Hotspots and super-spreaders: Modelling fine-scale malaria parasite transmission using mosquito flight behaviour.

Malaria hotspots have been the focus of public health managers for several years due to the potential elimination gains that can be obtained from targeting them. The identification of hotspots must be accompanied by the description of the overall network of stable and unstable hotspots of malaria, especially in medium and low transmission settings where malaria elimination is targeted. Targeting hotspots with malaria control interventions has, so far, not produced expected benefits. In this work we have employed a mechanistic-stochastic algorithm to identify clusters of super-spreader houses and their related stable hotspots by accounting for mosquito flight capabilities and the spatial configuration of malaria infections at the house level. Our results show that the number of super-spreading houses and hotspots is dependent on the spatial configuration of the villages. In addition, super-spreaders are also associated to house characteristics such as livestock and family composition. We found that most of the transmission is associated with winds between 6pm and 10pm although later hours are also important. Mixed mosquito flight (downwind and upwind both with random components) were the most likely movements causing the spread of malaria in two out of the three study areas. Finally, our algorithm (named MALSWOTS) provided an estimate of the speed of malaria infection progression from house to house which was around 200-400 meters per day, a figure coherent with mark-release-recapture studies of Anopheles dispersion. Cross validation using an out-of-sample procedure showed accurate identification of hotspots. Our findings provide a significant contribution towards the identification and development of optimal tools for efficient and effective spatio-temporal targeted malaria interventions over potential hotspot areas.

Mapping trends in insecticide resistance phenotypes in African malaria vectors.

Mitigating the threat of insecticide resistance in African malaria vector populations requires comprehensive information about where resistance occurs, to what degree, and how this has changed over time. Estimating these trends is complicated by the sparse, heterogeneous distribution of observations of resistance phenotypes in field populations. We use 6,423 observations of the prevalence of resistance to the most important vector control insecticides to inform a Bayesian geostatistical ensemble modelling approach, generating fine-scale predictive maps of resistance phenotypes in mosquitoes from the Anopheles gambiae complex across Africa. Our models are informed by a suite of 111 predictor variables describing potential drivers of selection for resistance. Our maps show alarming increases in the prevalence of resistance to pyrethroids and DDT across sub-Saharan Africa from 2005 to 2017, with mean mortality following insecticide exposure declining from almost 100% to less than 30% in some areas, as well as substantial spatial variation in resistance trends.

Unravelling the impact of insecticide-treated bed nets on childhood malaria in Malawi.

BACKGROUND: To achieve malaria elimination it is essential to understand the impact of insecticide-treated net (ITNs) programmes. Here, the impact of ITN access and use on malaria prevalence in children in Malawi was investigated using Malaria Indicator Survey (MIS) data. METHODS: MIS data from 2012, 2014 and 2017 were used to investigate the relationship between malaria prevalence in children (6-59 months) and ITN use. Generalized linear modelling (GLM), geostatistical mixed regression modelling and non-stationary GLM were undertaken to evaluate trends, spatial patterns and local dynamics, respectively. RESULTS: Malaria prevalence in Malawi was 27.1% (95% CI 23.1-31.2%) in 2012 and similar in both 2014 (32.1%, 95% CI 25.5-38.7) and 2017 (23.9%, 95% CI 20.3-27.4%). ITN coverage and use increased during the same time period, with household ITN access growing from 19.0% (95% CI 15.6-22.3%) of households with at least 1 ITN for every 2 people sleeping in the house the night before to 41.7% (95% CI 39.1-44.4%) and ITN use from 41.1% (95% CI 37.3-44.9%) of the population sleeping under an ITN the previous night to 57.4% (95% CI 55.0-59.9%). Both the geostatistical and non-stationary GLM regression models showed child malaria prevalence had a negative association with ITN population access and a positive association with ITN use although affected by large uncertainties. The non-stationary GLM highlighted the spatital heterogeneity in the relationship between childhood malaria and ITN dynamics across the country. CONCLUSION: Malaria prevalence in children under five had a negative association with ITN population access and a positive association with ITN use, with spatial heterogeneity in these relationships across Malawi. This study presents an important modelling approach that allows malaria control programmes to spatially disentangle the impact of interventions on malaria cases.

Monitoring and simulating landscape changes: how do long-term changes in land use and long-term average climate affect regional biophysical conditions in southern Malawi?

