This project will identify and characterize biomarkers for human filarial infections and generate monoclonal antibodies against circulating filarial antigens that will be more specific than those used in current tests. The need for improved diagnostic tests is pressing at this time. The World Health Organization?s (WHO) Global Program to Eliminate Lymphatic Filariasis (GPELF) is rapidly moving towards its goal of global elimination of lymphatic filariasis (LF) by 2020. However, problems with diagnosis represent a major challenge to the program in Central Africa, where false positive results with the current filarial antigen tests may result in unnecessary and potentially harmful overtreatment of populations. Candidate I have more than 10 years of experience and training in biomedical, translational, and public health research. My doctoral studies on Respiratory Syncytial Virus gave me a broad understanding of principles of immunology, virology, and host-pathogen interactions. My more recent work in epidemiology has given me an appreciation of the scope and potential impact of global public health programs and of the critical importance of accurate diagnostic tools for public health programs and research. I am board certified in Internal Medicine with subspecialty certification as an Infectious Diseases clinician. This project supports my long-term career goal of becoming an independent investigator in the area of global infectious diseases with a focus on translational research of neglected tropical diseases; the project plan will also allow me to further develop my clinical research skills and knowledge of infectious diseases. Environment My surroundings at Washington University in St. Louis (WUSTL) are ideal for my proposed project and career development. The intellectual environment is outstanding and I intend to take advantage of this by completing a structured program of coursework focused on conducting field research in resource-poor settings. My mentor?s laboratory group has a tremendous amount of experience in basic and applied research in parasitology, and WUSTL is one of only a handful of research centers in the nation with strong expertise in filarial diseases. My mentor is the PI of the Death to Onchocerciasis and LF project (a large-scale global health project funded by the Bill and Melinda Gates Foundation), and has extensive expertise in parasitology, immunology, and international field research. This outstanding environment for filarial research was the reason I joined the WUSTL faculty in 2014. Research LF is one of the world?s leading causes of disability, and is one of a small number of infectious diseases that are potentially eradicable. WHO?s GPELF coordinates and supports the efforts of corporate, academic, governmental, and non-governmental partners to eliminate LF in 73 endemic countries through repeated cycles of mass drug administration (MDA) using industry-donated drugs. GPELF is the largest MDA-based public health intervention to date with more than 5.3 billion doses of antiparasitic medications distributed between 2000 and 2014 in 60 countries. Over 90% of the world?s LF burden (including all cases in Africa) is caused by the filarial nematode Wuchereria bancrofti (Wb), and all aspects of global elimination programs for bancroftian filariasis (mapping, MDA, surveillance, and verification) rely on diagnosis of LF using point-of-care tests that employ monoclonal antibodies to detect Wb circulating filarial antigen in blood samples. Recent studies have shown that these tests often produce falsely positive results with samples from people that are infected with Loa loa, a different filarial parasite that occurs in 11 countries in Central Africa. Inaccurate diagnostic test results can have serious or even fatal implications since drugs used in MDA for LF can cause serious adverse reactions (including encephalopathy and death) when taken by people with heavy L. loa infections. We hypothesize that falsely-positive filarial Wb antigen tests in patients with loiasis are due to the presence of a cross-reactive circulating L. loa antigen. This project aims to identify the circulating Loa antigen and develop assays that can distinguish the two infections. Improved diagnostic tests would significantly improve chances for control of loiasis and elimination of LF in the 11 Central African nations that have both of these diseases.
This mentored proposal outlines an ambitious research and career development plan to generate monoclonal antibodies to circulating filarial antigens of Wucereria bancrofti and Loa loa; these antibodies will be used to create improved diagnostic tests for lymphatic filariasis and loiasis. While completing these studies, the PI will acquire skills in the areas of applied parasitology and immunology, and in conducting field studies in resource-poor settings. These skills, along with targeted didactic coursework, will allow the PI to develop an independent research career as a physician-scientist focused on neglected tropical diseases.
|Yahathugoda, Channa; Weiler, Michael J; Rao, Ramakrishna et al. (2017) Use of a Novel Portable Three-Dimensional Imaging System to Measure Limb Volume and Circumference in Patients with Filarial Lymphedema. Am J Trop Med Hyg 97:1836-1842|