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In the context of stalling progress against malaria, resistance of mosquitoes to insecticides, and residual transmission, mass drug administration (MDA) of ivermectin, an endectocide used for neglected tropical diseases (NTDs), has emerged as a promising complementary vector control method. Ivermectin reduces the life span of Anopheles mosquitoes that feed on treated humans and/or livestock, potentially decreasing malaria parasite transmission when administered at the community level. Following the publication by WHO of the preferred product characteristics for endectocides as vector control tools, this roadmap provides a comprehensive view of processes needed to make ivermectin available as a vector control tool by 2024 with a completely novel mechanism of action. The roadmap covers various aspects, which include 1) the definition of optimal dosage/regimens for ivermectin MDA in both humans and livestock, 2) the risk of resistance to the drug and environmental impact, 3) ethical issues, 4) political and community engagement, 5) translation of evidence into policy, and 6) operational aspects of large-scale deployment of the drug, all in the context of a drug given as a prevention tool acting at the community level. The roadmap reflects the insights of a multidisciplinary group of global health experts who worked together to elucidate the path to inclusion of ivermectin in the toolbox against malaria, to address residual transmission, counteract insecticide resistance, and contribute to the end of this deadly disease.

In addition to the direct effect of insecticide-treated nets (ITNs), there has been evidence for spatial indirect effects. Spatial analyses in cluster randomized trials (CRTs) are rare, but a large-scale CRT from 1993 was one of the first to conduct a spatial analysis of ITNs in CRTs. We revisit these data by applying a broader range of contemporary spatial methods to further explore spatial spillover. We conducted three analyses: 1) exploratory spatial analysis, considering spatial patterns and spillover in the data; 2) spatial modeling, estimating the intervention effect considering spatial effects; and 3) analysis of distance-based spillover and interaction with the intervention, characterizing the functional distance over which the spillover effect was present. There were consistent indications of spatial patterns from the exploratory analysis. Bed nets were associated with a 17% reduction in all-cause mortality for children aged 6-59 months, and the intervention estimate remained robust when allowing for the spatial structure of the data. There was strong evidence of a spatial spillover effect: for every additional 100 m that a control household was from an intervention household (and vice versa), the standardized mortality ratio (SMR) increased by 1.7% (SMR 1.017, 95% credible interval 1.006-1.026). Despite evidence of a spatial spillover effect, the conclusions of the trial remain unaffected by spatial model specifications. Use of ITNs was clearly beneficial for individuals, and there was compelling evidence that they provide an indirect benefit to individuals living nearby. This article demonstrates the extra utility that spatial methods can provide when analyzing a CRT.

The use of insecticide treated nets is effective in reducing all cause malaria mortality and morbidity between 17 and 43% in children under five years and provides protection to pregnant women who are most susceptible to malaria. ITNs (Insecticide Treated Nets) are easy to use and require less technical and capital outlay to implement compared with other vector control methods. They are cost-effective, which has led to widespread implementation of ITNs by countries on a large scale. ITN use has however been limited due to the cost outlay households require to make towards the purchase of nets, households' inability to associate the effectiveness of the net with the insecticide leading to low re-treatment rates in most settings and the seasonality associated with the spread of malaria. This chapter provides a review of research on ITN, strategies of improving the availability and effectiveness of the nets and a comparison of ITNs and other malaria preventive methods. The review highlights inequity in ITN use among various socio-economic groups with the poorest being the least to benefit from ITNs even where they are highly subsidized. It discusses the break through in the production of PermaNet to resolve the problem of low re-treatment of nets.

A 17% efficacy in preventing all-cause mortality in children aged 6-59 months was previously reported from a cluster-randomized controlled trial of insecticide-treated mosquito nets (ITNs) carried out in the Kassena-Nankana District of northern Ghana from July 1993-June 1995. A follow-up until the end of 2000 found no indication in any age group of increased mortality in the ITN group after the end of the randomized intervention. These results should further encourage the use of ITNs as a malaria control tool in areas of high endemicity of Plasmodium falciparum.

The impact of insecticide-treated bednet use on malaria and anaemia in pregnancy was assessed, as a supplementary study, in a major WHO/TDR-supported bednet trial in northern Ghana between July 1994 and April 1995. The study area was divided into 96 clusters of compounds, with 48 clusters being randomly allocated to intervention. All pregnant women were included in the study but the focus was on primigravidae and secundigravidae. 1961 pregnant women were recruited into the study--1033 (52.7%) in the treated bednet group and 928 (47.3%) in the no net group. 1806 (92.1%) had blood taken for malaria microscopy and haemoglobin determination in the third trimester. Pregnancy outcomes were reported for 847 women. The characteristics of women in intervention and control groups were comparable. The odds ratios, with 95% confidence interval (CI), for different study endpoints were, for Plasmodium falciparum parasitaemia--0.89 (0.73, 1.08), for anaemia--0.88 (0.70, 1.09), for low birthweight (LBW)--0.87 (0.63, 1.19), indicating no benefit for treated bednet use. Effective net use by parity varied from 42% in primigravidae to 63% in multigravidae, in spite of free nets and insecticide impregnation. The main reasons for not using a net were warm weather and perceived absence of mosquito biting. Chloroquine use in pregnancy was low and comparable in both groups. Implications of findings for malaria control in pregnancy and further research are discussed.

