Wellems T, Plowe C, 2001. Chloroquine-resistant malaria. J Infect Dis 184: 770ā776.
White NJ, 2004. Antimalarial drug resistance. J Clin Invest 113: 1084ā1092.
Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR, 2002. Epidemiology of drug-resistant malaria. Lancet Infect Dis 2: 209ā218.
Hayton K, Su XZ, 2004. Genetic and biochemical aspects of drug resistance in malaria parasites. Curr Drug Targets Infect Disord 4: 1ā10.
Sisowath C, Stromberg J, Martensson A, Msellem M, Obondo C, Bjƶrkman A, Gil JP, 2005. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis 191: 1014ā1017.
Basco LK, Tahar R, Ringwald P, 1998. Molecular basis of in vivo resistance to sulfadoxine-pyrimethamine in African adult patients infected with Plasmodium falciparum malaria parasites. Antimicrob Agents Chemother 42: 1811ā1844.
Cowman AF, Morry MJ, Biggs BA, Cross GA, Foote SJ, 1988. Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum. Proc Natl Acad Sci USA 85: 9109ā9113.
de Pecoulas PE, Basco LK, Le Bras J, Mazabraud A, 1996. Association between antifol resistance in vitro and DHFR gene point mutation in Plasmodium falciparum isolates. Trans R Soc Trop Med Hyg 90: 181ā182.
Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE, 1995. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg 52: 565ā568.
Sibley CH, Hyde JE, Sims PF, Plowe CV, Kublin JG, Mberu EK, Cowman AF, Winstanley PA, Watkins WM, Nzila AM, 2001. Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? Trends Parasitol 17: 582ā588.
Kublin JG, Dzinjalamala FK, Kamwendo DD, Malkin EM, Cortese JF, Martino LM, Mukadam RA, Rogerson SJ, Lescano AG, Molyneux ME, Winstanley PA, Chimpeni P, Taylor TE, Plowe CV, 2002. Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J Infect Dis 185: 380ā388.
Mberu EK, Mosobo MK, Nzila AM, Kokwaro GO, Sibley CH, Watkins WM, 2000. The changing in vitro susceptibility pattern to pyrimethamine/sulfadoxine in Plasmodium falciparum field isolates from Kilifi, Kenya. Am J Trop Med Hyg 62: 396ā401.
Nzila AM, Mberu EK, Sulo J, Dayo H, Winstanley PA, Sibley CH, Watkins WM, 2000. Towards an understanding of the mechanism of pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: genotyping of dihydrofolate reductase and dihydropteroate synthase of Kenyan parasites. Antimicrob Agents Chemother 44: 991ā996.
Balint GA, 2001. Artemisinin and its derivatives: an important new class of antimalarial agents. Pharmacol Ther 90: 261ā265.
World Health Organization, 2001. Antimalarial Drug Combination Therapy. Geneva: World Health Organization, WHO/CDS/RBM/2001.35.
Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, 2008. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med 359: 2619ā2620.
Jambou R, Legrand E, Niang M, Khim N, Lim P, Volney B, Ekala MT, Bouchier C, Esterre P, Fandeur T, Mercereau-Puijalon O, 2005. Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet 366: 1960ā1963.
Legrand E, Volney B, Meynard JB, Esterre P, Mercereau-Puijalon O, 2007. Resistance to dihydroartemisinin. Emerg Infect Dis 13: 808ā809.
Uhlemann AC, Cameron A, Eckstein-Ludwig U, Fischbarg J, Iserovich P, Zuniga FA, East M, Lee A, Brady L, Haynes RK, Krishna S, 2005. A single amino acid residue can determine the sensitivity of SERCAs to artemisinins. Nat Struct Mol Biol 12: 628ā629.
Eckstein-Ludwig U, Webb RJ, van Goethem IDA, East JM, Lee AG, Kimura M, O'Neill PM, Bray PG, Ward SA, Krishna S, 2003. Artemisinins target the SERCA of Plasmodium falciparum. Nature 424: 957ā961.
