Indoor residual spraying for preventing malaria.

BACKGROUND: Primary malaria prevention on a large scale depends on two vector control interventions: indoor residual spraying (IRS) and insecticide-treated mosquito nets (ITNs). Historically, IRS has reduced malaria transmission in many settings in the world, but the health effects of IRS have never been properly quantified. This is important, and will help compare IRS with other vector control interventions. OBJECTIVES: To quantify the impact of IRS alone, and to compare the relative impacts of IRS and ITNs, on key malariological parameters. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (September 2009), CENTRAL (The Cochrane Library 2009, Issue 3), MEDLINE (1966 to September 2009), EMBASE (1974 to September 2009), LILACS (1982 to September 2009), mRCT (September 2009), reference lists, and conference abstracts. We also contacted researchers in the field, organizations, and manufacturers of insecticides (June 2007). SELECTION CRITERIA: Cluster randomized controlled trials (RCTs), controlled before-and-after studies (CBA) and interrupted time series (ITS) of IRS compared to no IRS or ITNs. Studies examining the impact of IRS on special groups not representative of the general population, or using insecticides and dosages not recommended by the World Health Organization (WHO) were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed trials for inclusion. Two authors extracted data, assessed risk of bias and analysed the data. Where possible, we adjusted confidence intervals (CIs) for clustering. Studies were grouped into those comparing IRS with no IRS, and IRS compared with ITNs, and then stratified by malaria endemicity. MAIN RESULTS: IRS versus no IRSStable malaria (entomological inoculation rate (EIR) > 1): In one RCT in Tanzania IRS reduced re-infection with malaria parasites detected by active surveillance in children following treatment; protective efficacy (PE) 54%. In the same setting, malaria case incidence assessed by passive surveillance was marginally reduced in children aged one to five years; PE 14%, but not in children older than five years (PE -2%). In the IRS group, malaria prevalence was slightly lower but this was not significant (PE 6%), but mean haemoglobin was higher (mean difference 0.85 g/dL).In one CBA trial in Nigeria, IRS showed protection against malaria prevalence during the wet season (PE 26%; 95% CI 20 to 32%) but not in the dry season (PE 6%; 95% CI -4 to 15%). In one ITS in Mozambique, the prevalence was reduced substantially over a period of 7 years (from 60 to 65% prevalence to 4 to 8% prevalence; the weighted PE before-after was 74% (95% CI 72 to 76%).Unstable malaria (EIR < 1): In two RCTs, IRS reduced the incidence rate of all malaria infections;PE 31% in India, and 88% (95% CI 69 to 96%) in Pakistan. By malaria species, IRS also reduced the incidence of P. falciparum (PE 93%, 95% CI 61 to 98% in Pakistan) and P. vivax (PE 79%, 95% CI 45 to 90% in Pakistan); There were similar impacts on malaria prevalence for any infection: PE 76% in Pakistan; PE 28% in India. When looking separately by parasite species, for P. falciparum there was a PE of 92% in Pakistan and 34% in India; for P. vivax there was a PE of 68% in Pakistan and no impact demonstrated in India (PE of -2%).IRS versus Insecticide Treated Nets (ITNs)Stable malaria (EIR > 1): Only one RCT was done in an area of stable transmission (in Tanzania). When comparing parasitological re-infection by active surveillance after treatment in short-term cohorts, ITNs appeared better, but it was likely not to be significant as the unadjusted CIs approached 1 (risk ratio IRS:ITN = 1.22). When the incidence of malaria episodes was measured by passive case detection, no difference was found in children aged one to five years (risk ratio = 0.88, direction in favour of IRS). No difference was found for malaria prevalence or haemoglobin.Unstable malaria (EIR < 1): Two studies; for incidence and prevalence, the malaria rates were higher in the IRS group compared to the ITN group in one study. Malaria incidence was higher in the IRS arm in India (risk ratio IRS:ITN = 1.48) and in South Africa (risk ratio 1.34 but the cluster unadjusted CIs included 1). For malaria prevalence, ITNs appeared to give better protection against any infection compared to IRS in India (risk ratio IRS:ITN = 1.70) and also for both P. falciparum (risk ratio IRS:ITN = 1.78) and P. vivax (risk ratio IRS:ITN = 1.37). AUTHORS' CONCLUSIONS: Historical and programme documentation has clearly established the impact of IRS. However, the number of high-quality trials are too few to quantify the size of effect in different transmission settings. The evidence from randomized comparisons of IRS versus no IRS confirms that IRS reduces malaria incidence in unstable malaria settings, but randomized trial data from stable malaria settings is very limited. Some limited data suggest that ITN give better protection than IRS in unstable areas, but more trials are needed to compare the effects of ITNs with IRS, as well as to quantify their combined effects.

