mBio (Dec 2022)

Identifying Recent Cholera Infections Using a Multiplex Bead Serological Assay

  • 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

DOI
https://doi.org/10.1128/mbio.01900-22
Journal volume & issue
Vol. 13, no. 6

Abstract

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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 (cvAUC200) 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. IMPORTANCE 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.

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