PDF(Pubmed)
Abstract：
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.
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.
摘要：
背景：霍乱监测依赖于急性水样腹泻的临床诊断。疑似霍乱病例定义敏感性高但特异性低,挑战我们描述霍乱负担和流行病学的能力。我们的目标是估计临床上怀疑的霍乱是真正的霍乱弧菌感染的比例，并确定解释阳性变化的因素。
结果：我们对使用培养物检测≥10例疑似霍乱病例的霍乱弧菌O1/O139的研究进行了系统回顾，PCR,和/或快速诊断测试。我们搜索了PubMed,Embase,Scopus,和GoogleScholar的研究，在2000年1月1日至2023年4月19日期间对至少一例疑似病例进行了采样，以反映霍乱弧菌阳性的当代模式。我们使用潜在类别荟萃分析评估了诊断测试的敏感性和特异性。我们使用随机效应荟萃分析估计霍乱弧菌阳性，根据测试性能进行调整。我们纳入了来自30个国家的119项研究。在具有代表性抽样的研究和在疑似病例定义中设定最低年龄的研究中，霍乱弧菌阳性较低。试验性能调整后,平均而言,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。在调整测试性能和研究方法后，为应对疫情而启动监测时,疑似病例发生真正感染的几率是非疫情背景下的5.71倍(比值比95%CrI:1.53,15.43).研究之间的差异很大，我们的方法的局限性在于我们无法解释研究级别属性的所有异质性，包括使用的诊断测试，设置,和案例定义。
结论：在这项研究中，我们发现,仅根据疑似病例进行的负担估计可能会将医疗看护霍乱的发病率高估2倍.然而,对传统临床监测漏诊的病例进行核算是估计霍乱负担的关键.鉴于设置之间的积极性存在很大差异，从疑似病例到确诊病例的推断，这对于在没有详尽测试的情况下估计霍乱发病率是必要的，应该基于本地数据。
结果：我们对使用培养物检测≥10例疑似霍乱病例的霍乱弧菌O1/O139的研究进行了系统回顾，PCR,和/或快速诊断测试。我们搜索了PubMed,Embase,Scopus,和GoogleScholar的研究，在2000年1月1日至2023年4月19日期间对至少一例疑似病例进行了采样，以反映霍乱弧菌阳性的当代模式。我们使用潜在类别荟萃分析评估了诊断测试的敏感性和特异性。我们使用随机效应荟萃分析估计霍乱弧菌阳性，根据测试性能进行调整。我们纳入了来自30个国家的119项研究。在具有代表性抽样的研究和在疑似病例定义中设定最低年龄的研究中，霍乱弧菌阳性较低。试验性能调整后,平均而言,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。在调整测试性能和研究方法后，为应对疫情而启动监测时,疑似病例发生真正感染的几率是非疫情背景下的5.71倍(比值比95%CrI:1.53,15.43).研究之间的差异很大，我们的方法的局限性在于我们无法解释研究级别属性的所有异质性，包括使用的诊断测试，设置,和案例定义。
结论：在这项研究中，我们发现,仅根据疑似病例进行的负担估计可能会将医疗看护霍乱的发病率高估2倍.然而,对传统临床监测漏诊的病例进行核算是估计霍乱负担的关键.鉴于设置之间的积极性存在很大差异，从疑似病例到确诊病例的推断，这对于在没有详尽测试的情况下估计霍乱发病率是必要的，应该基于本地数据。
