Malaria J
-
Resistance to all available anti-malarial drugs has emerged and spread including artemisinin derivatives and their partner drugs. Several genes involved in artemisinin and partner drugs resistance, such as pfcrt, pfmdr1, pfK13 or pfpm2, have been identified. However, these genes do not properly explain anti-malarial drug resistance, and more particularly clinical failures observed in Africa. Mutations in genes encoding for Plasmodium falciparum proteins, such as P. falciparum Acetyl-CoA transporter (PfACT), P. falciparum UDP-galactose transporter (PfUGT) and P. falciparum cyclic amine resistance locus (PfCARL) have recently been associated to resistance to imidazolopiperazines and other unrelated drugs. ⋯ No evidence was found of involvement of these genes in reduced susceptibility to standard anti-malarial drugs in African P. falciparum isolates.
-
Mutations in the propeller domain of Plasmodium falciparum kelch 13 (Pfk13) gene are associated with artemisinin resistance in Southeast Asia. Artemisinin resistance is defined by increased ring survival rate and delayed parasite clearance half-life in patients. Additionally, an amplification of the Plasmodium falciparum plasmepsin II gene (pfpm2), encoding a protease involved in hemoglobin degradation, has been found to be associated with reduced in vitro susceptibility to piperaquine in Cambodian P. falciparum parasites and with dihydroartemisinin-piperaquine failures in Cambodia. ⋯ It is imperative to identify molecular markers or drug resistance genes that associate with artemisinin and piperaquine in Africa. K13 polymorphisms and Pfpm2 copy number variation analysis may not be sufficient for monitoring the emergence of dihydroartemisinin-piperaquine resistance in Africa. But, these markers should not be ruled out for tracking the emergence of resistance.