Monitoring the operational impact of insecticide usage for malaria control on Anopheles funestus from Mozambique.

BACKGROUND: Indoor residual spraying (IRS) has again become popular for malaria control in Africa. This combined with the affirmation by WHO that DDT is appropriate for use in the absence of longer lasting insecticide formulations in some malaria endemic settings, has resulted in an increase in IRS with DDT as a major malaria vector control intervention in Africa. DDT was re-introduced into Mozambique's IRS programme in 2005 and is increasingly becoming the main insecticide used for malaria vector control in Mozambique. The selection of DDT as the insecticide of choice in Mozambique is evidence-based, taking account of the susceptibility of Anopheles funestus to all available insecticide choices, as well as operational costs of spraying. Previously lambda cyhalothrin had replaced DDT in Mozambique in 1993. However, resistance appeared quickly to this insecticide and, in 2000, the pyrethroid was phased out and the carbamate bendiocarb introduced. Low level resistance was detected by biochemical assay to bendiocarb in 1999 in both An. funestus and Anopheles arabiensis, although this was not evident in WHO bioassays of the same population. METHODS: Sentinel sites were established and monitored for insecticide resistance using WHO bioassays. These assays were conducted on 1-3 day old F1 offspring of field collected adult caught An. funestus females to determine levels of insecticide resistance in the malaria vector population. WHO biochemical assays were carried out to determine the frequency of insecticide resistance genes within the same population. RESULTS: In surveys conducted between 2002 and 2006, low levels of bendiocarb resistance were detected in An. funestus, populations using WHO bioassays. This is probably due to significantly elevated levels of Acetylcholinesterase levels found in the same populations. Pyrethroid resistance was also detected in populations and linked to elevated levels of p450 monooxygenase activity. One site had shown reduction in pyrethroid resistance since the base line in 1999.

Developing a spatial-statistical model and map of historical malaria prevalence in Botswana using a staged variable selection procedure.

BACKGROUND: Several malaria risk maps have been developed in recent years, many from the prevalence of infection data collated by the MARA (Mapping Malaria Risk in Africa) project, and using various environmental data sets as predictors. Variable selection is a major obstacle due to analytical problems caused by over-fitting, confounding and non-independence in the data. Testing and comparing every combination of explanatory variables in a Bayesian spatial framework remains unfeasible for most researchers. The aim of this study was to develop a malaria risk map using a systematic and practicable variable selection process for spatial analysis and mapping of historical malaria risk in Botswana. RESULTS: Of 50 potential explanatory variables from eight environmental data themes, 42 were significantly associated with malaria prevalence in univariate logistic regression and were ranked by the Akaike Information Criterion. Those correlated with higher-ranking relatives of the same environmental theme, were temporarily excluded. The remaining 14 candidates were ranked by selection frequency after running automated step-wise selection procedures on 1000 bootstrap samples drawn from the data. A non-spatial multiple-variable model was developed through step-wise inclusion in order of selection frequency. Previously excluded variables were then re-evaluated for inclusion, using further step-wise bootstrap procedures, resulting in the exclusion of another variable. Finally a Bayesian geo-statistical model using Markov Chain Monte Carlo simulation was fitted to the data, resulting in a final model of three predictor variables, namely summer rainfall, mean annual temperature and altitude. Each was independently and significantly associated with malaria prevalence after allowing for spatial correlation. This model was used to predict malaria prevalence at unobserved locations, producing a smooth risk map for the whole country. CONCLUSION: We have produced a highly plausible and parsimonious model of historical malaria risk for Botswana from point-referenced data from a 1961/2 prevalence survey of malaria infection in 1-14 year old children. After starting with a list of 50 potential variables we ended with three highly plausible predictors, by applying a systematic and repeatable staged variable selection procedure that included a spatial analysis, which has application for other environmentally determined infectious diseases. All this was accomplished using general-purpose statistical software.