Sudan, Country Profile. Available at: http://rbm.who.int/wmr2005/profiles/sudan.pdf. Accessed April 28, 2005.
Malik EM, Nour SM, Hamid IK, Elmardi KA, Mohamed TA, Ahmed ES, 2005. From home to hospital: beliefs and practices related to severe malaria in Sudan. J Family Community Medicine 12: 85ā90.
Yousif MA, Adeel AA, 2000. Antimalarials prescribing pattern in Gazera State: precepts and practices. East Mediterr Health J 6: 939ā947.
Omer AH, 1978. Response of Plasmodium falciparum in Sudan to oral chloroquine. Am J Trop Med Hyg 27: 853ā857.
Kouznetsov RL, Rooney W, Wernsdorfer WH, El Gaddal AA, Payne D, Abdalla RE, 1980. Use of the in vitro microtechnique for the assessment of drug sensitivity of Plasmodium falciparum in Sennar, Sudan. Bull World Health Organ 58: 785ā789.
Ibrahim AM, Ali FR, Ali ME, 1992. Assessment of chloroquine resistance of Plasmodium falciparum in children of Wad Medani (central Sudan). J Trop Pediatr 38: 162ā166.
Nour BY, Faragalla IA, Saeed OK, Mohamadani AA, 2006. In vitro study assessing the response of Plasmodium falciparum malaria to chloroquine, sulfadoxine/pyrimethamine, quinine and mefloquine in Wad Medani District, Sudan. Saudi Med J 27: 808ā812.
Bayoumi RA, Babiker HA, Ibrahim SM, Ghalib HW, Saeed BO, Khider S, Elwasila M, Karim EA, 1989. Chloroquine resistant Plasmodium falciparum in Eastern Sudan. Acta Trop 461: 157ā165.
Babiker HA, Satti G, Ferguson H, Bayoumi R, Walliker D, 2005. Drug resistant Plasmodium falciparum in an area of seasonal transmission. Acta Trop 94: 260ā268.
Ibrahim ME, Awad-el-Kariem FM, el Hassan IM, el Mubarak ER, 1991. A case of Plasmodium falciparum malaria sensitive to chloroquine but resistant to pyrimethamine/sulfadoxine in Sennar, Sudan. Trans R Soc Trop Med Hyg 85: 446.
A-Elbasit IE, Khalil IF, Elbashir MI, Masuadi EM, Bygbjerg IC, Alifrangis M, Giha HA, 2008. High frequency of Plasmodium falciparum CICNI/SGEAA and CVIET haplotypes without association with resistance to sulfadoxine/pyrimethamine and chloroquine combination in the Daraweesh area, in Sudan. Eur J Clin Microbiol Infect Dis 27: 725ā732.
A-Elbasit IE, Elbashir MI, Khalil IF, Alifrangis M, Giha HA, 2006. The efficacy of sulfadoxine-pyrimethamine alone and in combination with chloroquine for malaria treatment in rural eastern Sudan: the interrelation between resistance, age and gametocytogenesis. Trop Med Int Health 11: 604ā612.
Alifrangis M, Enosse S, Khalil IF, Tarimo DS, Lemnge MM, Thompson R, Bygbjerg IC, RĆønn AM, 2003. Prediction of Plasmodium falciparum resistance to sulfadoxine/pyrimethamine in vivo by mutations in the dihydrofolate reductase and dihydropteroate synthetase genes: a comparative study between sites of differing endemicity. Am J Trop Med Hyg 69: 601ā606.
Anderson TJ, Nair S, Jacobzone C, Zavai A, Balkan S, 2003. Molecular assessment of drug resistance in Plasmodium falciparum from Bahr El Gazal province, Sudan. Trop Med Int Health 8: 1068ā1073.
National Malaria Control Program, 2004. The National Protocol for Treatment of Malaria. Khartoum, Sudan: Federal Ministry of Health.
Alker AP, Mwapasa V, Meshnick SR, 2004. Rapid real-time PCR genotyping of mutations associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum. Antimicrob Agents Chemother 48: 2924ā2929.
