DETECTION OF FILARIAL ASPARAGINYL-TRNA SYNTHETASE

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Lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi is endemic throughout the Philippine Island archipelago south of the fourteenth parallel and 20 million persons live in endemic areas. Efforts to control filariasis by the Philippines National Filariasis Control Program (NFCP) includes scientific support from the University of the Philippines (UP) and evaluation of new diagnostic methods to monitor community-based chemotherapy trials. Aminoacyl-tRNA synthetases (AARS) are an important family of enzymes that play a fundamental role in protein biosynthesis by maintaining fidelity of translation of the genetic code. Several lines of evidence suggest that asparaginyl-tRNA synthetase (AsnRS) in particular may be a useful molecular target for diagnosis of lymphatic filariasis. Filarial AsnRS is highly antigenic and structurally divergent from human enzymes. Antibody against B. malayi AsnRS is cross reactive with W. bancrofti AsnRS. Filarial AsnRS is excreted or secreted from parasites in a high molecular weight form, and several methods exist to identify filarial AsnRS. Therefore the objectives are to work with the Department of Biochemistry (UP) and the NFCP to assess the validity of filarial AsnRS as a marker of active filariasis. This research design addresses the sensitivity and specificity of methods to detect AsnRS as an antigen, and AsnRS enzyme activity. The NFCP is preparing to evaluate several diagnostic tests during combination drug treatment in five sentinel hyperendemic communities beginning in April of the year 2000. Thus the accuracy of AsnRS detection methods to identify subjects with active Bancroftian filariasis can be compared to three other methods under evaluation by the NFCP - a serum filarial antigen test (ICT), amplification of circulating parasite DNA by PCR, and acridine orange examination of nocturnal blood samples. The long term goals of this research are twofold: (1) Help develop and evaluate tools to monitor the effects of filariasis chemotherapy on human and vector populations, and (2) Expand investigations on the biological functions of filarial AARS.