Abstract
Plasmodium falciparum resistance to artemisinin and its derivatives is spreading in South-East Asia, and there is growing concern that this may reach other endemic countries. Methods used to assess P. falciparum resistance to artemisinin-based combination therapies (ACTs) are multiple and often divergent. This paper is a review of online accessible research publications from the past 20 years on ACTs, ranging from in vivo, in vitro/ex-vivo, molecular markers and pharmacokinetics studies. We highlight the procedures of the four main methods used for ACTs efficacy testing and provide a summary of published data. This review indicates that the most used method for ACT efficacy testing is the in vivo 28 days follow-up with molecular correction; the most widely used and reliable in vitro and ex-vivo method for artemisinin phenotyping is the ring stage survival assay from 0 to 3 h ring (RSA0-3h), and the main molecular marker of P. falciparum resistance to artemisinins are mutations on P. falciparum Kelch 13 propeller domain. Day 7 pharmacokinetics could help to predict resistance to artemether-lumefantrine and dihydroartemisinin-piperaquine. Findings from this review support that the combination of in vivo, in vitro/ex-vivo, molecular markers of drug resistance and day 7 PK levels of the partner drugs may be required for the optimal surveillance of artemisinin-based combination therapy efficacy in the field. Key words: Malaria, artemisinin-based combination therapies (ACTs), monitoring, drug resistance, review.
Highlights
Despite recent progress in malaria control and prevention, the disease remains a major public health problem in many endemic countries
All methods used for P. falciparum susceptibility to artemisinin-based combination therapies (ACTs) were described in a chronological order of use
MSP1 and Merozoite Surface Protein 2 (MSP2) were genotyped in order to differentiate recrudescence from re-infections for parasites that appeared after Day 14 and the re-infection rate was similar between study sites (Chanda et al, 2006)
Summary
Despite recent progress in malaria control and prevention, the disease remains a major public health problem in many endemic countries. Opinions resurgence of disease morbidity and mortality (Björkman et al, 2005; Björkman et al, 2002; Petersen et al, 2011; Talisuna et al, 2004; Trape et al, 1998) This makes it important to monitor the emergence and spread of parasite resistant to ACTs. Because of resistance to the existing antimalarial drugs (chloroquine, amodiaquine and sulfadoxinepyrimethamine), currently artemisinin-based combination therapy (ACT) are recommended for the treatment of uncomplicated Plasmodium falciparum malaria. Three years after the adoption of ACTs as first-line treatments by different national malaria control programs, cases of delayed parasite clearance and decreased susceptibility of P. falciparum to artemisinin derivatives were observed in South-East Asia (Ashley et al, 2014; Dondorp et al, 2009; Noedl et al, 2008). The present study enumerates each method, describe the principle of each method, summarize the main results and propose their respective strengths and weaknesses
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