Wilson PE, Kazadi W, Kamwendo DD, Mwapasa V, Purfield A, Meshnick SR, 2005. Prevalence of pfcrt mutations in Congolese and Malawian Plasmodium falciparum isolates as determined by a new Taqman assay. Acta Trop 93: 97ā106.
Duraisingh MT, Jones P, Sambou I, von Seidlein L, Pinder M, Warhurst DC, 2000. The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin. Mol Biochem Parasitol 108: 13ā23.
Duraisingh MT, Curtis J, Warhurst DC, 1998. Plasmodium falciparum: detection of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes by PCR and restriction digestion. Exp Parasitol 89: 1ā8.
Menegon M, Sannella AR, Majori G, Severini C, 2008. Detection of novel point mutations in the Plasmodium falciparum ATPase6 candidate gene for resistance to artemisinins. Parasitol Int 57: 233ā235.
World Health Organization, 2001. In vitro Micro-Test (MARK III) for the Assessment of the Response of Plasmodium falciparum to Chloroquine, Mefloquine, Quinine, Amodiaquine, Sulfadoxine/Pyrimethamine and Artemisinin. WHO/MAL/97.20.
Malik EM, Mohamed TA, Elmardi KA, Mowien RM, Elhassan AH, Elamin SB, Mannan AA, Ahmed ES, 2006. From chloroquine to artemisinin-based combination therapy: the Sudanese experience. Malar J 5: 65.
Osman ME, Mockenhaupt FP, Bienzle U, Elbashir MI, Giha HA, 2007. Field-based evidence for linkage of mutations associated with chloroquine (pfcrt/pfmdr1) and sulfadoxine-pyrimethamine (pfdhfr/pfdhps) resistance and for the fitness cost of multiple mutations in P. falciparum. Infect Genet Evol 7: 52ā59.
Babiker HA, Pringle SJ, Abdel-Muhsin A, Mackinnon M, Hunt P, Walliker D, 2001. High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance gene pfmdr1. J Infect Dis 183: 1535ā1538.
Borrmann S, Binder RK, Adegnika AA, Missinou MA, Issifou S, Ramharter M, Wernsdorfer WH, Kremsner PG, 2002. Reassessment of the resistance of Plasmodium falciparum to chloroquine in Gabon: implications for the validity of tests in vitro vs. in vivo. Trans R Soc Trop Med Hyg 96: 660ā663.
Noedl H, Wongsrichanalai C, Wernsdorfer WH, 2003. Malaria drug-sensitivity testing: new assays, new perspectives. Trends Parasitol 19: 175ā181.
Daily JP, Roberts C, Thomas SM, Ndir O, Dieng T, Mboup S, Wirth DF, 2003. Prevalence of Plasmodium falciparum pfcrt polymorphisms and in vitro chloroquine sensitivity in Senegal. Parasitology 126: 401ā405.
Thomas SM, Ndir O, Dieng T, Mboup S, Wypij D, Maguire JH, Wirth DF, 2002. In vitro chloroquine susceptibility and PCR analysis of pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from Senegal. Am J Trop Med Hyg 66: 474ā480.
Chen N, Russell B, Fowler E, Peters J, Cheng Q, 2002. Levels of chloroquine resistance in Plasmodium falciparum are determined by loci other than pfcrt and pfmdr1. J Infect Dis 185: 405ā407.
Laufer MK, Plowe CV, 2004. Withdrawing antimalarial drugs: impact on parasite resistance and implications for malaria treatment policies. Drug Resist Updat 7: 279ā288.
Laufer MK, Thesing PC, Eddington ND, Masonga R, Dzinjalamala FK, Takala SL, Taylor TE, Plowe CV, 2006. Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med 355: 1959ā1966.
Tahar R, Ringwald P, Basco LK, 2009. Molecular epidemiology of malaria in Cameroon. XXVIII. In vitro activity of dihydroartemisinin against clinical isolates of Plasmodium falciparum and sequence analysis of the P. falciparum ATPase 6 gene. Am J Trop Med Hyg 81: 13ā18.