We set out to reveal the effects of long-term changes in land use and long-term average climate on the regional biophysical environment in southern Malawi. Object-oriented supervised image classification was performed on Landsat 5 and 8 satellite images from 1990 to 2020 to identify and quantify past and present land use-land cover changes using a support vector machine classifier. Subsequently, using 2000 and 2010 land use-land cover in an artificial neural network, land use-land cover for 2020 driven by elevation, slope, precipitation and temperature, population density, poverty, distance to major roads, and distance to villages data was simulated. Between 1990 and 2020, area of land cover increased in built-up (209%), bare land (10%), and cropland (10%) and decreased in forest (30%), herbaceous (4%), shrubland (20%), and water area (20%). Overall, the findings reveal that southern Malawi is dominantly an agro-mosaic landscape shaped by the combined effects of urban and agricultural expansions and climate. The findings also suggest the need to enhance the machine learning algorithms to improve capacity for landscape modelling and, ultimately, prevention, preparedness, and response to environmental risks.

Correction to: Assessing the impact of the addition of pyriproxyfen on the durability of permethrin-treated bed nets in Burkina Faso: a compound-randomized controlled trial.

An amendment to this paper has been published and can be accessed via the original article.

Indoor residual spraying for malaria control in sub-Saharan Africa 1997 to 2017: an adjusted retrospective analysis.

BACKGROUND: Indoor residual spraying (IRS) is a key tool for controlling and eliminating malaria by targeting vectors. To support the development of effective intervention strategies it is important to understand the impact of vector control tools on malaria incidence and on the spread of insecticide resistance. In 2006, the World Health Organization (WHO) stated that countries should report on coverage and impact of IRS, yet IRS coverage data are still sparse and unspecific. Here, the subnational coverage of IRS across sub-Saharan Africa for the four main insecticide classes from 1997 to 2017 were estimated. METHODS: Data on IRS deployment were collated from a variety of sources, including the President's Malaria Initiative spray reports and National Malaria Control Programme reports, for all 46 malaria-endemic countries in sub-Saharan Africa from 1997 to 2017. The data were mapped to the applicable administrative divisions and the proportion of households sprayed for each of the four main insecticide classes; carbamates, organochlorines, organophosphates and pyrethroids was calculated. RESULTS: The number of countries implementing IRS increased considerably over time, although the focal nature of deployment means the number of people protected remains low. From 1997 to 2010, DDT and pyrethroids were commonly used, then partly replaced by carbamates from 2011 and by organophosphates from 2013. IRS deployment since the publication of resistance management guidelines has typically avoided overlap between pyrethroid IRS and ITN use. However, annual rotations of insecticide classes with differing modes of action are not routinely used. CONCLUSION: This study highlights the gaps between policy and practice, emphasizing the continuing potential of IRS to drive resistance. The data presented here can improve studies on the impact of IRS on malaria incidence and help to guide future malaria control efforts.

Assessing the impact of the addition of pyriproxyfen on the durability of permethrin-treated bed nets in Burkina Faso: a compound-randomized controlled trial.

BACKGROUND: Long-lasting insecticidal nets (LLINs) treated with pyrethroids are the foundation of malaria control in sub-Saharan Africa. Rising pyrethroid resistance in vectors, however, has driven the development of alternative net formulations. Here the durability of polyethylene nets with a novel combination of a pyrethroid, permethrin, and the insect juvenile hormone mimic, pyriproxyfen (PPF), compared to a standard permethrin LLIN, was assessed in rural Burkina Faso. METHODS: A compound-randomized controlled trial was completed in two villages. In one village 326 of the PPF-permethrin nets (Olyset Duo) and 327 standard LLINs (Olyset) were distributed to assess bioefficacy. In a second village, 170 PPF-permethrin nets and 376 LLINs were distributed to assess survivorship. Nets were followed at 6-monthly intervals for 3 years. Bioefficacy was assessed by exposing permethrin-susceptible and resistant Anopheles gambiae sensu lato mosquito strains to standard World Health Organization (WHO) cone and tunnel tests with impacts on fertility measured in the resistant strain. Insecticide content was measured using high-performance liquid chromatography. LLIN survivorship was recorded with a questionnaire and assessed by comparing the physical integrity using the proportionate hole index (pHI). RESULTS: The PPF-permethrin net met WHO bioefficacy criteria (≥ 80% mortality or ≥ 95% knockdown) for the first 18 months, compared to 6 months for the standard LLIN. Mean mosquito mortality for PPF-permethrin nets, across all time points, was 8.6% (CI 2.6-14.6%) higher than the standard LLIN. Fertility rates were reduced after PPF-permethrin net exposure at 1-month post distribution, but not later. Permethrin content of both types of nets remained within the target range of 20 g/kg ± 25% for 242/248 nets tested. The pyriproxyfen content of PPF-permethrin nets declined by 54%, from 10.4 g/kg (CI 10.2-10.6) to 4.7 g/kg (CI 3.5-6.0, p < 0.001) over 36 months. Net survivorship was poor, with only 13% of PPF-permethrin nets and 12% of LLINs still present in the original household after 36 months. There was no difference in the fabric integrity or survivorship between the two net types. CONCLUSION: The PPF-permethrin net, Olyset Duo, met or exceeded the performance of the WHO-recommended standard LLIN (Olyset) in the current study but both net types failed the 3-year WHO bioefficacy criteria.

