Towards estimating true cholera burden: a systematic review and meta-analysis of Vibrio cholerae positivity

Abstract

AbstractBackgroundCholera surveillance relies on clinical diagnosis of acute watery diarrhea. Suspected cholera case definitions have high sensitivity but low specificity, challenging our ability to characterize cholera burden and epidemiology. Our objective was to estimate the proportion of clinically suspected cholera that are true Vibrio cholerae infections and identify factors that explain variation in positivity.MethodsWe conducted a systematic review of studies from 2000-2021 that tested ≥10 suspected cholera cases for V. cholerae O1/O139 using culture, PCR and/or a rapid diagnostic test. We estimated diagnostic test sensitivity and specificity using a latent class meta-analysis. We estimated positivity using a random-effects meta-analysis, adjusting for test performance and study methodology.ResultsWe included 113 studies from 28 countries. V. cholerae positivity was lower in studies with representative sampling and lower minimum ages in suspected case definitions. After adjusting for sampling methods, case definitions, and tests, on average half (49%, 95% Credible Interval: 43%-54%) of suspected cases represented true V. cholerae infections, although variation across studies was high. Odds of a suspected case having a true infection were 1.64 (95% Credible Interval: 1.06-2.52) times higher when surveillance was initiated in response to an outbreak than in non-outbreak settings.ConclusionsBurden estimates based on suspected cases alone may overestimate the incidence of medically attended cholera about twofold. However, accounting for cases missed by traditional clinical surveillance is key to unbiased overall cholera burden estimates. Given variability between settings, assumptions about positivity, which are necessary without exhaustive testing, should be based on local data.Key pointsBy pooling results from 113 studies and adjusting for diagnostic tests and study methods, we find that approximately half of suspected cholera cases represent true Vibrio cholerae infections, though this fraction varies widely across epidemiological settings.