IgG4 antibodies to the recombinant filarial antigen Wb-Bhp-1 decrease dramatically following treatment of lymphatic filariasis

Author summaryLymphatic filariasis (LF) is a neglected tropical disease targeted for elimination by the World Health Organization. Public health programs aim to eliminate the infection with repeated rounds of mass distribution of anti-filarial medicines in areas with LF. These mass drug administration campaigns have been highly successful. Improved diagnostic tests are needed to monitor and verify the success of infection elimination efforts. We have previously shown that detection of antibodies to the recombinant parasite protein Wb-Bhp-1 are sensitive and specific for diagnosis of active filarial infections. Here, we show that antibodies to Wb-Bhp-1 are correlated with the persistence of filarial parasites in the blood after treatment, and that they decrease after effective anti-filarial treatment. Importantly, antibodies to Wb-Bhp-1 decrease after treatment more rapidly than other diagnostic markers such as circulating filarial antigenemia or antibodies to Bm14. Thus, this antibody test may be useful as a tool for monitoring the success of filariasis elimination programs. BackgroundLymphatic filariasis (LF) is a neglected tropical disease and a major cause of chronic disability. Improved diagnostic tests are needed because of long-term persistence of anti-filarial antibodies or circulating filarial antigenemia after treatments that clear microfilaremia. Here, we assess changes in levels of antibodies to the recombinant filarial antigens Wb-Bhp-1, Wb123, and Bm14 after anti-filarial treatment. Methodology/principal findingsIgG(4) antibodies to recombinant filarial antigens were assessed by ELISA. We tested serial plasma samples from a clinical trial in Papua New Guinea. Before treatment, 90%, 71% and 99% of participants had antibodies to Wb-Bhp-1, Wb123, and Bm14, respectively. Antibodies to Wb-Bhp-1 and Wb123, but not Bm14, were significantly higher in participants with persistent microfilaremia 24 months after treatment. Antibodies to all three antigens declined significantly by 60 months after treatment with ivermectin, diethylcarbamazine and albendazole despite circulating filarial antigen in 76% of participants. By 60 months follow up, antibodies to Wb-Bhp-1, Wb123, and Bm14 were detected in 17%, 7% and 90% of participants, respectively. Antibodies to Wb-Bhp-1 also declined more rapidly after treatment than antibodies to Bm14 in samples from a clinical trial conducted in Sri Lanka. We also tested archived serum samples from people living in filariasis-endemic communities in Egypt with different infection profiles. Antibodies to Wb-Bhp-1 were detected in 73% of microfilaremic people, 53% of amicrofilaremic people with circulating filarial antigen, and 17.5% of endemic individuals without microfilaria or circulating filarial antigen. Tests performed with legacy samples from India showed that few people with filarial lymphedema had antibodies to these recombinant antigens. ConclusionsAntibodies to Wb-Bhp-1 and Wb123 are more closely correlated with persistent microfilaremia than circulating filarial antigenemia or antibodies to Bm14, and they clear more rapidly after anti-filarial treatment. Additional studies are needed to assess the value of Wb-Bhp-1 serology as a tool for determining the success of LF elimination efforts.