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Background: Indoor residual spraying (IRS) is one of the most effective malaria control tools. However, its application has become limited to specific contexts due to the increased costs of IRS products and implementation programmes. Selective spraying—selective spray targeted to particular areas/surfaces of dwellings—has been proposed to maintain the malaria control and resistance-management benefits of IRS while decreasing the costs of the intervention. Methods: A literature search was conducted to find (1) studies that assessed the resting behaviour of Anopheles mosquitoes and (2) studies that evaluated the impact of selective spraying on entomological and malaria outcomes. Additional articles were identified through hand searches of all references cited in articles identified through the initial search. A cost model was developed from PMI VectorLink IRS country programmes, and comparative cost analysis reports to describe the overall cost benefits of selective IRS. Results: In some studies, there appeared to be a clear resting preference for certain Anopheles species in terms of the height at which they rested. However, for other species, and particularly the major African malaria vectors, a clear resting pattern was not detected. Furthermore, resting behaviour was not measured in a standardized way. For the selective spray studies that were assessed, there was a wide range of spray configurations, which complicates the comparison of methods. Many of these spray techniques were effective and resulted in reported 25–68% cost savings and reduced use of insecticide. The reported cost savings in the literature do not always consider all of the IRS implementation costs. Using the IRS cost model, these savings ranged from 17 to 29% for programs that targeted Anopheles spp. and 18–41% for programmes that targeted Aedes aegypti. Conclusions: Resting behaviour is generally measured in a simplistic way; noting the resting spot of mosquitoes in the morning. This is likely an oversimplification, and there is a need for better monitoring of resting mosquitoes. This may improve the target surface for selective spray techniques, which could reduce the cost of IRS while maintaining its effectiveness. Reporting of cost savings should be calculated considering the entire implementation costs, and a cost model was provided for future calculations. [ABSTRACT FROM AUTHOR]

Novel malaria vector control strategies targeting the odour-orientation of mosquitoes during host-seeking, such as 'attract-and-kill' or 'push-and-pull', have been suggested as complementary tools to indoor residual spraying and long-lasting insecticidal nets. These would be particularly beneficial if they can target vectors in the peri-domestic space where people are unprotected by traditional interventions. A randomized double-blind placebo-control study was implemented in western Kenya to evaluate: a 'push' intervention (spatial repellent) using transfluthrin-treated fabric strips positioned at open eave gaps of houses; a 'pull' intervention placing an odour-baited mosquito trap at a 5 m distance from a house; the combined 'push–pull' package; and the control where houses contained all elements but without active ingredients. Treatments were rotated through 12 houses in a randomized-block design. Outdoor biting was estimated using human landing catches, and indoor mosquito densities using light-traps. None of the interventions provided any protection from outdoor biting malaria vectors. The 'push' reduced indoor vector densities dominated by Anopheles funestus by around two thirds. The 'pull' device did not add any benefit. In the light of the high Anopheles arabiensis biting densities outdoors in the study location, the search for efficient outdoor protection and effective pull components needs to continue. [ABSTRACT FROM AUTHOR]

Presently, the most common malaria control tools–i.e., long lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS)–are limited to targeting indoor biting and resting behaviors of Anopheles mosquito species. Few interventions are targeted towards malaria control in areas where transmission is driven or persists due to outdoor biting behaviors. This study investigated a volatile pyrethroid-based spatial repellent (VPSR) designed to bridge this gap and provide protection from mosquito bites in outdoor spaces. Southern Province, Zambia, is one such environment where outdoor biting is suspected to contribute to malaria transmission, where people are active in the evening in open-walled outdoor kitchens. This study assessed the VPSR in replica kitchens within a controlled semi-field environment. Endpoints included effects on mosquito host seeking, immediate and delayed mortality, deterrence, blood feeding inhibition, and fertility. Host-seeking was reduced by approximately 40% over the course of nightly releases in chambers containing VPSR devices. Mosquito behavior was not uniform throughout the night, and the modeled effect of the intervention was considerably higher when hourly catch rates were considered. These two observations highlight a limitation of this overnight semi-field design and consideration of mosquito circadian rhythms is recommended for future semi-field studies. Additionally, deterrence and immediate mortality were both observed in treatment chambers, with evidence of delayed mortality and a dose related response. These results demonstrate a primarily personal protective mode of action with possible positive and negative community effects. Further investigation into this primary mode of action will be conducted through a field trial of the same product in nearby communities. [ABSTRACT FROM AUTHOR]