Within-host competition does not select for virulence in malaria parasites; studies with Plasmodium yoelii.

In endemic areas with high transmission intensities, malaria infections are very often composed of multiple genetically distinct strains of malaria parasites. It has been hypothesised that this leads to intra-host competition, in which parasite strains compete for resources such as space and nutrients. This competition may have repercussions for the host, the parasite, and the vector in terms of disease severity, vector fitness, and parasite transmission potential and fitness. It has also been argued that within-host competition could lead to selection for more virulent parasites. Here we use the rodent malaria parasite Plasmodium yoelii to assess the consequences of mixed strain infections on disease severity and parasite fitness. Three isogenic strains with dramatically different growth rates (and hence virulence) were maintained in mice in single infections or in mixed strain infections with a genetically distinct strain. We compared the virulence (defined as harm to the mammalian host) of mixed strain infections with that of single infections, and assessed whether competition impacted on parasite fitness, assessed by transmission potential. We found that mixed infections were associated with a higher degree of disease severity and a prolonged infection time. In the mixed infections, the strain with the slower growth rate was often responsible for the competitive exclusion of the faster growing strain, presumably through host immune-mediated mechanisms. Importantly, and in contrast to previous work conducted with Plasmodium chabaudi, we found no correlation between parasite virulence and transmission potential to mosquitoes, suggesting that within-host competition would not drive the evolution of parasite virulence in P. yoelii.

Strengthening adult mosquito surveillance in Africa for disease control: learning from the present.

Mosquito surveillance is essential to successfully control and eliminate mosquito-borne diseases. Yet, it is often done by numerous organizations with little collaboration, incomplete understanding of existing gaps, and limited long-term vision. There is a clear disconnect between entomological and epidemiological indices, with entomological data informing control efforts inadequately. Here, we discuss current mosquito surveillance practises across the heterogeneous disease landscape in Africa. We advocate for the development of mosquito surveillance strategic plans to increase the impact and functionality of mosquito surveillance. We urge for a proactive approach to set up centralized mosquito data systems under the custodian of national governments, focus on epidemiologically relevant mosquito data, and increase the robustness of mosquito surveillance using a more spatially explicit sampling design.

Mosquito (Diptera: Culicidae) Larval Ecology in Rubber Plantations and Rural Villages in Dabou (Côte d'Ivoire).

In Côte d'Ivoire, rubber cultivation has more than doubled since 2010. These mass agricultural areas require a large workforce with little information on how this environment might impact risk of mosquito-borne diseases. The objective of this study was to assess the larval ecology of mosquitoes in rubber areas of Dabou, Côte d'Ivoire. From January to June 2017, an entomological survey was conducted of mature (MP) and immature (IP) rubber plantations, as well as in villages surrounded by rubber plantations (SV) and remote from rubber plantations (RV). The number and type of potential and positive breeding sites were recorded, and mosquito larval densities and diversity were estimated. Seven genera divided into 31 species including major vector such as Anopheles gambiae s.l. and Aedes aegypti were identified. A total of 1,660 waterbodies were identified with a larvae positivity rate of 63.1%. A majority of waterbodies were identified in SV (N = 875, 53.4% positivity rate), followed by MP (N = 422, 81.8% positivity rate), IP (N = 194, 72.2% positivity rate) and least in RV (N = 169, 57.4% positivity rate). The most important breeding sites for disease vectors were leaf axils in IP (N = 108, 77.1%), latex collection cups in MP (N = 332, 96.2%) and the containers abandoned in the SV (N = 242, 51.8%) as well as in the RV (N = 59, 60.8%). All these results allow us to affirm that the cultivation of rubber trees has an impact on the larval ecology by increasing the number of available sites and favoring a high larval density and diversity.

