Melioidosis is caused by the soil-dwelling bacterium Burkholderia pseudomallei. Infection results in mortality rates approaching 50% in endemic regions, which is due in part to its resistance to commonly prescribed antibiotics. No approved vaccine is currently available. In addition, B. pseudomallei can be dispersed as an aerosol. For these reasons the CDC has classified B. pseudomallei as a potential biothreat.
Detection of B. pseudomallei by diagnostic microbiology laboratories is difficult due to limited experience of personnel and a lack of validated diagnostic reagent. Isolation of B. pseudomallei from cultures of patient samples remains the “gold standard” for the diagnosis of melioidosis. Unfortunately, culturing for B. pseudomallei is laborious; samples of blood, urine, pus, and other body fluids must be collected. Isolation of B. pseudomallei from any one of these cultures is diagnostic for melioidosis. Indirect hemagglutination assays are a rapid and inexpensive method used to detect antibodies specific to B. pseudomallei; however, most healthy individuals in endemic areas are seropositive.
The goal of the project is to identify B. pseudomallei antigens that are secreted during infection and develop an immunoassay that can detect these antigens. This will allow for rapid diagnosis of acute disease and timely administration of effective antibiotics. By utilizing our In vivo Microbial Antigen Discovery (InMAD) technology, we have identified a number of secreted antigens, the most encouraging is the capsular polysaccharide (CPS). A monoclonal antibody (mAb) has been produced that is reactive with CPS in melioidosis patient samples. InBios International (Seattle, WA) has utilized this mAb to construct a lateral flow immunoassay (LFI) for the rapid and inexpensive detection of CPS and diagnosis of melioidosis. The prototype LFI is currently being evaluated in melioidosis endemic areas of Australia and Thailand.
Project investigators: David AuCoin, Ph.D. (Principal Investigator) and InBios International, Inc. (Seattle, WA), a medical diagnostic company that specializes in developing and marketing diagnostic tests for the detection of infectious diseases.
Grant support: This study is supported by NIH grant R42AI102482, Antigen detection assay for the diagnosis of melioidosis, 2012-2017; DTRA grant HDTRA1-16-0055, Biomarker identification via In vivo Microbial Antigen Discovery, 2016-2018; DTRA contract N00173-16-C-2003, Field-deployable multianalyte diagnostics, 2015-2017; DTRA contract HDTRA1-16-C-0026, Design rules for vertical paper-based immuno-diagnostic system, 2016-2018.
Patent: April 2010. Provisional patent application number 61/323,236
Method of diagnosing and treating melioidosis - Inventors: AuCoin, Kozel