Efficacy of indoor residual spraying with dichlorodiphenyltrichloroethane against malaria in Gambian communities with high usage of long-lasting insecticidal mosquito nets: a cluster-randomised controlled trial.

BACKGROUND: Although many malaria control programmes in sub-Saharan Africa use indoor residual spraying with long-lasting insecticidal nets (LLINs), the two studies assessing the benefit of the combination of these two interventions gave conflicting results. We aimed to assess whether the addition of indoor residual spraying to LLINs provided a significantly different level of protection against clinical malaria in children or against house entry by vector mosquitoes. METHODS: In this two-arm cluster, randomised, controlled efficacy trial we randomly allocated clusters of Gambian villages using a computerised algorithm to LLINs alone (n=35) or indoor residual spraying with dichlorodiphenyltrichloroethane plus LLINs (n=35). In each cluster, 65-213 children, aged 6 months to 14 years, were surveyed at the start of the 2010 transmission season and followed in 2010 and 2011 by passive case detection for clinical malaria. Exposure to parasite transmission was assessed by collection of vector mosquitoes with both light and exit traps indoors. Primary endpoints were the incidence of clinical malaria assessed by passive case detection and number of Anopheles gambiae sensu lato mosquitoes collected per light trap per night. Intervention teams had no role in data collection and the data collection teams were not informed of the spray status of villages. The trial is registered at the ISRCTN registry, number ISRCTN01738840. FINDINGS: LLIN coverage in 2011 was 3510 (93%) of 3777 children in the indoor residual spraying plus LLIN group and 3622 (95.5%) of 3791 in the LLIN group. In 2010, 7845 children were enrolled, 7829 completed passive case detection, and 7697 (98%) had complete clinical and covariate data. In 2011, 7009 children remained in the study, 648 more were enrolled, 7657 completed passive case detection, and 7545 (98.5%) had complete data. Indoor residual spraying coverage per cluster was more than 80% for both years in the indoor residual spraying plus LLIN group. Incidence of clinical malaria was 0.047 per child-month at risk in the LLIN group and 0.044 per child-month at risk in the indoor residual spraying plus LLIN group in 2010, and 0.032 per child-month at risk in the LLIN group and 0.034 per child-month at risk in the indoor residual spraying plus LLIN group in 2011. The incident rate ratio was 1.08 (95% CI 0.80-1.46) controlling for confounders and cluster by mixed-effect negative binomial regression on all malaria attacks for both years. No significant difference was recorded in the density of vector mosquitoes caught in light traps in houses over the two transmission seasons; the mean number of A gambiae sensu lato mosquitoes per trap per night was 6.7 (4.0-10.1) in the LLIN group and 4.5 (2.4-7.4) in the indoor residual spraying plus LLIN group (p=0.281 in the random-effects linear regression model). INTERPRETATION: We identified no significant difference in clinical malaria or vector density between study groups. In this area with high LLIN coverage, moderate seasonal transmission, and susceptible vectors, indoor residual spraying did not provide additional benefit. FUNDING: UK Medical Research Council.

Improved housing versus usual practice for additional protection against clinical malaria in The Gambia (RooPfs): a household-randomised controlled trial.

BACKGROUND: In malaria-endemic areas, residents of modern houses have less malaria than those living in traditional houses. We aimed to assess whether children in The Gambia received an incremental benefit from improved housing, where current best practice of insecticide-treated nets, indoor residual spraying, seasonal malaria chemoprevention in children younger than 5 years, and prompt treatment against clinical malaria was in place. METHODS: In this randomised controlled study, 800 households with traditional thatched-roofed houses were randomly selected from 91 villages in the Upper River Region of The Gambia. Within each village, equal numbers of houses were randomly allocated to the control and intervention groups using a sampling frame. Houses in the intervention group were modified with metal roofs and screened doors and windows, whereas houses in the control group received no modifications. In each group, clinical malaria in children aged 6 months to 13 years was monitored by active case detection over 2 years (2016-17). We did monthly collections from indoor light traps to estimate vector densities. Primary endpoints were the incidence of clinical malaria in study children with more than 50% of observations each year and household vector density. The trial is registered at ISRCTN02622179. FINDINGS: In June, 2016, 785 houses had one child each recruited into the study (398 in unmodified houses and 402 in modified houses). 26 children in unmodified houses and 28 children in modified houses did not have at least 50% of visits in a year and so were excluded from analysis. 38 children in unmodified houses were recruited after study commencement, as were 21 children in modified houses, meaning 410 children in unmodified houses and 395 in modified houses were included in the parasitological analyses. At the end of the study, 659 (94%) of 702 children were reported to have slept under an insecticide-treated net; 662 (88%) of 755 children lived in houses that received indoor residual spraying; and 151 (90%) of 168 children younger than 5 years had seasonal malaria chemoprevention. Incidence of clinical malaria was 0·12 episodes per child-year in children in the unmodified houses and 0·20 episodes per child-year in the modified houses (unadjusted incidence rate ratio [RR] 1·68 [95% CI 1·11-2·55], p=0·014). Household vector density was 3·30 Anopheles gambiae per house per night in the unmodified houses compared with 3·60 in modified houses (unadjusted RR 1·28 [0·87-1·89], p=0·21). INTERPRETATION: Improved housing did not provide protection against clinical malaria in this area of low seasonal transmission with high coverage of insecticide-treated nets, indoor residual spraying, and seasonal malaria chemoprevention. FUNDING: Global Health Trials funded by Medical Research Council, UK Department for International Development, and Wellcome Trust.

Impact of increased ventilation on indoor temperature and malaria mosquito density: an experimental study in The Gambia.

In sub-Saharan Africa, cooler houses would increase the coverage of insecticide-treated bednets, the primary malaria control tool. We examined whether improved ventilation, using windows screened with netting, cools houses at night and reduces malaria mosquito house entry in The Gambia. Identical houses were constructed, with badly fitting doors the only mosquito entry points. Two men slept in each house and mosquitoes captured using light traps. First, temperature and mosquito density were compared in four houses with 0, 1, 2 and 3 screened windows. Second, carbon dioxide (CO2), a major mosquito attractant, was measured in houses with (i) no windows, (ii) screened windows and (iii) screened windows and screened doors. Computational fluid dynamic modelling captured the spatial movement of CO2. Increasing ventilation made houses cooler, more comfortable and reduced malaria mosquito house entry; with three windows reducing mosquito densities by 95% (95%CI = 90-98%). Screened windows and doors reduced the indoor temperature by 0.6°C (95%CI = 0.5-0.7°C), indoor CO2 concentrations by 31% between 21.00 and 00.00 h and malaria mosquito entry by 76% (95%CI = 69-82%). Modelling shows screening reduces CO2 plumes from houses. Under our experimental conditions, cross-ventilation not only reduced indoor temperature, but reduced the density of house-entering malaria mosquitoes, by weakening CO2 plumes emanating from houses.