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Artesunate plus sulfadoxine\u2013pyrimethamine (AS\u2009+\u2009SP) has been used in Saudi Arabia since 2007 as a first-line treatment for uncomplicated <jats:italic>Plasmodium falciparum<\/jats:italic> malaria. This study aimed to investigate the prevalence of mutations associated with resistance to artemisinin and sulfadoxine\u2013pyrimethamine (SP) resistance in <jats:italic>P. falciparum<\/jats:italic> parasites circulating in Jazan region, southwestern Saudi Arabia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A total of 151 <jats:italic>P. falciparum<\/jats:italic> isolates were collected between April 2018 and March 2019 from 12 of the governorates in Jazan region. Genomic DNA was extracted from dried blood spots and amplified using nested PCR. Polymorphisms in the propeller domain of the <jats:italic>P. falciparum<\/jats:italic> k13 (<jats:italic>pfkelch13<\/jats:italic>) gene and point mutations in the <jats:italic>P. falciparum<\/jats:italic> dihydrofolate reductase (<jats:italic>pfdhfr<\/jats:italic>) and dihydropteroate synthase (<jats:italic>pfdhps<\/jats:italic>) genes were identified by sequencing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>No mutations in the <jats:italic>pfkelch13<\/jats:italic> propeller domain were found in any of the 151 isolates. However, point mutations in the <jats:italic>pfdhfr<\/jats:italic> and <jats:italic>pfdhps<\/jats:italic> genes were detected in 90.7% (137\/151) of the isolates. The <jats:italic>pfdhfr<\/jats:italic> double mutations N51<jats:bold><jats:underline>I<\/jats:underline><\/jats:bold>\u2009+\u2009S108<jats:bold><jats:underline>N<\/jats:underline><\/jats:bold> (i.e. AC<jats:bold><jats:underline>I<\/jats:underline><\/jats:bold>C<jats:bold><jats:underline>N<\/jats:underline><\/jats:bold>I haplotype) and triple mutations N51<jats:bold><jats:underline>I<\/jats:underline><\/jats:bold>\u2009+\u2009C59<jats:bold><jats:underline>R<\/jats:underline><\/jats:bold>\u2009+\u2009S108<jats:bold><jats:underline>N<\/jats:underline><\/jats:bold> (i.e. AC<jats:bold><jats:underline>IRN<\/jats:underline><\/jats:bold>I haplotype) were detected in 47% and 37.8% of the isolates, respectively. Moreover, the <jats:italic>pfdhps<\/jats:italic> single mutation at codon A437<jats:bold>G<\/jats:bold> and double mutations A437<jats:bold><jats:underline>G<\/jats:underline><\/jats:bold>\u2009+\u2009K540<jats:bold><jats:underline>E<\/jats:underline><\/jats:bold> (i.e. S<jats:bold><jats:underline>GE<\/jats:underline><\/jats:bold>AAI haplotype) were observed in 4.6% and 51.7% of the isolates, respectively. Interestingly, 23.8%, 25.1 and 12.6% of the isolates had quintuple, quadruple and triple mutated combined <jats:italic>pfdhfr<\/jats:italic>\u2013<jats:italic>pfdhps<\/jats:italic> genotypes, respectively. Furthermore, significant associations were found between the prevalence of mutant haplotypes and the age, gender and nationality of the patients (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This study revealed a high prevalence of point mutations in the <jats:italic>pfdhfr<\/jats:italic> and <jats:italic>pfdhps<\/jats:italic> genes of <jats:italic>P. falciparum<\/jats:italic> isolates from Jazan region, with quintuple and quadruple mutant <jats:italic>pfdhfr<\/jats:italic>\u2013<jats:italic>pfdhps<\/jats:italic> genotypes reported for the first time in Saudi Arabia and the Arabian Peninsula. Despite the absence of the <jats:italic>pfkelch13<\/jats:italic> mutation in the isolates examined, the <jats:italic>pfdhfr<\/jats:italic> and <jats:italic>pfdhps<\/jats:italic> mutations undermine the efficacy of SP partner drug, thereby threatening the main falciparum malaria treatment policy in Saudi Arabia, i.e. the use of AS\u2009+\u2009SP. Therefore, the continuous molecular and in-vivo monitoring of ACT efficacy in Jazan region is highly recommended.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12936-020-03524-x","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T12:03:16Z","timestamp":1606910596000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Increased prevalence of pfdhfr and pfdhps mutations associated with sulfadoxine\u2013pyrimethamine resistance in Plasmodium falciparum isolates from Jazan Region, Southwestern Saudi Arabia: important implications for malaria treatment policy"],"prefix":"10.1186","volume":"19","author":[{"given":"Aymen M.","family":"Madkhali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2582-7410","authenticated-orcid":false,"given":"Hesham M.","family":"Al-Mekhlafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wahib M.","family":"Atroosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Hassn","family":"Ghzwani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid Ammash","family":"Zain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Abdulhaq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid Y.","family":"Ghailan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alkhansa A.","family":"Anwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaki M.","family":"Eisa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,2]]},"reference":[{"key":"3524_CR1","unstructured":"WHO. 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No. REC39\/6-261). The study was also approved by the Health Affairs Directorate of King Fahd Central Hospital, Jazan, Saudi Arabia (Registry No. 086). Written and signed informed consents were obtained from the adult patients or from the parents or guardians on behalf of their children prior to collecting blood samples. The patients were informed about the objective of the study. The voluntary participation was ensured, and patients were informed that they can refuse to take part in the study without any effect on the quality of health care provided to them.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"446"}}