{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:54:26Z","timestamp":1770512066066,"version":"3.49.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"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":[[2013,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Plasmodium falciparum<\/jats:named-content>\n            mutations associated with antimalarial resistance may be beneficial for parasites under drug pressure, although they may also cause a fitness cost. We herein present an\n            <jats:italic>in vitro<\/jats:italic>\n            model showing how this combined effect on parasite growth varies with the drug concentration and suggest a calculated drug-specific cost-benefit index, indicating the possible advantage for mutated parasites. We specifically studied the D-to-Y change at position 1246 encoded by the\n            <jats:italic>pfmdr1<\/jats:italic>\n            gene (\n            <jats:italic>pfmdr1<\/jats:italic>\n            D1246Y) in relation to amodiaquine resistance. Susceptibilities to amodiaquine, desethylamodiaquine, and chloroquine, as well as relative fitness, were determined for two modified isogenic\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">P. falciparum<\/jats:named-content>\n            clones differing only in the\n            <jats:italic>pfmdr1<\/jats:italic>\n            1246 position. Data were used to create a new comparative graph of relative growth in relation to the drug concentration and to calculate the ratio between the benefit of resistance and the fitness cost. Results were related to an\n            <jats:italic>in vivo<\/jats:italic>\n            allele selection analysis after amodiaquine or artesunate-amodiaquine treatment.\n            <jats:italic>pfmdr1<\/jats:italic>\n            1246Y was associated with decreased susceptibility to amodiaquine and desethylamodiaquine but at a growth fitness cost of 11%. Mutated parasites grew less in low drug concentrations due to a predominating fitness cost, but beyond a breakpoint concentration they grew more due to a predominating benefit of increased resistance. The cost-benefit indexes indicated that\n            <jats:italic>pfmdr1<\/jats:italic>\n            1246Y was most advantageous for amodiaquine-exposed parasites.\n            <jats:italic>In vivo<\/jats:italic>\n            , a first drug selection of mutant parasites followed by a fitness selection of wild-type parasites supported the\n            <jats:italic>in vitro<\/jats:italic>\n            data. This cost-benefit model may predict the risk for selection of drug resistance mutations in different malaria transmission settings.\n          <\/jats:p>","DOI":"10.1128\/aac.00950-12","type":"journal-article","created":{"date-parts":[[2012,12,4]],"date-time":"2012-12-04T14:01:14Z","timestamp":1354629674000},"page":"887-892","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Assessing the Cost-Benefit Effect of a Plasmodium falciparum Drug Resistance Mutation on Parasite Growth\n            <i>In Vitro<\/i>"],"prefix":"10.1128","volume":"57","author":[{"given":"Gabrielle","family":"Fr\u00f6berg","sequence":"first","affiliation":[{"name":"Malaria Research Group, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"}]},{"given":"Pedro Eduardo","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Malaria Research Group, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"},{"name":"Drug Resistance and Pharmacogenetics Group, Institute of Biotechnology and Bioengineering, Centre of Molecular and Structural Biomedicine, University of Algarve, Faro, Portugal"}]},{"given":"Andreas","family":"M\u00e5rtensson","sequence":"additional","affiliation":[{"name":"Malaria Research Group, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"},{"name":"Division of Global Health (IHCAR), Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden"}]},{"given":"Abdullah","family":"Ali","sequence":"additional","affiliation":[{"name":"Zanzibar Malaria Control Programme (ZMCP), Zanzibar, Tanzania"}]},{"given":"Anders","family":"Bj\u00f6rkman","sequence":"additional","affiliation":[{"name":"Malaria Research Group, Department of Medicine, Karolinska Institutet, Stockholm, Sweden"}]},{"given":"Jos\u00e9 Pedro","family":"Gil","sequence":"additional","affiliation":[{"name":"Drug Resistance and Pharmacogenetics Group, Institute of Biotechnology and Bioengineering, Centre of Molecular and Structural Biomedicine, University of Algarve, Faro, Portugal"},{"name":"Laboratory of Molecular Anthropology and Health, Department of Anthropology, Binghamton University, Binghamton, New York, USA"},{"name":"Drug Resistance Unit, Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Guidelines for the treatment of malaria.","author":"WHO","year":"2006","unstructured":"WHO. 2006. 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