Taylor-Robinson David C, Maayan Nicola, Donegan Sarah, Chaplin Marty, Garner Paul
Department of Public Health and Policy, University of Liverpool, Liverpool, Merseyside, UK.
Cochrane Database Syst Rev. 2019 Sep 11;9(9):CD000371. doi: 10.1002/14651858.CD000371.pub7.
The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common. Global advocacy organizations claim routine deworming has substantive health and societal effects beyond the removal of worms. In this update of the 2015 edition we included six new trials, additional data from included trials, and addressed comments and criticisms.
To summarize the effects of public health programmes to regularly treat all children with deworming drugs on child growth, haemoglobin, cognition, school attendance, school performance, physical fitness, and mortality.
We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; LILACS; the metaRegister of Controlled Trials (mRCT); reference lists; and registers of ongoing and completed trials up to 19 September 2018.
We included randomized controlled trials (RCTs) and quasi-RCTs that compared deworming drugs for soil-transmitted helminths (STHs) with placebo or no treatment in children aged 16 years or less, reporting on weight, height, haemoglobin, and formal tests of cognition. We also sought data on other measures of growth, school attendance, school performance, physical fitness, and mortality.
At least two review authors independently assessed the trials for inclusion, risk of bias, and extracted data. We analysed continuous data using the mean difference (MD) with 95% confidence intervals (CIs). Where data were missing, we contacted trial authors. We stratified the analysis based on the background burden of STH infection. We used outcomes at time of longest follow-up. We assessed the certainty of the evidence using the GRADE approach.
We identified 51 trials, including 10 cluster-RCTs, that met the inclusion criteria. One trial evaluating mortality included over one million children, and the remaining 50 trials included a total of 84,336 participants. Twenty-four trials were in populations categorized as high burden, including nine trials in children selected because they were helminth-stool positive; 18 with intermediate burden; and nine as low burden.First or single dose of deworming drugsFourteen trials reported on weight after a single dose of deworming drugs (4970 participants, 14 RCTs). The effects were variable. There was little or no effect in studies conducted in low and intermediate worm burden groups. In the high-burden group, there was little or no effect in most studies, except for a large effect detected from one study area in Kenya reported in two trials carried out over 30 years ago. These trials result in qualitative heterogeneity and uncertainty in the meta-analysis across all studies (I statistic = 90%), with GRADE assessment assessed as very low-certainty, which means we do not know if a first dose or single dose of deworming impacts on weight.For height, most studies showed little or no effect after a single dose, with one of the two trials in Kenya from 30 years ago showing a large average difference (2621 participants, 10 trials, low-certainty evidence). Single dose probably had no effect on average haemoglobin (MD 0.10 g/dL, 95% CI 0.03 lower to 0.22 higher; 1252 participants, five trials, moderate-certainty evidence), or on average cognition (1596 participants, five trials, low-certainty evidence). The data are insufficient to know if there is an effect on school attendance and performance (304 participants, one trial, low-certainty evidence), or on physical fitness (280 participants, three trials, very low-certainty evidence). No trials reported on mortality.Multiple doses of deworming drugsThe effect of regularly treating children with deworming drugs given every three to six months on weight was reported in 18 trials, with follow-up times of between six months and three years; there was little or no effect on average weight in all but two trials, irrespective of worm prevalence-intensity. The two trials with large average weight gain included one in the high burden area in Kenya carried out over 30 years ago, and one study from India in a low prevalence area where subsequent studies in the same area did not show an effect. This heterogeneity causes uncertainty in any meta-analysis (I = 78%). Post-hoc analysis excluding trials published prior to 2000 gave an estimate of average difference in weight gain of 0.02 kg (95%CI from 0.04 kg loss to 0.08 gain, I = 0%). Thus we conclude that we do not know if repeated doses of deworming drugs impact on average weight, with a fewer older studies showing large gains, and studies since 2000 showing little or no average gain.Regular treatment probably had little or no effect on the following parameters: average height (MD 0.02 cm higher, 95% CI 0.09 lower to 0.13 cm higher; 13,700 participants, 13 trials, moderate-certainty evidence); average haemoglobin (MD 0.01 g/dL lower; 95% CI 0.05 g/dL lower to 0.07 g/dL higher; 5498 participants, nine trials, moderate-certainty evidence); formal tests of cognition (35,394 participants, 8 trials, moderate-certainty evidence); school performance (34,967 participants, four trials, moderate-certainty evidence). The evidence assessing an effect on school attendance is inconsistent, and at risk of bias (mean attendance 2% higher, 95% CI 5% lower to 8% higher; 20,650 participants, three trials, very low-certainty evidence). No trials reported on physical fitness. No effect was shown on mortality (1,005,135 participants, three trials, low-certainty evidence).
