{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:56:22Z","timestamp":1789710982897,"version":"4.0.1"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In combination with antibiotics, quinine is recommended as the second-line treatment for uncomplicated malaria, an alternative first-line treatment for severe malaria, and for treatment of malaria in the first trimester of pregnancy. Quinine has been shown to have frequent clinical failures, and yet the mechanisms of action and resistance have not been fully elucidated. However, resistance is linked to polymorphisms in multiple genes, including multidrug resistance 1 (Pf\n            <jats:italic>mdr1<\/jats:italic>\n            ), the chloroquine resistance transporter (Pf\n            <jats:italic>crt<\/jats:italic>\n            ), and the sodium\/hydrogen exchanger gene (Pf\n            <jats:italic>nhe1<\/jats:italic>\n            ). Here, we investigated the association between\n            <jats:italic>in vitro<\/jats:italic>\n            quinine susceptibility and genetic polymorphisms in Pf\n            <jats:italic>mdr1<\/jats:italic>\n            codons 86 and 184, Pf\n            <jats:italic>crt<\/jats:italic>\n            codon 76, and Pf\n            <jats:italic>nhe1<\/jats:italic>\n            ms4760 in 88 field isolates from western Kenya.\n            <jats:italic>In vitro<\/jats:italic>\n            activity was assessed based on the drug concentration that inhibited 50% of parasite growth (the IC\n            <jats:sub>50<\/jats:sub>\n            ), and parasite genetic polymorphisms were determined from DNA sequencing. Data revealed there were significant associations between polymorphism in Pf\n            <jats:italic>mdr1<\/jats:italic>\n            -86Y, Pf\n            <jats:italic>mdr1<\/jats:italic>\n            -184F, or Pf\n            <jats:italic>crt<\/jats:italic>\n            -76T and quinine susceptibility (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001 for all three associations). Eighty-two percent of parasites resistant to quinine carried mutant alleles at these codons (Pf\n            <jats:italic>mdr1<\/jats:italic>\n            -86Y, Pf\n            <jats:italic>mdr1<\/jats:italic>\n            -184F, and Pf\n            <jats:italic>crt<\/jats:italic>\n            -76T), whereas 74% of parasites susceptible to quinine carried the wild-type allele (Pf\n            <jats:italic>mdr1<\/jats:italic>\n            -N86, Pf\n            <jats:italic>mdr1<\/jats:italic>\n            -Y184, and Pf\n            <jats:italic>crt<\/jats:italic>\n            -K76, respectively). In addition, quinine IC\n            <jats:sub>50<\/jats:sub>\n            values for parasites with Pf\n            <jats:italic>nhe1<\/jats:italic>\n            ms4760 3 DNNND repeats were significantly higher than for those with 1 or 2 repeats (\n            <jats:italic>P<\/jats:italic>\n            = 0.033 and\n            <jats:italic>P<\/jats:italic>\n            = 0.0043, respectively). Clinical efficacy studies are now required to confirm the validity of these markers and the importance of parasite genetic background.\n          <\/jats:p>","DOI":"10.1128\/aac.02472-14","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T03:52:32Z","timestamp":1398138752000},"page":"3737-3743","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Polymorphisms in Pf\n            <i>mdr1<\/i>\n            , Pf\n            <i>crt<\/i>\n            , and Pf\n            <i>nhe1<\/i>\n            Genes Are Associated with Reduced\n            <i>In Vitro<\/i>\n            Activities of Quinine in Plasmodium falciparum Isolates from Western Kenya"],"prefix":"10.1128","volume":"58","author":[{"given":"Jelagat","family":"Cheruiyot","sequence":"first","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"},{"name":"School of Biological\/Physical Sciences, Department of Zoology, Maseno University, Maseno, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luicer A.","family":"Ingasia","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela A.","family":"Omondi","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"},{"name":"School of Biological\/Physical Sciences, Department of Zoology, Maseno University, Maseno, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis W.","family":"Juma","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin H.","family":"Opot","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Ndegwa","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"},{"name":"School of Biological\/Physical Sciences, Department of Zoology, Maseno University, Maseno, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Mativo","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes C.","family":"Cheruiyot","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"},{"name":"School of Biological\/Physical Sciences, Department of Zoology, Maseno University, Maseno, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Redemptah","family":"Yeda","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Okudo","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peninah","family":"Muiruri","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngalah S.","family":"Bidii","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna J.","family":"Chebon","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul O.","family":"Angienda","sequence":"additional","affiliation":[{"name":"School of Biological\/Physical Sciences, Department of Zoology, Maseno University, Maseno, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrick L.","family":"Eyase","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob D.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wallace D.","family":"Bulimo","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Andagalu","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoseah M.","family":"Akala","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Kamau","sequence":"additional","affiliation":[{"name":"Global Emerging Infections Surveillance Program, United States Army Medical Research Unit\u2014Kenya, Kenya Medical Research Institute\u2014Walter Reed Project, Kisumu and Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Global antimalarial drug policies database\u2014WHO African region, September ed","author":"World Health Organization","year":"2009","unstructured":"World Health Organization. 2009. 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