Measuring the effect of insecticide resistance: are we making progress?
Authors: Emmanuel Chanda
Journal: The Lancet Infectious Diseases (2018)

Exceptional global efforts to fight malaria have greatly reduced the disease burden by more than 500 million cases since 2000 in sub-Saharan Africa.1WHOWorld Malaria Report 2017. World Health Organization, Geneva2017Google Scholar These gains are partly ascribed to vector control using long-lasting insecticidal nets and indoor residual spraying—core interventions within the framework of integrated vector management2Chanda E Ameneshewa B Bagayoko M Govere JM Macdonald MB Harnessing integrated vector management for enhanced disease prevention.Trends Parasitol. 2017; 33: 30-41Summary Full Text Full Text PDF PubMed Scopus (22) Google Scholar—thus renewing the optimism and prioritisation of universal coverage for vector control in the Global Technical Strategy for Malaria 2016–2030.3WHOGlobal technical strategy and targets for malaria 2016–2030.http://apps.who.int/gb/ebwha/pdf_files/WHA68/A68_R2-en.pdf?ua=1Date: May 22, 2015Google Scholar The 70th World Health Assembly approved the Global Vector Control Response 2017–2030 that set ambitious but attainable goals, and prioritised four strategic approaches, including evidence-driven scale-up and integration of vector control tools to maximize the effect on disease and reinvigorate vector control.4Alonso P Engels D Reeder J Renewed push to strengthen vector control globally.Lancet. 2017; 389: 2270-2271Summary Full Text Full Text PDF PubMed Scopus (16) Google Scholar To date, long-lasting insecticidal nets are the most extensively used transmission reducing intervention by people at risk of malaria. Recommendations on achieving and maintaining universal coverage of nets have been revised to improve effectiveness.5WHO Global Malaria ProgrammeAchieving and maintaining universal coverage with long-lasting insecticidal nets for malaria control. World Health Organization, Geneva2017Google Scholar Unfortunately, contemporary insecticide-based vector control efforts are threatened by insecticide resistance mediated by multiple mechanisms. This phenomenon was among the reasons for the failure of the Global Malaria Eradication Programme, and could potentially reverse the declining trends in malaria burden.6Hemingway J Ranson H Magill A et al.Averting a malaria disaster: will insecticide resistance derail malaria control?.Lancet. 2016; 387: 1785-1788Summary Full Text Full Text PDF PubMed Scopus (252) Google Scholar To this effect, implementation of the global plan for insecticide resistance management in malaria vectors is being encouraged, albeit with dismal amounts of uptake by national malaria programmes.7WHO Global Malaria ProgrammeGlobal plan for insecticide resistance management in malaria vectors. World Health Organization, Geneva2012Google Scholar However, convincing quantifiable evidence of the effect of resistance on malaria transmission and inherent disease burden is scarce and questionable. Although appreciable proof of the entomological effect of resistance exists, indication of an epidemiological effect has been lacking. In this context, assessment of the effect of resistance has become a topical subject of discourse with public health significance. In The Lancet Infectious Diseases, Immo Kleinschmidt and colleagues8Kleinschmidt I Bradley J Knox TB et al.Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: a WHO-coordinated, prospective, international, observational cohort study.Lancet Infect Dis. 2018; (published online April 9.)http://dx.doi.org/10.1016/S1473-3099(18)30172-5Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar report the results of a coordinated multicountry observational cohort study on the implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets in Africa and India. The study aimed to establish the effect of net use (Olyset Net; Sumitomo Chemical, Tokyo, Japan; 1 g/m2 permethrin; and PermaNet 2.0; Vestergaard, Lausanne, Switzerland; 55 mg/m2 deltamethrin) on malaria transmission and disease burden relative to pyrethroid resistance in malaria vectors with unprecedented spatial scale. As resistance cannot be randomly assigned, the authors used an observational study design. In the context of diverse amounts of resistance, the authors hypothesised the odds of using and not using a net to be weaker in clusters with high resistance compared to clusters with low resistance. The authors measured the effectiveness of nets by comparing malaria incidence in net users with that of non-users. They observed a lower infection prevalence and disease incidence in net users than in non-users across a range of resistance levels. Although both users and non-users