AUTHORS' CONCLUSIONS: Public health programmes to regularly treat all children with deworming drugs do not appear to improve height, haemoglobin, cognition, school performance, or mortality. We do not know if there is an effect on school attendance, since the evidence is inconsistent and at risk of bias, and there is insufficient data on physical fitness. Studies conducted in two settings over 20 years ago showed large effects on weight gain, but this is not a finding in more recent, larger studies. We would caution against selecting only the evidence from these older studies as a rationale for contemporary mass treatment programmes as this ignores the recent studies that have not shown benefit.The conclusions of the 2015 edition have not changed in this update.
世界卫生组织(WHO)建议,在蠕虫感染常见的地区,定期对所有学童使用驱虫药物进行治疗。全球宣传组织称,常规驱虫除了能清除蠕虫外,还会对健康和社会产生重大影响。在本次对2015年版的更新中,我们纳入了六项新试验、纳入试验的更多数据,并回应了相关评论和批评。
总结公共卫生项目定期对所有儿童使用驱虫药物治疗对儿童生长、血红蛋白、认知、上学出勤率、学业成绩、身体素质和死亡率的影响。
我们检索了Cochrane传染病组专业注册库;Cochrane对照试验中心注册库(CENTRAL);MEDLINE;Embase;LILACS;对照试验元注册库(mRCT);参考文献列表;以及截至2018年9月19日的正在进行和已完成试验的注册库。
我们纳入了随机对照试验(RCT)和半随机对照试验,这些试验比较了16岁及以下儿童使用抗土壤传播蠕虫(STH)的驱虫药物与安慰剂或不治疗的效果,并报告了体重、身高、血红蛋白和认知能力的正式测试结果。我们还收集了关于其他生长指标、上学出勤率、学业成绩、身体素质和死亡率的数据。
至少两名综述作者独立评估试验是否纳入、偏倚风险,并提取数据。我们使用平均差(MD)及95%置信区间(CI)分析连续数据。数据缺失时,我们会联系试验作者。我们根据STH感染的背景负担进行分层分析。我们使用最长随访期的结果。我们使用GRADE方法评估证据的确定性。
我们确定了51项符合纳入标准的试验,其中包括10项整群随机对照试验。一项评估死亡率的试验纳入了超过100万名儿童,其余50项试验共纳入了84336名参与者。24项试验针对高负担人群,其中9项试验的儿童因粪便蠕虫检测呈阳性而入选;18项针对中等负担人群;9项针对低负担人群。
首剂或单剂驱虫药物
14项试验报告了单剂驱虫药物后的体重情况(4970名参与者,14项随机对照试验)。效果各不相同。在低蠕虫负担和中等蠕虫负担组进行的研究中,几乎没有或没有效果。在高负担组中,除了30多年前在肯尼亚一个研究地区进行的两项试验中检测到的一项较大效果外,大多数研究几乎没有或没有效果。这些试验导致所有研究的荟萃分析存在定性异质性和不确定性(I统计量 = 90%),GRADE评估为极低确定性,这意味着我们不知道首剂或单剂驱虫药物是否会影响体重。
对于身高,大多数研究表明单剂后几乎没有或没有效果,30年前在肯尼亚进行的两项试验中的一项显示出较大的平均差异(2621名参与者,10项试验,低确定性证据)。单剂可能对平均血红蛋白没有影响(MD 0.10 g/dL,95% CI为降低0.03至升高0.22;1252名参与者,5项试验,中等确定性证据),或对平均认知能力没有影响(1596名参与者,5项试验,低确定性证据)。数据不足以确定对上学出勤率和学业成绩是否有影响(304名参与者,1项试验,低确定性证据),或对身体素质是否有影响(280名参与者,3项试验,极低确定性证据)。没有试验报告死亡率情况。
多剂驱虫药物
18项试验报告了每三至六个月定期给儿童使用驱虫药物治疗对体重的影响,随访时间为六个月至三年;除两项试验外,对平均体重几乎没有或没有影响,无论蠕虫感染率强度如何。两项平均体重增加较大的试验包括一项30多年前在肯尼亚高负担地区进行的试验,以及一项来自印度低感染率地区的研究,该地区随后的研究未显示出效果。这种异质性导致任何荟萃分析都存在不确定性(I = 78%)。排除2000年前发表的试验的事后分析得出体重增加的平均差异估计值为0.02 kg(95%CI从体重减轻0.04 kg至增加0.08 kg,I = 0%)。因此,我们得出结论,我们不知道重复使用驱虫药物是否会影响平均体重,较少的 older研究显示体重增加较大,而2000年以来的研究显示平均增加很少或没有增加。
平均身高(MD升高0.02 cm,95% CI为降低0.09至升高0.13 cm;13700名参与者,13项试验,中等确定性证据);平均血红蛋白(MD降低0.01 g/dL;95% CI为降低0.05 g/dL至升高0.07 g/dL;5498名参与者,9项试验,中等确定性证据);认知能力的正式测试(35394名参与者