Dahlstrƶm S, Veiga MI, Ferreira P, MĆ„rtensson A, Kaneko A, Andersson B, Bjƶrkman A, Gil JP, 2008. Diversity of the sarco/endoplasmic reticulum Ca(2+)-ATPase orthologue of Plasmodium falciparum (PfATP6). Infect Genet Evol 8: 340ā345.
A-Elbasit IE, Alifrangis M, Khalil IF, Bygbjerg IC, Masuadi EM, Elbashir MI, Giha HA, 2007. The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics. Malar J 6: 108.
Mockenhaupt FP, Bousema JT, Eggelte TA, Ehrhardt S, Otchwemah RN, Sauerwein RW, Bienzle U, 2005. Concurrence of Plasmodium falciparum dhfr and crt mutations in northern Ghana. Malar J 4: 42.
Mockenhaupt FP, Eggelte TA, Till H, Bienzle U, 2001. Plasmodium falciparum pfcrt and pfmdr1 polymorphisms are associated with the pfdhfr N108 pyrimethamine-resistance mutation in isolates from Ghana. Trop Med Int Health 6: 749ā755.
Toteja R, Nair L, Bhasin V, 2001. Genome comparison of progressively drug resistant Plasmodium falciparum lines derived from drug sensitive clone. Mem Inst Oswaldo Cruz 96: 427ā433.
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In 2004, Sudan adopted artesunate + sulfadoxine/pyrimethamine (SP) combination as the first-line drug, in response to the high level of falciparum resistance to antimalarials. In 2007, a molecular study on antimalarial resistance linked genes, pfcrt, pfmdr1, pfdhfr, pfdhps, and pfATPase6, was conducted on 198 isolates from central and eastern Sudan. We observed a high frequency of point mutations at almost all loci analyzed, mainly of pfcrt 76T (72.7%), pfdhfr 51I (75.3%), and pfdhfr 108N (72.7%) alleles. The MARK III in vitro test for chloroquine sensitivity in 45 P. falciparum isolates showed that 37.8% of the isolates were low resistant and 6.7% were fully resistant. This study represents the most recent molecular investigation on antimalarial resistance in this area after the adoption of artemisinin-based combination therapy (ACT), and underlines the importance of the analysis of SP resistance evolution to monitor the efficacy of ACT therapy in endemic areas.
Financial support: Part of this work has been carried out with the financial support from a Technical Service Agreement (HQ/07/100294) between the World Health Organization, Global Malaria Programme, Geneva, Switzerland, and Istituto Superiore di SanitĆ , Roma, Italy.
Authors' addresses: Michela Menegon, Carlo Severini, and Giancarlo Majori, Department of Infectious, Parasitic and Immunomediated Diseases and WHO Collaborating Centre for Research and Training in Tropical Diseases Control, Istituto Superiore di SanitĆ , Rome, Italy, E-mails: michela.menegon@iss.it, carlo.severini@iss.it, and giancarlo.majori@iss.it. Albadawi A. Talha and Ahmed A. Mohamedani, Faculty of Medical Laboratory Sciences, University of Gezira, WadMedani, Sudan. E-mails: badawiat@yahoo.com and a_mohamedani@hotmail.com. Sayed M. Elbushra and Bakri Y. M. Nour, Blue Nile Research National Institute for Communicable Diseases, University of Gezira, Wad Medani, Sudan, E-mails: sayedelbushra@yahoo.com and bakrinour@hotmail.com. Elfatih M. Malik, Directorate of Communicable Diseases ControlāFederal Ministry of Health, Khartoum, Sudan, E-mail: fatihmmalik@hotmail.com. Tarig A. Mohamed, National Malaria Control ProgramāFederal Ministry of Health, Khartoum, Sudan, E-mail: tarigmohmed_ali@hotmail.com. Walther H. Wernsdorfer, National Malaria Control ProgramāFederal Ministry of Health, Khartoum, Sudan, Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University, Vienna, Austria, E-mail: walter.wernsdorfer@meduniwien.ac.at.
