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

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.

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. FUNDING: Bill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.

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

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.

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.

Microdistribution of the resistance of malaria vectors to deltamethrin in the region of Plateau (southeastern Benin) in preparation for an assessment of the impact of resistance on the effectiveness of Long Lasting Insecticidal Nets (LLINs).

BACKGROUND: This study aims to research two areas, one with a resistant and the other with a susceptible profile of An. gambiae to deltamethrin in the region of Plateau (southern Benin). In each area, eight localities were sought. Both areas were needed for the assessment of the impact of malaria vector resistance to pyrethroids on the effectiveness of Long Lasting Insecticidal Nets (LLINs). The susceptible area of An. gambiae to deltamethrin was used as a control. METHODS: In total, 119 localities in the region of Plateau were screened by sampling An. gambiae s.l larvae. Female mosquitoes resulting from these larvae were exposed to 0.05% deltamethrin following WHO standards. PCR was used to identify species and molecular forms of the dead and alive mosquitoes. Finally, we identified kdr mutations (1014 F and 1014S) using the HOLA technique. RESULTS: Fifty-six out of 119 prospected localities tested positive for Anopheles gambae s.l breeding sites. The results showed that An. gambiae was resistant to deltamethrin in 39 localities and susceptible in only 2 localities; resistance to deltamethrin was suspected in 15 localities. The HOLA technique confirmed the presence of kdr 1014 F mutation and the absence of kdr 1014S mutation. The kdr 1014 F mutation was found in both M and S molecular forms at relatively high frequencies therefore confirming the susceptibility tests. CONCLUSION: We were unable to identify the eight susceptible areas due to the overall resistance of An. gambiae to deltamethrin in the region of Plateau. To implement the study, we kept two areas, one with high resistance (R+++) and the other with low resistance (R+) of An. gambiae to deltamethrin.