Research Project
9681177
7. Project Summary / Abstract Lymphatic filariasis (LF), caused by the parasitic filarial worm Wuchereria bancrofti, is a disfiguring and debilitating neglected tropical disease that affects 40 million people in 72 countries. Through the World Health Organization?s (WHO) Global Program for the Elimination of Lymphatic Filariasis (GPELF), 6.2 billion drug regimens have been distributed via mass drug administration (MDA) to 820 million people to treat the disease and prevent its spread. Many countries are now approaching the elimination point, where transmission is permanently interrupted, at least in theory. As per WHO guidelines, these countries will require a 5-year surveillance plan to demonstrate that transmission is no longer occurring, and to allow for rapid intervention in case of reemergence of the disease. Effective surveillance strategies will need to be supported by sensitive and specific diagnostic tools. The only field-deployable test recommended by WHO for transmission assessment surveys (TAS) of lymphatic filariasis is the immunochromatography testcard (ICT, Alere). Although this test has been used for 2 decades to detect active infections, it remains suboptimal for surveillance activities, as it detects an antigen measurable in circulation only 18 months post-infection and lacks sensitivity in post-MDA settings (due to low parasite burden). Experts agree that what is required for surveillance is a rapid diagnostic test (RDT) indicative of early exposure to W. bancrofti infective larvae (L3 development stage), for which the best biomarker are IgG4 antibodies specific to the Wb123 antigen expressed by L3 larvae. Herein, we propose an ultrasensitive RDT for the detection of Wb123-specific IgG4 antibodies. We have introduced a novel class of plasmonic gold nanoshells to increase the sensitivity of lateral flow immunoassays, and in preliminary experiments have demonstrated their superior performance for detecting a Wb123-specific IgG4 serological response. We now aim at delivering 1,000 advanced prototypes as sensitive and specific as the reference Wb123 ELISA (InBios) test used at the CDC. By the end of this Phase I STTR grant these prototypes will be available for field evaluation studies. This new RDT will ultimately support the end-game of the GPELF.
