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Background: Insecticide-treated nets (ITNs) contributed significantly to the decline in malaria since 2000. Their protective efficacy depends not only on access, use, and net integrity, but also location of people within the home environment and mosquito biting profiles. Anopheline mosquito biting and human location data were integrated to identify potential gaps in protection and better understand malaria transmission dynamics in Busia County, western Kenya. Methods: Direct observation of human activities and human landing catches (HLC) were performed hourly between 1700 to 0700 h. Household members were recorded as home or away; and, if at home, as indoors/outdoors, awake/asleep, and under a net or not. Aggregated data was analysed by weighting hourly anopheline biting activity with human location. Standard indicators of human-vector interaction were calculated using a Microsoft Excel template. Results: There was no significant difference between indoor and outdoor biting for Anopheles gambiae sensu lato (s.l.) (RR = 0.82; 95% CI 0.65–1.03); significantly fewer Anopheles funestus were captured outdoors than indoors (RR = 0.41; 95% CI 0.25–0.66). Biting peaked before dawn and extended into early morning hours when people began to awake and perform routine activities, between 0400–0700 h for An. gambiae and 0300–0700 h for An. funestus. The study population away from home peaked at 1700–1800 h (58%), gradually decreased and remained constant at 10% throughout the night, before rising again to 40% by 0600–0700 h. When accounting for resident location, nearly all bites within the peri-domestic space (defined as inside household structures and surrounding outdoor spaces) occurred indoors for unprotected people (98%). Using an ITN while sleeping was estimated to prevent 79% and 82% of bites for An. gambiae and An. funestus, respectively. For an ITN user, most remaining exposure to bites occurred indoors in the hours before bed and early morning. Conclusion: While use of an ITN was estimated to prevent most vector bites in this context, results suggest gaps in protection, particularly in the early hours of the morning when biting peaks and many people are awake and active. Assessment of additional human exposure points, including outside of the peri-domestic setting, are needed to guide supplementary interventions for transmission reduction. [ABSTRACT FROM AUTHOR]

Introduction: Malaria presents a significant global public health burden, although substantial progress has been made, with vector control initiatives such as indoor residual surface spraying with insecticides and insecticide-treated nets. There now exists many different approaches to apply residual insecticide to indoor and outdoor surfaces in malaria-endemic settings, although no comprehensive systematic reviews exist evaluating these interventions. This manuscript outlines the protocol for a systematic review which aims to synthesise the best available evidence regarding full or partial indoor or outdoor residual insecticide surface treatment for preventing malaria. Methods and analysis: This review will comprehensively search the literature (both published and unpublished) for any studies investigating the effectiveness of residual insecticide surface treatment for malaria. 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-analysis will be carried out where possible for epidemiological outcomes such as malaria, anaemia, malaria-related mortality, all-cause mortality and adverse effects. Certainty in the evidence will be established with GRADE assessments. Ethics and dissemination: A full review report will be submitted to the Vector Control & 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 residual insecticide treatment for malaria. This systematic review does not require ethics approval as it is a review of primary studies. Systematic review registration: PROSPERO 293194. [ABSTRACT FROM AUTHOR]

