{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:48:01Z","timestamp":1791287281499,"version":"4.1.0"},"reference-count":25,"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":[[2008,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The emergence of <jats:italic>Plasmodium falciparum<\/jats:italic> resistant to most currently used antimalarial drugs is the major problem in malaria control along the Thai-Myanmar and Thai-Cambodia borders. Although artemisinin-based combination therapy has been recommended for the treatment of multidrug-resistant falciparum malaria, these combinations are not available for some people, such as travelers from North America. A fixed-dose combination of atovaquone and proguanil (Malarone) has been proved to be effective for the treatment and prophylaxis of malaria which is already approved by countries in North America and Europe. Determination of the phenotypes and genotypes related to atovaquone\/proguanil response in Thai isolates of <jats:italic>P. falciparum<\/jats:italic> will be useful for rationale drug use. The main purpose of this study was to explore the <jats:italic>in vitro<\/jats:italic> atovaquone\/proguanil susceptibility of recently adapted Thai isolates of <jats:italic>P. falciparum<\/jats:italic>. Genotypic characterization of the <jats:italic>cytb<\/jats:italic> gene of these isolates was also determined since it has been reported that point mutations, particularly codon 268 in the cytochrome b gene (<jats:italic>cytb<\/jats:italic>) have been linked to atovaquone\/proguanil treatment failure.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Eighty three <jats:italic>P. falciparum<\/jats:italic> isolates collected during 1998 to 2005 from four different multidrug resistance areas of Thailand were determined for the <jats:italic>in vitro<\/jats:italic> atovaquone\/proguanil susceptibilities using radioisotopic assay. Mutations in the <jats:italic>cytb<\/jats:italic> gene were determined by PCR-RFLP and sequence analysis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The mean atovaquone and proguanil IC<jats:sub>50<\/jats:sub> was 3.4 nM and 36.5 \u03bcM, respectively. All 83 Thai isolates were atovaquone sensitive. None of the 83 isolates contained the mutations at codon 268 of the <jats:italic>cytb<\/jats:italic> gene. DNA sequencing of the <jats:italic>cytb<\/jats:italic> gene of 20 parasite isolates showed no other mutations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>In agreement with a recent efficacy study of atovaquone\/proguanil, the present information indicates that atovaquone\/proguanil can be one of the drugs of choice for the treatment and prophylaxis of multidrug-resistant falciparum malaria in Thailand.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1475-2875-7-23","type":"journal-article","created":{"date-parts":[[2008,1,29]],"date-time":"2008-01-29T07:15:49Z","timestamp":1201590949000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["In vitro atovaquone\/proguanil susceptibility and characterization of the cytochrome b gene of Plasmodium falciparum from different endemic regions of Thailand"],"prefix":"10.1186","volume":"7","author":[{"given":"Rommanee","family":"Khositnithikul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peerapan","family":"Tan-ariya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathirut","family":"Mungthin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2008,1,28]]},"reference":[{"key":"498_CR1","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1111\/j.1365-3156.2005.01557.x","volume":"11","author":"S Vijaykadga","year":"2006","unstructured":"Vijaykadga S, Rojanawatsirivej C, Cholpol S, Phoungmanee D, Nakavej A, Wongsrichanalai C: In vivo sensitivity monitoring of mefloquine monotherapy and artesunate-mefloquine combinations for the treatment of uncomplicated falciparum malaria in Thailand in 2003. Trop Med Int Health. 