Malaria vector control by indoor residual insecticide spraying on the tropical island of Bioko, Equatorial Guinea.

BACKGROUND: A comprehensive malaria control intervention was initiated in February 2004 on Bioko Island, Equatorial Guinea. This manuscript reports on the continuous entomological monitoring of the indoor residual spray (IRS) programme during the first two years of its implementation. METHODS: Mosquitoes were captured daily using window traps at 16 sentinel sites and analysed for species identification, sporozoite rates and knockdown resistance (kdr) using polymerase chain reaction (PCR) to assess the efficacy of the vector control initiative from December 2003 to December 2005. RESULTS: A total of 2,807 and 10,293 Anopheles funestus and Anopheles gambiae s.l. respectively were captured throughout the study period. Both M and S molecular forms of An. gambiae s.s. and Anopheles melas were identified. Prior to the first round of IRS, sporozoite rates were 6.0, 8.3 and 4.0 for An. gambiae s.s., An. melas and An. funestus respectively showing An. melas to be an important vector in areas in which it occurred. After the third spray round, no infective mosquitoes were identified. After the first spray round using a pyrethroid spray the number of An. gambiae s.s. were not reduced due to the presence of the kdr gene but An funestus and An. melas populations declined from 23.5 to 3.1 and 5.3 to 0.8 per trap per 100 nights respectively. After the introduction of a carbamate insecticide in the second round, An. gambiae s.s. reduced from 25.5 to 1.9 per trap per 100 nights and An. funestus and An. melas remained at very low levels. Kdr was found only in the M-form of An. gambiae s.s. with the highest frequency at Punta Europa (85%). CONCLUSION: All three vectors that were responsible for malaria transmission before the start of the intervention were successfully controlled once an effective insecticide was used. Continuous entomological surveillance including resistance monitoring is of critical importance in any IRS based malaria vector control programme. This paper demonstrates that sufficient resources for such monitoring should be included in any proposal in order to avoid programme failures.

Seven years of regional malaria control collaboration--Mozambique, South Africa, and Swaziland.

The Lubombo Spatial Development Initiative is a joint development program between the governments of Mozambique, Swaziland, and South Africa, which includes malaria control as a core component of the initiative. Vector control through indoor residual spraying (IRS) was incrementally introduced in southern Mozambique between November 2000 and February 2004. Surveillance to monitor its impact was conducted by annual cross-sectional surveys to assess the prevalence of Plasmodium falciparum infection, entomologic monitoring, and malaria case notification in neighboring South Africa and Swaziland. In southern Mozambique, there was a significant reduction in P. falciparum prevalence after the implementation of IRS, with an overall relative risk of 0.74 for each intervention year (P < 0.001), ranging from 0.66 after the first year to 0.93 after the fifth intervention year. Substantial reductions in notified malaria cases were reported in South Africa and Swaziland over the same period. The success of the program in reducing malaria transmission throughout the target area provides a strong argument for investment in regional malaria control.

Patterns of malaria-related hospital admissions and mortality among Malawian children: an example of spatial modelling of hospital register data.

