Choi Leslie, Pryce Joseph, Garner Paul
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK, L3 5QA.
Cochrane Database Syst Rev. 2019 May 23;5(5):CD012688. doi: 10.1002/14651858.CD012688.pub2.
Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) are used to control malaria vectors. Both strategies use insecticides to kill mosquitoes that bite and rest indoors. For ITNs, the World Health Organization (WHO) only recommended pyrethroids until 2018, but mosquito vectors are becoming resistant to this insecticide. For IRS, a range of insecticides are recommended. Adding IRS to ITNs may improve control, simply because two interventions may be better than one; it may improve malaria control where ITNs are failing due to pyrethroid resistance; and it may slow the emergence and spread of pyrethroid resistance.
To summarize the effect on malaria of additionally implementing IRS, using non-pyrethroid-like or pyrethroid-like insecticides, in communities currently using ITNs.
We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; LILACS; the WHO International Clinical Trials Registry Platform; ClinicalTrials.gov; and the ISRCTN registry up to 18 March 2019.
Cluster-randomized controlled trials (cRCTs), interrupted time series (ITS), or controlled before-and-after studies (CBAs) comparing IRS plus ITNs with ITNs alone.
Two review authors independently assessed trials for eligibility, analyzed risk of bias, and extracted data. We used risk ratio (RR) and 95% confidence intervals (CI). We stratified by type of insecticide: 'non-pyrethroid-like', as this could improve malaria control better than adding IRS insecticides that have the same way of working as the insecticide on ITNs ('pyrethroid-like'). We used subgroup analysis of ITN usage in the trials to explore heterogeneity. We assessed the certainty of evidence using the GRADE approach.
Six cRCTs (eight comparisons) met our inclusion criteria conducted since 2008 in sub-Saharan Africa. Malaria transmission in all sites was from mosquitoes belonging to the Anopheles gambiae s.l. complex species; two trials in Benin and Tanzania also reported the vector Anopheles funestus. Three trials used insecticide with targets different to pyrethroids (two used bendiocarb and one used pirimiphos-methyl); two trials used dichloro-diphenyl-trichlorethane (DDT), an insecticide with the same target as pyrethroids; and one trial used both types of insecticide (pyrethroid deltamethrin in the first year, switching to bendiocarb for the second-year). ITN usage was greater than 50% in three trials, and less than 50% in the remainder.Indoor residual spraying using 'non-pyrethroid-like' insecticides Adding IRS with a non-pyrethroid-like insecticide had mixed results. Overall, we do not know if the addition of IRS impacted on malaria incidence (rate ratio 0.93, 95% CI 0.46 to 1.86; 2 cRCTs, 566 child-years; very low-certainty evidence); it may have reduced malaria parasite prevalence (0.67, 95% CI 0.35 to 1.28; 5 comparisons from 4 cRCTs, 10,440 participants; low-certainty evidence); and it may have reduced the prevalence of anaemia (RR CI 0.46, 95% 0.18 to 1.20; 3 comparisons from 2 cRCTs, 2026 participants; low-certainty evidence). Three trials reported the impact on EIR, with variable results; overall, we do not know if IRS had any effect on the EIR in communities using ITNs (very low-certainty evidence). Trials also reported the adult mosquito density and the sporozoite rate, but we could not summarize or pool these entomological outcomes due to unreported data. ITN usage did not explain the variation in malaria outcomes between different studies. One trial reported no effect on malaria incidence or parasite prevalence in the first year, when the insecticide used for IRS had the same target as pyrethroids, but showed an effect on both outcomes in the second year, when the insecticide was replaced by one with a different target.Two trials measured the prevalence of pyrethroid resistance before and after IRS being introduced: no difference was detected, but these data are limited.Indoor residual spraying using 'pyrethroid-like' insecticidesAdding IRS using a pyrethroid-like insecticide did not appear to markedly alter malaria incidence (rate ratio 1.07, 95% CI 0.80 to 1.43; 2 cRCTs, 15,717 child-years; moderate-certainty evidence), parasite prevalence (RR 1.11, 95% CI 0.86 to 1.44; 3 cRCTs, 10,820 participants; moderate-certainty evidence), or anaemia prevalence (RR 1.12, 95% CI 0.89 to 1.40; 1 cRCT, 4186 participants; low-certainty evidence). Data on the entomological inoculation rate (EIR) were limited, and therefore we do not know if IRS had any effect on the EIR in communities using ITNs (very low-certainty evidence).
AUTHORS' CONCLUSIONS: Four trials have evaluated adding IRS using 'non-pyrethroid-like' insecticides in communities using ITNs. Some of these trials showed effects, and others did not. Three trials have evaluated adding IRS using 'pyrethroid-like' insecticides in communities using ITNs, and these studies did not detect an additional effect of the IRS. Given the wide geographical variety of malaria endemicities, transmission patterns, and insecticide resistance, we need to be cautious with inferences to policy from the limited number of trials conducted to date, and to develop relevant further research to inform decisions.
