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      The epidemiological benefit of pyrethroid–pyrrole insecticide treated nets against malaria: an individual-based malaria transmission dynamics modelling study

      research-article
      , Prof, PhD a , * , * , , PhD a , * , , PhD a , * , , MD a , , PhD b , , Prof, PhD c , , PhD b , , PhD d , , PhD d , , PhD a , , PhD a , , PhD a , , PhD a , , PhD a , , PhD a , , PhD a , , PhD e , , PhD e , f , , PhD f , , PhD d , , PhD c , , PhD g , , Prof, PhD h , i , , Prof, PhD i , , Prof, PhD i , , PhD d , , PhD b , , PhD c , d , , PhD c , , PhD c , g , , PhD i , , PhD a
      The Lancet. Global Health
      Elsevier Ltd

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          Summary

          Background

          Insecticide treated nets (ITNs) are the most important malaria prevention tool in Africa but the rise of pyrethroid resistance in mosquitoes is likely impeding control. WHO has recommended a novel pyrethroid–pyrrole ITN following evidence of epidemiological benefit in two cluster-randomised, controlled trials (CRTs). It remains unclear how effective more costly pyrethroid–pyrrole ITNs are compared with other tools, or whether they should be deployed when budgets are limited. We aimed to compare the epidemiological impact and cost-effectiveness of the mass distribution of pyrethroid–pyrrole ITNs relative to other ITNs over 3 years in different African settings.

          Methods

          In this individual-based malaria transmission dynamics modelling study we characterise the entomological impact of ITNs using data from a systematic review of experimental hut trials from across Africa. This African entomological data was used to inform an individual-based malaria transmission dynamics model, which was validated against CRT results from Benin and Tanzania. The full impact of new ITNs was quantified for trial sites and simulation was used to project impact in different settings which were included within an accessible interface (the Malaria Intervention Tool) to support National Malaria Programmes to explore how vector control tools and budgets could be allocated across regions to avert the most cases.

          Findings

          The model projects that distributing pyrethroid–pyrrole ITNs averted 65% (95% credible interval 48–74) of cases over 3 years in Tanzania, and 75% (28–93) in Benin. The model indicates that trials might have underestimated the benefits of switching ITNs by 12–16% over 3 years because participants stopped using trial-allocated nets. In moderate endemicity non-trial settings, pyrethroid–pyrrole ITNs are projected to reduce malaria prevalence by 25–60% and switching from pyrethroid-only ITNs is probably highly cost-effective in most locations given current prices, averting an additional 10–30% of cases.

          Interpretation

          The benefit of pyrethroid–pyrrole ITNs varies by setting but is generally the most cost-effective indoor vector control intervention in Africa. National Malaria Programmes can strategise deployment to maximise impact. Entomological data could broadly predict epidemiological impact, although there are some inconsistencies, illustrating the challenge in capturing the dynamics across diverse settings.

          Funding

          Unitaid, Bill & Melinda Gates Foundation, the UK Medical Research Council, Wellcome Trust, and the UK Foreign, Commonwealth & Development Office.

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          Most cited references23

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          The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015

          Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015 and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542–753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.
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            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

