Objectives: Melioidosis is an emerging tropical disease caused by B. pseudomallei that can rapidly prove fatal and require prompt and appropriate antibiotic treatment. Diagnosis currently relies on culture; however, this delays appropriate antibiotics and contributes to mortality as results can take up to one week or more. Several non-culture based diagnostic tests are available; however, their role remains a point of contention. This review was performed to characterise the accuracy of various diagnostic tests.
Methods: Medline/Pubmed, CINAHL, Informit, Scopus, The Cochrane Library, Web of Science and Embase databases were searched from inception to April 2020. Clinical trials investigating diagnostic tests capable of providing results in ≤48 hours using samples from suspected human cases; with bacterial culture as the reference test, and reporting sensitivity and specificity were eligible for inclusion. Data was pooled using bivariate analysis for diagnostic tests reported in ≥4 studies.
Results: 22 publications comprising 10963 individual tests were included. Meta-analysis was able to be performed for immunofluorescence assay (sensitivity 63.8% [95% CI, 45.6-78.7%]; specificity 99.4% [95% CI, 97.2-99.9%]), polymerase chain reaction (sensitivity 77.1 [95% CI, 20.8%-97.8%]; specificity 99.8 [95% CI, 91.6%-100.0%]) and lateral flow immunoassay (sensitivity 58.2% [95% CI, 34.1%-78.9%]; specificity 95.0% [95% CI, 93.3%-96.3%]). Measures of sensitivity were overall similar although specificity of immunofluorescence assay was statistically superior to lateral flow immunoassay. There was a trend for reduced sensitivity of direct detection methods applied to blood samples compared to other sample types, although statistically insignificant. Serological methods were unable to be meta-analysed due to an insufficient number of studies, but their sensitivities were generally higher than direct detection methods (median 84% [IQR 71.5-88%] vs 51% [IQR 39-79%]), however they lacked specificity compared to direct detection (median 82% [IQR 70-86%] vs 98% [IQR 95-100%]).
Conclusions: Overall, no method showed sensitivity and specificity which would allow it to substitute culture. Serological tests may play a role in ruling out infection in endemic regions given their higher sensitivity, with direct detection methods being used for diagnostic confirmation. Further research into cost-effectiveness and implementation studies are required before diagnostic tests can be introduced clinically in the detection of melioidosis.
Keywords: Burkholderia pseudomallei; Diagnostic accuracy; Diagnostic test; Melioidosis.
Copyright © 2020. Published by Elsevier B.V.