2006, 11: 211-219. 10.1111\/j.1365-3156.2005.01557.x.","journal-title":"Trop Med Int Health"},{"key":"498_CR2","first-page":"CD004529","volume":"4","author":"A Osei-Akoto","year":"2005","unstructured":"Osei-Akoto A, Orton L, Owusu-Ofori SP: Atovaquone-proguanil for treating uncomplicated malaria. Cochrane Database Syst Rev. 2005, 4: CD004529-","journal-title":"Cochrane Database Syst Rev"},{"key":"498_CR3","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1093\/jac\/dkm337","volume":"60","author":"H Nakato","year":"2007","unstructured":"Nakato H, Vivancos R, Hunter PR: A systematic review and meta-analysis of the effectiveness and safety of atovaquone proguanil (Malarone) for chemoprophylaxis against malaria. Antimicrob Chemother. 2007, 60: 929-936. 10.1093\/jac\/dkm337.","journal-title":"Antimicrob Chemother"},{"key":"498_CR4","doi-asserted-by":"publisher","first-page":"3961","DOI":"10.1074\/jbc.272.7.3961","volume":"272","author":"IK Srivastava","year":"1997","unstructured":"Srivastava IK, Rottenberg H, Vaidya AB: Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in a malarial parasite. J Biol Chem. 1997, 272: 3961-3966. 10.1074\/jbc.272.52.33360.","journal-title":"J Biol Chem"},{"key":"498_CR5","doi-asserted-by":"publisher","first-page":"17142","DOI":"10.1074\/jbc.M500388200","volume":"280","author":"JJ Kessl","year":"2005","unstructured":"Kessl JJ, Ha KH, Merritt AK, Lange BB, Hill P, Meunier B, Meshnick SR, Trumpower BL: Cytochrome b mutations that modify the ubiquinol-binding pocket of the cytochrome bc1 complex and confer anti-malarial drug resistance in Saccharomyces cerevisiae. J Biol Chem. 2005, 280: 17142-17148. 10.1074\/jbc.M500388200.","journal-title":"J Biol Chem"},{"key":"498_CR6","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1006\/expr.1994.1058","volume":"79","author":"I Ittarat","year":"1994","unstructured":"Ittarat I, Asawamahasakda W, Meshnick SR: The effects of antimalarials on the Plasmodium falciparum dihydroorotate dehydrogenase. Exp Parasitol. 1994, 79: 50-56. 10.1006\/expr.1994.1058.","journal-title":"Exp Parasitol"},{"key":"498_CR7","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1128\/AAC.43.6.1334","volume":"43","author":"I Srivastava","year":"1999","unstructured":"Srivastava I, Vadiya A: A mechanism for the synergistic antimalarial action of atovaquone and proguanil. Antimicrob Agents Chemother. 1999, 43: 1334-1339.","journal-title":"Antimicrob Agents Chemother"},{"key":"498_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1475-2875-1-1","volume":"1","author":"QL Fivelman","year":"2002","unstructured":"Fivelman QL, Butcher GA, Adagu IS, Warhurst DC, Pasvol G: Malarone treatment failure and in vitro confirmation of resistance of Plasmodium falciparum isolate from Lagos, Nigeria. Malar J. 2002, 1: 1-10.1186\/1475-2875-1-1.","journal-title":"Malar J"},{"key":"498_CR9","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/1475-2875-2-5","volume":"2","author":"B Schwobel","year":"2003","unstructured":"Schwobel B, Alifrangis M, Salanti A, Jelinek T: Different mutation patterns of atovaquone resistance to Plasmodium falciparum in vitro and in vivo: rapid detection of codon 268 polymorphisms in the cytochrome b as potential in vivo resistance marker. Malar J. 2003, 2: 5-10.1186\/1475-2875-2-5.","journal-title":"Malar J"},{"key":"498_CR10","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1080\/00365540310016862","volume":"35","author":"KP David","year":"2003","unstructured":"David KP, Alifrangis M, Salanti A, Vestergaard LS, Ronn A, Bygbjerg IB: Atovaquone\/proguanil resistance in Africa: a case report. Scand J Infect Dis. 2003, 35: 897-898.","journal-title":"Scand J Infect Dis"},{"key":"498_CR11","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1136\/bmj.326.7390.628","volume":"326","author":"A Farnert","year":"2003","unstructured":"Farnert A, Lindberg J, Gil P, Swedberg G, Berqvist Y, Thapar MM, Lindegardh N, Berezcky S, Bjorkman A: Evidence of Plasmodium falciparum malaria resistant to atovaquone and proguanil hydrochloride: case reports. BMJ. 2003, 326: 628-629. 