Background: Semi-field experiments with human landing catch (HLC) measure as the outcome are an important step in the development of novel vector control interventions against outdoor transmission of malaria since they provide good estimates of personal protection. However, it is often infeasible to determine whether the reduction in HLC counts is due to mosquito mortality or repellency, especially considering that spatial repellents based on volatile pyrethroids might induce both. Due to the vastly different impact of repellency and mortality on transmission, the community-level impact of spatial repellents can not be estimated from such semi-field experiments. Methods: We present a new stochastic model that is able to estimate for any product inhibiting outdoor biting, its repelling effect versus its killing and disarming (preventing host-seeking until the next night) effects, based only on time-stratified HLC data from controlled semi-field experiments. For parameter inference, a Bayesian hierarchical model is used to account for nightly variation of semi-field experimental conditions. We estimate the impact of the products on the vectorial capacity of the given Anopheles species using an existing mathematical model. With this methodology, we analysed data from recent semi-field studies in Kenya and Tanzania on the impact of transfluthrin-treated eave ribbons, the odour-baited Suna trap and their combination (push–pull system) on HLC of Anopheles arabiensis in the peridomestic area. Results: Complementing previous analyses of personal protection, we found that the transfluthrin-treated eave ribbons act mainly by killing or disarming mosquitoes. Depending on the actual ratio of disarming versus killing, the vectorial capacity of An. arabiensis is reduced by 41 to 96% at 70% coverage with the transfluthrin-treated eave ribbons and by 38 to 82% at the same coverage with the push–pull system, under the assumption of a similar impact on biting indoors compared to outdoors. Conclusions: The results of this analysis of semi-field data suggest that transfluthrin-treated eave ribbons are a promising tool against malaria transmission by An. arabiensis in the peridomestic area, since they provide both personal and community protection. Our modelling framework can estimate the community-level impact of any tool intervening during the mosquito host-seeking state using data from only semi-field experiments with time-stratified HLC. [ABSTRACT FROM AUTHOR]

Today, malaria prevention hinges upon two domestic interventions: insecticide-treated bed nets and indoor residual spraying. As mosquitoes grow resistant to these tools, however, novel approaches to vector control have become a priority area of malaria research and development. Spatial repellency, a volumetric mode of action that seeks to reduce disease transmission by creating an atmosphere inimical to mosquitoes, represents one way forward. Drawing from research that sought to develop new repellent chemicals in conversation with users from sub-Saharan Africa and the United States, we consider the implications of a non-insecticidal paradigm of vector control for how we understand the political ecology of malaria. [ABSTRACT FROM AUTHOR]

Background: Efforts to control malaria vectors have primarily focused on scaling-up of long-lasting insecticidal nets (LLINs) and indoor residual spraying. Although highly efficient against indoor-biting and indoor-resting vectors, these interventions have lower impact on outdoor-biting mosquitoes. Innovative vector control tools are required to prevent outdoor human--mosquito contacts. In this work, the potential of spatial repellents, delivered in an active system that requires minimal user compliance, to provide personal protection against exophagic mosquitoes active in the early evening was explored. Methods: A device previously used as an odour-baited lure and kill apparatus, the mosquito landing box (MLB), was modified to dispense the volatile synthetic pyrethroid, transfluthrin, as a spatial repellent. The MLB has an active odourdispensing mechanism that uses a solar-powered fan and switches on at dusk to provide long duration dispensing of volatile compounds without the need for the user to remember to employ it. Two MLBs were located 5 m from a human volunteer to investigate the repellent effects of a transfluthrin -bubble' created between the MLBs. Transfluthrin was emanated from polyester strips, hanging inside the MLB odour-dispensing unit. A fully randomized cross-over design was performed in a large, semi-field, screened cage to assess the effect of the repellent against laboratory-reared Anopheles arabiensis mosquitoes under ambient outdoor conditions. The knock-down capacity of the transfluthrin-treated strips was also evaluated at different time points up to 3 weeks after being impregnated to measure duration of efficacy. Results: The protective transfluthrin bubble provided 68.9% protection against An. arabiensis bites under these simulated outdoor conditions. Volatile transfluthrin caused low mortality among mosquitoes in the semi-field system. Transfluthrin-treated strips continued to knock down mosquitoes in laboratory tests, 3 weeks after impregnation, although this effect diminished with time. Conclusion: Modified MLBs can be used as efficient and long-lasting dispensers of volatile spatial repellents such as transfluthrin, thereby providing high levels of protection against outdoor-biting mosquitoes in the peri-domestic space. They have a potential role in combatting outdoor malaria transmission without interfering with effective indoor interventions such as LLINs. [ABSTRACT FROM AUTHOR]

