Pryce Joseph, Richardson Marty, Lengeler Christian
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK, L3 5QA.
Cochrane Database Syst Rev. 2018 Nov 6;11(11):CD000363. doi: 10.1002/14651858.CD000363.pub3.
A previous version of this Cochrane Review identified that insecticide-treated nets (ITNs) are effective at reducing child mortality, parasite prevalence, and uncomplicated and severe malaria episodes. Insecticide-treated nets have since become a core intervention for malaria control and have contributed greatly to the dramatic decline in disease incidence and malaria-related deaths seen since the turn of the millennium. However, this time period has also seen a rise in resistance to pyrethroids (the insecticide used in ITNs), raising questions over whether the evidence from trials conducted before resistance became widespread can be applied to estimate the impact of ITNs on malaria transmission today.
The primary objective of this review was to assess the impact of ITNs on mortality and malaria morbidity, incorporating any evidence published since the previous update into new and existing analyses, and assessing the certainty of the resulting evidence using GRADE.
We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) published in the Cochrane Library, MEDLINE, Embase, LILACS, the World Health Organization (WHO) International Clinical Trials Registry Platform, ClinicalTrials.gov, and the ISRCTN registry for new trials published since 2004 and up to 18 April 2018.
We included individual randomized controlled trials (RCTs) and cluster RCTs comparing bed nets or curtains treated with a synthetic pyrethroid insecticide at a minimum target impregnation dose recommended by the WHO with no nets or untreated nets.
One review author assessed the identified trials for eligibility and risk of bias, and extracted data. We compared intervention and control data using risk ratios (RRs), rate ratios, and mean differences, and presented all results with their associated 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach. We drew on evidence from a meta-analysis of entomological outcomes stratified by insecticide resistance from 2014 to inform the GRADE assessments.
Our updated search identified three new trials. A total of 23 trials met the inclusion criteria, enrolling more than 275,793 adults and children. The included studies were conducted between 1987 and 2001.ITN versus no netsInsecticide-treated nets reduce child mortality from all causes by 17% compared to no nets (rate ratio 0.83, 95% CI 0.77 to 0.89; 5 trials, 200,833 participants, high-certainty evidence). This corresponds to a saving of 5.6 lives (95% CI 3.6 to 7.6) each year for every 1000 children protected with ITNs. Insecticide-treated nets also reduce the incidence of uncomplicated episodes of Plasmodium falciparum malaria by almost a half (rate ratio 0.55, 95% CI 0.48 to 0.64; 5 trials, 35,551 participants, high-certainty evidence) and probably reduce the incidence of uncomplicated episodes of Plasmodium vivax malaria (risk ratio (RR) 0.61, 95% CI 0.48 to 0.77; 2 trials, 10,967 participants, moderate-certainty evidence).Insecticide-treated nets were also shown to reduce the prevalence of P falciparum malaria by 17% compared to no nets (RR 0.83, 95% CI 0.71 to 0.98; 6 trials, 18,809 participants, high-certainty evidence) but may have little or no effect on the prevalence of P vivax malaria (RR 1.00, 95% CI 0.75 to 1.34; 2 trials, 10,967 participants, low-certainty evidence). A 44% reduction in the incidence of severe malaria episodes was seen in the ITN group (rate ratio 0.56, 95% CI 0.38 to 0.82; 2 trials, 31,173 participants, high-certainty evidence), as well as an increase in mean haemoglobin (expressed as mean packed cell volume) compared to the no-net group (mean difference 1.29, 95% CI 0.42 to 2.16; 5 trials, 11,489 participants, high-certainty evidence).ITN versus untreated netsInsecticide-treated nets probably reduce child mortality from all causes by a third compared to untreated nets (rate ratio 0.67, 95% CI 0.36 to 1.23; 2 trials, 25,389 participants, moderate-certainty evidence). This corresponds to a saving of 3.5 lives (95% CI -2.4 to 6.8) each year for every 1000 children protected with ITNs. Insecticide-treated nets also reduce the incidence of uncomplicated P falciparum malaria episodes (rate ratio 0.58, 95% CI 0.44 to 0.78; 5 trials, 2036 participants, high-certainty evidence) and may also reduce the incidence of uncomplicated P vixax malaria episodes (rate ratio 0.73, 95% CI 0.51 to 1.05; 3 trials, 1535 participants, low-certainty evidence).Use of an ITN probably reduces P falciparum prevalence by one-tenth in comparison to use of untreated nets (RR 0.91, 95% CI 0.78 to 1.05; 3 trials, 2,259 participants, moderate-certainty evidence). However, based on the current evidence it is unclear whether or not ITNs impact on P vivax prevalence (1 trial, 350 participants, very low certainty evidence) or mean packed cell volume (2 trials, 1,909 participants, low certainty evidence).
AUTHORS' CONCLUSIONS: Although there is some evidence that insecticide resistance frequency has some effects on mosquito mortality, it is unclear how quantitatively important this is. It appeared insufficient to downgrade the strong evidence of benefit on mortality and malaria illness from the trials conducted earlier.