Background: Despite the scale-up of insecticide-treated nets and indoor residual spraying, the bulk of malaria transmission in western Kenya still occurs indoors, late at night. House improvement is a potential long-term solution to further reduce malaria transmission in the region. Methods: The impact of eave screening on mosquito densities was evaluated in two rural villages in western Kenya. One-hundred-and-twenty pairs of structurally similar, neighbouring houses were used in the study. In each pair, one house was randomly selected to receive eave screening at the beginning of the study while the other remained unscreened until the end of the sampling period. Mosquito sampling was performed monthly by motorized aspiration method for 4 months. The collected mosquitoes were analysed for species identification. Results: Compared to unscreened houses, significantly fewer female Anopheles funestus (RR = 0.40, 95% CI 0.29–0.55), Anopheles gambiae Complex (RR = 0.46, 95% CI 0.34–0.62) and Culex species (RR = 0.53, 95% CI 0.45–0.61) were collected in screened houses. No significant differences in the densities of the mosquitoes were detected in outdoor collections. Significantly fewer Anopheles funestus were collected indoors from houses with painted walls (RR = 0.05, 95% CI 0.01–0.38) while cooking in the house was associated with significantly lower numbers of Anopheles gambiae Complex indoors (RR = 0.60, 95% CI 0.45–0.79). Nearly all house owners (99.6%) wanted their houses permanently screened, including 97.7% that indicated a willingness to use their own resources. However, 99.2% required training on house screening. The cost of screening a single house was estimated at KES6,162.38 (US$61.62). Conclusion: Simple house modification by eave screening has the potential to reduce the indoor occurrence of both Anopheles and Culex mosquito species. Community acceptance was very high although education and mobilization may be needed for community uptake of house modification for vector control. Intersectoral collaboration and favourable government policies on housing are important links towards the adoption of house improvements for malaria control. [ABSTRACT FROM AUTHOR]

Simple Summary: New types of bed nets are being developed which contain a pyrethroid plus a second chemical because of the development and increased frequency of mosquito mechanisms to avoid being killed by pyrethroids. When insecticide-treated bed nets are being trialed for efficacy or released onto the market it is essential to measure how effective the net is in killing mosquitoes, which includes testing how quickly insecticide is lost or degraded due to routine wear and tear. Pyrethroid-resistant mosquitoes are needed to test the effectiveness and insecticidal persistence of the second chemical, because they are not all killed by the pyrethroid, allowing the killing effect of the two chemicals to be evaluated independently. However, because resistance status varies between populations of mosquitoes that possess different resistance mechanisms, and because resistance intensity in a population can change over time, a method is needed to characterise the resistant mosquitoes. A focus group of experts discussed how this should best be done, considering pros and cons of different approaches, and co-wrote a protocol, which will be valuable for malaria control programmes and stakeholders wanting to test the effective lifespan of a new bed net in terms of the active ingredient bioefficacy. Durability monitoring of insecticide-treated nets (ITNs) containing a pyrethroid in combination with a second active ingredient (AI) must be adapted so that the insecticidal bioefficacy of each AI can be monitored independently. An effective way to do this is to measure rapid knock down of a pyrethroid-susceptible strain of mosquitoes to assess the bioefficacy of the pyrethroid component and to use a pyrethroid-resistant strain to measure the bioefficacy of the second ingredient. To allow robust comparison of results across tests within and between test facilities, and over time, protocols for bioefficacy testing must include either characterisation of the resistant strain, standardisation of the mosquitoes used for bioassays, or a combination of the two. Through a series of virtual meetings, key stakeholders and practitioners explored different approaches to achieving these goals. Via an iterative process we decided on the preferred approach and produced a protocol consisting of characterising mosquitoes used for bioefficacy testing before and after a round of bioassays, for example at each time point in a durability monitoring study. We present the final protocol and justify our approach to establishing a standard methodology for durability monitoring of ITNs containing pyrethroid and a second AI. [ABSTRACT FROM AUTHOR]

