Topical repellents for malaria prevention

Background Insecticide‐based interventions, such as long‐lasting insecticide‐treated nets (LLINs) and indoor residual spraying (IRS), remain the backbone of malaria vector control. These interventions target mosquitoes that prefer to feed and rest indoors, but have limited capacity to prevent transmission that occurs outdoors or outside regular sleeping hours. In low‐endemicity areas, malaria elimination will require that these control gaps are addressed, and complementary tools are found. The use of topical repellents may be particularly useful for populations who may not benefit from programmatic malaria control measures, such as refugees, the military, or forest goers. This Cochrane Review aims to measure the effectiveness of topical repellents to prevent malaria infection among high‐ and non‐high‐risk populations living in malaria‐endemic regions. Objectives To assess the effect of topical repellents alone or in combination with other background interventions (long‐lasting insecticide‐treated nets, or indoor residual spraying, or both) for reducing the incidence of malaria in high‐ and non‐high‐risk populations living in endemic areas. Search methods We searched the following databases up to 11 January 2023: the Cochrane Infectious Diseases Group Specialised Register; CENTRAL (in the Cochrane Library); MEDLINE; Embase; CAB Abstracts; and LILACS. We also searched trial registration platforms and conference proceedings; and contacted organizations and companies for ongoing and unpublished trials. Selection criteria We included randomized controlled trials (RCTs) and cluster‐randomized controlled trials (cRCTs) of topical repellents proven to repel mosquitoes. We also included non‐randomized studies that complied with pre‐specified inclusion criteria: controlled before‐after studies (CBA), controlled interrupted time series (ITS), and controlled cross‐over trials. Data collection and analysis Four review authors independently assessed trials for inclusion, and extracted the data. Two authors independently assessed the risk of bias (RoB) using the Cochrane RoB 2 tool. A fifth review author resolved any disagreements. We analysed data by conducting a meta‐analysis, stratified by whether studies included populations considered to be at high‐risk of developing malaria infection (for example, refugees, forest goers, or deployed military troops). We combined results from cRCTs with RCTs by adjusting for clustering and presented results using forest plots. We used the GRADE framework to assess the certainty of the evidence. We only included data on Plasmodium falciparum infections in the meta‐analysis. Main results Thirteen articles relating to eight trials met the inclusion criteria and were qualitatively described. We included six trials in the meta‐analysis (five cRCTs and one RCT). Effect on malaria incidence Topical repellents may slightly reduce P falciparum infection and clinical incidence when both outcomes are considered together (incidence rate ratio (IRR) 0.74, 95% confidence interval (CI) 0.56 to 0.98; 3 cRCTs and 1 RCT, 61,651 participants; low‐certainty evidence); but not when these two outcomes were considered independently. Two cRCTs and one RCT (12,813 participants) evaluated the effect of topical repellents on infection incidence (IRR 0.76, 95% CI 0.56 to 1.02; low‐certainty evidence). One cRCT (48,838 participants) evaluated their effect on clinical case incidence (IRR 0.66, 95% CI 0.32 to 1.36; low‐certainty evidence). Three studies (2 cRCTs and 1 RCT) included participants belonging to groups considered at high‐risk of being infected, while only one cRCT did not include participants at high risk. Adverse events Topical repellents are considered safe. The prevalence of adverse events among participants who used topical repellents was very low (0.6%, 283/47,515) and limited to mild skin reactions. Effect on malaria prevalence Topical repellents may slightly reduce P falciparum prevalence (odds ratio (OR) 0.81, 95% CI 0.67 to 0.97; 3 cRCTs and 1 RCT; 55,366 participants; low‐certainty evidence). Two of these studies (1 cRCT and 1 RCT) were carried out in refugee camps, and included exclusively high‐risk populations that were not receiving any other background vector control intervention. Authors' conclusions There is insufficient evidence to conclude that topical repellents can prevent malaria in settings where other vector control interventions are in place. We found the certainty of evidence for all outcomes to be low, primarily due to the risk of bias. A protective effect was suggested among high‐risk populations, specially refugees, who might not have access to other standard vector control measures. More adequately powered clinical trials carried out in refugee camps could provide further information on the potential benefit of topical repellents in this setting. Individually randomized studies are also likely necessary to understand whether topical repellents have an effect on personal protection, and the degree to which diversion to non‐protected participants affects overall transmission dynamics. Despite this, the potential additional benefits of topical repellents are most likely limited in contexts where other interventions are available

Potential metabolic resistance mechanisms to ivermectin in Anopheles gambiae: a synergist bioassay study.

