Date Published: November 30, 2017
Publisher: Public Library of Science
Abstract: Resistance to first-line treatments for Plasmodium falciparum malaria and the insecticides used for Anopheles vector control are threatening malaria elimination efforts. Suboptimal responses to drugs and insecticides are both spreading geographically and emerging independently and are being seen at increasing intensities. Whilst resistance is unavoidable, its effects can be mitigated through resistance management practices, such as exposing the parasite or vector to more than one selective agent. Resistance contributed to the failure of the 20th century Global Malaria Eradication Programme, and yet the global response to this issue continues to be slow and poorly coordinated—too often, too little, too late. The Malaria Eradication Research Agenda (malERA) Refresh process convened a panel on resistance of both insecticides and antimalarial drugs. This paper outlines developments in the field over the past 5 years, highlights gaps in knowledge, and proposes a research agenda focused on managing resistance. A deeper understanding of the complex biological processes involved and how resistance is selected is needed, together with evidence of its public health impact. Resistance management will require improved use of entomological and parasitological data in decision making, and optimisation of the useful life of new and existing products through careful implementation, combination, and evaluation. A proactive, collaborative approach is needed from basic science and the development of new tools to programme and policy interventions that will ensure that the armamentarium of drugs and insecticides is sufficient to deal with the challenges of malaria control and its elimination.
Partial Text: Over the past decade, unprecedented progress has been made in reducing malaria morbidity and mortality . However, growing resistance to the first-line treatment for P. falciparum malaria, artemisinin-based combination therapies (ACTs), and the insecticides used to suppress mosquito vectors threaten the sustainability of recent gains in malaria control and longer-term prospects for elimination.
The findings presented in this paper result from an extensive literature review of published and unpublished materials and the deliberations of the 2015 malERA Refresh Consultative Panel on Insecticide and Drug Resistance. Electronic databases were systematically searched for published literature between January 1, 2010, and November 2, 2015, without language limitations. Panellists were invited to recommend additional literature. A 2-day workshop was held with the majority of the panel members, including specialists from basic science and product development, field researchers, and WHO representatives. The panel broke into 2 working groups to identify the problems that need to be solved in insecticide and drug resistance and what research is needed to address these problems. Each group fed back to the plenary session, in which further robust discussions and input occurred. This helped refine the opportunities and gap areas in which research is needed. The final findings were arrived at with input from all panellists and several iterations of the manuscript.
Resistance is an inevitable consequence of drug and insecticide treatment, but the malaria community as a whole has repeatedly failed to respond to this issue in a proactive way. Programme and policy decisions should be based on comprehensive resistance data, and this should be coupled with improved efforts to understand the complex biological processes that select for resistant phenotypes. The tools to surmount resistance are limited and little is known about the most effective resistance management measures, so new therapeutics and vector control products should have a clear route to market and be carefully implemented and evaluated to optimise the choice of interventions. Multidrug and insecticide regimens are not unique to malaria control and other disease systems such as HIV , tuberculosis , and agricultural pest control  offer important insights into the management of insecticide- and drug-based approaches. The malaria community must learn from other disease groups and industries and heed the lessons of the past or risk further erosion of the malaria elimination agenda as renewed efforts are undermined by resistance.