Background: Spatial repellents are widely used for prevention of mosquito bites and evidence is building on their public health value, but their efficacy against malaria incidence has never been evaluated in Africa. To address this knowledge gap, a trial to evaluate the efficacy of Mosquito Shield™, a spatial repellent incorporating transfluthrin, was developed for implementation in Busia County, western Kenya where long-lasting insecticidal net coverage is high and baseline malaria transmission is moderate to high year-round.Methods: This trial is designed as a cluster-randomized, placebo-controlled, double-blinded clinical trial. Sixty clusters will be randomly assigned in a 1:1 ratio to receive spatial repellent or placebo. A total of 6120 children aged ≥6 months to 10 years of age will be randomly selected from the study clusters, enrolled into an active cohort (baseline, cohort 1, and cohort 2), and sampled monthly to determine time to first infection by smear microscopy. Each cohort following the implementation of the intervention will be split into two groups, one to estimate direct effect of the spatial repellent and the other to estimate degree of diversion of mosquitoes and malaria transmission to unprotected persons. Malaria incidence in each cohort will be estimated and compared (primary indicator) to determine benefit of using a spatial repellent in a high, year-round malaria transmission setting. Mosquitoes will be collected monthly using CDC light traps to determine if there are entomological correlates of spatial repellent efficacy that may be useful for the evaluation of new spatial repellents. Quarterly human landing catches will assess behavioral effects of the intervention.Discussion: Findings will serve as the first cluster-randomized controlled trial powered to detect spatial repellent efficacy to reduce malaria in sub-Saharan Africa where transmission rates are high, insecticide-treated nets are widely deployed, and mosquitoes are resistant to insecticides. Results will be submitted to the World Health Organization Vector Control Advisory Group for assessment of public health value towards an endorsement to recommend inclusion of spatial repellents in malaria control programs.Trial Registration: ClinicalTrials.gov NCT04766879 . Registered February 23, 2021. [ABSTRACT FROM AUTHOR]

Background: Efforts to improve the impact of long-lasting insecticidal nets (LLINs) should be informed by understanding of the causes of decay in effect. Holes in LLINs have been estimated to account for 7–11% of loss in effect on vectorial capacity for Plasmodium falciparum malaria in an analysis of repeated cross-sectional surveys of LLINs in Kenya. This does not account for the effect of holes as a cause of net attrition or non-use, which cannot be measured using only cross-sectional data. There is a need for estimates of how much these indirect effects of physical damage on use and attrition contribute to decay in effectiveness of LLINs. Methods: Use, physical integrity, and survival were assessed in a cohort of 4514 LLINs followed for up to 4 years in Kenya. Flow diagrams were used to illustrate how the status of nets, in terms of categories of use, physical integrity, and attrition, changed between surveys carried out at 6-month intervals. A compartment model defined in terms of ordinary differential equations (ODEs) was used to estimate the transition rates between the categories. Effects of physical damage to LLINs on use and attrition were quantified by simulating counterfactuals in which there was no damage. Results: Allowing for the direct effect of holes, the effect on use, and the effect on attrition, 18% of the impact on vectorial capacity was estimated to be lost because of damage. The estimated median lifetime of the LLINs was 2.9 years, but this was extended to 5.7 years in the counterfactual without physical damage. Nets that were in use were more likely to be in a damaged state than unused nets but use made little direct difference to LLIN lifetimes. Damage was reported as the reason for attrition for almost half of attrited nets, but the model estimated that almost all attrited nets had suffered some damage before attrition. Conclusions: Full quantification of the effects of damage will require measurement of the supply of new nets and of household stocks of unused nets, and also of their impacts on both net use and retention. The timing of mass distribution campaigns is less important than ensuring sufficient supply. In the Kenyan setting, nets acquired damage rapidly once use began and the damage led to rapid attrition. Increasing the robustness of nets could substantially increase their lifetime and impact but the impact of LLIN programmes on malaria transmission is ultimately limited by levels of use. Longitudinal analyses of net integrity data from different settings are needed to determine the importance of physical damage to nets as a driver of attrition and non-use, and the importance of frequent use as a cause of physical damage in different contexts. [ABSTRACT FROM AUTHOR]

