Molecular monitoring of Plasmodium falciparum resistance to artemisinin in Tanzania

Abstract

Artemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria, such as sub-Saharan Africa. However, their longterm usefulness in these high transmission areas remains unclear. It has been suggested that documentation of the S769N PfATPase6 mutations may indicate an emergence of artemisinin resistance of Plasmodium falciparum in the field. The present study assessed PfATPase6 mutations (S769N and A623E) in 615 asymptomatic P. falciparum infections in Tanzania but no mutant genotype was detected. This observation suggests that resistance to artemisinin has not yet been selected in Tanzania, supporting the Ministry of Health's decision to adopt artemether+lumefantrine as first-line malaria treatment. The findings recommend further studies to assess PfATPase6 mutations in sentinel sites and verify their usefulness in monitoring emergency of ACT resistance.

Emerging artemisinin resistance in the border areas of Thailand

“…Resistance to ACTs may evolve even when the two drugs within the combination are taken simultaneously, and amplification of the PfMDR1 gene may partly contribute to this phenotype. Multiple new single nucleotide polymorphisms have also been detected in PfATP6 (S769N, L263E, E431K, A623E, H243Y and I89T), but their associations with artemisinin resistance have not been well established [33,35, [106][107][108][109][110][111][112][113][114][115][116]. It is therefore concluded that polymorphisms of PfMDR1 and PfATP6 may not constitute a major determinant of delayed parasite clearance, as supported by recent genotyping of PfMDR1, PfATP6 and PcUBP1 (a gene associated with resistance from artemisinin selection studies in P. chabaudi), which revealed no association between these genes and P. falciparum clearance rates in patients from western Cambodia and northwestern Thailand [113,117,118].…”

DNA Microarrays for Pathogen Detection

“…They also described the assay as suitable to cope with the problem of multiplicity of infections and the determination of the most dominant haplotype representing the clinical malaria-causing clone. While the present study only worked with cultured organisms, the authors and collaborators conducted further successful field studies on the basis of the microarray system using patient samples in Tanzania [176], Niger [177], Papua New Guinea [178], and the Solomon Islands [179]. In an interesting study, the group around Hans-Peter Beck used the same technological approach to genotype polymorphisms, that is, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, and NAT2, which are known to have an impact on human malarial drug metabolisms [180].…”

A golden phoenix arising from the herbal nest — A review and reflection on the study of antimalarial drug Qinghaosu

“…Since artemisinins (mainly monotherapy) were widely used in China and South-East Asia, continuous in vitro and in vivo surveillances have been made, especially in the area where resistance developed seriously in the history, such as Hainan and Yunnan provinces in China and the Thai/Cambodian and Thai/Myanmar borders. According to the results of surveillances, the sensitivity of P. falciparum to artemisinins dropped somewhat in some areas, but no QHS-resistant line of P. falciparum arose [382][383][384][385][386][387][388][389][390][391][392][393][394][395][396].…”