Abstract
Parasite resistance against anti-malarial drugs is a major threat to the ongoing malaria control and elimination strategies. This is especially true since resistance to the currently recommended artemisinins and partner drugs has been confirmed in South East Asia (SEA) and new anti-malarial compounds are not expected to be available in the near future. Spread from SEA or independent emergence of artemisinin resistance in sub-Saharan Africa (SSA) could reverse the achievements in malaria control that have been attained in the past two decades and derail the ongoing elimination strategies. The current surveillance of clinical efficacy and resistance to anti-malarial drugs is based on efficacy trials to assess the clinical performance of anti-malarials, in vivo/ex vivo assessment of parasite susceptibility to anti-malarials and prevalence of known molecular markers of drug resistance. Whereas clinical efficacy trials are restricted by cost and the complex logistics of patient follow-up, molecular detection of genetic mutations associated with resistance or reduced susceptibility to anti-malarials is by contrast a simple and powerful tool for early detection and monitoring of the prevalence of resistant parasites at population level. This provides needed information before clinical failure emerges, allowing policy makers to anticipate problems and respond. The various methods previously used in detection of molecular markers of drug resistance share some limitations: low-throughput, and high costs per sample and demanding infrastructure. However, recent technological advances including next-generation sequencing (NGS) methodologies promise greatly increased throughput and reduced costs, essentially providing unprecedented potential to address different research and operational questions of relevance for drug policy. This review assesses the potential role of NGS to provide comprehensive information that could guide drug policies in malaria endemic countries and looks at the foreseeable challenges facing the establishment of NGS approaches for routine surveillance of parasite resistance to anti-malarials in SSA.
Highlights
The Global Technical Strategy for malaria (GTSm) 2016–2030 was formulated by the World Health Organization (WHO) to provide a framework to guide endemic counties toward malaria elimination. It sets out targets for the coming decade which include; 90% reduction of global malaria mortality and case incidence by 2030; eliminating malaria in at least 35 countries; and preventing re-introduction of malaria in all countries that are disease-free [1]
The interventions recommended by GTSm include current vector control methods [with long-lasting insecticidetreated bed nets (LLINs) and/or insecticide-treated bed nets (ITNs), and indoor residual spraying (IRS)] and effective case management [involving prompt diagnosis with rapid diagnostic tests (RDTs) and treatment using artemisinin-based combination therapy (ACT)]
GTSm recommends promoting and implementing malaria surveillance as a core intervention [1]. The impact of these interventions on malaria burden will be undermined by insufficient funding for malaria [2], weak health systems [3, 4], resistance to insecticides by Anopheles vectors [5] and emergence of parasites resistant to commonly used anti-malarials [6]
Summary
The Global Technical Strategy for malaria (GTSm) 2016–2030 (https://www.who.int/malaria/publications/ atoz/9789241564991/en/) was formulated by the World Health Organization (WHO) to provide a framework to guide endemic counties toward malaria elimination. Parasite resistance to anti-malarial drugs is a major obstacle to current initiatives for effective control and elimination of malaria. A strong and reliable surveillance framework which uses molecular markers could potentially inform drug policy and support timely intervention to forestall widespread treatment failure.
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