Background: Spatial determinants of malaria risk within communities are associated with heterogeneity of exposure to vector mosquitoes. The abundance of adult malaria vectors inside people's houses, where most transmission takes place, should be associated with several factors: proximity of houses to larval habitats, structural characteristics of houses, indoor use of vector control tools containing insecticides, and human behavioural and environmental factors in and near houses. While most previous studies have assessed the association of larval habitat proximity in landscapes with relatively low densities of larval habitats, in this study these relationships were analysed in a region of rural, lowland western Kenya with high larval habitat density. Methods: 525 houses were sampled for indoor-resting mosquitoes across an 8 by 8 km study area using the pyrethrum spray catch method. A predictive model of larval habitat location in this landscape, previously verified, provided derivations of indices of larval habitat proximity to houses. Using geostatistical regression models, the association of larval habitat proximity, long-lasting insecticidal nets (LLIN) use, house structural characteristics (wall type, roof type), and peridomestic variables (cooking in the house, cattle near the house, number of people sleeping in the house) with mosquito abundance in houses was quantified. Results: Vector abundance was low (mean, 1.1 adult Anopheles per house). Proximity of larval habitats was a strong predictor of Anopheles abundance. Houses without an LLIN had more female Anopheles gambiae s.s., Anopheles arabiensis and Anopheles funestus than houses where some people used an LLIN (rate ratios, 95% CI 0.87, 0.85-0.89; 0.84, 0.82-0.86; 0.38, 0.37-0.40) and houses where everyone used an LLIN (RR, 95% CI 0.49, 0.48-0.50; 0.39, 0.39-0.40; 0.60, 0.58-0.61). Cooking in the house also reduced Anopheles abundance across all species. The number of people sleeping in the house, presence of cattle near the house, and house structure modulated Anopheles abundance, but the effect varied with Anopheles species and sex. Conclusions: Variation in the abundance of indoor-resting Anopheles in rural houses of western Kenya varies with clearly identifiable factors. Results suggest that LLIN use continues to function in reducing vector abundance, and that larval source management in this region could lead to further reductions in malaria risk by reducing the amount of an obligatory resource for mosquitoes near people's homes. [ABSTRACT FROM AUTHOR]

Background: Although it is well known that drug pressure selects for drug-resistant parasites, the role of transmission reduction by insecticide-treated bed nets (ITNs) on drug resistance remains unclear. In this study, the drug resistance profile of current and previous first-line anti-malarials in Kenya was assessed within the context of drug policy change and scale-up of ITNs. National first-line treatment changed from chloroquine (CQ) to sulphadoxine-pyrimethamine (SP) in 1998 and to artemether-lumefantrine (AL) in 2004. ITN use was scaled-up in the Asembo, Gem and Karemo areas of western Kenya in 1997, 1999 and 2006, respectively. Methods: Smear-positive samples (N = 253) collected from a 2007 cross-sectional survey among children in Asembo, Gem and Karemo were genotyped for mutations in pfcrt and pfmdr1 (CQ), dhfr and dhps (SP), and at pfmdr-N86 and the gene copy number in pfmdr1 (lumefantrine). Results were compared among the three geographic areas in 2007 and to retrospective molecular data from children in Asembo in 2001. Results: In 2007, 69 and 85% of samples harboured the pfmdr1-86Y mutation and dhfr/dhps quintuple mutant, respectively, with no significant differences by study area. However, the prevalence of the pfcrt-76T mutation differed significantly among areas (p <0.02), between 76 and 94%, with the highest prevalence in Asembo. Several 2007 samples carried mutations at dhfr-164L, dhps-436A, or dhps-613T. From 2001 to 2007, there were significant increases in the pfcrt-76T mutation from 82 to 94% (p <0.03), dhfr/dhps quintuple mutant from 62 to 82% (p <0.03), and an increase in the septuple CQ and SP combined mutant haplotype, K76Y86I51R59N108G437E540, from 28 to 39%. The prevalence of the pfmdr1-86Y mutation remained unchanged. All samples were single copy for pfmdr1. Conclusions: Molecular markers associated with lumefantrine resistance were not detected in 2007. More recent samples will be needed to detect any selective effects by AL. The prevalence of CQ and SP resistance markers increased from 2001 to 2007 in the absence of changes in transmission intensity. In 2007, only the prevalence of pfcrt-76T mutation differed among study areas of varying transmission intensity. Resistant parasites were most likely selected by sustained drug pressure from the continued use of CQ, SP, and mechanistically similar drugs, such as amodiaquine and cotrimoxazole. There was no clear evidence that differences in transmission intensity, as a result of ITN scale-up, influenced the prevalence of drug resistance molecular markers. [ABSTRACT FROM AUTHOR]