Sampling Adult Populations of Anopheles Mosquitoes.

For the control and elimination of malaria, information on the local vector dynamics is essential. This information provides guidance on appropriate and timely deployment of vector control tools and their subsequent success. The data on the dynamics of local mosquito populations can be collected using many different Anopheles sampling methods. Dependent on the objectives, resources, time, and local environment, different traps and methods can be chosen. This chapter describes the sampling of adult populations, focusing on the important preparatory stages and some of the widely used sampling methods. The trapping methods discussed in this chapter are the human landing catch, human-baited net trap, animal landing catch, animal-baited net trap, CDC miniature light trap, Biogents Suna trap, peripheral net collection, pyrethrum collection, exit/entry trap, and resting shelter. For optimal deployment in the field, a step-by-step description of the sampling methods is given.

Field evaluation of personal protection methods against outdoor-biting mosquitoes in Lao PDR.

BACKGROUND: Protecting people outdoors against mosquito-borne diseases is a major challenge. Here we compared commercially available personal protection methods to identify the most effective method for outdoor use in northern Lao PDR. METHODS: From June to August 2016 the protective efficacy of treatments were compared in a secondary forest during the afternoon and a village during the evening. Comparisons were made using a replicated Latin square design between: (i) short permethrin-treated overalls; (ii) long permethrin-treated overalls; (iii) short untreated overalls with para-menthane-3,8-diol (PMD) applied topically; (iv) short permethrin-treated overalls plus PMD applied topically; (v) short untreated overalls with metofluthrin coils in a metal casing worn on a belt; and (vi) long untreated overalls. Short untreated overalls served as the control. Cone tests were conducted on the treated and untreated fabric before and after field experiments. A questionnaire survey was used to measure social acceptability. RESULTS: Mosquito coils in a metal casing worn on a belt resulted in 92.3% (95% confidence interval, CI: 88.9-94.6%). landing protection from female mosquitoes in the afternoon and 68.8% (95% CI: 41.7-83.3%) protection in the evening compared to short untreated clothing. PMD was protective both when combined with short permethrin-treated overalls (afternoon, 68.2%, 95% CI: 52.6-78.7%; evening, 52.3%, 95% CI: 33.8-65.7%) and when used in combination with short untreated overalls (afternoon, 55.0%, 95% CI: 41.7-65.2%; evening, 25.2%, 95% CI: 9.4-38.2%). Whilst long permethrin-treated overalls were protective (afternoon, 61.1%, 95% CI: 51.4-68.8%; evening, 43.0%, 95% CI: 25.5-56.4%), short permethrin-treated overalls and long untreated overalls were not. Exposure to new permethrin-treated fabric in cone tests resulted in 25.0% (95% CI, 17.8-32.2%) and 26.2% (95% CI 16.7-35.8%) mortality for susceptible Ae. albopictus and susceptible Ae. aegypti, respectively. There was a loss of efficacy of permethrin-treated clothing after use in the field, with 3 min knockdown rates of Ae. albopictus and 1 h knockdown of Ae. aegypti decreasing over time. Participants considered all treatments acceptable. CONCLUSIONS: The portable mosquito coils were highly protective against outdoor biting mosquitoes, although there are safety concerns related to its use. The combination of permethrin-treated clothing and PMD repellent represent an alternative treatment for protection against outdoor-biting mosquitoes.

Bionomics and insecticide resistance of the arboviral vector Aedes albopictus in northern Lao PDR.

