Tools for surveillance of anti-malarial drug resistance: an assessment of the current landscape

Abstract

To limit the spread and impact of anti-malarial drug resistance and react accordingly, surveillance systems able to detect and track in real-time its emergence and spread need to be strengthened or in some places established. Currently, surveillance of anti-malarial drug resistance is done by any of three approaches: (1) in vivo studies to assess the efficacy of drugs in patients; (2) in vitro/ex vivo studies to evaluate parasite susceptibility to the drugs; and/or (3) molecular assays to detect validated gene mutations and/or gene copy number changes that are associated with drug resistance. These methods are complementary, as they evaluate different aspects of resistance; however, standardization of methods, especially for in vitro/ex vivo and molecular techniques, is lacking. The World Health Organization has developed a standard protocol for evaluating the efficacy of anti-malarial drugs, which is used by National Malaria Control Programmes to conduct their therapeutic efficacy studies. Regional networks, such as the East African Network for Monitoring Antimalarial Treatment and the Amazon Network for the Surveillance of Antimalarial Drug Resistance, have been set up to strengthen regional capacities for monitoring anti-malarial drug resistance. The Worldwide Antimalarial Resistance Network has been established to collate and provide global spatial and temporal trends information on the efficacy of anti-malarial drugs and resistance. While exchange of information across endemic countries is essential for monitoring anti-malarial resistance, sustainable funding for the surveillance and networking activities remains challenging. The technology landscape for molecular assays is progressing quite rapidly, and easy-to-use and affordable new techniques are becoming available. They also offer the advantage of high throughput analysis from a simple blood spots obtained from a finger prick. New technologies combined with the strengthening of national reference laboratories in malaria-endemic countries through standardized protocols and training plus the availability of a proficiency testing programme, would contribute to the improvement and sustainability of anti-malarial resistance surveillance networks worldwide.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2185-9) contains supplementary material, which is available to authorized users.

Antimalarial activity of traditional Kampo medicine Coptis Rhizome extract and its major active compounds

“…Since P. falciparum has quickly acquired resistance against currently available all antimalarials [40,41,42], it is urgently required to develop novel antimalarial drugs. Here we found that Coptis Rhizome showed 1.9 µg/ml and 4.9 µg/ml of IC 50 and >263 and >103 SI for Chloroquine sensitive and resistant P.…”

Strengthening Surveillance Systems for Malaria Elimination by Integrating Molecular and Genomic Data

“…However, the use of NGS could be centralized to very few sub-regional reference laboratories located in malaria endemic countries [36,83,84]. This requires a lot of effort to develop the capacity not only for sequencing but more importantly for data analysis, a critical part in the path for developing countries to get access to these techniques [85][86][87]. This should be a concerted effort not only from the malaria community but from the global health community, as other diseases such as tuberculosis (TB), human immunodeficiency virus (HIV), and other bacterial and viral infections may benefit as well from these centers of excellence [88].…”

Molecular assays for antimalarial drug resistance surveillance: A target product profile

“…Antimalarial drug resistance is a major concern for malaria control and elimination programmes. Indeed, Plasmodium falciparum parasites have consistently developed resistance to the most widely used antimalarials, pushing national malaria control programmes to regular changes in antimalarial drug policy [ 1 ]. Artemisinin-based combination therapy (ACT) is now the mainstay for malaria treatment in endemic regions, following recommendations from the World Health Organization (WHO) [ 2 ].…”

“…After markers of resistance have been identified by genotype-phenotype discovery studies, detection of these molecular markers provides a feasible means of tracking emergence and/or spread of antimalarial drug resistance, as easy-to-collect dried blood spot (DBS) samples can be used [ 22 , 23 ]. While numerous methodologies for blood spot collection, DNA extraction, PCR amplification, and analysis of molecular markers have been described, standardisation of these approaches is lacking [ 1 ]. Given the potential role of molecular surveillance of drug resistance markers, a standardised approach is important to allow for comparability across the globe.…”