Estimating the proportion of clinically suspected cholera cases that are true Vibrio cholerae infections: A systematic review and meta-analysis.

Estimating the proportion of clinically suspected cholera cases that are true Vibrio cholerae infections: A systematic review and meta-analysis.
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DOI:
10.1371/journal.pmed.1004286
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发表时间:
2023-09
期刊:
影响因子:
15.8
通讯作者:
--
中科院分区:
医学1区
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霍乱监测依赖于急性水样腹泻的临床诊断。霍乱疑似病例定义的敏感性高,但特异性低,对我们描述霍乱负担和流行病学特征的能力提出了挑战。我们的目标是估计临床疑似霍乱真正霍乱弧菌感染的比例,并确定解释阳性率变化的因素。我们对使用培养、PCR 和/或快速诊断测试对≥10 例疑似霍乱病例进行霍乱弧菌 O1/O139 检测的研究进行了系统回顾。我们搜索了 PubMed、Embase、Scopus 和 Google Scholar,查找在 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采样的研究,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估计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率,并根据测试表现进行调整。我们纳入了来自 30 个国家的 119 项研究。在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,霍乱弧菌阳性率较低。调整测试性能后,平均 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。调整测试性能和研究方法后,为应对疫情而启动监测时,疑似病例真正感染的几率比非疫情爆发时高出 5.71 倍(比值比 95% CrI:1.53,15.43)。研究之间的差异很大,我们方法的局限性在于我们无法用研究级别的属性来解释所有异质性,包括使用的诊断测试、设置和病例定义。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就医霍乱的发病率高估两倍。然而,考虑到传统临床监测遗漏的病例是公正估计霍乱负担的关键。鉴于不同环境之间的阳性率存在很大差异,从疑似病例到确诊病例的外推应基于当地数据,这对于在不进行详尽检测的情况下估计霍乱发病率是必要的。 Kirsten E. Wiens 及其同事利用从 30 个国家的 119 项研究中提取的综合数据,估计了霍乱弧菌阳性率的真实负担。霍乱监测通常依赖于急性水样腹泻(即“疑似霍乱”)的临床诊断,但该定义对霍乱的特异性较低。我们的目标是估计疑似霍乱病例中真正的霍乱弧菌感染的比例,并确定导致观察到的阳性率变化的因素。我们对 2000 年至 2023 年的研究进行了系统回顾,这些研究使用 3 种不同的实验室检测之一来检测疑似霍乱病例是否感染霍乱弧菌。我们纳入了来自 30 个国家的 119 项研究,在考虑了实验室检测的准确性后,发现平均有一半疑似霍乱病例代表真正的霍乱弧菌感染。我们还发现研究之间存在很大差异,与非爆发环境相比,爆发期间疑似病例真正感染的可能性更高。我们的研究结果表明,仅根据疑似病例进行的负担估计可能会将就医霍乱的发病率高估两倍。研究之间的高度变异性还表明,当详尽的测试不可行时,应使用本地测试数据来告知有关阳性的假设。我们方法的一个局限性是我们无法解释临床监测遗漏的病例,这对于公正的总体霍乱负担估计至关重要,也是未来工作的一个重要领域。
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. Using combined data extracted from 119 studies from 30 countries, Kirsten E. Wiens and colleagues estimate the true burden Vibrio Cholerae positivity. Cholera surveillance typically relies on the clinical diagnosis of acute watery diarrhea (i.e., “suspected cholera”), but this definition has a low specificity for cholera. Our goal was to estimate the proportion of suspected cholera cases that are true Vibrio cholerae infections and identify factors that contribute to variation in observed positivity. We conducted a systematic review of studies from 2000 to 2023 that tested suspected cholera cases for V. cholerae infection using one of 3 different laboratory tests. We included 119 studies from 30 countries and found that, on average, half of suspected cholera cases represented true V. cholerae infections, after accounting for laboratory test accuracy. We also found high variability between studies and that the odds of a suspected case being a true infection were higher during outbreaks compared to non-outbreak settings. Our findings suggest that burden estimates based solely on suspected cases may overestimate the incidence of medically attended cholera by 2-fold. The high variability across studies suggests also that local testing data should be used to inform assumptions about positivity when exhaustive testing is not feasible. A limitation of our approach was that we could not account for cases missed by clinical surveillance, which is crucial for unbiased overall cholera burden estimates and an important area for future work.
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