Mitigating the threat of artemisinin resistance in Africa: improvement of drug-resistance surveillance and response systems

Abstract

Artemisinin-resistant Plasmodium falciparum malaria has emerged in western Cambodia and has been detected in western Thailand. The situation is ominously reminiscent of the emergence of resistance to chloroquine and to sulfadoxine-pyrimethamine several decades ago. Artemisinin resistance is a major threat to global public health, with the most severe potential effects in sub-Saharan Africa, where the disease burden is highest and systems for monitoring and containment of resistance are inadequate. The mechanisms that underlie artemisinin resistance are not fully understood. The main phenotypic trait associated with resistance is a substantial delay in parasite clearance, so far reported in southeast Asia but not in Africa. One of the pillars of the WHO global plan for artemisinin resistance containment is to increase monitoring and surveillance. In this Personal View, we propose strategies that should be adopted by malaria-endemic countries in Africa: resource mobilisation to reactivate regional surveillance networks, establishment of baseline parasite clearance profiles to serve as benchmarks to track emerging artemisinin resistance, improved data sharing to allow pooled analyses to identify rare events, modelling of risk factors for drug resistance, and development and validation of new approaches to monitor resistance.

Figure 1. Evolution of antimalarial drug resistance

Drug resistance first appears as delayed parasite clearance, which progresses to recrudescent infections and increased gametocyte carriage, which in turn leads to enhanced malaria transmission and an increased reservoir of infection. Increased numbers of infections leads to increases in drug use, which intensifies the selection pressure that drives drug resistance in the population.

Figure 2. Risk-factor analysis for emergence of drug-resistant malaria

On the basis of the framework shown in this figure and our proposition that artemisinin resistance fits the definition of a public health emergency of international concern (in accordance with the revised international health regulations), clear policies for travellers from areas of confirmed artemisinin resistance (tier 1 areas as defined by the WHO global plan for artemisinin resistance containment) are urgently needed. Such policies could include the screening and treatment of all travellers from tier 1 areas to malaria-endemic regions of Africa with a highly effective gametocytocidal drug (such as primaquine) and revision of guidelines for prophylaxis.

Figure 3. Malaria migration, drug resistance, and surveillance networks in Africa

Malaria migration (A) and dispersal of drug resistance (B) both reflect the regional affiliations between neighbouring countries that were also apparent in the first surveillance networks (C). Countries connected by relatively high Plasmodium falciparum malaria migration can be divided into regional blocks (A). Lineages are each derived from one ancestral mutant. Relative abundance of resistant lineages in each population are shown by pie charts (B) in which each colour represents one resistant lineage. Country membership of previous African drug-resistance surveillance networks (C). (A) is reproduced from reference , by permission of Proceedings of the National Academy of Sciences of the United States of America. (B) is reproduced from reference , by permission of PLoS Medicine.