The Artesunate-Amodiaquine / Artemether Lumefantrine (AS-AQ/AL) Molecular Marker Study Group demonstrated that if patients are infected with malaria parasites that carry particular mutations in genes pfcrt and pfmdr1, they are at higher risk of treatment failure after artemether-lumefantrine (AL). The group showed that artesunate-amodiaquine (ASAQ) and AL exerted opposing selective effects on mutations known as, single-nucleotide polymorphisms, in pfcrt and pfmdr1.
The Study Group recommends that prevalence of molecular markers, at least pfcrt K76T and pfmdr1 N86Y, should be determined routinely to track any changes in their prevalence, as an indicator of changes in efficacy of the lumefantrine and amodiaquine partners of the artemisinin combination therapies, artemether-lumefantrine and artesunate-amodiaquine.
The study: Polymorphisms in Plasmodium falciparum Chloroquine Resistance Transporter and Multidrug Resistance 1 Genes: Parasite Risk Factors that Affect Treatment Outcomes for P. falciparum Malaria after Artemether-Lumefantrine and Artesunate-Amodiaquine was published in the American Journal of Tropical Medicine and Hygiene in October 2014. Since publication a correction is under review for this paper. Details of changes are available in a revised manuscript.
The Study Group pooled individual patient and linked parasite genotype data from 31 studies. Data from 7,249 patients who were treated with AL (5,003) or ASAQ (2,246) were included in the analysis. 27 studies were published, representing 91% of all published clinical data on AL and ASAQ in which pfcrt or pfmdr1 genotypes were determined.
The Study Group formed in October 2011, with an open invitation to potential participants. Known research groups with relevant data sets were contacted in October-November 2011. Potential participants met at the ASTMH Annual Meeting in December 2011 to discuss governance and publication policy. The Study Group closed in April 2012, the analyses were completed in 2013.