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 3-5 days. Our goal is to develop a rapid point-of-care lateral flow immunoassay for the detection of the B. pseudomallei capsular antigen (CPS) directly from patient samples. Our previous studies have determined that the CPS is a shed antigen and a prototype LFI has yielded encouraging results. The goals of the project are to (i) produce a library of high affinity CPS specific mAbs (ii) optimize LFI construction, (iii) determine compatibe sample types and sample preparation and (iv) quantify CPS in patient samples. 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. Dr. AuCoin's laboratory is already collaborating with InBios on development of a prototype LFI. In addition, both groups will work closely with experts in endemic areas (Thailand and Australia) who will be conducting evaluation of the LFI with different sample types.

Public Health Relevance

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 Category B Select Agent. In the endemic areas (Thailand, Southeast Asia and northern parts of Australia), melioidosis is a public health concern. Rapid diagnosis of melioidosis is needed in order to properly administer effective treatment with antibiotics. At present, the diagnostic gold standard is culturing of patient samples, which takes 3-5 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 rapid diagnostic test can assist in detecting and monitoring acute and chronic B. pseudomallei infections in the field both in endemic areas as well as following a bioterrorist attack.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
5R41AI102482-02
Application #
8490302
Study Section
Special Emphasis Panel (ZRG1-IDM-V (12))
Program Officer
Ritchie, Alec
Project Start
2012-06-15
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$299,699
Indirect Cost
Name
Inbios International, Inc.
Department
Type
DUNS #
004006628
City
Seattle
State
WA
Country
United States
Zip Code
98104
Houghton, Raymond L; Reed, Dana E; Hubbard, Mark A et al. (2014) Development of a prototype lateral flow immunoassay (LFI) for the rapid diagnosis of melioidosis. PLoS Negl Trop Dis 8:e2727