BACKGROUND: Malaria is a leading cause of hospitalization and in-hospital mortality among children in Africa, yet, few studies have described the spatial distribution of the two outcomes. Here spatial regression models were applied, aimed at quantifying spatial variation and risk factors associated with malaria hospitalization and in-hospital mortality. METHODS: Paediatric ward register data from Zomba district, Malawi, between 2002 and 2003 were used, as a case study. Two spatial models were developed. The first was a Poisson model applied to analyse hospitalization and minimum mortality rates, with age and sex as covariates. The second was a logistic model applied to individual level data to analyse case-fatality rate, adjusting for individual covariates. RESULTS AND CONCLUSION: Rates of malaria hospitalization and in-hospital mortality decreased with age. Case fatality rate was associated with distance, age, wet season and increased if the patient was referred to the hospital. Furthermore, death rate was high on first day, followed by relatively low rate as length of hospital stay increased. Both outcomes showed substantial spatial heterogeneity, which may be attributed to the varying determinants of malaria risk, health services availability and accessibility, and health seeking behaviour. The increased risk of mortality of children referred from primary health facilities may imply inadequate care being available at the referring facility, or the referring facility are referring the more severe cases which are expected to have a higher case fatality rate. Improved prognosis as the length of hospital stay increased suggest that appropriate care when available can save lives. Reducing malaria burden may require integrated strategies encompassing availability of adequate care at primary facilities, introducing home or community case management as well as encouraging early referral, and reinforcing interventions to interrupt malaria transmission.

Spatial analysis and mapping of malaria risk in Malawi using point-referenced prevalence of infection data.

BACKGROUND: Current malaria control initiatives aim at reducing malaria burden by half by the year 2010. Effective control requires evidence-based utilisation of resources. Characterizing spatial patterns of risk, through maps, is an important tool to guide control programmes. To this end an analysis was carried out to predict and map malaria risk in Malawi using empirical data with the aim of identifying areas where greatest effort should be focussed. METHODS: Point-referenced prevalence of infection data for children aged 1-10 years were collected from published and grey literature and geo-referenced. The model-based geostatistical methods were applied to analyze and predict malaria risk in areas where data were not observed. Topographical and climatic covariates were added in the model for risk assessment and improved prediction. A Bayesian approach was used for model fitting and prediction. RESULTS: Bivariate models showed a significant association of malaria risk with elevation, annual maximum temperature, rainfall and potential evapotranspiration (PET). However in the prediction model, the spatial distribution of malaria risk was associated with elevation, and marginally with maximum temperature and PET. The resulting map broadly agreed with expert opinion about the variation of risk in the country, and further showed marked variation even at local level. High risk areas were in the low-lying lake shore regions, while low risk was along the highlands in the country. CONCLUSION: The map provided an initial description of the geographic variation of malaria risk in Malawi, and might help in the choice and design of interventions, which is crucial for reducing the burden of malaria in Malawi.

The Innovative Vector Control Consortium: improved control of mosquito-borne diseases.

Few new insecticides have been produced for control of disease vectors for public health in developing countries over the past three decades, owing to market constraints, and the available insecticides are often poorly deployed. The Innovative Vector Control Consortium will address these market failures by developing a portfolio of chemical and technological tools that will be directly and immediately accessible to populations in the developing world. The Bill and Melinda Gates Foundation has supported this new initiative to enable industry and academia to change the vector control paradigm for malaria and dengue and to ensure that vector control, alongside drugs, case management and vaccines, can be better used to reduce disease.

Effect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal, South Africa.

