Supporting WHO Lymphatic Filariasis Elimination Programs: Progressing a Highly Sensitive and Specific Rapid Diagnostic Test for Brugia Species Infection to Commercialization Readiness

PROJECT SUMMARY / ABSTRACT Herein we propose a field-deployable, cost-effective, highly sensitive and specific Rapid Diagnostic Test (RDT) for the surveillance of lymphatic filariasis (LF) caused by Brugia species. Our new test, termed Brugia Test Plus (BT+), was developed during a previous project phase funded jointly by the US Agency for International Development (USAID) and the Gates Foundation. It has been shown to perform exceptionally well both in the laboratory (100% sensitivity, 100% specificity) and in the field (85% sensitivity, Belitung-East/Indonesia) and to satisfy all key criteria of WHO’s Target Product Profile (TPP) for the surveillance of LF (sensitivity, specificity, shelf life, time-to-result, portability, cost). With BT+ on the verge of programmatic adoption, we now request Direct-to-Phase II funding from NIH to quickly progress BT+ to manufacturing and commercialization within a maximum of 2 years. LF is a painful and profoundly disfiguring disease which affects 40 million people globally and causing 1.6 million Disability Adjusted Life Years. In 2021, over 882 million people in 44 countries were threatened by LF, requiring preventive chemotherapy to stop a further spread of the disease. LF is caused by two species of parasites: Wuchereria bancrofti found globally (90% of cases), and Brugia species confined to Southeast Asia (10% of cases). Elimination of LF is a WHO top priority project: the Global Program for the Elimination of Lymphatic Filariasis (GPELF), launched by WHO in 2000, is the most ambitious mass drug administration (MDA) program ever deployed by WHO with an astounding 9 billion preventative treatments having been distributed between 2000 and 2021. WHO’s NTD Road Map requires all LF endemic countries to implement post-MDA or post-validation surveillance by 2030. In 2021, WHO released a Target Product Profile (TPP) for LF surveillance defining the criteria for new RDTs, which is the strongest signal WHO can give regarding the urgency of developing such new tests. Current methods for diagnosing infection by Brugia spp. include examination of nighttime blood by microscopy and PCR. This is logistically too complicated and costly for programmatic use. ELISA formats exist, but remain confined to laboratory use. One field-deployable test is available, the Brugia Rapid Test (BRT, Reszon Diagnostics). However, over the years, BRT has been plagued by erratic quality, which has led some countries (notably Indonesia, the country with the highest disease burden) to abandon its use for Transmission Assessment Surveys. This, combined with the absence of any tests to substitute the BRT, leaves many Brugia programs in a quandary. Given the exciting results obtained with BT+, the massive relevance for public health, and the big momentum already garnered with key players (USAID, Gates Foundation, WHO), there is now a shared desire that DDTD’s new Brugia test be progressed without delays to large-scale manufacturing followed by commercialization. Direct-to-Phase II funding from the NIH would enable us to achieve this objective within a maximum of 2 years.