Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
Department of Epidemiology and Biostatistics, College of Public Health, Temple University, Philadelphia, Pennsylvania, United States of America.
PLoS Med. 2023 Sep 14;20(9):e1004286. doi: 10.1371/journal.pmed.1004286. eCollection 2023 Sep.
Cholera 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.
We conducted a systematic review of studies that tested ≥10 suspected cholera cases for V. cholerae O1/O139 using culture, PCR, and/or a rapid diagnostic test. We searched PubMed, Embase, Scopus, and Google Scholar for studies that sampled at least one suspected case between January 1, 2000 and April 19, 2023, to reflect contemporary patterns in V. cholerae positivity. We estimated diagnostic test sensitivity and specificity using a latent class meta-analysis. We estimated V. cholerae positivity using a random-effects meta-analysis, adjusting for test performance. We included 119 studies from 30 countries. V. cholerae positivity was lower in studies with representative sampling and in studies that set minimum ages in suspected case definitions. After adjusting for test performance, on average, 52% (95% credible interval (CrI): 24%, 80%) of suspected cases represented true V. cholerae infections. After adjusting for test performance and study methodology, the odds of a suspected case having a true infection were 5.71 (odds ratio 95% CrI: 1.53, 15.43) times higher when surveillance was initiated in response to an outbreak than in non-outbreak settings. Variation across studies was high, and a limitation of our approach was that we were unable to explain all the heterogeneity with study-level attributes, including diagnostic test used, setting, and case definitions.
In this study, we found that burden estimates based on suspected cases alone may overestimate the incidence of medically attended cholera by 2-fold. However, accounting for cases missed by traditional clinical surveillance is key to unbiased cholera burden estimates. Given the substantial variability in positivity between settings, extrapolations from suspected to confirmed cases, which is necessary to estimate cholera incidence rates without exhaustive testing, should be based on local data.
霍乱监测依赖于对急性水样腹泻的临床诊断。疑似霍乱病例的定义具有很高的灵敏度，但特异性低，这给我们描述霍乱负担和流行病学特征带来了挑战。我们的目标是估计临床上疑似霍乱中有多少是真正的霍乱弧菌感染，并确定导致阳性率差异的因素。
我们对使用培养、PCR 和/或快速诊断检测方法检测至少 10 例疑似霍乱弧菌 O1/O139 感染的研究进行了系统综述。我们在 PubMed、Embase、Scopus 和 Google Scholar 中检索了 2000 年 1 月 1 日至 2023 年 4 月 19 日期间至少有一例疑似病例的研究，以反映当代霍乱弧菌阳性率的变化情况。我们使用潜在类别荟萃分析估计诊断检测的灵敏度和特异性。我们使用随机效应荟萃分析估计霍乱弧菌阳性率，并根据检测性能进行调整。我们纳入了来自 30 个国家的 119 项研究。在具有代表性采样的研究和在疑似病例定义中设定最低年龄的研究中，霍乱弧菌阳性率较低。在调整检测性能后，平均有 52%（95%可信区间（CrI）：24%，80%）的疑似病例代表真正的霍乱弧菌感染。在调整检测性能和研究方法后，与非暴发环境相比，在暴发环境中启动监测时，疑似病例发生真正感染的可能性高 5.71 倍（比值比 95% CrI：1.53，15.43）。研究间的变异很大，我们方法的一个局限性是，我们无法用研究水平的属性（包括使用的诊断检测、环境和病例定义）来解释所有的异质性。
在这项研究中，我们发现仅基于疑似病例的估计可能会使医学上关注的霍乱发病率高估 2 倍。然而，考虑到传统临床监测遗漏的病例，是进行无偏霍乱负担估计的关键。鉴于不同环境之间的阳性率存在很大差异，在没有全面检测的情况下，从疑似病例推断确诊病例，以估计霍乱发病率，应基于当地数据。
