Thailand population

New pfk13 polymorphisms in the population of Plasmodium falciparum in Ghana

Malaria remains a challenge in Africa, where an estimated 94% of global malaria-related morbidity and mortality occurs1. The most virulent malaria parasite, Plasmodium falciparum is resistant to most antimalarials. In order to slow the development of parasite resistance, the use of artemisinin-based combination therapy (ACT) has been introduced in malaria-endemic countries by the World Health Organization (WHO).2. However, the report on decreasing effectiveness of artemisinin (ART) in South East Asia (SEA)3.4 is a huge obstacle to disease control efforts. The discovery of mutations in the P. falciparum kelch helix domain on chromosome 13 (pfk13) as markers has contributed enormously to molecular surveillance in malaria-endemic countries4. the pfk13 validated markers include F446I, N458Y, M476I, Y493H, R539T, I543T, P553L, R561H, P574L and C580Y1,5,6. The other markers not yet validated are P441L, G449A, C469F/Y, A481V, R515K, P527H, N537I/D, G538V, V568G, R622I and A675V1. The list of validated pfk13 resistant SNPs are increasing and updates are made by WHO over time.

In Africa, molecular surveillance studies have reported multiple SNPs including M472I, Y558C, K563R, P570L, P615S in Niger7R622I in Ethiopia8C473F in Senegal9F434S, F442F, I684N in Nigeriaten and M472I, A569T in the Democratic Republic of Congo11. These observed SNPs, although have not yet been functionally characterized to determine their role in ART resistance. However, these need to be documented due to the possibility that they could be selected with increasing drug pressure and become the markers of ART resistance in Africa. This scenario is possible due to the reported local emergence of pfk13 mutations in the Amazon12.13.

Pfk13 SNPs reported by other endemic countries, including some of the validated SNPs and their variants that have been observed in Ghanaian malaria parasites from the same samples, have already been published.14. In this report, we document all new SNPs that have been observed only in the Ghanaian parasite population, as they may be of interest in the future. These SNPs have not been reported in any country, as revealed by searches of published PUBMED articles up to the date of submission of this article.