Risk of drug resistance in Plasmodium falciparum malaria therapy-a systematic review and meta-analysis.

Plasmodium falciparum is responsible for the vast majority of the morbidity and mortality associated with malaria infection globally. Although a number of studies have reported the emergence of drug resistance in different therapies for P. falciparum infection, the degree of the drug resistance in different antimalarials is still unclear. This research investigated the risk of drug resistance in the therapies with different medications based on meta-analyses. Relevant original randomized control trials (RCTs) were searched in all available electronic databases. Pooled relative risks (RRs) with 95% confidence intervals (95% CIs) were used to evaluate the risk of drug resistance resulting from different treatments. Seventy-eight studies were included in the meta-analysis to compare drug resistance in the treatment of P. falciparum infections and yielded the following results: chloroquine (CQ) > sulfadoxine-pyrimethamine (SP) (RR = 3.67, p < 0.001 ), mefloquine (MQ) < SP (RR = 0.26, p < 0.001), artesunate + sulfadoxine-pyrimethamine (AS + SP) > artemether + lumefantrine (AL) (RR = 2.94, p < 0.001), dihydroartemisinin + piperaquine (DHA + PQ) < AL (RR = 0.7, p < 0.05), and non-artemisinin-based combination therapies (NACTs) > artemisinin-based combination therapies (ACTs) (RR = 1.93, p < 0.001); no significant difference was found in amodiaquine (AQ) vs. SP, AS + AQ vs. AS + SP, AS + AQ vs. AL, or AS + MQ vs. AL. These results presented a global view for the current status of antimalarial drug resistance and provided a guidance for choice of antimalarials for efficient treatment and prolonging the life span of the current effective antimalarial drugs.