Background: Long-lasting insecticidal nets (LLINs) have limited effect on malaria transmitted outside of sleeping hours. Topical repellents have demonstrated reduction in the incidence of malaria transmitted in the early evening. This study assessed whether 15% DEET topical repellent used in combination with LLINs can prevent greater malaria transmission than placebo and LLINs, in rural Tanzania. Methods: A cluster-randomized, placebo-controlled trial was conducted between July 2009 and August 2010 in a rural Tanzanian village. Sample size calculation determined that 10 clusters of 47 households with five people/household were needed to observe a 24% treatment effect at the two-tailed 5% significance level, with 90% power, assuming a baseline malaria incidence of one case/person/year. Ten clusters each were randomly assigned to repellent and control groups by lottery. A total of 4,426 individuals older than six months were enrolled. All households in the village were provided with an LLIN per sleeping space. Repellent and placebo lotion was replaced monthly. The main outcome was rapid diagnostic test (RDT)-confirmed malaria measured by passive case detection (PCD). Incidence rate ratios were estimated from a Poisson model, with adjustment for potential confounders, determined a priori. According-to-protocol approach was used for all primary analyses. Results: The placebo group comprised 1972.3 person-years with 68.29 (95% C.I 37.05-99.53) malaria cases/1,000 person-years. The repellent group comprised 1,952.8 person-years with 60.45 (95% C.I 48.30-72.60) cases/1,000 person-years, demonstrating a non-significant 11.44% reduction in malaria incidence rate in this group, (Wilcoxon rank sum z = 0.529, p = 0.596). Principal components analysis (PCA) of the socio-economic status (SES) of the two groups demonstrated that the control group had a higher SES (Pearson's chi square = 13.38, p = 0.004). Conclusions: Lack of an intervention effect was likely a result of lack of statistical power, poor capture of malaria events or bias caused by imbalance in the SES of the two groups. Low malaria transmission during the study period could have masked the intervention effect and a larger study size was needed to increase discriminatory power. Alternatively, topical repellents may have no impact on malaria transmission in this scenario. Design and implementation of repellent intervention studies is discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Malaria control relies on insecticide-based tools which target the mosquito vector. Predominantly, a group of insecticides called pyrethroids are used in these tools. Globally, however, mosquitoes are increasingly developing resistance to pyrethroids. Subsequently, new products, such as insecticide-treated nets (ITNs), which contain combinations of insecticides from different classes, or chemicals that work synergistically with pyrethroids, are being developed. Several of these new net types are being rolled out for testing and use. However, standardized methods to measure how long these nets remain active against mosquitoes are lacking, which makes evaluating the long-term efficacy of these products challenging. In this publication, we propose a pipeline used to collate and interrogate several different methods to produce a singular 'consensus standard operating procedure (SOP)', for monitoring the residual efficacy of three new net types: pyrethroid + piperonyl butoxide (PBO), pyrethroid + pyriproxyfen (PPF), and pyrethroid + chlorfenapyr (CFP). In response to growing concerns over the sustained effectiveness of pyrethroid-only based control tools, new products are being developed and evaluated. Some examples of these are dual-active ingredient (AI) insecticide-treated nets (ITNs) which contain secondary insecticides, or synergist ITNs which contain insecticide synergist, both in combination with a pyrethroid. These net types are often termed 'next-generation' insecticide-treated nets. Several of these new types of ITNs are being evaluated in large-scale randomized control trials (RCTs) and pilot deployment schemes at a country level. However, no methods for measuring the biological durability of the AIs or synergists on these products are currently recommended. In this publication, we describe a pipeline used to collate and interrogate several different methods to produce a singular 'consensus standard operating procedure (SOP)', for monitoring the biological durability of three new types of ITNs: pyrethroid + piperonyl butoxide (PBO), pyrethroid + pyriproxyfen (PPF), and pyrethroid + chlorfenapyr (CFP). This process, convened under the auspices of the Innovation to Impact programme, sought to align methodologies used for conducting durability monitoring activities of next-generation ITNs. [ABSTRACT FROM AUTHOR]

