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Cycle 1

Development of an antigen-capture immunoassay for the rapid diagnosis of acute leptospirosis.

Leptospirosis is a globally important zoonotic disease that is endemic in South East Asia with human infection commonly reported throughout the region. Leptospirosis is classified as a neglected disease in Indonesia and has been an increasing public health issue in the country. A number of outbreaks of leptospirosis have occurred in several areas in Indonesia during 2004-2012 with mortality rates as high as 35%. Laboratory diagnosis of leptospirosis is difficult due to limitations in laboratory diagnostics. Clinical diagnosis is also difficult since leptospirosis symptoms are variable, ranging from a classical flu syndrome to Weil’s disease, which typically causes major hepatic and renal failures, often leading to death. Specific laboratory tests, including bacteria isolation, DNA testing and serology using the microagglutination test (MAT), still remain limited to highly specialized laboratories. The goal of this study is to develop a sensitive, noninvasive and inexpensive immunoassay for point-of-care diagnosis of leptospirosis. The project will significantly improve the diagnosis of leptospirosis, as well as provide a better understanding of leptospirosis endemicity within Indonesia. This study will also aid and enhance the Ministry of Health’s efforts to control leptospirosis. This project has three components: 1.) Production of a library of monoclonal antibodies (mAbs) specific to LPS or other circulating antigens that are secreted or shed during infection of Leptospira spp. for the development of a prototype antigen-capture ELISA. 2.)  Construction of prototype immunoassay for leptospirosis diagnosis. 3.) Conduct a prevalence survey of Leptospirosis in Endemic areas in Indonesia using the immunoassay developed in Phase 2.

Summary of Recent Activities

Created in the lab of U.S. partner Dr. David AuCoin at the University of Nevada-Reno, three monoclonal antibodies (mAbs) specific to a leptospiral surface lipoprotein arrived at the PI Farida Handayani’s lab in late February 2021. Because the package had been delayed in transit, she and her team first had to test the samples to ensure that they were still active and their concentrations were still adequate. They were then able to proceed to conduct several other lab tests as part of the process of developing a rapid diagnostic test (RDT) prototype, including antibody level measurement, conjugation optimization, and Immobilization of conjugate complex on the pad. The resulting prototypes are still being tested against negative samples (water), with those giving a "true negative" result then being tested against known positive samples and subsequently against patient samples.

In addition to the laboratory work, Ms. Handayani and her colleagues have also been meeting virtually and in person with potential collaborators, including from Sebelas Maret University, University of Indonesia, Gadjah Mada University, ITD Airlangga University, Pattimura University, Braunschweig University (Germany), University of Science (Malaysia), University Nova Lisboa (Portugal), and the Moscow Institute of Hematology and Blood Transfusion (Russia). They are also working out plans for cooperation with PT Konimex, a well-known Indonesian pharmaceutical company, so that their RDT might be commercialized once the research and development process is complete. The Indonesian Ministry of Health is also interested in distributing the test to public health centers and hospitals. Leptospirosis is still a problem in Indonesia and is among the top five priority zoonotic diseases in the country. By using this antigen-capture leptospirosis lateral flow immunoassay (LFIA), patients suspected of having leptospirosis can be treated properly and the case fatality rate can be reduced. The need for an accurate RDT is especially acute, as leptospirosis is often misdiagnosed because its symptoms are similar to other acute febrile illnesses. The COVID-19 pandemic has also led to a decrease in the detection rate of leptospirosis cases, as the virus is monopolizing the attention of health workers while the associated travel restrictions are limiting patients’ access to health facilities for diagnosis and treatment.

In the coming months, the PI and her team would like to optimize their LFIA components further to reduce the limit of detection and confirm the performance of the test using patient samples. They expect that this will lead to a point-of-care diagnostic tool that will be easy to use even in resource-poor settings where advanced clinical microbiology lab services are not available. This project will help and enhance the Ministry of Health’s efforts to control leptospirosis. Ms. Handayani and her colleagues look forward to meeting with stakeholders to inform them about their results and hope their cooperation with PT Konimex can be continued and expanded.

Health Cycle 1 Recipients