Dual-active-ingredient, insecticidal nets for preventing malaria: a systematic review protocol

Background: Malaria is caused by the Plasmodium parasite and is a highly transmissible disease representing a significant global public health burden. The provision of insecticide-treated mosquito nets (ITNs) has contributed to the reduction of malaria across endemic countries. However, the detection of insecticide resistance in many mosquito vector species potentially threatens the long-term effectiveness of ITNs. A novel method to reduce the impact of insecticide resistance is to treat mosquito nets with multiple active ingredients. Methods and analysis: This review will comprehensively search the literature (both published and unpublished) for any studies investigating the effectiveness of mosquito nets treated with multiple active ingredients, known henceforth as dual-active-ingredient (DAI) ITNs. The DAI ITNs of interest include those treated with a pyrethroid and non-pyrethroid insecticide (review question 1) or with a pyrethroid and an insect growth regulator (review question 2). Studies will be screened to meet the inclusion criteria by a minimum of two authors, followed by assessment of risk of bias (using appropriate risk of bias tools for randomised and non-randomised studies) and extraction of relevant information using structured forms by two independent authors. Meta-analyses will be carried out where possible for epidemiological outcomes and subgrouping will be considered. Certainty in the evidence will be established with GRADE assessments. Ethics and dissemination: A full review report will be submitted to the Vector Control and Insecticide Resistance Unit, Global Malaria Program, WHO. A version of this report will be submitted for publication in an open access peer-reviewed journal. The report will inform the development of WHO recommendations regarding the use of DAI ITNs for the prevention of malaria. This systematic review does not require ethics approval as it is a review of primary studies.Timothy Barker, Jennifer Stone, Sabira Hasanoff, Jennifer Stevenson, Carrie Price, Alinune Kabaghe, Zachary Mun

Tools to assess the risk of bias of evidence syntheses: a scoping review

This scoping review will identify and examine risk of bias tools, critical appraisal tools, and assessment of methodological quality tools, including their items and domains, used for all types of evidence synthesis

Effectiveness of dual active ingredient insecticide-treated nets in preventing malaria: A systematic review and meta-analysis

Malaria vectors have demonstrated resistance to pyrethroid-based insecticides used in insecticide-treated nets, diminishing their effectiveness. This systematic review and meta-analysis investigated two forms of dual active-ingredient (DAI) insecticide-treated nets (ITN(s)) for malaria prevention. A comprehensive search was conducted on July 6th 2022. The databases searched included PubMed, Embase, CINAHL, amongst others. Trials were eligible if they were conducted in a region with ongoing malaria transmission. The first DAI ITN investigated were those that combined a pyrethroid with a non-pyrethroid insecticides. The second DAI ITN investigated were that combined a pyrethroid with an insect growth regulator. These interventions were compared against either a pyrethroid-only ITN, or ITNs treated with pyrethroid and piperonyl-butoxide. Assessment of risk of bias was conducted in duplicate using the Cochrane risk of bias 2 tool for cluster-randomised trials. Summary data was extracted using a custom data-extraction instrument. This was conducted by authors THB, JCS and SH. Malaria case incidence was the primary outcome and has been meta-analysed, adverse events were narratively synthesised. The review protocol is registered on PROSPERO (CRD42022333044). From 9494 records, 48 reports were screened and 13 reports for three studies were included. These studies contained data from 186 clusters and all reported a low risk of bias. Compared to pyrethroid-only ITNs, clusters that received pyrethroid-non-pyrethroid DAI ITNs were associated with 305 fewer cases per 1000-person years (from 380 fewer cases to 216 fewer cases) (IRR = 0.55, 95%CI: 0.44–0.68). However, this trend was not observed in clusters that received pyrethroid-insect growth regulator ITNs compared to pyrethroid-only ITNs (from 280 fewer cases to 135 more) (IRR = 0.90, 95%CI: 0.73–1.13). Pyrethroid-non-pyrethroid DAI ITNs demonstrated consistent reductions in malaria case incidence and other outcomes across multiple comparisons. Pyrethroid-non-pyrethroid DAI ITNs may present a novel intervention for the control of malaria