10.1136\/bmj.326.7390.628.","journal-title":"BMJ"},{"key":"498_CR12","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1086\/375599","volume":"37","author":"E Schwartz","year":"2003","unstructured":"Schwartz E, Bujanover S, Kain KC: Genetic confirmation of atovaquone-proguanil-resistant Plasmodium falciparum malaria acquired by a nonimmune traveler to East Africa. Clin Infect Dis. 2003, 37: 450-451. 10.1086\/375599.","journal-title":"Clin Infect Dis"},{"key":"498_CR13","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1086\/424469","volume":"190","author":"O Wichmann","year":"2004","unstructured":"Wichmann O, Muehlberger N, Jelinek T, Alifrangis M, Peyerl-Hoffmann G, Muhlen M, Grobusch MP, Gascon J, Matteelli A, Laferl H, Bisoffi Z, Ehrhardt S, Cuadros J, Hatz C, Gjorup I, McWhinney P, Beran J, da Cunha S, Schulze M, Kollaritsch H, Kern P, Fry G, Richter J, European Network on Surveillance of Imported Infectious Diseases: Screening for mutations related to atovaquone\/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe. J Infect Dis. 2004, 190: 1541-1546. 10.1086\/424469.","journal-title":"J Infect Dis"},{"key":"498_CR14","doi-asserted-by":"crossref","first-page":"407","DOI":"10.4269\/ajtmh.2005.72.407","volume":"72","author":"S Kuhn","year":"2005","unstructured":"Kuhn S, Gill MJ, Kain KC: Emergence of atovaquone-proguanil resistance during treatment of Plasmodium falciparum malaria acquired by a non-immune north American traveller to west Africa. Am J Trop Med Hyg. 2005, 72: 407-409.","journal-title":"Am J Trop Med Hyg"},{"key":"498_CR15","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1093\/jac\/dki420","volume":"57","author":"L Musset","year":"2006","unstructured":"Musset L, Pradines B, Parzy D, Durand R, Bigot P, Le Bras J: Apparent absence of atovaquone\/proguanil resistance in 477 Plasmodium falciparum isolates from untreated French travellers. J Antimicrob Chemother. 2006, 57: 110-115. 10.1093\/jac\/dki420.","journal-title":"J Antimicrob Chemother"},{"key":"498_CR16","doi-asserted-by":"publisher","first-page":"2599","DOI":"10.1016\/j.micinf.2006.07.011","volume":"8","author":"L Musset","year":"2006","unstructured":"Musset L, Bouchaud O, Matheron S, Massias L, Le Bras J: Clinical atovaquone-proguanil resistance of Plasmodium falciparum associated with cytochrome b codon 268 mutations. Microbes Infect. 2006, 8: 2599-2604. 10.1016\/j.micinf.2006.07.011.","journal-title":"Microbes Infect"},{"key":"498_CR17","doi-asserted-by":"publisher","first-page":"2100","DOI":"10.1128\/AAC.44.8.2100-2108.2000","volume":"44","author":"M Korsinczky","year":"2000","unstructured":"Korsinczky M, Chen N, Kotecka B, Saul A, Rieckmann K, Cheng Q: Mutations in Plasmodium falciparum cytochrome b that are associated with atovaquone resistance are located at a putative drug-binding site. Antimicrob Agents Chemother. 2000, 44: 2100-2108. 