A plasma proteomic diagnostic for melioidosis

The University of Washington received a $229,870 Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), effective September 23, 2025, with completion targeted for August 31, 2027. This award funds the development and validation of a novel plasma proteomic diagnostic tool for melioidosis, a tropical infectious disease caused by Burkholderia pseudomallei with mortality rates exceeding 40% in endemic areas of Southeast Asia and an estimated 165,000 annual cases worldwide. The research team will externally validate an eight-protein aptamer-based signature in plasma samples across two geographically independent prospective patient cohorts (Thai and Australian populations) and confirm diagnostic accuracy using orthogonal immunoassay methods. This work addresses a critical clinical need, as traditional melioidosis diagnosis requires bacterial culture that may take several days to complete and is unavailable in many resource-limited settings.

The primary deliverables include validation data demonstrating the diagnostic accuracy of the proteomic signature for melioidosis detection compared to other infectious causes, conversion of aptamer-derived findings to immunoassay-compatible formats, and documentation supporting potential development of a rapid, culture-independent diagnostic platform. These products leverage the institution's existing expertise in melioidosis proteomics, human immunology, and established access to independent patient cohorts, positioning the research to generate evidence for a transformative diagnostic approach that could significantly improve patient outcomes in endemic regions by enabling rapid treatment initiation.

Abstract

Melioidosis is a tropical infection caused by inoculation, inhalation, or ingestion of the gram-negative soil saprophyte and tier 1 select agent burkholderia pseudomallei (BPS). The overall melioidosis mortality rate exceeds 40% in endemic areas of southeast asia such as northeastern thailand (despite appropriate treatment), and modeling indicates that 165,000 cases of human melioidosis occur annually worldwide. For decades, diagnosis of melioidosis has required culture of BPS from a clinical specimen. This may take several days, delaying appropriate treatment, and in many resource-limited settings the necessary microbiology facilities for bacterial culture and identification are not available. Few suitable non-culture-based diagnostics exist. Performing a case-control analysis nested within a prospective, single-center cohort study of patients hospitalized with infection (ubon-sepsis study), we have developed an eight-protein signature in plasma that, in preliminary studies, has high accuracy differentiating melioidosis from other causes of infection. These results suggest that measuring a limited number of circulating proteins during initial presentation has significant diagnostic potential for melioidosis. Our central hypothesis is that this proteomic signature is a novel and accurate diagnostic tool in identifying patients with melioidosis. To test this potentially high impact hypothesis, we will leverage our singular expertise in melioidosis proteomics, human immunology, and access to independent thai and australian cohorts of melioidosis patients in the following specific aims: 1) externally validate the diagnostic accuracy of the eight-protein aptamer-based signature for the detection of melioidosis in two geographically independent prospective studies. 2) confirm the diagnostic accuracy of the aptamer- derived proteomic classifier for melioidosis using orthogonal immunoassays. If our hypotheses are proven, the use of blood proteins as a melioidosis diagnostic could significantly enhance our present approaches to identifying melioidosis. Subsequent development of this tool for clinical use could have a beneficial impact on the burden of this often-lethal infectious disease.