Burkholderia pseudomallei is a Gram-negative bacterium that is the causative agent of melioidosis. The bacterium causes significant morbidity and mortality in tropical regions and endemic areas are expanding. Melioidosis is difficult to trea and diagnose due to the fact that B. pseudomallei is resistant to common antibiotics and symptoms are non-specific. Mortality rates reach 45% and 20% in Thailand and Australia respectively, even with antibiotic treatment. Currently, there is no validated diagnostic product for the diagnosis of melioidosis. Culturing of patient samples is the "gold standard" for diagnosis;however this can take 3-7 days. Our goal is to develop a rapid point-of-care lateral flow immunoassay (LFI) for the detection of the B. pseudomallei capsular antigen (CPS) directly from patient samples. Phase I STTR Specific Aims focused on producing a library of anti-CPS monoclonal antibodies (mAbs), optimizing the LFI components and sample preparation, and performing a feasibility study on archived melioidosis patient samples. The objectives of this Phase II application is advanced development and validation of the prototype AMD LFI that incorporates a higher affinity CPS mAb. By completing these goals we hope to produce an optimized LFI that possesses sensitivity equal to or greater than culturing of patient samples. To achieve these goals we have established an experienced team. A strong partnership exists between Dr. AuCoin's laboratory and InBios International that has led to the development of an encouraging prototype LFI. In addition, both groups will work closely with experts in endemic areas (Thailand and Australia) who will be conducting a large preclinical evaluation of the LFI with different patient sample types.
Melioidosis is a rapidly progressing and frequently fatal disease if left untreated. Burkholderia pseudomallei is the causative agent of melioidosis;this soil dwelling bacterium has been listed as a Tier I Select Agent by the CDC. In the endemic areas of Thailand and northern Australia melioidosis is a major public health concern. Rapid diagnosis of melioidosis is needed in order to properly administer effective treatment with specific antibiotics. At present, the diagnostic gold standard is culturing of patient samples, which takes 3-7 days and significantly delays administration of proper treatment. In this application, we offer to develop a point-of-care, cost-effective, and rapid diagnostic for melioidosis that can deliver results within minutes. Such a rapid diagnostic test will have the capability to detect acute B. pseudomallei infections in endemic areas as well as following a bioterrorist attack.