Wellems T, Plowe C, 2001. Chloroquine-resistant malaria. J Infect Dis 184: 770ā776.
White NJ, 2004. Antimalarial drug resistance. J Clin Invest 113: 1084ā1092.
Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR, 2002. Epidemiology of drug-resistant malaria. Lancet Infect Dis 2: 209ā218.
Hayton K, Su XZ, 2004. Genetic and biochemical aspects of drug resistance in malaria parasites. Curr Drug Targets Infect Disord 4: 1ā10.
Sisowath C, Stromberg J, Martensson A, Msellem M, Obondo C, Bjƶrkman A, Gil JP, 2005. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis 191: 1014ā1017.
Basco LK, Tahar R, Ringwald P, 1998. Molecular basis of in vivo resistance to sulfadoxine-pyrimethamine in African adult patients infected with Plasmodium falciparum malaria parasites. Antimicrob Agents Chemother 42: 1811ā1844.
Cowman AF, Morry MJ, Biggs BA, Cross GA, Foote SJ, 1988. Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum. Proc Natl Acad Sci USA 85: 9109ā9113.
de Pecoulas PE, Basco LK, Le Bras J, Mazabraud A, 1996. Association between antifol resistance in vitro and DHFR gene point mutation in Plasmodium falciparum isolates. Trans R Soc Trop Med Hyg 90: 181ā182.
Plowe CV, Djimde A, Bouare M, Doumbo O, Wellems TE, 1995. Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg 52: 565ā568.
Sibley CH, Hyde JE, Sims PF, Plowe CV, Kublin JG, Mberu EK, Cowman AF, Winstanley PA, Watkins WM, Nzila AM, 2001. Pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: what next? Trends Parasitol 17: 582ā588.
Kublin JG, Dzinjalamala FK, Kamwendo DD, Malkin EM, Cortese JF, Martino LM, Mukadam RA, Rogerson SJ, Lescano AG, Molyneux ME, Winstanley PA, Chimpeni P, Taylor TE, Plowe CV, 2002. Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. J Infect Dis 185: 380ā388.
Mberu EK, Mosobo MK, Nzila AM, Kokwaro GO, Sibley CH, Watkins WM, 2000. The changing in vitro susceptibility pattern to pyrimethamine/sulfadoxine in Plasmodium falciparum field isolates from Kilifi, Kenya. Am J Trop Med Hyg 62: 396ā401.
Nzila AM, Mberu EK, Sulo J, Dayo H, Winstanley PA, Sibley CH, Watkins WM, 2000. Towards an understanding of the mechanism of pyrimethamine-sulfadoxine resistance in Plasmodium falciparum: genotyping of dihydrofolate reductase and dihydropteroate synthase of Kenyan parasites. Antimicrob Agents Chemother 44: 991ā996.
Balint GA, 2001. Artemisinin and its derivatives: an important new class of antimalarial agents. Pharmacol Ther 90: 261ā265.
World Health Organization, 2001. Antimalarial Drug Combination Therapy. Geneva: World Health Organization, WHO/CDS/RBM/2001.35.
Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, 2008. Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med 359: 2619ā2620.
Jambou R, Legrand E, Niang M, Khim N, Lim P, Volney B, Ekala MT, Bouchier C, Esterre P, Fandeur T, Mercereau-Puijalon O, 2005. Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet 366: 1960ā1963.
Legrand E, Volney B, Meynard JB, Esterre P, Mercereau-Puijalon O, 2007. Resistance to dihydroartemisinin. Emerg Infect Dis 13: 808ā809.
Uhlemann AC, Cameron A, Eckstein-Ludwig U, Fischbarg J, Iserovich P, Zuniga FA, East M, Lee A, Brady L, Haynes RK, Krishna S, 2005. A single amino acid residue can determine the sensitivity of SERCAs to artemisinins. Nat Struct Mol Biol 12: 628ā629.