In the last four decades there has been a staggering increase in the geographical range of the arboviral vector Aedes albopictus (Skuse, 1894). This species is now found in every continent except Antarctica, increasing the distribution of arboviral diseases such as dengue and chikungunya. In Lao PDR dengue epidemics occur regularly, with cases of chikungunya also reported. As treatment methods for arboviral diseases is limited, the control of the vector mosquitoes are essential. There is a paucity of information on the bionomics and resistance status of this mosquito for successful vector control efforts. Here we describe the bionomics and insecticide resistance status of Ae. albopictus in Laos to identify opportunities for control. Adult Ae. albopictus were collected using human-baited double bed net (HDN) traps in forests, villages and rubber plantations and tested for alpha- and flaviviruses with RT-PCR. Surveys were also conducted to identify larval habitats. Seven adult and larval populations originating from Vientiane Capital and Luang Prabang province were tested against DDT, malathion, permethrin, deltamethrin and, temephos following WHO protocols. Aedes albopictus were found throughout the year, but were six-fold greater in the rainy season than the dry season. Adult females were active for 24 hours, with peak of behaviour at 18.00 h. The secondary forest and rubber plantation samples showed evidence of Pan-flaviviruses, while samples from the villages did not. More than half of the emerged Ae. albopictus were collected from mature rubber plantations (53.9%; 1,533/2,845). Most Ae. albopictus mosquitoes emerged from latex collection cups (19.7%; 562/2,845), small water containers (19.7%; 562/2,845) and tyres (17.4%; 495/2,845). Adult mosquitoes were susceptible to pyrethroids, apart from one population in Vientiane city. All populations were resistant to DDT (between 27-90% mortality) and all except one were resistant to malathion (20-86%). Three of the seven larval populations were resistant to temephos (42-87%), with suspected resistance found in three other populations (92-98%).This study demonstrates that rural areas in northern Laos are potential hot spots for arboviral disease transmission. Multiple-insecticide resistance was found. Aedes albopictus control efforts in villages need to expand to include secondary forests and rubber plantations, with larval source management and limited use of insecticides.

Risk of exposure to potential vector mosquitoes for rural workers in Northern Lao PDR.

BACKGROUND: One major consequence of economic development in South-East Asia has been a rapid expansion of rubber plantations, in which outbreaks of dengue and malaria have occurred. Here we explored the difference in risk of exposure to potential dengue, Japanese encephalitis (JE), and malaria vectors between rubber workers and those engaged in traditional forest activities in northern Laos PDR. METHODOLOGY/PRINCIPAL FINDINGS: Adult mosquitoes were collected for nine months in secondary forests, mature and immature rubber plantations, and villages. Human behavior data were collected using rapid participatory rural appraisals and surveys. Exposure risk was assessed by combining vector and human behavior and calculating the basic reproduction number (R0) in different typologies. Compared to those that stayed in the village, the risk of dengue vector exposure was higher for those that visited the secondary forests during the day (odds ratio (OR) 36.0), for those living and working in rubber plantations (OR 16.2) and for those that tapped rubber (OR 3.2). Exposure to JE vectors was also higher in the forest (OR 1.4) and, similar when working (OR 1.0) and living in the plantations (OR 0.8). Exposure to malaria vectors was greater in the forest (OR 1.3), similar when working in the plantations (OR 0.9) and lower when living in the plantations (OR 0.6). R0 for dengue was >2.8 for all habitats surveyed, except villages where R0≤0.06. The main malaria vector in all habitats was Anopheles maculatus s.l. in the rainy season and An. minimus s.l. in the dry season. CONCLUSIONS/SIGNIFICANCE: The highest risk of exposure to vector mosquitoes occurred when people visit natural forests. However, since rubber workers spend long periods in the rubber plantations, their risk of exposure is increased greatly compared to those who temporarily enter natural forests or remain in the village. This study highlights the necessity of broadening mosquito control to include rubber plantations.

Diversity of Mosquitoes (Diptera: Culicidae) Attracted to Human Subjects in Rubber Plantations, Secondary Forests, and Villages in Luang Prabang Province, Northern Lao PDR.

The impact of the rapid expansion of rubber plantations in South-East Asia on mosquito populations is uncertain. We compared the abundance and diversity of adult mosquitoes using human-baited traps in four typical rural habitats in northern Lao PDR: secondary forests, immature rubber plantations, mature rubber plantations, and villages. Generalized estimating equations were used to explore differences in mosquito abundance between habitats, and Simpson's diversity index was used to measure species diversity. Over nine months, 24,927 female mosquitoes were collected, including 51 species newly recorded in Lao PDR. A list of the 114 mosquito species identified is included. More mosquitoes, including vector species, were collected in the secondary forest than immature rubber plantations (rainy season, odds ratio [OR] 0.33, 95% confidence interval [CI] 0.31-0.36; dry season, 0.46, 95% CI 0.41-0.51), mature rubber plantations (rainy season, OR 0.25, 95% CI 0.23-0.27; dry season, OR 0.25, 95% CI 0.22-0.28), and villages (rainy season, OR 0.13, 95% CI 0.12-0.14; dry season, 0.20, 95% CI 0.18-0.23). All habitats showed high species diversity (Simpson's indexes between 0.82-0.86) with vectors of dengue, Japanese encephalitis (JE), lymphatic filariasis, and malaria. In the secondary forests and rubber plantations, Aedes albopictus (Skuse), a dengue vector, was the dominant mosquito species, while in the villages, Culex vishnui (Theobald), a JE vector, was most common. This study has increased the overall knowledge of mosquito fauna in Lao PDR. The high abundance of Ae. albopictus in natural and man-made forests warrants concern, with vector control measures currently only implemented in cities and villages.