Background: Eliminating malaria requires vector control interventions that dramatically reduce adult mosquito population densities and survival rates. Indoor applications of insecticidal nets and sprays are effective against an important minority of mosquito species that rely heavily upon human blood and habitations for survival. However, complementary approaches are needed to tackle a broader diversity of less human-specialized vectors by killing them at other resource targets. Methods: Impacts of strategies that target insecticides to humans or animals can be rationalized in terms of biological coverage of blood resources, quantified as proportional coverage of all blood resources mosquito vectors utilize. Here, this concept is adapted to enable impact prediction for diverse vector control strategies based on measurements of utilization rates for any definable, targetable resource subset, even if that overall resource is not quantifiable. Results: The usefulness of this approach is illustrated by deriving utilization rate estimates for various blood, resting site, and sugar resource subsets from existing entomological survey data. Reported impacts of insecticidal nets upon human-feeding vectors, and insecticide-treated livestock upon animal-feeding vectors, are approximately consistent with model predictions based on measured utilization rates for those human and animal blood resource subsets. Utilization rates for artificial sugar baits compare well with blood resources, and are consistent with observed impact when insecticide is added. While existing data was used to indirectly measure utilization rates for a variety of resting site subsets, by comparison with measured rates of blood resource utilization in the same settings, current techniques for capturing resting mosquitoes underestimate this quantity, and reliance upon complex models with numerous input parameters may limit the applicability of this approach. Conclusions: While blood and sugar consumption can be readily quantified using existing methods for detecting natural markers or artificial tracers, improved techniques for labelling mosquitoes, or other arthropod pathogen vectors, will be required to assess vector control measures which target them when they utilize non-nutritional resources such as resting, oviposition, and mating sites. [ABSTRACT FROM AUTHOR]

Despite the clear public health benefit of insecticide-treated bednets (ITNs), the impact of malaria transmission-reduction by vector control on the spread of drug resistance is not well understood. In the present study, the effect of sustained transmission reduction by ITNs on the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) in children under the age of five years was investigated during an ITN trial in Asembo area, western Kenya. During the ITN trial, the national first line antimalarial treatment changed from CQ to SP. Smear-positive samples collected from cross sectional surveys prior to ITN introduction (baseline, n = 250) and five years post-ITN intervention (year 5 survey, n = 242) were genotyped for single nucleotide polymorphisms (SNPs) at dhfr-51, 59, 108, 164 and dhps-437, 540 (SP resistance), and pfcrt-76 and pfmdr1-86 (CQ resistance). The association between the drug resistance mutations and epidemiological variables was evaluated. There were significant increases in the prevalence of SP dhps mutations and the dhfr/dhps quintuple mutant, and a significant reduction in the proportion of mixed infections detected at dhfr-51, 59 and dhps-437, 540 SNPs from baseline to the year 5 survey. There was no change in the high prevalence of pfcrt-76 and pfmdr1-86 mutations. Multivariable regression analysis further showed that current antifolate use and year of survey were significantly associated with more SP drug resistance mutations. These results suggest that increased antifolate drug use due to drug policy change likely led to the high prevalence of SP mutations 5 years post-ITN intervention and reduced transmission had no apparent effect on the existing high prevalence of CQ mutations. There is no evidence from the current study that sustained transmission reduction by ITNs reduces the prevalence of genes associated with malaria drug resistance. [ABSTRACT FROM AUTHOR]

The article discusses the ecology of mosquitoes for the eradication of malaria across the world. It says that eradication of malaria parasites will require interventions that can eliminate transmission anywhere such as insecticide-treated nets (ITNs), and indoor residual spraying (IRS). However these measures are not sufficient to eliminate transmission in Africa because of the entomological inoculation rate (EIR). Several key areas for ecological research investment are also mentioned.