Eckstein-Ludwig U, Webb RJ, van Goethem IDA, East JM, Lee AG, Kimura M, O'Neill PM, Bray PG, Ward SA, Krishna S, 2003. Artemisinins target the SERCA of Plasmodium falciparum. Nature 424: 957ā961.
Sudan, Country Profile. Available at: http://rbm.who.int/wmr2005/profiles/sudan.pdf. Accessed April 28, 2005.
Malik EM, Nour SM, Hamid IK, Elmardi KA, Mohamed TA, Ahmed ES, 2005. From home to hospital: beliefs and practices related to severe malaria in Sudan. J Family Community Medicine 12: 85ā90.
Yousif MA, Adeel AA, 2000. Antimalarials prescribing pattern in Gazera State: precepts and practices. East Mediterr Health J 6: 939ā947.
Omer AH, 1978. Response of Plasmodium falciparum in Sudan to oral chloroquine. Am J Trop Med Hyg 27: 853ā857.
Kouznetsov RL, Rooney W, Wernsdorfer WH, El Gaddal AA, Payne D, Abdalla RE, 1980. Use of the in vitro microtechnique for the assessment of drug sensitivity of Plasmodium falciparum in Sennar, Sudan. Bull World Health Organ 58: 785ā789.
Ibrahim AM, Ali FR, Ali ME, 1992. Assessment of chloroquine resistance of Plasmodium falciparum in children of Wad Medani (central Sudan). J Trop Pediatr 38: 162ā166.
Nour BY, Faragalla IA, Saeed OK, Mohamadani AA, 2006. In vitro study assessing the response of Plasmodium falciparum malaria to chloroquine, sulfadoxine/pyrimethamine, quinine and mefloquine in Wad Medani District, Sudan. Saudi Med J 27: 808ā812.
Bayoumi RA, Babiker HA, Ibrahim SM, Ghalib HW, Saeed BO, Khider S, Elwasila M, Karim EA, 1989. Chloroquine resistant Plasmodium falciparum in Eastern Sudan. Acta Trop 461: 157ā165.
Babiker HA, Satti G, Ferguson H, Bayoumi R, Walliker D, 2005. Drug resistant Plasmodium falciparum in an area of seasonal transmission. Acta Trop 94: 260ā268.
Ibrahim ME, Awad-el-Kariem FM, el Hassan IM, el Mubarak ER, 1991. A case of Plasmodium falciparum malaria sensitive to chloroquine but resistant to pyrimethamine/sulfadoxine in Sennar, Sudan. Trans R Soc Trop Med Hyg 85: 446.
A-Elbasit IE, Khalil IF, Elbashir MI, Masuadi EM, Bygbjerg IC, Alifrangis M, Giha HA, 2008. High frequency of Plasmodium falciparum CICNI/SGEAA and CVIET haplotypes without association with resistance to sulfadoxine/pyrimethamine and chloroquine combination in the Daraweesh area, in Sudan. Eur J Clin Microbiol Infect Dis 27: 725ā732.
A-Elbasit IE, Elbashir MI, Khalil IF, Alifrangis M, Giha HA, 2006. The efficacy of sulfadoxine-pyrimethamine alone and in combination with chloroquine for malaria treatment in rural eastern Sudan: the interrelation between resistance, age and gametocytogenesis. Trop Med Int Health 11: 604ā612.
Alifrangis M, Enosse S, Khalil IF, Tarimo DS, Lemnge MM, Thompson R, Bygbjerg IC, RĆønn AM, 2003. Prediction of Plasmodium falciparum resistance to sulfadoxine/pyrimethamine in vivo by mutations in the dihydrofolate reductase and dihydropteroate synthetase genes: a comparative study between sites of differing endemicity. Am J Trop Med Hyg 69: 601ā606.
Anderson TJ, Nair S, Jacobzone C, Zavai A, Balkan S, 2003. Molecular assessment of drug resistance in Plasmodium falciparum from Bahr El Gazal province, Sudan. Trop Med Int Health 8: 1068ā1073.
