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PubMed: 36286520 DOI: 10.1128/mbio.01900-22
Identifying Recent Cholera Infections Using a Multiplex Bead Serological Assay.
mBio 13(6):e0190022
Authors: Forrest K Jones, Taufiqur R Bhuiyan, Rachel E Muise, Ashraful I Khan, Damien M Slater, Kian Robert Hutt Vater, Fahima Chowdhury, Meagan Kelly, Peng Xu, Pavol Kováč, Rajib Biswas, Mohammad Kamruzzaman, Edward T Ryan, Stephen B Calderwood, Regina C LaRocque, Justin Lessler, Richelle C Charles, Daniel T Leung, Firdausi Qadri, Jason B Harris, Andrew S Azman
Affiliations
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
- Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
- Division of Infectious Diseases, Massachusetts General Hospitalgrid.32224.35, Boston, Massachusetts, USA.
- Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Healthgrid.94365.3d, Bethesda, Maryland, USA.
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
- Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.
- University of North Carolina Population Center, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.
- Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City, Utah, USA.
- Division of Microbiology and Immunology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
- Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
- Institute of Global Health, University of Geneva, Geneva, Switzerland.
Abstract
Estimates of incidence based on medically attended cholera can be severely biased. Vibrio cholerae O1 leaves a lasting antibody signal and recent advances showed that these can be used to estimate infection incidence rates from cross-sectional serologic data. Current laboratory methods are resource intensive and challenging to standardize across laboratories. A multiplex bead assay (MBA) could efficiently expand the breadth of measured antibody responses and improve seroincidence accuracy. We tested 305 serum samples from confirmed cholera cases (4 to 1083 d postinfection) and uninfected contacts in Bangladesh using an MBA (IgG/IgA/IgM for 7 Vibrio cholerae O1-specific antigens) as well as traditional vibriocidal and enzyme-linked immunosorbent assays (2 antigens, IgG, and IgA). While postinfection vibriocidal responses were larger than other markers, several MBA-measured antibodies demonstrated robust responses with similar half-lives. Random forest models combining all MBA antibody measures allowed for accurate identification of recent cholera infections (e.g., past 200 days) including a cross-validated area under the curve (cvAUC) of 92%, with simpler 3 IgG antibody models having similar accuracy. Across infection windows between 45 and 300 days, the accuracy of models trained on MBA measurements was non-inferior to models based on traditional assays. Our results illustrated a scalable cholera serosurveillance tool that can be incorporated into multipathogen serosurveillance platforms. Reliable estimates of cholera incidence are challenged by poor clinical surveillance and health-seeking behavior biases. We showed that cross-sectional serologic profiles measured with a high-throughput multiplex bead assay can lead to accurate identification of those infected with pandemic Vibrio cholerae O1, thus allowing for estimates of seroincidence. This provides a new avenue for understanding the epidemiology of cholera, identifying priority areas for cholera prevention/control investments, and tracking progress in the global fight against this ancient disease.
MeSH
Incidence, Infections, Cholera, Microbiological Phenomena, Vibrio, Laboratories
Cited by
- Long-term sialidase-specific immune responses after natural infection with cholera: Findings from a longitudinal cohort study in Bangladesh. Front Immunol, 2023
- Clinical surveillance systems obscure the true cholera infection burden in an endemic region. Nat Med, 2024
- Inferring the proportion of undetected cholera infections from serological and clinical surveillance in an immunologically naive population. medRxiv, 2023
- Predicting Vibrio cholerae infection and symptomatic disease: a systems serology study. Lancet Microbe, 2023
- Inferring the proportion of undetected cholera infections from serological and clinical surveillance in an immunologically naive population. Epidemiol Infect, 2024
- Expanding cholera serosurveillance to vaccinated populations. medRxiv, 2025
- Estimating the gap between clinical cholera and true community infections: findings from an integrated surveillance study in an endemic region of Bangladesh. medRxiv, 2023