Rethinking cholera diagnostic test performance, interpretation, and evaluation : a field-based latent-class analysis in Bangladesh

Article Article scientifique Article Rethinking cholera diagnostic test performance, interpretation, and evaluation : a field-based latent-class analysis in Bangladesh eng 2025-09-26 2025-10 author Perez Javier Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland. 986947 author Rahman Bhuiyan Taufiqur Infectious Disease Division, International Centre for Diarrhoeal Disease Research (Bangladesh), Dhaka, Bangladesh. author Hegde Sonia T 0000-0001-6426-0096 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MA, USA. author Khan Ishtiakul Islam Infectious Disease Division, International Centre for Diarrhoeal Disease Research (Bangladesh), Dhaka, Bangladesh. author Islam Md Taufiqul Infectious Disease Division, International Centre for Diarrhoeal Disease Research (Bangladesh), Dhaka, Bangladesh. author Khan Zahid Hasan Infectious Disease Division, International Centre for Diarrhoeal Disease Research (Bangladesh), Dhaka, Bangladesh. author Amin Mohammad Ashraful Infectious Disease Division, International Centre for Diarrhoeal Disease Research (Bangladesh), Dhaka, Bangladesh. author Hulse Juan Dent Infectious Disease Division, International Centre for Diarrhoeal Disease Research (Bangladesh), Dhaka, Bangladesh; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MA, USA. author Ahmed Shakeel Bangladesh Institute of Tropical and Infectious Diseases, Chattogram, Bangladesh. author Rashid Mamunur Bangladesh Institute of Tropical and Infectious Diseases, Chattogram, Bangladesh. author Rashid Rumana Bangladesh Institute of Tropical and Infectious Diseases, Chattogram, Bangladesh. author Hossain Md Zakir Bangladesh Institute of Tropical and Infectious Diseases, Chattogram, Bangladesh. author Khan Ashraful Islam Infectious Disease Division, International Centre for Diarrhoeal Disease Research (Bangladesh), Dhaka, Bangladesh. author Qadri Firdausi Infectious Disease Division, International Centre for Diarrhoeal Disease Research (Bangladesh), Dhaka, Bangladesh. author Azman Andrew 0000-0001-8662-9077 Geneva Centre for Emerging Viral Diseases, Geneva University Hospitals, Geneva, Switzerland; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MA, USA; Division of Tropical and Humanitarian Medicine, Geneva University Hospitals, Geneva, Switzerland. Electronic address: azman@jhu.edu. 954616 Institut de santé globale (COSPR) 101170 10.1016/j.lanmic.2025.101170 41022093 2666-5247 PMC12510910 https://www.sciencedirect.com/science/article/pii/S2666524725000989 Background: Accurate and reliable diagnostics, including rapid diagnostic tests (RDTs), are crucial components of cholera control programmes, although their estimated performance has varied greatly across studies. The aim of this study was to assess cholera diagnostics performance accounting for possible sources of variability, including reference assay choice and patient-level and sampling characteristics, and the implications on result interpretation and test performance evaluation. Methods: We enrolled all individuals aged 1 year and older presenting with suspected cholera seeking care at two health-care facilities in Sitakunda, Bangladesh. All participants (or, if younger than 18 years, their legal guardians) provided written informed consent and were given a short structured questionnaire on patient history and demographics, alongside a rectal swab or stool sample. All stool samples were tested with the CholKit Rapid Diagnostic Test (CholKit RDT; Incepta, Dhaka, Bangladesh), and a subset of samples (all positive RDTs and a random subset of approximately half of negative RDTs) were tested by PCR and culture. Test performance was estimated using a latent-class Bayesian framework accounting for imperfect test performance, incomplete PCR and culture testing, and time-varying changes in cholera incidence. Patient-level factor effects (including age [age 1-4 years vs ≥5 years] and previous antibiotic use) and sampling factor effects (season and testing delays) were estimated, and simulations were used to assess the bias in RDT performance estimates for sensitivity and specificity with 95% credible intervals (CrIs) when using traditional reference assays. Findings: Between Jan 24, 2021, and Aug 31, 2022, we enrolled 3744 individuals with suspected cholera. Of the 3744 overall participants, 1918 (51·2%) were male and 1826 (48·8%) were female; 1095 (29·2%) were aged 1-4 years and 2649 (70·8%) were 5 years and older. Among the suspected cases of cholera, 692 (18·5%) participants tested positive by the CholKit RDT. Among the RDT-positive samples, 573 (82·8%) also tested positive by PCR, and 450 (65·0%) tested positive by culture. For RDT, PCR, and culture, we estimated a sensitivity of 93·5% (95% CrI 91·3-95·4), 90·3% (88·4-92·1), and 73·7% (70·8-76·5), respectively; and a specificity of 97·3% (96·7-97·8) and 97·2% (96·6-97·8) for RDT and PCR, respectively. Culture specificity was assumed perfect at 100%. We found that younger age (1-4 years), antibiotic use, and testing delays decreased culture sensitivity, but RDT performance remained relatively constant. The RDT positive predictive value ranged from <15% in children aged 1-4 years to >80% in participants 5 years and older, varying greatly across seasons. Simulations of field trials demonstrated underestimation of RDT sensitivity in low prevalence settings when evaluated against PCR, and underestimation of specificity in high prevalence settings regardless of the reference assay. Adolescent Adult Bangladesh / epidemiology Bayes Theorem Child Child, Preschool Cholera / diagnosis Cholera / epidemiology Cholera / microbiology Diagnostic Tests, Routine / methods Diagnostic Tests, Routine / standards Feces / microbiology Female Humans Infant Latent Class Analysis Male Middle Aged Polymerase Chain Reaction Sensitivity and Specificity Vibrio cholerae / genetics Vibrio cholerae / isolation & purification Young Adult Dewey 613 Dewey 616 Gates Foundation INV-021879 66 Institut de santé globale 22A1 56 Département de médecine 221 false https://github.com/HopkinsIDD/rethinking_cholera_diagnostics/ The Lancet microbe 6 10 ddf5a61b-e90b-43c8-9cb2-414ae0e3866e Article (Published version) Public 1-s2.0-S2666524725000989-main.pdf 603548 application/pdf CC BY-4.0 9fecaed9659986c1fa7cea4011858b40286a49433fd14b371e6fd70af44d2076 fa9b1806-041a-44eb-8eb1-8bb056f68797 Supplemental data Public 1-s2.0-S2666524725000989-mmc1.pdf 3291404 application/pdf b19394cc1a5ae98c2303b3a2f6f6208bf8f6094c386e00963c0a84c11921f39a openAccess Faculté de médecine / Section de médecine clinique / Département de santé et médecine communautaires / Institut de santé globale Faculté de médecine / Section de médecine clinique / Département de médecine

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Rethinking cholera diagnostic test performance, interpretation, and evaluation : a field-based latent-class analysis in Bangladesh	The Lancet microbe			2025	2	0

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Perez, Javier