Risk and Control of Mosquito-Borne Diseases in Southeast Asian Rubber Plantations.

Unprecedented economic growth in Southeast Asia (SEA) has encouraged the expansion of rubber plantations. This land-use transformation is changing the risk of mosquito-borne diseases. Mature plantations provide ideal habitats for the mosquito vectors of malaria, dengue, and chikungunya. Migrant workers may introduce pathogens into plantation areas, most worryingly artemisinin-resistant malaria parasites. The close proximity of rubber plantations to natural forest also increases the threat from zoonoses, where new vector-borne pathogens spill over from wild animals into humans. There is therefore an urgent need to scale up vector control and access to health care for rubber workers. This requires an intersectoral approach with strong collaboration between the health sector, rubber industry, and local communities.

The Human-Baited Double Net Trap: An Alternative to Human Landing Catches for Collecting Outdoor Biting Mosquitoes in Lao PDR.

Estimating the exposure of individuals to mosquito-borne diseases is a key measure used to evaluate the success of vector control operations. The gold standard is to use human landing catches where mosquitoes are collected off the exposed limbs of human collectors. This is however an unsatisfactory method since it potentially exposes individuals to a range of mosquito-borne diseases. In this study several sampling methods were compared to find a method that is representative of the human-biting rate outdoors, but which does not expose collectors to mosquito-borne infections. The sampling efficiency of four odour-baited traps were compared outdoors in rural Lao PDR; the human-baited double net (HDN) trap, CDC light trap, BG sentinel trap and Suna trap. Subsequently the HDN, the best performing trap, was compared directly with human landing catches (HLC), the 'gold standard', for estimating human-biting rates. HDNs collected 11-44 times more mosquitoes than the other traps, with the exception of the HLC. The HDN collected similar numbers of Anopheles (Rate Ratio, RR = 1.16, 95% Confidence Intervals, 95% CI = 0.61-2.20) and Culex mosquitoes (RR = 1.26, 95% CI = 0.74-2.17) as HLC, but under-estimated the numbers of Aedes albopictus (RR = 0.45, 95% CI = 0.27-0.77). Simpson's index of diversity was 0.845 (95% CI 0.836-0.854) for the HDN trap and 0.778 (95% CI 0.769-0.787) for HLC, indicating that the HDN collected a greater diversity of mosquito species than HLC. Both HLC and HDN can distinguish between low and high biting rates and are crude ways to measure human-biting rate. The HDN is a simple and cheap method to estimate the human-biting rate outdoors without exposing collectors to mosquito bites.

Alternative treatments for indoor residual spraying for malaria control in a village with pyrethroid- and DDT-resistant vectors in the Gambia.

BACKGROUND: Malaria vector control is threatened by resistance to pyrethroids, the only class of insecticides used for treating bed nets. The second major vector control method is indoor residual spraying with pyrethroids or the organochloride DDT. However, resistance to pyrethroids frequently confers resistance to DDT. Therefore, alternative insecticides are urgently needed. METHODOLOGY/PRINCIPAL FINDINGS: Insecticide resistance and the efficacy of indoor residual spraying with different insecticides was determined in a Gambian village. Resistance of local vectors to pyrethroids and DDT was high (31% and 46% mortality, respectively) while resistance to bendiocarb and pirimiphos methyl was low (88% and 100% mortality, respectively). The vectors were predominantly Anopheles gambiae s.s. with 94% of them having the putative resistant genotype kdr 1014F. Four groups of eight residential compounds were each sprayed with either (1) bendiocarb, a carbamate, (2) DDT, an organochlorine, (3) microencapsulated pirimiphos methyl, an organophosphate, or (4) left unsprayed. All insecticides tested showed high residual activity up to five months after application. Mosquito house entry, estimated by light traps, was similar in all houses with metal roofs, but was significantly less in IRS houses with thatched roofs (p=0.02). Residents participating in focus group discussions indicated that IRS was considered a necessary nuisance and also may decrease the use of long-lasting insecticidal nets. CONCLUSION/SIGNIFICANCE: Bendiocarb and microencapsulated pirimiphos methyl are viable alternatives for indoor residual spraying where resistance to pyrethroids and DDT is high and may assist in the management of pyrethroid resistance.