10.1128\/AAC.44.8.2100-2108.2000.","journal-title":"Antimicrob Agents Chemother"},{"key":"498_CR18","doi-asserted-by":"crossref","first-page":"655","DOI":"10.4269\/ajtmh.2007.76.655","volume":"76","author":"S Krudsood","year":"2007","unstructured":"Krudsood S, Patel SN, Tangpukdee N, Thanachartwet W, Leowattana W, Pornpininworakij K, Boggild AK, Looareesuwan S, Kain KC: Efficacy of atovaquone-proguanil for treatment of acute multidrug-resistant Plasmodium falciparum malaria in Thailand. Am J Trop Med Hyg. 2007, 76: 655-658.","journal-title":"Am J Trop Med Hyg"},{"key":"498_CR19","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/1475-2875-5-82","volume":"5","author":"CT Happi","year":"2006","unstructured":"Happi CT, Gbotosho GO, Folarin OA, Milner D, Sarr O, Sowunmi A, Kyle DE, Milhous WK, Wirth DF, Oduola AM: Confirmation of emergence of mutations associated with atovaquone-proguanil resistance in unexposed Plasmodium falciparum isolates from Africa. Malar J. 2006, 5: 82-10.1186\/1475-2875-5-82.","journal-title":"Malar J"},{"key":"498_CR20","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1126\/science.781840","volume":"193","author":"W Trager","year":"1976","unstructured":"Trager W, Jensen JB: Human malaria parasites in continuous culture. Science. 1976, 193: 673-675. 10.1126\/science.781840.","journal-title":"Science"},{"key":"498_CR21","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1128\/AAC.16.6.710","volume":"16","author":"RE Desjardins","year":"1979","unstructured":"Desjardins RE, Canfield CJ, Haynes JD, Chulay JD: Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother. 1979, 16: 710-718.","journal-title":"Antimicrob Agents Chemother"},{"key":"498_CR22","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/0014-4894(92)90180-I","volume":"75","author":"J Wooden","year":"1992","unstructured":"Wooden J, Gould EE, Paull AT, Sibley CH: Plasmodium falciparum: a simple polymerase chain reaction method for differentiating strains. Exp Parasitol. 1992, 75: 207-212. 10.1016\/0014-4894(92)90180-I.","journal-title":"Exp Parasitol"},{"key":"498_CR23","doi-asserted-by":"crossref","first-page":"315","DOI":"10.4269\/ajtmh.1997.56.315","volume":"56","author":"F Gay","year":"1997","unstructured":"Gay F, Bustos D, Traore B, Jardinel C, Southammavong M, Ciceron L, Danis MM: In vitro response of Plasmodium falciparum to atovaquone and correlation with other antimalarials: comparison between African and Asian strains. Am J Trop Med Hyg. 1997, 56: 315-317.","journal-title":"Am J Trop Med Hyg"},{"key":"498_CR24","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1016\/j.trstmh.2006.02.004","volume":"100","author":"A Berry","year":"2006","unstructured":"Berry A, Senescau A, Leli\u00e8vre J, Benoit-Vical F, Fabre R, Marchou B, Magnaval JF: Prevalence of Plasmodium falciparum cytochrome b gene mutations in isolates imported from Africa, and implications for atovaquone resistance. Trans R Soc Trop Med Hyg. 2006, 100: 986-988. 10.1016\/j.trstmh.2006.02.004.","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"498_CR25","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.tmaid.2006.07.002","volume":"5","author":"Y Naoshima-Ishibashi","year":"2007","unstructured":"Naoshima-Ishibashi Y, Iwagami M, Kawazu S, Looareesuwan S, Kano S: Analyses of cytochrome b mutations in Plasmodium falciparum isolates in Thai-Myanmar border. Travel Med Infect Dis. 2007, 5: 132-134. 10.1016\/j.tmaid.2006.07.002.","journal-title":"Travel Med Infect Dis"}],"container-title":["Malaria Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1475-2875-7-23.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T01:52:40Z","timestamp":1630461160000},"score":1,"resource":{"primary":{"URL":"https:\/\/malariajournal.biomedcentral.com\/articles\/10.1186\/1475-2875-7-23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1,28]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["498"],"URL":"https:\/\/doi.org\/10.1186\/1475-2875-7-23","relation":{},"ISSN":["1475-2875"],"issn-type":[{"value":"1475-2875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,1,28]]},"assertion":[{"value":"29 October 2007","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2008","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2008","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"23"}}