Cholera rapid diagnostic test performance at the host-microbe interface: a prospective longitudinal study in Bangladesh

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• Picked for Microbiology (medical) (top studies of the week, 25 October 2026): Prospective evaluation of cholera rapid-test performance against culture and qPCR

Abstract

BACKGROUND: Effective cholera outbreak response requires accurate bedside rapid diagnostic tests (RDTs) because of poor laboratory access. Formative studies suggest that cholera diagnostics have multiple vulnerabilities, including target degradation by virulent bacteriophage (phage) specific to Vibrio cholerae and antibiotics. Our study objectives were to evaluate the performance of RDTs as a function of these antimicrobials to improve deployment and guide future diagnostic development. METHODS: In this prospective longitudinal study, participants were enrolled at seven hospitals across Bangladesh from March 13, 2018, to April 9, 2019. Inclusion criteria were participants aged 2 months or older with uncomplicated diarrhoeal disease. Exclusion criteria were the presence of severe comorbidity or the absence of participant or guardian consent or assent. Stool samples were analysed using culture, quantitative PCR (qPCR), and mass spectrometry. The primary outcome was RDT performance (eg, sensitivity and specificity) as a function of phage detection. Exploratory outcomes were the effects of antibiotics and disease severity on RDT performance. FINDINGS: 2574 participants were enrolled, and for 2078 samples, all assays were completed for analysis of the primary outcome. 394 samples without RDT data and 102 samples without qPCR data were excluded. Using the current gold standard of culture or qPCR positivity for V cholerae, we found that phage detection had no effect on RDT performance. When the diagnostic criteria were expanded to include phage detection, RDT sensitivity decreased from 0·46 (95% CI 0·41-0·51) to 0·38 (0·34-0·43), and the odds of RDT positivity among patients with cholera decreased with phage exposure (odds ratio 0·428; 95% CI 0·296-0·613). Antibiotics were detected in more than 80% of samples using liquid chromatography-tandem mass spectrometry, limiting assessment of their effects on RDT performance. Among patients with moderate and severe dehydration, large increases in sensitivity and specificity were observed. We estimated that restricting RDT use to patients with severe dehydration and no reported antibiotic exposure increased sensitivity by 50% compared with unrestricted RDT use. If the presence of phage is considered a diagnostic proxy for V cholerae infection, then RDTs might not detect an additional 17% of cholera cases. INTERPRETATION: Cholera RDTs have limitations that require consideration during global deployments. Inclusion of phage detection in diagnostic criteria might improve case detection, although this requires further research in diverse settings. The implications of these findings likely extend to other diseases in which diagnostics share similar vulnerabilities. FUNDING: Wellcome Trust (DFID grant), NIH, and Thrasher Research Fund.

Abstract as published, via PubMed.