the age group 12-65 years and in males Sixty-nine patients (15.13%) were admitted to the intensive care unit
Xess et al., 2004

Virulence factors Fungal Melanin- UV irradiation - Enzymatic lysis - Oxidants - Extremes of temperatures Two types DOPA melanin & DHN- melanin Non pathogenic fungi also produce melanin AntioxidantsCatalase, peroxidases & superoxide dismutases ProteinasesElastase

 Toxins Two classes 18-kDa or Mitogillin family : Asf1 Ag, mitogillin & restrictocin - Inhibits proteins synthesis - Ribonucleolytic activity Gliotoxin - Inhibits phagocytosis Galleria model to assay the virulence

Disease in man Local Invasive

Local Asthma Allergic bronchopulmonary Aspergillosis (ABPA) Allergic sinusitis Aspergillomas Otomycosis - A. niger Immune system reacts inappropriately to Aspergillus spp and causes allergic disease

Asthma Mold sensitivity has been associated with increased asthma severity and death Allergic bronchopulmonary aspergillosis Extreme form of Aspergillus sppdriven asthma CD4 Th-2 response - Aspergillus sppspecific serum IgE Inflammatory and obstructive bronchopulmonary injury Fever and hemoptysis, bronchiectasis, airway destruction The prevalence of ABPA cystic fibrosis- 6% and 25% asthmatic patients- 1% and 2%

Allergic fungal sinusitis Non-invasive but recurrent inflammatory sinusitis history of - Atopy - Hypertrophic sinus disease - Nasal polyps Diagnosis depends on the findings of type I hypersensitivity, nasal polyps and mucus containing fungal elements and Charcot-Leyden crystals (allergic mucin)

Aspergillomas Aspergillomas are mycelial balls grow in areas of devitalized lung such as a - Damaged bronchial tree - Pulmonary cyst - Patients who have underlying cavitary lung diseases Upper lobes most affected Also found in sinuses Surgical & endoscopic removal

Invasive sinopulmonary aspergillosis Represent a direct failure of the immune system to control local infection at risk - Malnourished - Recipients of corticosteroids - HIV - Diabetes - Underlying pulmonary disease - Cancer - Colonized with Aspergillus spp - Recipients of organ transplants - Neutropenia

Disease In man Dissiminated to different parts of the body Cerebral Aspergillosis Cardiac Aspergillosis Pulmonary Aspergillosis Aspergillus endolphthomitis

Cerebral Aspergillosis

Aspergillus brain abscess- H & E

Stained with methanamine silver

Aspergillus fumigatus growing in burn

Cardiac Aspergillosis

Disease in animals Cattle- Mycotic abortion Inhalation/ingestion

Local multiplication

Invasion of blood vessels

Placentitis Abortion

Mycotic abortion cont

75% of mycotic abortions

Stabled animals
3rd trimester Retention of placenta Wrinkled & leathery placenta Cotyledons swell & turn brownish gray colour

Fetus- Bronchopneumonia and dermatitis

Horse Associated with enterocolitis Abortion Dogs Confined to nasal cavities or paranasal sinuses A. fumigatus & A. terreus Fowl Brooder pneumonia

Acute
chicks Fever Loss of appetite Labored breathing Diarrhea emaciation

Chronic
A. fumigatus & A. flavus Adult birds Yellowish granulomas in lungs

Diagnosis Combination of clinical, radiologic & laboratory parameters Radiographic evidence includes pulmonary infiltrates

Microscopy and isolationBronchial lavage Bronchoalveolar lavage Endotracheal aspirarations

Staining- calcafluor white & others

Serology Detection of specific serum IgE against recombinant antigens of A. fumigatus is sensitive and specific for ABPA, with levels of at least 500 IU/mL thought to be diagnostic Detection of IgG and IgE specific for Aspergillus spp-

immunoassays(ELISA, CRIA)
Skin prick test- recombinant Aspergillus fumigatus allergen I/a (rAsp f I/a)

 G- test- for circulating 1,3--D glucan modification of limulus assay Can not distinguish the Aspergillus and other major fungi Aspergillus EIA- Approved by the FDA in 2003 Commercially PlateliaTM For circulating galactomannan Molecular test- PCR

Examination of tissue section

H & E stain
Grocotts stain

Aspergillus hyphae in sputum

Treatment

 Control