Adapting a Novel Lateral Flow Immunoassay to Rapidly Detect Burkholderia pseudomallei in Sarawak, Malaysia

Abstract

<p>Background</p><p>Melioidosis is a neglected tropical disease that is highly prevalent in Southeast Asia. Misdiagnoses are common as the presenting symptoms are similar to other diseases including upper respiratory infections. When not treated with antibiotics, the disease can lead to severe morbidity or death. Current diagnostics in low- and middle-income countries are often not sensitive nor rapid. Point-of-care rapid diagnostic tests (POC-RDTs) are a potential solution. Few studies have compared the accuracy of POC-RDTs and molecular assays against blood culture. The goal of this study was to conduct such comparisons in detecting Burkholderia pseudomallei infections among infection-suspected patients in Kapit, Sarawak, Malaysia. </p><p>Methods</p><p>We used an informed consent process as approved by two institutional review boards. In this cross-sectional study, we engaged patients meeting a melioidosis-like case definition that included classical symptoms such as prolonged fever with joint pain and/or abscess. We studied the patients routinely collected clinical specimens with a POC-RDT (Active Melioidosis DetectTM) and a molecular assay compared with the B. pseudomallei bacterial culture for isolation of the bacterial organism. </p><p>Results</p><p>One hundred patients aged 6 months - 79 years from Kapit Hospital were enrolled in the study from June 12, 2018 to January 8, 2019. Of the 100 sera, 97 urine, and 16 bodily fluid samples (total n= 213) tested with the RDT, 23 samples gave positive results (7 sera, 15 urine, and 1 bodily fluids). Compared to the molecular assay, the POC-RDT had a sensitivity of 40% (95% CI, 5%- 85%), specificity of 94% (95% CI, 87% - 98%), and an accuracy of 90% (95 CI, 82% - 95%) for sera; and a sensitivity of 80% (95% CI, 28%- 99%),a specificity of 65% (95% CI, 55% - 75%), and an accuracy of 87% (95 CI, 77% - 94%) for urine; and a sensitivity of 80% (95% CI, 28%- 99%), a specificity of 65% (95% CI, 55% - 75%), and an accuracy of 81% (95 CI, 54% - 96%) for other bodily fluids. Additionally, when compared to the bacterial culture results, the POC-RDT showed a sensitivity of 38% (95% CI, 9%- 76%), specificity of 95% (95% CI, 88% - 99%), and an accuracy of 90% (95 CI, 82% - 95%) for sera; a sensitivity of 88% (95% CI, 47%- 100%), a specificity of 88% (95% CI, 77% - 95%), and an accuracy of 94% (95 CI, 84% - 98%) for urine; and a sensitivity of 25% (95% CI, 1%- 81%), a specificity of 100% (95% CI, 74% - 100%), and an accuracy of 81% (95 CI, 54% - 96%) for other bodily fluids. </p><p>Conclusion</p><p>While study enrollment will continue, data from the first 100 participants, suggests the POC-RDT had poor sensitivity, good accuracy, and high specificity in detecting B. pseudomallei infection. Thus far, the POC-RDT assay seems to work better on urine specimens. Due to low sensitivity, the study data do not support recommending POC-RDT strips as a single diagnostic method. However, as the POC-RDT had high specificity when the test is positive it seems appropriate for clinicians to assume the patient is infected and to prescribe specific antimicrobial therapy. While more participant data are needed, it seems likely that the POC-RDT could be useful in helping physicians to begin treatment early with the high specificity that the POC-RDT has exhibited. If paired with an RDT with high sensitivity, this POC-RDT would add a great value to infection management.</p>