Effects of the distribution in space of permethrin (insecticide)-impregnated bed nets (IIBNS) on child mortality were studied in a randomized controlled trial of IIBNs in a an area highly endemic for Plasmodium falciparum malaria in rural northern Ghana. Eight hundred sixty-two deaths occurred among children 6-59 months of age during 16,841 child-years-at-risk. Mortality increased with the distance from health facilities but not with proximity to identifiable anopheline breeding sites (reservoirs). The efficacy of IIBNs was independent of these distances. Mortality in users of IIBNs was independent of the proximity of nonusers, and mortality rates of nonusers and users living close to each other were similar. Poisson regression estimated a 6.7% increase in mortality among nonusers with each 100-m shift away from the nearest compound with IIBNS, indicating that the insecticide protects nearby nonusers. High coverage of IIBNs achieves maximum impact, but users of IIBNs offer some protection to less fortunate neighbors if coverage is incomplete.

Four recently completed large-scale randomized controlled trials have assessed the impact of insecticide-treated bednets and curtains on overall child mortality in Africa. These results have sparked numerous discussions among implementing agency representatives and researchers about the public health significance of the results. For the interpretation of impact, most of the arguments have been based on the observed decrease in protective efficacy (a relative measure of impact) with increasing malaria transmission (range: 14-29%, regression for trend: F = 245 on 1,2 DF, P < 0.003). However, an analysis of the absolute measure of impact (the risk difference) showed a different pattern. The impact ranges from 3.8 to 6.9 lives saved per 1000 children protected per year, without a significant trend (F = 2.8 on 1,2 DF, P = 0.2) and with equally high values in both low and high transmission sites. When assessing the public health importance of an intervention, both relative and absolute decrease in risk should be considered.

Permethrin impregnated bednets are now being widely promoted as an effective means of protecting African children against malaria, but there is little evidence of their cost-effectiveness. The impact on child mortality of introducing permethrin impregnated bednets was evaluated in a rural district of northern Ghana in a controlled trial. The cost-effectiveness of the intervention is reported in this paper. The total cost of the intervention over the 2 years of follow-up was US $148,245. Cost per impregnated bednet per year and per person protected per year was US $2.4 and 1.2, respectively. Approximately 16,800 child years were protected and 74 child deaths averted at an estimated cost of US $8.8 per child year protected and US $2003 per death averted. In this rural community, where life expectancy at the mean age of death of trial children was 57.5 years, the estimated cost per discounted healthy life-year gained was US $73.5. Sensitivity analysis suggested that this cost-effectiveness ratio might be reduced substantially by feasible changes in programme implementation. This study supports the argument that the cost-effectiveness of bednet impregnation is sufficiently attractive to make it part of a package of high priority interventions for children. Issues of how to finance the provision of nets and insecticide, and especially the relative contribution of governments, households and donors, need urgently to be addressed.

A district-wide study was undertaken in a rural population of northern Ghana to identify factors influencing the acceptance and use of insecticide-impregnated bednets (IIBNs). A series of focus group discussions were conducted during 2 years of implementation of IIBNs to gauge community reactions to the introduction of the nets and a structured questionnaire was administered to approximately 2000 randomly selected individuals. Although the IIBNs were accepted and used because they provided protection from mosquito bites, seasonal factors, patterns of use, and questions of cost were key factors likely to influence the dissemination and effectiveness of bednets. Use of the bednets was highly seasonal. Almost all recipients used their IIBNs in the rainy season (99%), corresponding to the period of high mosquito density and 20% used them in the dry seasons, the period of low mosquito density. Mothers with young children were more likely to wash the bednets frequently (because the children soiled the bednets with faeces and urine), resulting in no protection from the insecticide. Provision of wider bednets, or the provision of plastic sheets with the bednets or possible incorporation of the insecticide in washing soaps could improve protection for young children. The success of the promotion of IIBNs in malaria control programmes will depend on the cost of the package and the time of year that it is delivered. Financing mechanisms for individual and village groups are discussed. Social research effectively monitored the intervention in this study, and it should be included as an important component of national malaria control programmes.

A community-based randomized, controlled trial of permethrin impregnated bednets was carried out in a rural area of northern Ghana, between July 1993 and June 1995, to assess the impact on the mortality of young children in an area of intense transmission of malaria and no tradition of bednet use. The district around Navrongo was divided into 96 geographical areas and in 48 randomly selected areas households were provided with permethrin impregnated bednets which were re-impregnated every 6 months. A longitudinal demographic surveillance system was used to record births, deaths and migrations, to evaluate compliance and to measure child mortality. The use of permethrin impregnated bednets was associated with 17% reduction in all-cause mortality in children aged 6 months to 4 years (RR = 0.83; 95% CI 0.69-1.00; P = 0.05). The reduction in mortality was confined to children aged 2 years of younger, and was greater in July-December, during the wet season and immediately after (RR = 0.79; 95% CI 0.63-1.00), a period when malaria mortality is likely to be increased, than in the dry season (RR = 0.92, 95% CI 0.73-1.14). The ready acceptance of bednets, the high level of compliance in their use and the subsequent impact on all-cause mortality in this study has important implications for programmes to control malaria in sub-Saharan Africa.