Protecting the malaria drug arsenal: halting the rise and spread of amodiaquine resistance by monitoring the PfCRT SVMNT type

Juliana M Sa,Olivia Twu

doi:10.1186/1475-2875-9-374

Juliana M Sa, Olivia Twu

Open Access

https://doi.org/10.1186/1475-2875-9-374

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Abstract

The loss of chloroquine due to selection and spread of drug resistant Plasmodium falciparum parasites has greatly impacted malaria control, especially in highly endemic areas of Africa. Since chloroquine removal a decade ago, the guidelines to treat falciparum malaria suggest combination therapies, preferentially with an artemisinin derivative. One of the recommended partner drugs is amodiaquine, a pro-drug that relies on its active metabolite monodesethylamodiaquine, and is still effective in areas of Africa, but not in regions of South America. Genetic studies on P. falciparum parasites have shown that different pfcrt mutant haplotypes are linked to distinct levels of chloroquine and amodiaquine responses. The pfcrt haplotype SVMNT (termed after the amino acids from codon positions 72-76) is stably present in several areas where amodiaquine was introduced and widely used. Parasites with this haplotype are highly resistant to monodesethylamodiaquine and also resistant to chloroquine. The presence of this haplotype in Africa was found for the first time in 2004 in Tanzania and a role for amodiaquine in the selection of this haplotype was suggested. This commentary discusses the finding of a second site in Africa with high incidence of this haplotype. The >50% SVMNT haplotype prevalence in Angola represents a threat to the rise and spread of amodiaquine resistance. It is paramount to monitor pfcrt haplotypes in every country currently using amodiaquine and to re-evaluate current combination therapies in areas where SVMNT type parasites are prevalent.

Highlights

The article “Plasmodium falciparum isolates from Angola show the StctVMNT haplotype in the pfcrt gene” by Gama BE et al [1] provides results that are more worrisome than surprising
Gama et al examined the prevalence of different haplotypes of the Plasmodium falciparum chloroquine (CQ) resistance transporter gene pfcrt, and the multiple drug resistance transporter pfmdr1, from patients in Angola with uncomplicated malaria in 2007
The article reports on the “unexpected” prevalence (> 50%) of a CQ-resistant pfcrt haplotype often found in other countries including Brazil, India, Papua New Guinea, and the Philippines

Summary

Background

The article “Plasmodium falciparum isolates from Angola show the StctVMNT haplotype in the pfcrt gene” by Gama BE et al [1] provides results that are more worrisome than surprising. Gama et al examined the prevalence of different haplotypes of the Plasmodium falciparum chloroquine (CQ) resistance transporter gene pfcrt, and the multiple drug resistance transporter pfmdr, from patients in Angola with uncomplicated malaria in 2007. Since the characterization of pfcrt as the main genetic determinant of CQ resistance [4] and the removal of CQ from WHO antimalarial guidelines in 2000, this is the second report of this haplotype in Africa. Follow up from Tanzania, in which no SVMNT haplotype was found in 2006 and 2007 after removal of AQ [6] It is not clear whether differential patterns of parasite transmission levels in distinct geographic locations or drug policy changes may account for this “patchy” distribution of SVMNT type parasites. The appearance and spread of the SVMNT haplotype in Africa, where AQ has been widely used in the past decade in combination therapies should be more expected than surprising

Discussion

Conclusions