Background: Bio-efficacy and residual activity of insecticides used for indoor residual spraying (IRS) and long-lasting insecticide nets (LLINs) were assessed against laboratory-reared and wild populations of the malaria vector, Anopheles arabiensis in south eastern Tanzania. Implications of the findings are examined in the context of potential synergies and redundancies where IRS and LLINs are combined. Methods: Bioassays were conducted monthly for six months on three LLIN types (Olyset® PermaNet 2.0®,and Icon Life®) and three IRS treatments (2 g/m² pirimiphos-methyl, 2 g/m2 DDT and 0.03 g/m² lambda-cyhalothrin, sprayed on mud walls and palm ceilings of experimental huts). Tests used susceptible laboratory-reared An. arabiensis exposed in cones (nets and IRS) or wire balls (nets only). Susceptibility of wild populations was assessed using WHO diagnostic concentrations and PCR for knock-down resistance (kdr) genes. Results: IRS treatments killed = 85% of mosquitoes exposed on palm ceilings and = 90% of those exposed on mud walls, but up to 50% of this toxicity decayed within 1-3 months, except for DDT. By 6th month, only 7.5%, 42.5% and 30.0% of mosquitoes died when exposed to ceilings sprayed with pirimiphos-methyl, DDT or lambda-cyhalothrin respectively, while 12.5%, 36.0% and 27.5% died after exposure to mud walls sprayed with the same insecticides. In wire-ball assays, mortality decreased from 98.1% in 1st month to 92.6% in 6th month in tests on PermaNet 2.0®, from 100% to 61.1% on Icon Life® and from 93.2% to 33.3% on Olyset® nets. In cone bioassays, mortality reduced from 92.8% in 1st month to 83.3% in 6th month on PermaNet 2.0®, from 96.9% to 43.80% on Icon Life® and from 85.6% to 14.6% on Olyset®. ®ld An. arabiensis were 100% susceptible to DDT, 95.8% to deltamethrin, 90.2% to lambda cyhalothrin and 95.2% susceptible to permethrin. No kdr gene mutations were detected. Conclusions: In bioassays where sufficient contact with treated surfaces is assured, LLINs and IRS kill high proportions of susceptible An. arabiensis mosquitoes, though these efficacies decay gradually for LLINs and rapidly for IRS. It is, therefore, important to always add intact nets in sprayed houses, guaranteeing protection even after the IRS decays, and to ensure accurate timing, quality control and regular re-spraying in IRS programmes. By contrast, adding IRS in houses with intact LLINs is unlikely to improve protection relative to LLINs alone, since there is no guarantee that unfed vectors would rest long enough on the sprayed surfaces, and because of the rapid IRS decay. However, there is need to clarify these effects using data from observations of free flying mosquitoes in huts. Physiological susceptibility of An. arabiensis in the area remains 100% against DDT, but is slightly reduced against pyrethroids, necessitating caution over possible spread of resistance. The loss of LLIN toxicity, particularly Olyset® nets suggests that protection offered by these nets against An. arabiensis may be primarily due to physical bite prevention rather than insecticidal efficacy. [ABSTRACT FROM AUTHOR]

