Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia

Abstract

Background Artemisinin-based combination therapy (ACT) is recommended at the initial phase for treatment of Plasmodium falciparum, to reduce morbidity and mortality in all countries where malaria is endemic. Polymorphism in portions of P. falciparum gene encoding kelch (K13)-propeller domains is associated with delayed parasite clearance after ACT. Of about 124 different non-synonymous mutations, 46 have been identified in Southeast Asia (SEA), 62 in sub-Saharan Africa (SSA) and 16 in both the regions. This is the first study designed to analyse the prevalence of polymorphism in the P. falciparum k13-propeller domain in the Jazan region of southwest Saudi Arabia, where malaria is endemic. Methods One-hundred and forty P. falciparum samples were collected from Jazan region of southwest Saudi Arabia at three different times: 20 samples in 2011, 40 samples in 2016 and 80 samples in 2020 after the implementation of ACT. Plasmodium falciparum kelch13 (k13) gene DNA was extracted, amplified, sequenced, and analysed using a basic local alignment search tool (BLAST). Results This study obtained 51 non-synonymous (NS) mutations in three time groups, divided as follows: 6 single nucleotide polymorphisms (SNPs) ‘11.8%’ in samples collected in 2011 only, 3 (5.9%) in 2011and 2016, 5 (9.8%) in 2011 and 2020, 5 (9.8%) in 2016 only, 8 (15.7%) in 2016 and 2020, 14 (27.5%) in 2020 and 10 (19.6%) in all the groups. The BLAST revealed that the 2011 isolates were genetically closer to African isolates (53.3%) than Asian ones (46.7%). Interestingly, this proportion changed completely in 2020, to become closer to Asian isolates (81.6%) than to African ones (18.4%). Conclusions Despite the diversity of the identified mutations in the k13-propeller gene, these data did not report widespread artemisinin-resistant polymorphisms in the Jazan region where these samples were collected. Such a process would be expected to increase frequencies of mutations associated with the resistance of ACT.

Kelch 13 gene polymorphisms of Plasmodium falciparum among human population in Nasarawa-West Senatorial District, Nasarawa State, Nigeria

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The Laboratory Diagnosis of Malaria: A Focus on the Diagnostic Assays in Non-Endemic Areas

“…Small subunit ribosomal RNA (ssRNA) genes are the most used targets of primers used in most of the nested-PCR based assays as such genes are widely used for phylogenetic analysis and are also well characterized from various Plasmodium sp. [14]; for the same reasons the highly conserved dpfk13, encoding the Kelch13 protein are also used as target [79]. When morphological problems hinder the identification of malaria parasites at the species level at microscopy nested-and multiplex-PCR results can give an accurate identification [80].…”

Current Epidemiological Characteristics of Imported Malaria, Vector Control Status and Malaria Elimination Prospects in the Gulf Cooperation Council (GCC) Countries

“…Soliman et al [ 51 ] and Dafalla et al [ 62 ] investigated the presence of different gene mutations concerning antimalarial drug resistance (pfdhfr, pfdhps, pfmdr1, pfcrt, pfcytb, pfkelch13) to identify whether drug-resistant alleles are present in Saudi Arabia. Among 26 positive cases, 13 were infected with P. falciparum (including 4 cases due to indigenous transmission) and 13 with P. vivax .…”

“…No mutation in genes related to resistance to artemisinin or atovaquone was detected. The chloroquine resistance alleles were detected in 31% of samples and point mutations in the pfdhfr and pfdhps genes involved in antifolate drug resistance were also detected [ 62 ]. Although several mutations in the k13-propeller gene were detected, no widespread artemisinin-resistant polymorphisms were reported.…”