of nets were subject to high malaria infection risk, the observation that insecticide resistance was neither associated with infection prevalence nor with disease incidence is striking. Consequently, the authors emphasise the need for continued use of nets by populations at risk in endemic settings, irrespective of resistance, and call for development and bringing to market of other innovative vector control tools. Other attempts have been made to assess the epidemiological effect of resistance, albeit with minimal data and little or no consideration for confounding variables. To date, compelling evidence of the epidemiological impact of resistance comes from South Africa, potentially confounded by artemether and lumefantrine combination therapy.9Maharaj R Mthembu DJ Sharp BL Impact of DDT re-introduction on malaria transmission in KwaZulu-Natal.S Afr Med J. 2005; 95: 871-874PubMed Google Scholar Kleinschmidt and colleagues8Kleinschmidt I Bradley J Knox TB et al.Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: a WHO-coordinated, prospective, international, observational cohort study.Lancet Infect Dis. 2018; (published online April 9.)http://dx.doi.org/10.1016/S1473-3099(18)30172-5Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar provide evidence that nets afford protection against malaria regardless of resistance, which corroborates previous research.10Lindblade KA Mwandama D Mzilahowa T et al.A cohort study of the effectiveness of insecticide-treated bed nets to prevent malaria in an area of moderate pyrethroid resistance, Malawi.Malar J. 2015; 14: 31Crossref PubMed Scopus (67) Google Scholar In west Africa, despite variable levels of pyrethroid resistance, experimental hut trials provide evidence of an entomological impact, with nets remaining protective.11N'guessan R Corbel V Akogbéto M Rowland M Reduced efficacy of insecticide-treated nets and indoor residual spraying for malaria control in pyrethroid resistance area, Benin.Emerg Infect Dis. 2007; 13: 199-206Crossref PubMed Scopus (404) Google Scholar Compared with previous research, the authors of this study8Kleinschmidt I Bradley J Knox TB et al.Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: a WHO-coordinated, prospective, international, observational cohort study.Lancet Infect Dis. 2018; (published online April 9.)http://dx.doi.org/10.1016/S1473-3099(18)30172-5Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar provide more robust epidemiological datasets amenable for analysis and interpretation and highlight more confounders that could shape further research. Epidemiological data from a cluster randomised controlled trial informed recommendations for deployment of mosquito nets treated with pyrethroids and piperonyl butoxide in areas with intermediate pyrethroid resistance conferred by monooxygenase-based mechanisms.12WHO Global Malaria ProgrammeConditions for deployment of mosquito nets treated with pyrethroids and piperonyl butoxide. World Health Organization, Geneva2017Google Scholar Although further data are required to validate guidance,12WHO Global Malaria ProgrammeConditions for deployment of mosquito nets treated with pyrethroids and piperonyl butoxide. World Health Organization, Geneva2017Google Scholar Kleinschmidt and colleagues8Kleinschmidt I Bradley J Knox TB et al.Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: a WHO-coordinated, prospective, international, observational cohort study.Lancet Infect Dis. 2018; (published online April 9.)http://dx.doi.org/10.1016/S1473-3099(18)30172-5Summary Full Text Full Text PDF PubMed Scopus (114) Google Scholar provide additional insight on the epidemiological implications of resistance for malaria vector control, giving malaria programmes guidance for evidence-driven scale-up towards achieving and maintaining universal coverage.5WHO Global Malaria ProgrammeAchieving and maintaining universal coverage with long-lasting insecticidal nets for malaria control. World Health Organization, Geneva2017Google Scholar The authors of this study make a substantial contribution to dispelling the misconception that resistance renders nets ineffective, and are cognisant of challenges of confounders, including constraints for resistance management. The conclusions drawn are pertinent to malaria control and elimination efforts. More research on the quantification of epidemiological effects and rational insecticide resistance management is required to further reduce malaria burden. I declare no competing interests. Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: a WHO-coordinated, prospective, international, observational cohort studyIrrespective 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. Full-Text PDF Open Access