经杀虫剂处理的蚊帐(ITNs)和室内滞留喷洒(IRS)用于控制疟疾媒介。这两种策略都使用杀虫剂来杀死在室内叮咬和栖息的蚊子。对于经杀虫剂处理的蚊帐,世界卫生组织(WHO)直到2018年才仅推荐拟除虫菊酯类杀虫剂,但疟疾媒介对这种杀虫剂正产生抗药性。对于室内滞留喷洒,推荐使用一系列杀虫剂。在经杀虫剂处理的蚊帐基础上增加室内滞留喷洒可能会改善防控效果,原因很简单,两种干预措施可能比一种更好;在因拟除虫菊酯类抗药性导致经杀虫剂处理的蚊帐失效的地区,它可能会改善疟疾防控;并且它可能会减缓拟除虫菊酯类抗药性的出现和传播。
总结在目前使用经杀虫剂处理的蚊帐的社区中,额外实施使用非拟除虫菊酯类或拟除虫菊酯类杀虫剂的室内滞留喷洒对疟疾的影响。
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);医学索引(MEDLINE);Embase;拉丁美洲和加勒比卫生科学数据库(LILACS);世界卫生组织国际临床试验注册平台;临床试验.gov;以及截至2019年3月18日的ISRCTN注册库。
比较室内滞留喷洒加经杀虫剂处理的蚊帐与单纯经杀虫剂处理的蚊帐的整群随机对照试验(cRCTs)、中断时间序列(ITS)或前后对照研究(CBAs)。
两位综述作者独立评估试验的合格性、分析偏倚风险并提取数据。我们使用风险比(RR)和95%置信区间(CI)。我们按杀虫剂类型分层:“非拟除虫菊酯类”,因为与在经杀虫剂处理的蚊帐上使用具有相同作用方式的杀虫剂(“拟除虫菊酯类”)相比,添加这种杀虫剂可能会更好地改善疟疾防控。我们对试验中经杀虫剂处理的蚊帐的使用情况进行亚组分析以探索异质性。我们使用GRADE方法评估证据的确定性。
自2008年以来在撒哈拉以南非洲进行的六项整群随机对照试验(八项比较)符合我们的纳入标准。所有地点的疟疾传播均来自冈比亚按蚊复合种的蚊子;在贝宁和坦桑尼亚的两项试验还报告了媒介嗜人按蚊。三项试验使用了与拟除虫菊酯类目标不同的杀虫剂(两项使用残杀威,一项使用甲基嘧啶磷);两项试验使用了二氯二苯三氯乙烷(DDT),一种与拟除虫菊酯类目标相同的杀虫剂;一项试验使用了两种类型的杀虫剂(第一年使用拟除虫菊酯类溴氰菊酯,第二年改用残杀威)。三项试验中经杀虫剂处理的蚊帐使用率大于50%,其余试验中使用率小于50%。
使用“非拟除虫菊酯类”杀虫剂进行室内滞留喷洒
添加使用非拟除虫菊酯类杀虫剂的室内滞留喷洒结果不一。总体而言,我们不知道添加室内滞留喷洒是否会影响疟疾发病率(率比0.93,95%CI 0.46至1.86;2项整群随机对照试验;566儿童年;极低确定性证据);它可能降低了疟原虫感染率(0.67,95%CI 0.35至1.28;来自4项整群随机对照试验的5项比较;10440名参与者;低确定性证据);并且它可能降低了贫血患病率(RR CI 0.46,95% 0.18至1.20;来自2项整群随机对照试验的3项比较;2026名参与者;低确定性证据)。三项试验报告了对昆虫接种率(EIR)的影响,结果各异;总体而言,我们不知道室内滞留喷洒对使用经杀虫剂处理的蚊帐的社区中的昆虫接种率是否有任何影响(极低确定性证据)。试验还报告了成蚊密度和子孢子率,但由于数据未报告,我们无法汇总或合并这些昆虫学结果。经杀虫剂处理的蚊帐使用率并不能解释不同研究之间疟疾结果的差异。一项试验报告,当用于室内滞留喷洒的杀虫剂与拟除虫菊酯类目标相同时,第一年对疟疾发病率或疟原虫感染率没有影响,但在第二年,当杀虫剂被替换为目标不同的杀虫剂时,对这两个结果都有影响。两项试验在引入室内滞留喷洒前后测量了拟除虫菊酯类抗药性的患病率:未检测到差异,但这些数据有限。
使用“拟除虫菊酯类”杀虫剂进行室内滞留喷洒
添加使用拟除虫菊酯类杀虫剂的室内滞留喷洒似乎并未显著改变疟疾发病率(率比1.07,95%CI 0.80至1.43;2项整群随机对照试验;15717儿童年;中等确定性证据)、疟原虫感染率(RR 1.11,95%CI 0.86至1.44;3项整群随机对照试验;10820名参与者;中等确定性证据)或贫血患病率(RR 1.12,95%CI 0.89至1.40;1项整群随机对照试验;4186名参与者;低确定性证据)。关于昆虫接种率(EIR)的数据有限,因此我们不知道室内滞留喷洒对使用经杀虫剂处理的蚊帐的社区中的昆虫接种率是否有任何影响(极低确定性证据)。
四项试验评估了在使用经杀虫剂处理的蚊帐的社区中添加使用“非拟除虫菊酯类”杀虫剂的室内滞留喷洒。其中一些试验显示出了效果,而另一些则没有。三项试验评估了在使用经杀虫剂处理的蚊帐的社区中添加使用“拟除虫菊酯类”杀虫剂的室内滞留喷洒,这些研究未发现室内滞留喷洒有额外效果。鉴于疟疾流行程度、传播模式和杀虫剂抗药性在地理上的广泛差异,我们需要谨慎地从迄今为止进行的有限数量的试验中推断政策,并开展相关的进一步研究以为决策提供依据。