BACKGROUND Despite remarkable success obtained with current malaria vector control strategies in the last 15 years, additional innovative measures will be needed to achieve the ambitious goals for malaria control set for 2030 by the World Health Organization (WHO). New tools will need to address insecticide resistance and residual transmission as key challenges. Endectocides such as ivermectin are drugs that kill mosquitoes which feed on treated subjects. Mass administration of ivermectin can effectively target outdoor and early biting vectors, complementing the still effective conventional tools. Although this approach has garnered attention, development of ivermectin resistance is a potential pitfall. Herein, we evaluate the potential role of xenobiotic pumps and cytochrome P450 enzymes in protecting mosquitoes against ivermectin by active efflux and metabolic detoxification, respectively. METHODS We determined the lethal concentration 50 for ivermectin in colonized Anopheles gambiae; then we used chemical inhibitors and inducers of xenobiotic pumps and cytochrome P450 enzymes in combination with ivermectin to probe the mechanism of ivermectin detoxification. RESULTS Dual inhibition of xenobiotic pumps and cytochromes was found to have a synergistic effect with ivermectin, greatly increasing mosquito mortality. Inhibition of xenobiotic pumps alone had no effect on ivermectin-induced mortality. Induction of xenobiotic pumps and cytochromes may confer partial protection from ivermectin. CONCLUSION There is a clear pathway for development of ivermectin resistance in malaria vectors. Detoxification mechanisms mediated by cytochrome P450 enzymes are more important than xenobiotic pumps in protecting mosquitoes against ivermectin

Detection of Plasmodium falciparum infected Anopheles gambiae using near-infrared spectroscopy

Background: Large-scale surveillance of mosquito populations is crucial to assess the intensity of vector-borne disease transmission and the impact of control interventions. However, there is a lack of accurate, cost-effective and high-throughput tools for mass-screening of vectors. Methods: A total of 750 Anopheles gambiae (Keele strain) mosquitoes were fed Plasmodium falciparum NF54 gametocytes through standard membrane feeding assay (SMFA) and afterwards maintained in insectary conditions to allow for oocyst (8 days) and sporozoite development (14 days). Thereupon, each mosquito was scanned using near infra-red spectroscopy (NIRS) and processed by quantitative polymerase chain reaction (qPCR) to determine the presence of infection and infection load. The spectra collected were randomly assigned to either a training dataset, used to develop calibrations for predicting oocyst- or sporozoite-infection through partial least square regressions (PLS); or to a test dataset, used for validating the calibration’s prediction accuracy. Results: NIRS detected oocyst- and sporozoite-stage P. falciparum infections with 88% and 95% accuracy, respectively. This study demonstrates proof-of-concept that NIRS is capable of rapidly identifying laboratory strains of human malaria infection in African mosquito vectors. Conclusions: Accurate, low-cost, reagent-free screening of mosquito populations enabled by NIRS could revolutionize surveillance and elimination strategies for the most important human malaria parasite in its primary African vector species. Further research is needed to evaluate how the method performs in the field following adjustments in the training datasets to include data from wild-caught infected and uninfected mosquitoes

Correction to: Detection of Plasmodium falciparum infected Anopheles gambiae using near-infrared spectroscopy

Following publication of the original article [1], it was flagged that the name of the author Lisa Ranford-Cartwright had been (incorrectly) given as ‘Lisa-Ranford Cartwright

Replication Data for: Near infrared spectra and calibration for detection of malaria infection in Anopheles gambiae (Keele strain)

Anopheles gambiae (Keele Strain) mosquitoes were infected in the lab with cultured Plasmodium falciparum gametocytes (PfN54) to generate oocyst and sporozoite infected vectors. Controls, uninfected mosquitoes, were generated by feeding mosquitoes on the same blood after gametogenesis had occurred which was triggered by dropping the temperature in the glass feeders to below 30 degrees Celsius. After feeding, mosquitoes were kept for 7 and 14 days to allow parasite development after which each individual mosquito was scanned with near infrared spectroscopy (NIRS) and stored at -20 until processed by qPCR (quantitative polymerase chain reaction) for confirmation of infection and quantification of parasite load. The data shared is composed of all the spectra that were collected (in .spc format for GRAMS IQ software) labeled with a unique identifier which links to the STATA files where the mean number of parasite genomes and age for each individual mosquito are listed. The files used to generate the calibration through partial least square (PLS) regression on GRAMS IQ have also been shared (.tfdx) along with the calibration file (.cal) for uploading on IQ Predict software. We have also shared the prediction outputs of the independent samples that were predicted with the calibrations here developed.</p

A chromosomal reference genome sequence for the malaria mosquito, Anopheles moucheti, Evans, 1925.

We present a genome assembly from an individual male Anopheles moucheti (the malaria mosquito; Arthropoda; Insecta; Diptera; Culicidae), from a wild population in Cameroon. The genome sequence is 271 megabases in span. The majority of the assembly is scaffolded into three chromosomal pseudomolecules with the X sex chromosome assembled. The complete mitochondrial genome was also assembled and is 15.5 kilobases in length

A chromosomal reference genome sequence for the malaria mosquito, Anopheles moucheti, Evans, 1925

International audienceWe present a genome assembly from an individual male Anopheles moucheti (the malaria mosquito; Arthropoda; Insecta; Diptera; Culicidae), from a wild population in Cameroon. The genome sequence is 271 megabases in span. The majority of the assembly is scaffolded into three chromosomal pseudomolecules with the X sex chromosome assembled. The complete mitochondrial genome was also assembled and is 15.5 kilobases in length