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 subSaharan 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.

Artemisinin Ameliorates Osteoarthritis by Inhibiting the Wnt/β-Catenin Signaling Pathway

“…Artemisinin and its derivatives are currently identified as the most effective drugs to treat chloroquine-resistant [9, 10]. In addition, with minimal side effects and nonresistant characteristics, ART can selectively kill parasite-infected red blood cells, but preserve the healthy cells [11, 12].…”

How Robust Are Malaria Parasite Clearance Rates as Indicators of Drug Effectiveness and Resistance?

“…At least three reviews (15)(16)(17) have pointed out that declining levels of immunity may have contributed to the decreased clearance rates observed in Southeast Asia and have been confused with changes in drug sensitivity levels (see also references 52 and 53 for examples of the subsequent discussion). Given the concerns over the impact of possible artemisinin resistance (8)(9)(10)(11)(12), it seems imperative to properly design a surveillance strategy and recognize the dangers of overreliance on iRBC clearance rates as the sole surveillance tool. The properties of the K13 mutations, principally, their resistance to artemisinins while in circulating early ring forms (54) combined with possible changes in progression through early (but not later) stages of the parasite's nominal 48-h cycle (35), seem ready made to allow their detection through reduced iRBC clearance rates.…”

“…The current generation of antimalarial drugs centers on artemisininbased combination therapies (ACTs), and recent reports that tolerance of and/or resistance to artemisinins is evolving (2-7) have caused considerable concern (8)(9)(10)(11)(12). ACTs remain largely effective in clearing malaria infections, but reduced parasite clearance rates (i.e., the rate at which parasitemia declines after treatment [13]) have been widely interpreted as indicating the presence of reduced parasite sensitivity to the artemisinin component and hence indicative of the early stages of resistance (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Parasite clearance rates have also been used to evaluate the likely clinical impact of alterations in artemisinin or ACT dosing regimens (14) that may be able to increase ACT effectiveness and hence reduce the threat of resistance.…”

US Department of Defense contributions to malaria surveillance

“…In response to an Article 1 and a Personal View 2 on the spread of artemisinin resistance in the November 2012, issue of The Lancet Infectious Diseases , , we would like to present several examples of previous and continuing malaria resistance work sponsored by the US Department of Defense (DoD).…”

“…Ambrose Talisuna and colleagues 2 called for the reinstitution of pan-African malaria-surveillance networks, citing the need for additional antimalarial-resistance surveillance, and calling for the rapid sharing of baseline parasite clearance-rate data derived from clinical trials. We agree with these sentiments and designed the GEIS harmonised artesunate–mefloquine clinical trials with those needs in mind.…”