Sustained malaria control is underway using a combination of vector control, prompt diagnosis and treatment of malaria cases. Progress is excellent, but for long-term control, low-cost, sustainable tools that supplement existing control programs are needed. Conventional vector control tools such as indoor residual spraying and house screening are highly effective, but difficult to deliver in rural areas. Therefore, an additional means of reducing mosquito house entry was evaluated: the screening of mosquito house entry points by planting the tall and densely foliated repellent plant Lantana camara L. around houses. A pilot efficacy study was performed in Kagera Region, Tanzania in an area of high seasonal malaria transmission, where consenting families within the study village planted L. camara (Lantana) around their homes and were responsible for maintaining the plants. Questionnaire data on house design, socioeconomic status, malaria prevention knowledge, attitude and practices was collected from 231 houses with Lantana planted around them 90 houses without repellent plants. Mosquitoes were collected using CDC Light Traps between September 2008 and July 2009. Data were analysed with generalised negative binomial regression, controlling for the effect of sampling period. Indoor catches of mosquitoes in houses with Lantana were compared using the Incidence Rate Ratio (IRR) relative to houses without plants in an adjusted analysis. There were 56% fewer Anopheles gambiae s.s. (IRR 0.44, 95% CI 0.28-0.68, p,0.0001); 83% fewer Anopheles funestus s.s. (IRR 0.17, 95% CI 0.09-0.32, p<0.0001), and 50% fewer mosquitoes of any kind (IRR 0.50, 95% CI 0.38-0.67, p<0.0001) in houses with Lantana relative to controls. House screening using Lantana reduced indoor densities of malaria vectors and nuisance mosquitoes with broad community acceptance. Providing sufficient plants for one home costs US $1.50 including maintenance and labour costs, (30 cents per person). L. camara mode of action and suitability for mosquito control is discussed. [ABSTRACT FROM AUTHOR]

Background: Partial mosquito-proofing of houses with screens and ceilings has the potential to reduce indoor densities of malaria mosquitoes. We wish to measure whether it will also reduce indoor densities of vectors of neglected tropical diseases. Methodology: The main house entry points preferred by anopheline and culicine vectors were determined through controlled experiments using specially designed experimental huts and village houses in Lupiro village, southern Tanzania. The benefit of screening different entry points (eaves, windows and doors) using PVC-coated fibre glass netting material in terms of reduced indoor densities of mosquitoes was evaluated compared to the control. Findings: 23,027 mosquitoes were caught with CDC light traps; 77.9% (17,929)were Anopheles gambiae sensu lato, of which 66.2% were An. arabiensis and 33.8% An. gambiae sensu stricto. The remainder comprised 0.2% (50) An. funestus, 10.2% (2359) Culex spp. and 11.6% (2664) Mansonia spp. Screening eaves reduced densities of Anopheles gambiae s. l. (Relative ratio (RR) = 0.91; 95% CI = 0.84, 0.98; P 0.01); Mansonia africana (RR = 0.43; 95% CI = 0.26, 0.76; P,0.001) and Mansonia uniformis (RR = 0.37; 95% CI =0.25, 0.56; P,0.001) but not Culex quinquefasciatus, Cx. univittatus or Cx. theileri. Numbers of these species were reduced by screening windows and doors but this was not significant. Significance: This study confirms that across Africa, screening eaves protects households against important mosquito vectors of filariasis, Rift Valley Fever and O'Nyong nyong as well as malaria. While full house screening is required to exclude Culex species mosquitoes, screening of eaves alone or fitting ceilings has considerable potential for integrated control of other vectors of filariasis, arbovirus and malaria. [ABSTRACT FROM AUTHOR]