本Cochrane系统评价的上一版本指出,经杀虫剂处理的蚊帐(ITNs)在降低儿童死亡率、寄生虫感染率以及单纯性和重症疟疾发作方面有效。自那时起,经杀虫剂处理的蚊帐已成为疟疾控制的核心干预措施,并为自世纪之交以来疾病发病率和疟疾相关死亡的大幅下降做出了巨大贡献。然而,在此期间,对拟除虫菊酯(用于经杀虫剂处理蚊帐的杀虫剂)的耐药性也有所上升,这引发了人们对在耐药性广泛传播之前进行的试验证据是否可用于估计经杀虫剂处理蚊帐对当今疟疾传播的影响的质疑。
本系统评价的主要目的是评估经杀虫剂处理蚊帐对死亡率和疟疾发病率的影响,将自上次更新以来发表的所有证据纳入新的和现有的分析中,并使用GRADE方法评估所得证据的确定性。
我们检索了Cochrane传染病专业组专门注册库、Cochrane图书馆中发表的Cochrane对照试验中心注册库(CENTRAL)、MEDLINE、Embase、LILACS、世界卫生组织(WHO)国际临床试验注册平台、ClinicalTrials.gov以及ISRCTN注册库,以查找2004年至2018年4月18日期间发表的新试验。
我们纳入了个体随机对照试验(RCT)和整群RCT,这些试验比较了按照世界卫生组织推荐的最低目标浸渍剂量用合成拟除虫菊酯杀虫剂处理的蚊帐或窗帘与未使用蚊帐或未处理蚊帐。
一位综述作者评估了纳入试验的合格性和偏倚风险,并提取了数据。我们使用风险比(RRs)、率比和均值差比较了干预组和对照组的数据,并呈现了所有结果及其相关的95%置信区间(CIs)。我们使用GRADE方法评估证据的确定性。我们借鉴了2014年对按杀虫剂耐药性分层的昆虫学结果进行的一项荟萃分析的证据,以告知GRADE评估。
我们更新后的检索识别出三项新试验。共有23项试验符合纳入标准,纳入了超过275,793名成人和儿童。纳入的研究在1987年至2001年期间进行。
经杀虫剂处理蚊帐与未使用蚊帐相比
与未使用蚊帐相比,经杀虫剂处理的蚊帐可使所有原因导致的儿童死亡率降低17%(率比0.83,95%CI 0.77至0.89;5项试验,200,833名参与者,高确定性证据)。这相当于每1000名使用经杀虫剂处理蚊帐保护的儿童每年可挽救5.6条生命(95%CI 3.6至7.6)。经杀虫剂处理的蚊帐还可使恶性疟原虫单纯性发作的发生率降低近一半(率比0.55,95%CI 0.48至0.64;5项试验,35,551名参与者,高确定性证据),并且可能降低间日疟原虫单纯性发作的发生率(风险比(RR)0.61,95%CI 0.48至0.77;2项试验,10,967名参与者,中等确定性证据)。
与未使用蚊帐相比,经杀虫剂处理的蚊帐还可使恶性疟原虫疟疾的感染率降低17%(RR 0.83,95%CI 0.71至0.98;6项试验,18,809名参与者,高确定性证据),但对间日疟原虫疟疾的感染率可能几乎没有影响或没有影响(RR 1.00,95%CI 0.75至1.34;2项试验,10,967名参与者,低确定性证据)。在经杀虫剂处理蚊帐组中,重症疟疾发作的发生率降低了44%(率比0.56,95%CI 0.38至0.82;2项试验,31,173名参与者,高确定性证据),与未使用蚊帐组相比,平均血红蛋白(以平均红细胞压积表示)也有所增加(均值差1.29,95%CI 0.42至2.16;5项试验,11,489名参与者,高确定性证据)。
经杀虫剂处理蚊帐与未处理蚊帐相比
与未处理蚊帐相比,经杀虫剂处理的蚊帐可能使所有原因导致的儿童死亡率降低三分之一(率比0.67,95%CI 0.36至1.23;2项试验,25,389名参与者,中等确定性证据)。这相当于每1000名使用经杀虫剂处理蚊帐保护的儿童每年可挽救3.5条生命(95%CI -2.4至6.8)。经杀虫剂处理的蚊帐还可降低恶性疟原虫单纯性发作的发生率(率比0.58,95%CI 0.44至0.78;5项试验,2036名参与者,高确定性证据),并且可能也降低间日疟原虫单纯性发作的发生率(率比0.73,95%CI 0.51至1.05;3项试验,1535名参与者,低确定性证据)。与使用未处理蚊帐相比,使用经杀虫剂处理的蚊帐可能使恶性疟原虫感染率降低十分之一(RR 0.91,95%CI 0.78至1.05;3项试验,2,259名参与者,中等确定性证据)。然而,根据目前的证据,尚不清楚经杀虫剂处理蚊帐是否会影响间日疟原虫感染率(1项试验,350名参与者,极低确定性证据)或平均红细胞压积(2项试验,1,909名参与者,低确定性证据)。
尽管有一些证据表明杀虫剂耐药频率对蚊虫死亡率有一定影响,但尚不清楚这在数量上有多重要。这似乎不足以降低早期试验中关于对死亡率和疟疾疾病有益的有力证据的等级。