            Summary Background Progress in malaria control is under threat by wide-scale insecticide resistance in malaria vectors. Two recent vector control products have been developed: a long-lasting insecticidal net that incorporates a synergist piperonyl butoxide (PBO) and a long-lasting indoor residual spraying formulation of the insecticide pirimiphos-methyl. We evaluated the effectiveness of PBO long-lasting insecticidal nets versus standard long-lasting insecticidal nets as single interventions and in combination with the indoor residual spraying of pirimiphos-methyl. Methods We did a four-group cluster randomised controlled trial using a two-by-two factorial design of 48 clusters derived from 40 villages in Muleba (Kagera, Tanzania). We randomly assigned these clusters using restricted randomisation to four groups: standard long-lasting insecticidal nets, PBO long-lasting insecticidal nets, standard long-lasting insecticidal nets plus indoor residual spraying, or PBO long-lasting insecticidal nets plus indoor residual spraying. Both standard and PBO nets were distributed in 2015. Indoor residual spraying was applied only once in 2015. We masked the inhabitants of each cluster to the type of nets received, as well as field staff who took blood samples. Neither the investigators nor the participants were masked to indoor residual spraying. The primary outcome was the prevalence of malaria infection in children aged 6 months to 14 years assessed by cross-sectional surveys at 4, 9, 16, and 21 months after intervention. The endpoint for assessment of indoor residual spraying was 9 months and PBO long-lasting insecticidal nets was 21 months. This trial is registered with ClinicalTrials.gov, number NCT02288637. Findings 7184 (68·0%) of 10 560 households were selected for post-intervention survey, and 15 469 (89·0%) of 17 377 eligible children from the four surveys were included in the intention-to-treat analysis. Of the 878 households visited in the two indoor residual spraying groups, 827 (94%) had been sprayed. Reported use of long-lasting insecticidal nets, across all groups, was 15 341 (77·3%) of 19 852 residents after 1 year, decreasing to 12 503 (59·2%) of 21 105 in the second year. Malaria infection prevalence after 9 months was lower in the two groups that received PBO long-lasting insecticidal nets than in the two groups that received standard long-lasting insecticidal nets (531 [29%] of 1852 children vs 767 [42%] of 1809; odds ratio [OR] 0·37, 95% CI 0·21–0·65; p=0·0011). At the same timepoint, malaria prevalence in the two groups that received indoor residual spraying was lower than in groups that did not receive indoor residual spraying (508 [28%] of 1846 children vs 790 [44%] of 1815; OR 0·33, 95% CI 0·19–0·55; p<0·0001) and there was evidence of an interaction between PBO long-lasting insecticidal nets and indoor residual spraying (OR 2·43, 95% CI 1·19–4·97; p=0·0158), indicating redundancy when combined. The PBO long-lasting insecticidal net effect was sustained after 21 months with a lower malaria prevalence than the standard long-lasting insecticidal net (865 [45%] of 1930 children vs 1255 [62%] of 2034; OR 0·40, 0·20–0·81; p=0·0122). Interpretation The PBO long-lasting insecticidal net and non-pyrethroid indoor residual spraying interventions showed improved control of malaria transmission compared with standard long-lasting insecticidal nets where pyrethroid resistance is prevalent and either intervention could be deployed to good effect. As a result, WHO has since recommended to increase coverage of PBO long-lasting insecticidal nets. Combining indoor residual spraying with pirimiphos-methyl and PBO long-lasting insecticidal nets provided no additional benefit compared with PBO long-lasting insecticidal nets alone or standard long-lasting insecticidal nets plus indoor residual spraying. Funding UK Department for International Development, Medical Research Council, and Wellcome Trust.
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              Threats to the effectiveness of insecticide-treated bednets for malaria control: thinking beyond insecticide resistance

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                Author and article information

                Contributors
                Journal
                Lancet Glob Health
                Lancet Glob Health
                The Lancet. Global Health
                Elsevier Ltd
                2214-109X
                20 November 2024
                December 2024
                20 November 2024
                : 12
                : 12
                : e1973-e1983
                Affiliations
                [a ]School of Public Health, Imperial College London, London, UK
                [b ]Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso
                [c ]Department of Disease Control, London School of Hygiene & Tropical Medicine, London, UK
                [d ]Department of Parasitology, National Institute for Medical Research, Mwanza Medical Research Centre, Mwanza, Tanzania
                [e ]Innovative Vector Control Consortium, Liverpool, UK
                [f ]PATH, Washington, DC, USA
                [g ]Centre de Recherches Entomologiques de Cotonou, Cotonou, Benin
                [h ]Institut Régional de Santé Publique, University of Abomey-Caliva, Abomey-Calavi, Benin
                [i ]Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK
                Author notes
                [* ]Correspondence to: Prof Thomas S Churcher, School of Public Health, Imperial College London, London W12 0BZ, UK thomas.churcher@ 123456imperial.ac.uk
                [*]

                Joint first author

                Article
                S2214-109X(24)00329-2
                10.1016/S2214-109X(24)00329-2
                11584316
                39577971
                e98bb289-9cb8-4ef8-8ff4-08cb4cecccf9
                © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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