Background: Traps baited with synthetic human odors have been proposed as suitable technologies for controlling malaria and other mosquito-borne diseases. We investigated the potential benefits of such traps for preventing malaria transmission in Africa and the essential characteristics that they should possess so as to be effective. Methods and Principal Findings: An existing mathematical model was reformulated to distinguish availability of hosts for attack by mosquitoes from availability of blood per se. This adaptation allowed the effects of pseudo-hosts such as odor-baited mosquito traps, which do not yield blood but which can nonetheless be attacked by the mosquitoes, to be simulated considering communities consisting of users and non-users of insecticide-treated nets (ITNs), currently the primary malaria prevention method. We determined that malaria transmission declines as trap coverage (proportion of total availability of all hosts and pseudo hosts that traps constitute) increases. If the traps are more attractive than humans and are located in areas where mosquitoes are most abundant, 20-130 traps per 1000 people would be sufficient to match the impact of 50% community-wide ITN coverage. If such traps are used to complement ITNs, malaria transmission can be reduced by 99% or more in most scenarios representative of Africa. However, to match cost-effectiveness of ITNs, the traps delivery, operation and maintenance would have to cost a maximum of US$4.25 to 27.61 per unit per year. Conclusions and Significance: Odor-baited mosquito traps might potentially be effective and affordable tools for malaria control in Africa, particularly if they are used to complement, rather than replace, existing methods. We recommend that developers should focus on super-attractive baits and cheaper traps to enhance cost-effectiveness, and that the most appropriate way to deploy such technologies is through vertical delivery mechanisms. [ABSTRACT FROM AUTHOR]

Background: Malaria control in remote, forested areas of the Mekong region relies on personal protection from mosquito bites. Uptake of these methods may be limited by knowledge of the link between mosquitoes and malaria as well as social and economic aspects. Understanding barriers to uptake will inform malaria control programmes on targets for improvement of delivery. Methods: A total 748 key respondents: health providers and village heads, from 187 villages and 25 different ethnic groups, were interviewed using structured questionnaires. Differences in use of personal protection, and knowledge of malaria between groups were analysed using chi-square; and binary logistic regression used for multivariate analysis. Results: Malaria knowledge was poor with 19.4% of women and 37.5% of men linking mosquitoes with malaria, although 95.6% knew one or more methods of mosquito control. Virtually all respondents used personal protection at some time during the year; and understanding of malaria transmission was strongly associated with bednet use. Those working in forest agriculture were significantly more likely to know that mosquitoes transmit malaria but this did not translate into a significantly greater likelihood of using bednets. Furthermore, use of personal protection while woing outdoors was rare, and less than 3% of respondents knew about the insecticide impregnation of bednets. The use of bednets, synthetic repellents and mosquito coils varied between ethnic groups, but was significantly more frequent among those with higher income, more years of education and permanent housing. The reported use of repellents and coils was also more common among women despite their low knowledge of malaria transmission, and low likelihood of having heard information on malaria within the last year. Conclusion: The use of personal protection must be increased, particularly among outdoor workers that have higher malaria risk. However, personal protection is widely used and widely accepted to prevent nuisance biting mosquitoes, with the major barrier to use being affordability. Therefore, social marketing campaigns aimed at women and those that work outdoors that provide highly subsidised products, especially insecticide impregnation kits for bednets and hammock nets are most likely to succeed in lowering malaria morbidity among non Han-Chinese groups in rural China. [ABSTRACT FROM AUTHOR]

Over 2.2 billion long-lasting insecticidal nets (LLINs) for malaria control have been delivered to recipient countries. LLINs are the largest single item in the global malaria control budget. To be eligible for donor-funded procurement and distribution schemes, LLIN products must attain and retain World Health Organization (WHO) prequalification status by passing safety, quality, and efficacy benchmarks. Predelivery inspections further test product quality before distribution. We have shown that, despite these quality-assurance measures, substandard LLINs were distributed in Papua New Guinea (PNG) for at least 6 years (2013–2019). Other countries may have received similar LLINs. Here, we discuss the most important weaknesses of the current LLIN quality-assurance framework that have made this possible. Based on a series of concerning observations of a sudden decrease in the bioefficacy of long-lasting insecticidal nets (LLINs) in Papua New Guinea in 2013, we discuss the urgent need for a revision of the framework for the quality assessment of LLINs for both prequalification (PQ) purposes and post-PQ monitoring. The most important deficiencies of the current system include the absence of regular bioefficacy assessment for quality assurance, the ambivalence of the currently recommended bioassay methodologies, and the lack of capacity in many recipient countries for basic LLIN quality assurance. It is in the interest of manufacturers, donors, recipient countries, and most importantly, those relying on LLINs for protection against malaria, that the quality-assurance framework for these important commodities remains rigorous, adaptive, and transparent. [ABSTRACT FROM AUTHOR]