Effectiveness of a long-lasting piperonyl butoxide-treated insecticidal net and indoor residual spray interventions, separately and together, against malaria transmitted by pyrethroid-resistant mosquitoes: a cluster, randomised controlled, two-by-two factorial design trial

BackgroundInsecticide‐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.ObjectivesTo summarize the effect on malaria of additionally implementing IRS, using non‐pyrethroid‐like or pyrethroid‐like insecticides, in communities currently using ITNs.Search methodsWe 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.Selection criteriaCluster‐randomized controlled trials (cRCTs), interrupted time series (ITS), or controlled before‐and‐after studies (CBAs) comparing IRS plus ITNs with ITNs alone.Data collection and analysisTwo 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, ‘pyrethroid‐like’ and ‘non‐pyrethroid‐like’; the latter 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.Main resultsSix 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' insecticidesAdding 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 e...

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Summary Of Findingsmentioning

confidence: 99%

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Indoor residual spraying for preventing malaria in communities using insecticide-treated nets

Choi

Pryce

Garner

2019

Indoor residual spraying for preventing malaria in communities using insecticide-treated nets

Pryce

Medley

Choi

2022

Background Insecticide‐treated nets (ITNs) and indoor residual spraying (IRS) are used to prevent malaria transmission. Both interventions use insecticides to kill mosquitoes that bite and rest indoors. Adding IRS to ITNs may improve malaria control simply because two interventions can be better than one. Furthermore, IRS may improve malaria control where ITNs are failing due to insecticide resistance. Pyrethroid insecticides are the predominant class of insecticide used for ITNs, as they are more safe than other insecticide classes when in prolonged contact with human skin. While many mosquito populations have developed some resistance to pyrethroid insecticides, a wider range of insecticides can be used for IRS. This review is an update of the previous Cochrane 2019 edition. Objectives To summarize the effect on malaria of additionally implementing IRS, using non‐pyrethroid‐like or pyrethroid‐like insecticides, in communities currently using ITNs. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; CENTRAL; MEDLINE; and five other databases for records from 1 January 2000 to 8 November 2021, on the basis that ITN programmes did not begin to be implemented as policy before the year 2000. Selection criteria We included cluster‐randomized controlled trials (cRCTs), interrupted time series (ITS), or controlled before‐after studies (CBAs) comparing IRS plus ITNs with ITNs alone. We included studies with at least 50% ITN ownership (defined as the proportion of households owning one or more ITN) in both study arms. Data collection and analysis Two review authors independently assessed studies 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, 'pyrethroid‐like' and 'non‐pyrethroid‐like'; the latter 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 studies to explore heterogeneity. We assessed the certainty of evidence using the GRADE approach. Main results Eight cRCTs (10 comparisons), one CBA, and one ITS study, all conducted since 2008 in sub‐Saharan Africa, met our inclusion criteria. The primary vectors in all sites were mosquitoes belonging to the Anopheles gambiae s.l. complex species; five studies in Benin, Mozambique, Ghana, Sudan, and Tanzania also reported the vector Anopheles funestus . Five cRCTs and both quasi‐experimental design studies used insecticides with targets different to pyrethroids (two used bendiocarb, three used pirimiphos‐methyl, and one used propoxur. Each of these studies were conducted in areas where the vectors were described as resistant or highly resistant to pyrethroids. Two...

Piperonyl butoxide (PBO) combined with pyrethroids in insecticide-treated nets to prevent malaria in Africa

Gleave

Lissenden

Richardson

et al. 2018

102

BackgroundPublic health strategies that target mosquito vectors, particularly pyrethroid long‐lasting insecticidal nets (LLINs), have been largely responsible for the substantial reduction in the number of people in Africa developing malaria. The spread of insecticide resistance in Anopheles mosquitoes threatens these impacts. One way to control insecticide‐resistant populations is by using insecticide synergists. Piperonyl butoxide (PBO) is a synergist that inhibits specific metabolic enzymes within mosquitoes and has been incorporated into pyrethroid‐LLINs to form pyrethroid‐PBO nets. Pyrethroid‐PBO nets are currently produced by four LLIN manufacturers and, following a recommendation from the World Health Organization (WHO) in 2017, are being included in distribution campaigns in countries. This review examines epidemiological and entomological evidence on whether the addition of PBO to LLINs improves their efficacy.Objectives1. Evaluate whether adding PBO to pyrethroid LLINs increases the epidemiological and entomological effectiveness of the nets.2. Compare the effects of pyrethroid‐PBO nets currently in commercial development or on the market with their non‐PBO equivalent in relation to:a. malaria infection (prevalence or incidence); b. entomological outcomes.Search methodsWe searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register; CENTRAL, MEDLINE, Embase, Web of Science, CAB Abstracts, and two clinical trial registers (ClinicalTrials.gov and WHO International Clinical Trials Registry Platform) up to 24 August 2018. We contacted organizations for unpublished data. We checked the reference lists of trials identified by the above methods.Selection criteriaWe included laboratory trials, experimental hut trials, village trials, and randomized clinical trials with mosquitoes from the Anopheles gambiae complex or Anopheles funestus group.Data collection and analysisTwo review authors assessed each trial for eligibility, extracted data, and determined the risk of bias for included trials. We resolved disagreements through discussion with a third review author. We analysed the data using Review Manager 5 and assessed the certainty of the evidence using the GRADE approach.Main resultsFifteen trials met the inclusion criteria: two laboratory trials, eight experimental hut trials, and five cluster‐randomized controlled village trials.One village trial examined the effect of pyrethroid‐PBO nets on malaria infection prevalence in an area with highly pyrethroid‐resistant mosquitoes. The latest endpoint at 21 months post‐intervention showed that malaria prevalence probably decreased in the intervention arm (OR 0.40, 95% CI 0.20 to 0.80; 1 trial, 1 comparison, moderate‐certainty evidence).In highly pyrethroid‐resistant areas (< 30% mosquito mortality), in comparisons of unwashed pyrethroid‐PBO nets to unwashed standard‐LLINs, PBO nets resulted in higher mosquito mortality (risk ratio (RR) 1.84, 95% CI 1.60 to 2.11; 14,620 mosquitoes, 5 trials, 9 comparisons, high‐certainty evidence) and lower blood feed...