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

Christian Nsanzabana,Djibrine Djalle,Philippe J Guérin,Didier Ménard,Iveth J González

doi:10.1186/s12936-018-2185-9

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.

Highlights

To limit the spread and impact of anti-malarial drug resistance and react surveillance systems able to detect and track in real-time its emergence and spread need to be strengthened or in some places established
The results show if the drug has reached the required therapeutic concentration that correlates with elimination of the parasite, or if the concentration has been sub-optimal, in which case a treatment failure should not be interpreted as parasite resistance [66, 67]
The in vivo approach has a standardized protocol from World Health Organization (WHO) [44], and remains the gold standard to evaluate the therapeutic efficacy of anti-malarial drugs

Summary

Introduction

To limit the spread and impact of anti-malarial drug resistance and react surveillance systems able to detect and track in real-time its emergence and spread need to be strengthened or in some places established. 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. 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. 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. Following the failure of MQ in Southeast Asia, the use of drugs in combination was, proposed as the best way to circumvent resistance, as the probability of a parasite to develop resistance to two drugs simultaneously is considered to be lower than for a single drug [20, 21]

Findings

Discussion

Conclusion