BACKGROUND: Between 1995 and 2000, KwaZulu-Natal province, South Africa, experienced a marked increase in Plasmodium falciparum malaria, fuelled by pyrethroid and sulfadoxine-pyrimethamine resistance. In response, vector control was strengthened and artemether-lumefantrine (AL) was deployed in the first Ministry of Health artemisinin-based combination treatment policy in Africa. In South Africa, effective vector and parasite control had historically ensured low-intensity malaria transmission. Malaria is diagnosed definitively and treatment is provided free of charge in reasonably accessible public-sector health-care facilities. METHODS AND FINDINGS: We reviewed four years of malaria morbidity and mortality data at four sentinel health-care facilities within KwaZulu-Natal's malaria-endemic area. In the year following improved vector control and implementation of AL treatment, malaria-related admissions and deaths both declined by 89%, and outpatient visits decreased by 85% at the sentinel facilities. By 2003, malaria-related outpatient cases and admissions had fallen by 99%, and malaria-related deaths had decreased by 97%. There was a concomitant marked and sustained decline in notified malaria throughout the province. No serious adverse events were associated causally with AL treatment in an active sentinel pharmacovigilance survey. In a prospective study with 42 d follow up, AL cured 97/98 (99%) and prevented gametocyte developing in all patients. Consistent with the findings of focus group discussions, a household survey found self-reported adherence to the six-dose AL regimen was 96%. CONCLUSION: Together with concurrent strengthening of vector control measures, the antimalarial treatment policy change to AL in KwaZulu-Natal contributed to a marked and sustained decrease in malaria cases, admissions, and deaths, by greatly improving clinical and parasitological cure rates and reducing gametocyte carriage.

The residual life of bendiocarb: a field-based evaluation from Mozambique.

The residual life of bendiocarb was evaluated under field conditions in southern Mozambique. Bioassays conducted at monthly intervals using susceptible Anopheles arabiensis demonstrated that bendiocarb had an effective residual life of 6 mo. The different types of surfaces sprayed did not affect the residual life of bendiocarb. Therefore, to achieve effective control in a malaria-endemic area such as southern Mozambique, two spray rounds per annum are necessary.

The cost and cost-effectiveness of malaria vector control by residual insecticide house-spraying in southern Mozambique: a rural and urban analysis.

OBJECTIVES: To compare two separately funded, but operationally similar, residual household-spraying (RHS) initiatives; one rural and one peri-urban in southern Mozambique. METHODS: The rural programme is a regional project involving the participation and co-ordination of organizations across three countries in southern Africa and is focussed on control in an area in Mozambique of 7552 km2. The second programme focuses on spraying a peri-urban community within a 10-km radius around MOZAL, an aluminium smelter plant of area 410 km2. An ingredients approach was used to derive unit costs for both the rural and peri-urban spraying programmes using detail retrospective cost data and effectiveness indicators. RESULTS: The economic cost per person covered per year using Carbamates for indoor residual spraying (IRS) in the rural area, excluding the costs of project management and monitoring and surveillance was $3.48 and in the peri-urban area, $2.16. The financial costs per person covered in the rural area and peri-urban area per year were $3.86 and $2.41, respectively. The economic costs per person covered were respectively increased by 39% and 31% when project management and monitoring and surveillance were included. The main driving forces behind the costs of delivering RHS are twofold: the population covered and insecticide used. Computed economic and financial costs are presented for all four insecticide families available for use in RHS. CONCLUSIONS: The results from both these initiatives, especially the rural area, should be interpreted as conservative cost estimates as they exclude the additional health gains that the newly introduced programmes have had on malaria rates in the neighbouring areas of South Africa and Swaziland. Both these initiatives show that introducing an IRS programme can deliver a reduction in malaria-related suffering providing financial support, political will, collaborative management and training and community involvement are in place.

Enhancing malaria control using a computerised management system in southern Africa.

BACKGROUND: Malaria control programmes utilising indoor residual spraying are only effective if a high coverage of targeted structures is achieved and an insecticide that is effective against the specific mosquito vector is correctly applied. Ongoing monitoring of spraying operations is essential to assure optimal programme performance and early corrective action, where indicated. METHODS: Successful development and application of a computerised spraying operations management system in Mpumalanga Province, South Africa during 1998 resulted in its adaptation and introduction in neighbouring Maputo Province, southern Mozambique during 2000. The structure and components of this computerised management system are described, and its' operational benefit in southern Mozambique, where community-based spray operators apply intradomiciliary insecticide, are reviewed. CONCLUSIONS: The computerised management system allowed malaria programme management and field supervisors to monitor spraying coverage, insecticide consumption and application rates on an ongoing basis. The system supported a successful transition to community-based spraying, while assuring correct insecticide application and spraying completion according to schedule.