{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T08:51:43Z","timestamp":1778316703252,"version":"3.51.4"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>\n              <jats:italic>Plasmodium vivax<\/jats:italic> is the most prevalent malaria species in Pakistan, with a distribution that coincides with <jats:italic>Plasmodium falciparum<\/jats:italic> in many parts of the country. Both species are likely exposed to drug pressure from a number of anti-malarials including chloroquine, sulphadoxine-pyrimethamine (SP), and artemisinin combination therapy, yet little is known regarding the effects of drug pressure on parasite genes associated with drug resistance. The aims of this study were to determine the prevalence of polymorphisms in the SP resistance-associated genes <jats:italic>pvdhfr<\/jats:italic>, <jats:italic>pvdhps<\/jats:italic> and chloroquine resistance-associated gene <jats:italic>pvmdr1<\/jats:italic> in <jats:italic>P. vivax<\/jats:italic> isolates collected from across the country.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In 2011, 801 microscopically confirmed malaria-parasite positive filter paper blood samples were collected at 14 sites representing four provinces and the capital city of Islamabad. Species-specific polymerase chain reaction (PCR) was used to identify human <jats:italic>Plasmodium<\/jats:italic> species infection. PCR-positive <jats:italic>P. vivax<\/jats:italic> isolates were subjected to sequencing of <jats:italic>pvdhfr<\/jats:italic>, <jats:italic>pvdhps<\/jats:italic> and <jats:italic>pvmdr1<\/jats:italic> and to real-time PCR analysis to assess <jats:italic>pvmdr1<\/jats:italic> copy number variation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Of the 801 samples, 536 were determined to be <jats:italic>P. vivax<\/jats:italic>, 128 were <jats:italic>P. falciparum<\/jats:italic>, 43 were mixed <jats:italic>vivax<\/jats:italic>\/<jats:italic>falciparum<\/jats:italic> infections and 94 were PCR-negative for <jats:italic>Plasmodium<\/jats:italic> infection. Of PCR-positive <jats:italic>P. vivax<\/jats:italic> samples, 372 were selected for sequence analysis. Seventy-six of the isolates (23%) were double mutant at positions S58R and S117N in <jats:italic>pvdhfr<\/jats:italic>. Additionally, two mutations at positions N50I and S93H were observed in 55 (15%) and 24 (7%) of samples, respectively. Three 18 base pair insertion-deletions (indels) were observed in <jats:italic>pvdhfr<\/jats:italic>, with two insertions at different nucleotide positions in 36 isolates and deletions in 10. Ninety-two percent of samples contained the <jats:italic>pvdhps<\/jats:italic> (S382\/A383G\/K512\/A553\/V585) SAKAV wild type haplotype. For <jats:italic>pvmdr1<\/jats:italic>, all isolates were wild type at position Y976F and 335 (98%) carried the mutation at codon F1076L. All isolates harboured single copies of the <jats:italic>pvmdr1<\/jats:italic> gene.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The prevalence of mutations associated with SP resistance in <jats:italic>P. vivax<\/jats:italic> is low in Pakistan. The high prevalence of <jats:italic>P. vivax<\/jats:italic> mutant <jats:italic>pvmdr1<\/jats:italic> codon F1076L indicates that efficacy of chloroquine plus primaquine could be in danger of being compromised, but further studies are required to assess the clinical relevance of this observation. These findings will serve as a baseline for further monitoring of drug-resistant <jats:italic>P. vivax<\/jats:italic> malaria in Pakistan.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1475-2875-12-310","type":"journal-article","created":{"date-parts":[[2013,9,5]],"date-time":"2013-09-05T08:16:13Z","timestamp":1378368973000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Prevalence and patterns of antifolate and chloroquine drug resistance markers in Plasmodium vivax across Pakistan"],"prefix":"10.1186","volume":"12","author":[{"given":"Aamer A","family":"Khattak","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meera","family":"Venkatesan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lubna","family":"Khatoon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amed","family":"Ouattara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo J","family":"Kenefic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad F","family":"Nadeem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farida","family":"Nighat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salman A","family":"Malik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher V","family":"Plowe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,9,5]]},"reference":[{"key":"2918_CR1","volume-title":"World malaria report 2012","author":"WHO","year":"2013","unstructured":"WHO: World malaria report 2012. 2013, Geneva: World Health Organization"},{"key":"2918_CR2","volume-title":"Malaria No More","author":"D MC","year":"2013","unstructured":"D MC: Malaria No More. 2013, Islamabad: Directorate of Malaria Control, Ministry of National Health Services"},{"key":"2918_CR3","doi-asserted-by":"crossref","first-page":"525","DOI":"10.4269\/ajtmh.2009.81.525","volume":"81","author":"L Khatoon","year":"2009","unstructured":"Khatoon L, Baliraine FN, Bonizzoni M, Malik SA, Yan G: Prevalence of antimalarial drug resistance mutations in Plasmodium vivax and P. falciparum from a malaria-endemic area of Pakistan. 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