{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T06:28:39Z","timestamp":1747204119194,"version":"3.40.5"},"posted":{"date-parts":[[2020,3,6]]},"group-title":"In Review","reference-count":0,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T00:00:00Z","timestamp":1583452800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2020,3,2]]},"abstract":"<title>Abstract<\/title>\n        <p><bold>Background: <\/bold>The spread of artemisinin resistance in the Greater Mekong Subregion of Southeast Asia poses a significant threat for current anti-malarial treatment guidelines globally. The aim of this study was to assess the current prevalence of molecular markers of drug resistance in<italic> Plasmodium falciparum<\/italic> in the four provinces with the highest malaria burden in Pakistan, after introducing artemether-lumefantrine as first line treatment in 2017.<bold>Methods:<\/bold> Samples were collected during routine malaria surveillance in Punjab, Sindh, Baluchistan, and Khyber Pakhtunkhwa provinces of Pakistan between January 2018 and February 2019. <italic>P. falciparum <\/italic>infections were confirmed by rapid diagnostic test or microscopy. <italic>P. falciparum <\/italic>positive isolates (n = 179) were screened by Sanger sequencing for single nucleotide polymorphisms (SNPs) in the <italic>P. falciparum<\/italic> <italic>kelch<\/italic> <italic>13 <\/italic>(<italic>pfk13)<\/italic> propeller domain and in<italic> P. falciparum<\/italic> <italic>coronin<\/italic> (<italic>pfcoronin<\/italic>). SNPs in <italic>P. falciparum multidrug resistance 1 (pfmdr1) <\/italic>N86Y, Y184F, D1246Y and <italic>P. falciparum chloroquine resistance transporter<\/italic> (<italic>pfcrt) <\/italic>K76T were genotyped by PCR-restriction fragment length polymorphism. <bold>Results:<\/bold> No artemisinin resistance associated SNPs were identified in the <italic>pfk13 <\/italic>propeller domain or in <italic>pfcoronin<\/italic>. The <italic>pfmdr1 <\/italic>N86, 184F, D1246 and <italic>pfcrt <\/italic>K76 alleles associated with reduced lumefantrine sensitivity were present in 83.8% (150\/179), 16.9% (29\/172), 100.0% (173\/173), and 8.4% (15\/179) of all infections, respectively. The chloroquine resistance associated <italic>pfcrt <\/italic>76T allele was present in 98.3% (176\/179) of infections.<bold>Conclusion:<\/bold> This study provides an update on the current prevalence of molecular markers associated with reduced sensitivity to artemether and\/or lumefantrine in <italic>P. falciparum<\/italic>, including a first baseline assessment of polymorphisms in <italic>pfcoronin<\/italic>. No mutations associated with artemisinin resistance were observed in <italic>pfk13<\/italic> or <italic>pfcoronin<\/italic>. However, the prevalence of the <italic>pfmdr1<\/italic> N86 and D1246 alleles, that have been associated with decreased susceptibility to lumefantrine, remain high. Although clinical and molecular data suggest that the current malaria treatment guideline for <italic>P. falciparum<\/italic> are presently effective in Pakistan, close monitoring for artemisinin and lumefantrine resistance will be critical to ensure early detection and enhanced containment of emerging<italic> <\/italic>ACT resistance spreading across from Southeast Asia.<\/p>","DOI":"10.21203\/rs.3.rs-16248\/v1","type":"posted-content","created":{"date-parts":[[2020,3,6]],"date-time":"2020-03-06T16:06:32Z","timestamp":1583510792000},"source":"Crossref","is-referenced-by-count":0,"title":["Surveillance of genetic markers associated with Plasmodium falciparum resistance to artemisinin-based combination therapy in Pakistan, 2018-2019"],"prefix":"10.21203","author":[{"given":"Abdul Qader","family":"Khan","sequence":"first","affiliation":[{"name":"Kohat University of Science and Technology"}]},{"given":"Leyre","family":"Pernaute-Lau","sequence":"additional","affiliation":[{"name":"Karolinska Institutet"}]},{"given":"Aamer Ali","family":"Khattak","sequence":"additional","affiliation":[{"name":"University of Haripur"}]},{"given":"Sanna","family":"Luijcx","sequence":"additional","affiliation":[{"name":"Karolinska Institutet"}]},{"given":"Berit","family":"Aydin-Schmidt","sequence":"additional","affiliation":[{"name":"Karolinska Institutet"}]},{"given":"Mubashir","family":"Hussain","sequence":"additional","affiliation":[{"name":"Kohat University of Science and Technology"}]},{"given":"Taj Ali","family":"Khan","sequence":"additional","affiliation":[{"name":"Kohat University of Science and Technology"}]},{"given":"Farees Uddin","family":"Mufti","sequence":"additional","affiliation":[{"name":"Quaid-i-Azam University"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4734-5754","authenticated-orcid":false,"given":"Ulrika","family":"Morris","sequence":"additional","affiliation":[]}],"member":"297","container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-16248\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-16248\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T19:50:29Z","timestamp":1659037829000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-16248\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,6]]},"references-count":0,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-16248\/v1","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1186\/s12936-020-03276-8","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2020,3,6]]},"subtype":"preprint"}}