SBIR-STTR Award

This Small Business Innovation Research Phase I project aims to develop a bivalent monoclonal antibody using novel Plasmodium falciparum (Pf) and P. vivax (Pv) proteins shed in the urine of febrile malaria patients. Using a bioinformatics approach, we will create, score, and select in silico-generated recombinants of natural antigen variants designed to express mosaics that maximize the inclusion of common potential in one structure and minimize the inclusion of rare epitopes. Antigenic properties of the recombinant antigens are validated by indirect ELISA using panels of well-characterized sera from apparently healthy individuals and clinical Pf and Pv malaria patients. The utility of the recombinant antibodies are evaluated in a dipstick test using a range of clinical urine samples from Pf/Pv endemic regions. Our overall objective is to develop a simple one-step urine-based dipstick test for the simultaneous but specific diagnosis of clinical Pf and/or Pv malaria. The broader impact/commercial potential of this project relates to the development of a broad-based one step urine test for home-based or point-of-care diagnosis of clinical Pf and/or Pv malaria in persons with fever. The test will potentially provide a reliable tool to differentiate between symptomatic and asymptomatic disease, and provide better treatment options to those in need. It will potentially offer wider acceptability of clinical malaria diagnosis in endemic regions, especially in remote settings and in places where mixed infections frequently occur by obviating the occupational hazards involved with phlebotomy, thus helping to reduce the unnecessary use of antimalarial drugs. Overall, it has the potential to markedly impact the way over 95% of all clinical malaria is diagnosed and treated in endemic regions, and drive the current global effort towards home-based or point-of-care testing for malaria mandated by the World Health Organization prior to treatment in all cases of fever. Since it is based on the same platform as current RDTs, this test can be easily integrated into current healthcare structures to provide significant benefits to public health in most endemic countries. No such test is currently available

This Small Business Innovation Research (SBIR) Phase II project will develop and validate a broad-based non-invasive, single-step Urine Malaria Test (UMT-Pf/Pv) for the clinical diagnosis of Plasmodium falciparum (Pf) and P. vivax (Pv) malaria, which account for ~800,000 deaths a year. Since malaria deaths occur within 48 hours of onset of symptoms, the ability to manage malaria at home or in village settings where most cases occur would (i) facilitate prompt access to antimalarial treatment, (ii) target treatment to those who need it, and (iii) reduce malaria mortality. In this project, monoclonal antibodies (MAbs) to novel poly-asparagine protein fragments identified in the urine of febrile malaria patients will be used to develop a UMT-Pf/Pv dipstick. The four overlapping specific aims are to (1) perform a detailed characterization of the diagnostic utility of MAbs developed in Phase I; (2) develop, test and optimize a prototype to meet design input specifications; (3) implement preliminary performance evaluation studies to evaluate sensitivity/specificity, and; (4)undertake preliminary clinical testing. As a non-invasive alternative to blood-based tests, the UMT-Pf/Pv could facilitate the delivery of rapid malaria diagnosis in settings across all geographical areas where malaria is endemic, markedly impacting the way malaria is diagnosed and treated worldwide. The broader impact/commercial potential of this project is the development of a broad-based one-step urine test for the home-based or point-of-care diagnosis of clinical Pf and/or Pv malaria in persons with fever. With the UMT-Pf/Pv dipstick, the number of steps that the operator is required to perform is significantly reduced, permitting greater utility, convenience and reliability in primary care settings. The test will also facilitate the effective integration of malaria RDTs into private sector malaria case management and encourage wider acceptability of clinical malaria diagnosis in endemic regions, especially in rural areas and in places where mixed infections frequently occur. Overall, the test has the potential to markedly impact the way over 95% of all clinical malaria is diagnosed and treated, and drive current global efforts toward home-based or point-of-care testing for malaria prior to treatment in all cases of fever, as mandated by the World Health Organization. Since it is based on the same platform as current RDTs, this test can be easily integrated into current healthcare structures to provide significant benefits to public health in most endemic countries. No such test is currently available.