Department of Global Health, University of Washington, Seattle, WA, USA.
Department of Epidemiology, University of Washington, Seattle, WA, USA.
Lancet Glob Health. 2017 Dec;5(12):e1235-e1248. doi: 10.1016/S2214-109X(17)30392-3.
Shigella infections are a leading cause of diarrhoeal death among children in low-income and middle-income countries. WHO guidelines reserve antibiotics for treating children with dysentery. Reliance on dysentery for identification and management of Shigella infection might miss an opportunity to reduce Shigella-associated morbidity and mortality. We aimed to systematically review and evaluate Shigella-associated and dysentery-associated mortality, the diagnostic value of dysentery for the identification of Shigella infection, and the efficacy of antibiotics for children with Shigella or dysentery, or both.
We did three systematic reviews (for mortality, diagnostic value, and antibiotic treatment of Shigella and dysentery), and meta-analyses where appropriate, of studies in resource-limited settings. We searched MEDLINE, Embase, and LILACS database for studies published before Jan 1, 2017, in English, French, and Spanish. We included studies of human beings with diarrhoea and accepted all study-specific definitions of dysentery. For the mortality and diagnostic value searches, we excluded studies that did not include an effect estimate or data necessary to calculate this estimate. The search for treatment included only randomised controlled trials that were done after Jan 1, 1980, and assessed antibiotics in children (aged <18 years) with dysentery or laboratory-confirmed Shigella. We extracted or calculated odds ratios (ORs) and 95% CIs for relative mortality and did random-effects meta-analysis to arrive at pooled ORs. We calculated 95% CIs assuming a binomial distribution and did random-effects meta-regression of log-transformed sensitivity and specificity estimates for diagnostic value. We assessed the heterogeneity of papers included in these meta-analyses using the I statistic and evaluated publication bias using funnel plots. This review is registered with PROSPERO (CRD42017063896).
3649 papers were identified and 60 studies were included for analyses: 13 for mortality, 27 for diagnostic value, and 20 for treatment. Shigella infection was associated with mortality (pooled OR 2·8, 95% CI 1·6-4·8; p=0·000) whereas dysentery was not associated with mortality (1·3, 0·7-2·3; p=0·37). Between 1977 and 2016, dysentery identified 1·9-85·9% of confirmed Shigella infections, with sensitivity decreasing over time (p=0·04). Ten (50%) of 20 included antibiotic trials were among children with dysentery, none were placebo-controlled, and two (10%) evaluated antibiotics no longer recommended for acute infectious diarrhoea. Ciprofloxacin showed superior microbiological, but not clinical, effectiveness compared with pivmecillinam, and no superior microbiological and clinical effectiveness compared with gatifloxacin. Substantial heterogeneity was reported for meta-analyses of the Shigella-associated mortality studies (I=78·3%) and dysentery-associated mortality studies (I=73·2%). Too few mortality studies were identified to meaningfully test for publication bias. No evidence of publication bias was found in this analysis of studies of diagnostic value.
Current WHO guidelines appear to manage dysentery effectively, but might miss opportunities to reduce mortality among children infected with Shigella who present without bloody stool. Further studies should quantify potential decreases in mortality and morbidity associated with antibiotic therapy for children with non-dysenteric Shigella infection.
Bill & Melinda Gates Foundation and the Center for AIDS Research International Core.
志贺氏菌感染是中低收入国家儿童腹泻死亡的主要原因。世界卫生组织的指南保留抗生素用于治疗痢疾儿童。依赖痢疾来识别和管理志贺氏菌感染可能会错过减少志贺氏菌相关发病率和死亡率的机会。我们旨在系统地审查和评估志贺氏菌相关和痢疾相关死亡率、痢疾对志贺氏菌感染的识别的诊断价值，以及抗生素对志贺氏菌或痢疾或两者的儿童的疗效。
我们进行了三项系统评价（死亡率、诊断价值和志贺氏菌和痢疾的抗生素治疗），并在适当的情况下进行了元分析，这些研究都是在资源有限的环境中进行的。我们在 MEDLINE、Embase 和 LILACS 数据库中搜索了截至 2017 年 1 月 1 日之前发表的英语、法语和西班牙语的研究。我们纳入了有腹泻症状的人类研究，并接受了所有特定于研究的痢疾定义。对于死亡率和诊断价值搜索，我们排除了未包括效应估计值或计算该估计值所需数据的研究。治疗搜索仅包括在 1980 年 1 月 1 日之后进行的随机对照试验，评估了患有痢疾或实验室确诊志贺氏菌的儿童（年龄<18 岁）的抗生素治疗。我们提取或计算了相对死亡率的比值比（OR）和 95%置信区间（CI），并进行了随机效应荟萃分析以得出汇总 OR。我们假设二项分布计算了 95%CI，并对诊断价值的敏感性和特异性估计值进行了随机效应荟萃回归。我们使用 I 统计量评估了这些荟萃分析中包含的论文的异质性，并使用漏斗图评估了发表偏倚。这项综述已在 PROSPERO（CRD42017063896）中注册。
共发现 3649 篇论文，纳入了 60 项研究进行分析：13 项用于死亡率，27 项用于诊断价值，20 项用于治疗。志贺氏菌感染与死亡率相关（汇总 OR 2.8，95%CI 1.6-4.8；p=0.000），而痢疾与死亡率无关（1.3，0.7-2.3；p=0.37）。1977 年至 2016 年间，痢疾识别出 1.9%-85.9%的确诊志贺氏菌感染，其敏感性随时间降低（p=0.04）。纳入的 20 项抗生素试验中有 10 项（50%）是针对痢疾儿童的，没有安慰剂对照，其中两项（10%）评估了不再推荐用于急性传染性腹泻的抗生素。与匹美西林相比，环丙沙星显示出更好的微生物学效果，但临床效果没有优势，与加替沙星相比，也没有更好的微生物学和临床效果。对志贺氏菌相关死亡率研究（I=78.3%）和痢疾相关死亡率研究（I=73.2%）的荟萃分析报告了大量的异质性。由于纳入的死亡率研究太少，无法对发表偏倚进行有意义的检验。这项对诊断价值研究的分析没有发现发表偏倚的证据。
目前的世界卫生组织指南似乎有效地管理了痢疾，但可能会错过减少无血便志贺氏菌感染儿童死亡率的机会。应进一步研究量化与非痢疾性志贺氏菌感染儿童的抗生素治疗相关的死亡率和发病率降低的潜力。
比尔和梅林达盖茨基金会和艾滋病研究国际中心核心。
