malERA: An updated research agenda for insecticide and drug resistance in malaria elimination and eradication

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.

Malaria Elimination: Challenges and Opportunities

“…Resistance to first-line treatments for Plasmodium falciparum malaria and to the insecticides used for Anopheles vector control is threatening malaria elimination efforts [4]. Artemisinin and its derivatives provide the fastest parasite clearance among available antimalarial drugs and have been combined with an antimalarial drug of a different class in order to (i) enhance complete cure rates, (ii) shorten the duration of therapy for artemisinin monotherapies, and (iii) delay the selection and spread of resistant parasites [5,6].…”

“…Besides artemisinin resistance, the prevalence of molecular markers correlated to resistance to the partner drugs has increased. For example, changes in the prevalence of pfcrt and pfmdr1 alleles have been observed in many areas where ACTs including amodiaquine or lumefantrine have been intensively used [4]. However, outside the GMS, recommended ACTs' efficacy remains acceptable (4).…”

“…For example, changes in the prevalence of pfcrt and pfmdr1 alleles have been observed in many areas where ACTs including amodiaquine or lumefantrine have been intensively used [4]. However, outside the GMS, recommended ACTs' efficacy remains acceptable (4). In Southeast Asia, the intensive use of dihydroartemisininpiperaquine (DP) has resulted in selection of parasites with multiple resistance mechanisms, and in Cambodia high levels of treatment failure to DP are now observed [15].…”

Behavioral response of insecticide-resistant mosquitoes against spatial repellent: a modified self-propelled particle model simulation

“…Pyrethroids, along with other pesticides, are also widely used to control agricultural pests on livestock and field crops worldwide [3]. The past decade has seen a dramatic increase in reports of physiological pyrethroid resistance in malaria vectors [4][5][6][7][8][9][10][11][12][13][14][15]. The rapid increase in pyrethroid resistance necessitates an immediate proactive resistance management response to avoid compromising existing effective interventions.…”

Preparing for the Next Global Threat: A Call for Targeted, Immediate Decisive Action in Southeast Asia to Prevent the Next Pandemic in Africa

“…Today, a two-fold increase in mortality [14] would cause in the order of 7 million malaria deaths over a decade. The threat will also be magnified by widespread resistance to insecticides already reported in Africa [16] (again history is repeating itself, in the "malaria eradication" era of 1955-1972, it was DDT resistance [17]). The concomitant threat of insecticide resistance, particularly as it affects the efficacy of insecticide-treated bed nets (ITNs) and household spraying, is widely recognized.…”