INTRODUCTION:

ASPERGILLOSIS:

Aspergillosis is an infection caused by the fungus Aspergillus[1].These species are highly aerobic and are found in environments rich in oxygen where they grow as moulds on a substrate due to high oxygen tension. Aspergillosis describes a large number of diseases involving both infection growths of fungus as well as allergic response [2].

The most common sites of infection are the respiratory apparatus including the lungs and sinuses [3]. These infections can be Invasive (e.g. Invasive pulmonary aspergillosis-IPA) Non-invasive (e.g. Allergic pulmonary aspergillosis-ABPA)

Chronic pulmonary and Aspergilloma (e.g. Chronic cavitary, semi-invasive), Severe asthma with fungal sensitisation. (SAFS) [4]

ASPERGILLOMA:
Aspergilloma refers to a “fungal ball" that grows in either scarred lungs or pre-existing lung cavity which may have been caused by a previous infection. Patients with a history of tuberculosis, sarcoidosis or cystic fibrosis are more prone [5][6].A common symptom of Aspergilloma is hemoptysis which is coughing up of blood. This results due to the disruption of the blood vessels in the wall of the cavity occupied by the fungus [7].

CHRONIC PULMONARY ASPERGILLOSIS:

It is a long term infection of the lungs and it is mainly caused by the species of Aspergillus called Aspergillus fumigatus [8]. Patients with this diseased condition fall into several categories:

Those with an Aspergilloma, chronic cavitary pulmonary aspergillosis: cavities are present in the lungs but not necessarily with a fungal ball.

Chronic fibrinosing pulmonary aspergillosis: this occurs when pulmonary aspergillosis remains untreated and scarring of the lung is seen.

Most patients with chronic pulmonary aspergillosis have or had an underlying lung disease including tuberculosis, atypical mycobacterium infection, lung cancer, asthma, silicosis etc.

CAUSATIVE SPECIES OF THE INFECTION:

The fungus causing chronic pulmonary aspergillosis is Aspergillus fumigatus. It obtains food osmotically from dissolved organic matter. It plays a key role in recycling the carbon and nitrogen from deceased organisms [5] .The conidia of this fungus can be taken up with the wind and float through the air. It is estimated that there are approximately ten conidia found within every cubic meter of air [9]. The fungus enters an individual through the respiratory tract and lead to the infection which when severe results in death [10].

SYMPTOMS:
They include coughing up blood (hemoptysis) [7] or brownish mucus plugs; fever; wheezing; weight loss; breathlessness and fatigue.

Other symptoms depend on the part of the body affected and may include blood in the urine; bone pain; chest pain; chills; decreased urine output; headaches; increased phlegm production which may be bloody; skin sores and vision problems [11] [12] .

DIAGNOSIS:
Tests to diagnose this disease are chest X-rays; Aspergillus antibody test[13] [14] total blood count CT Scan [15] Galactomannan ( a molecule from the fungus sometimes seen in blood) [16] [17] Immunoglobulin IgE level in blood ; Lung function tests , Sputum stain and culture for aspergillus [18] [19] and tissue biopsy.

TREATMENT:
The treatment of chronic pulmonary aspergillosis requires intravenous anti fungal therapy. The drugs of choice include voriconazole; amphotericin B and iatroconazole.[20]

AMPHOTERICIN B:

This has been regarded as the gold standard anti fungal drug used in the treatment of aspergillosis[21]. Transmembrane channels are created when this drug binds with membrane sterols, resulting in increased permeability to monovalent cations [22]. It causes increased membrane fragility and calcium leakage by inhibiting proton ATPase pump and depleting cellular energy[23-25] .Two major drawbacks of this drug are its insolubility in water and toxicity of then molecule to the patient[26]. Major side effects include nephrotoxicity [5].

VORICONAZOLE:
Voriconazole is initiated to patients suffering from aspergillosis with a loading dose of 6mg/kg IV every 12hours for 2 doses followed by 4mg/kg every 12hours.
Because of the more accelerated metabolic clearance in pediatric patients the doses may be higher. This drug has an in vitro fungicidal activity against Aspergillus. It was found to be efficient in patients with the disease and oral administration is possible with acceptable tolerance. The side effects include transient visual disturbances, nausea, vomiting, hallucinations and sepsis.[27] [20]

ITRACONAZOLE:
200mg of itraconazole is seen to show symptomatic benefits [2]. The free sole nitrogen competes for oxygen with the catalytic heme iron atom of cytochrome P 450 enzyme. Inhibition of cytochrome P 450 14 alpha demethylase prevents the synthesis of ergo sterol from the fungal membranes. The lack of ergosterol6 in the fungal membranes causes membrane fluid alteration and accumulation of phospholipids and unsaturated fatty acids in the fungal cells. Since its binding to mammalian cytochrome P 450 is weak, toxicity is reduced [28] [29]. Two major drawbacks include IV preparation in availability and continuous monitoring of the concentration in serum is necessary because absorption varies among patients.[30]

Patients require long term maintenance of antifungal therapy to prevent relapse and may continue to have some disability like fatigue and intermittent secondary infections of remaining pulmonary cavities.[31]

CONCLUSION:
Aspergillus fumigatus has become the most important airborne pathogen causing a fatal increase in aspergillosis. Aspergillus gradually destroys the lung tissue resulting in the formation and expansion of the cavities. If untreated, destruction can eventually encompass an entire lobe or lung; even with treatment the mortality rate of chronic pulmonary aspergillosis remains high. Thus it is necessary to create an awareness on this deadly disease, by educating common people.

REFERENCES:

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Received on 08.12.2013 Modified on 07.01.2014

Research J. Pharm. and Tech. 7(3): Mar., 2014; Page 389-391