Design of a study to determine the impact of insecticide resistance on malaria vector control: a multi-country investigation.

BACKGROUND: Progress in reducing the malaria disease burden through the substantial scale up of insecticide-based vector control in recent years could be reversed by the widespread emergence of insecticide resistance. The impact of insecticide resistance on the protective effectiveness of insecticide-treated nets (ITN) and indoor residual spraying (IRS) is not known. A multi-country study was undertaken in Sudan, Kenya, India, Cameroon and Benin to quantify the potential loss of epidemiological effectiveness of ITNs and IRS due to decreased susceptibility of malaria vectors to insecticides. The design of the study is described in this paper. METHODS: Malaria disease incidence rates by active case detection in cohorts of children, and indicators of insecticide resistance in local vectors were monitored in each of approximately 300 separate locations (clusters) with high coverage of malaria vector control over multiple malaria seasons. Phenotypic and genotypic resistance was assessed annually. In two countries, Sudan and India, clusters were randomly assigned to receive universal coverage of ITNs only, or universal coverage of ITNs combined with high coverage of IRS. Association between malaria incidence and insecticide resistance, and protective effectiveness of vector control methods and insecticide resistance were estimated, respectively. RESULTS: Cohorts have been set up in all five countries, and phenotypic resistance data have been collected in all clusters. In Sudan, Kenya, Cameroon and Benin data collection is due to be completed in 2015. In India data collection will be completed in 2016. DISCUSSION: The paper discusses challenges faced in the design and execution of the study, the analysis plan, the strengths and weaknesses, and the possible alternatives to the chosen study design

Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: evidence from health facility data from Benin

Abstract Background Insecticide-based interventions have averted more than 500 million malaria cases since 2000, but insecticide resistance in mosquitoes could bring about a rebound in disease and mortality. This study investigated whether insecticide resistance was associated with increased incidence of clinical malaria. Methods In an area of southern Benin with insecticide resistance and high use of insecticide-treated nets (ITNs), malaria morbidity and insecticide resistance were measured simultaneously in 30 clusters (villages or collections of villages) multiple times over the course of 2 years. Insecticide resistance frequencies were measured using the standard World Health Organization bioassay test. Malaria morbidity was measured by cases recorded at health facilities both in the whole population using routinely collected data and in a passively followed cohort of children under 5 years old. Results There was no evidence that incidence of malaria from routinely collected data was higher in clusters with resistance frequencies above the median, either in children aged under 5 (RR = 1.27 (95% CI 0.81–2.00) p = 0.276) or in individuals aged 5 or over (RR = 1.74 (95% CI 0.91–3.34) p = 0.093). There was also no evidence that incidence was higher in clusters with resistance frequencies above the median in the passively followed cohort (RR = 1.11 (0.52–2.35) p = 0.777). Conclusions This study found no association between frequency of resistance and incidence of clinical malaria in an area where ITNs are the principal form of vector control. This may be because, as other studies have shown, ITNs continue to offer some protection from malaria even in the presence of insecticide resistance. Irrespective of resistance, nets provide only partial protection so the development of improved or supplementary vector control tools is required to reduce Africa’s unacceptably high malaria burden

Insecticide-treated nets provide protection against malaria to children in an area of insecticide resistance in Southern Benin

Abstract Background Malaria control is heavily reliant on insecticides, especially pyrethroids. Resistance of mosquitoes to insecticides may threaten the effectiveness of insecticide-based vector control and lead to a resurgence of malaria in Africa. Methods In 21 villages in Southern Benin with high levels of insecticide resistance, the resistance status of local vectors was measured at the same time as the prevalence of malaria infection in resident children. Results Children who used LLINs had lower levels of malaria infection [odds ratio = 0.76 (95% CI 0.59, 0.98, p = 0.033)]. There was no evidence that the effectiveness of nets was different in high and low resistance locations (p = 0.513). There was no association between village level resistance and village level malaria prevalence (p = 0.999). Conclusions LLINs continue to offer individual protection against malaria infection in an area of high resistance. Insecticide resistance is not a reason to stop efforts to increase coverage of LLINs in Africa

Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: a WHO-coordinated, prospective, international, observational cohort study

Background Scale-up of insecticide-based interventions has averted more than 500 million malaria cases since 2000. Increasing insecticide resistance could herald a rebound in disease and mortality. We aimed to investigate whether insecticide resistance was associated with loss of effectiveness of long-lasting insecticidal nets and increased malaria disease burden. Methods This WHO-coordinated, prospective, observational cohort study was done at 279 clusters (villages or groups of villages in which phenotypic resistance was measurable) in Benin, Cameroon, India, Kenya, and Sudan. Pyrethroid long-lasting insecticidal nets were the principal form of malaria vector control in all study areas; in Sudan this approach was supplemented by indoor residual spraying. Cohorts of children from randomly selected households in each cluster were recruited and followed up by community health workers to measure incidence of clinical malaria and prevalence of infection. Mosquitoes were assessed for susceptibility to pyrethroids using the standard WHO bioassay test. Country-specific results were combined using meta-analysis. Findings Between June 2, 2012, and Nov 4, 2016, 40 000 children were enrolled and assessed for clinical incidence during 1·4 million follow-up visits. 80 000 mosquitoes were assessed for insecticide resistance. Long-lasting insecticidal net users had lower infection prevalence (adjusted odds ratio [OR] 0·63, 95% CI 0·51–0·78) and disease incidence (adjusted rate ratio [RR] 0·62, 0·41–0·94) than did non-users across a range of resistance levels. We found no evidence of an association between insecticide resistance and infection prevalence (adjusted OR 0·86, 0·70–1·06) or incidence (adjusted RR 0·89, 0·72–1·10). Users of nets, although significantly better protected than non-users, were nevertheless subject to high malaria infection risk (ranging from an average incidence in net users of 0·023, [95% CI 0·016–0·033] per person-year in India, to 0·80 [0·65–0·97] per person year in Kenya; and an average infection prevalence in net users of 0·8% [0·5–1·3] in India to an average infection prevalence of 50·8% [43·4–58·2] in Benin). Interpretation Irrespective of resistance, populations in malaria endemic areas should continue to use long-lasting insecticidal nets to reduce their risk of infection. As nets provide only partial protection, the development of additional vector control tools should be prioritised to reduce the unacceptably high malaria burden

Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: trends in pyrethroid resistance during a WHO-coordinated multi-country prospective study

BackgroundIncreasing pyrethroid resistance has been an undesirable correlate of the rapid increase in coverage of insecticide-treated nets (ITNs) since 2000. Whilst monitoring of resistance levels has increased markedly over this period, longitudinal monitoring is still lacking, meaning the temporal and spatial dynamics of phenotypic resistance in the context of increasing ITN coverage are unclear.MethodsAs part of a large WHO-co-ordinated epidemiological study investigating the impact of resistance on malaria infection, longitudinal monitoring of phenotypic resistance to pyrethroids was undertaken in 290 clusters across Benin, Cameroon, India, Kenya and Sudan. Mortality in response to pyrethroids in the major anopheline vectors in each location was recorded during consecutive years using standard WHO test procedures. Trends in mosquito mortality were examined using generalised linear mixed-effect models.ResultsInsecticide resistance (using the WHO definition of mortality < 90%) was detected in clusters in all countries across the study period. The highest mosquito mortality (lowest resistance frequency) was consistently reported from India, in an area where ITNs had only recently been introduced. Substantial temporal and spatial variation was evident in mortality measures in all countries. Overall, a trend of decreasing mosquito mortality (increasing resistance frequency) was recorded (Odds Ratio per year: 0.79 per year (95% CI: 0.79-0.81, P < 0.001). There was also evidence that higher net usage was associated with lower mosquito mortality in some countries.DiscussionPyrethroid resistance increased over the study duration in four out of five countries. Insecticide-based vector control may be compromised as a result of ever higher resistance frequencies