National Malaria Control Program, 2004. The National Protocol for Treatment of Malaria. Khartoum, Sudan: Federal Ministry of Health.
Alker AP, Mwapasa V, Meshnick SR, 2004. Rapid real-time PCR genotyping of mutations associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum. Antimicrob Agents Chemother 48: 2924ā2929.
Wilson PE, Kazadi W, Kamwendo DD, Mwapasa V, Purfield A, Meshnick SR, 2005. Prevalence of pfcrt mutations in Congolese and Malawian Plasmodium falciparum isolates as determined by a new Taqman assay. Acta Trop 93: 97ā106.
Duraisingh MT, Jones P, Sambou I, von Seidlein L, Pinder M, Warhurst DC, 2000. The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin. Mol Biochem Parasitol 108: 13ā23.
Duraisingh MT, Curtis J, Warhurst DC, 1998. Plasmodium falciparum: detection of polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes by PCR and restriction digestion. Exp Parasitol 89: 1ā8.
Menegon M, Sannella AR, Majori G, Severini C, 2008. Detection of novel point mutations in the Plasmodium falciparum ATPase6 candidate gene for resistance to artemisinins. Parasitol Int 57: 233ā235.
World Health Organization, 2001. In vitro Micro-Test (MARK III) for the Assessment of the Response of Plasmodium falciparum to Chloroquine, Mefloquine, Quinine, Amodiaquine, Sulfadoxine/Pyrimethamine and Artemisinin. WHO/MAL/97.20.
Malik EM, Mohamed TA, Elmardi KA, Mowien RM, Elhassan AH, Elamin SB, Mannan AA, Ahmed ES, 2006. From chloroquine to artemisinin-based combination therapy: the Sudanese experience. Malar J 5: 65.
Osman ME, Mockenhaupt FP, Bienzle U, Elbashir MI, Giha HA, 2007. Field-based evidence for linkage of mutations associated with chloroquine (pfcrt/pfmdr1) and sulfadoxine-pyrimethamine (pfdhfr/pfdhps) resistance and for the fitness cost of multiple mutations in P. falciparum. Infect Genet Evol 7: 52ā59.
Babiker HA, Pringle SJ, Abdel-Muhsin A, Mackinnon M, Hunt P, Walliker D, 2001. High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance gene pfmdr1. J Infect Dis 183: 1535ā1538.
Borrmann S, Binder RK, Adegnika AA, Missinou MA, Issifou S, Ramharter M, Wernsdorfer WH, Kremsner PG, 2002. Reassessment of the resistance of Plasmodium falciparum to chloroquine in Gabon: implications for the validity of tests in vitro vs. in vivo. Trans R Soc Trop Med Hyg 96: 660ā663.
Noedl H, Wongsrichanalai C, Wernsdorfer WH, 2003. Malaria drug-sensitivity testing: new assays, new perspectives. Trends Parasitol 19: 175ā181.
Daily JP, Roberts C, Thomas SM, Ndir O, Dieng T, Mboup S, Wirth DF, 2003. Prevalence of Plasmodium falciparum pfcrt polymorphisms and in vitro chloroquine sensitivity in Senegal. Parasitology 126: 401ā405.
Thomas SM, Ndir O, Dieng T, Mboup S, Wypij D, Maguire JH, Wirth DF, 2002. In vitro chloroquine susceptibility and PCR analysis of pfcrt and pfmdr1 polymorphisms in Plasmodium falciparum isolates from Senegal. Am J Trop Med Hyg 66: 474ā480.
Chen N, Russell B, Fowler E, Peters J, Cheng Q, 2002. Levels of chloroquine resistance in Plasmodium falciparum are determined by loci other than pfcrt and pfmdr1. J Infect Dis 185: 405ā407.
Laufer MK, Plowe CV, 2004. Withdrawing antimalarial drugs: impact on parasite resistance and implications for malaria treatment policies. Drug Resist Updat 7: 279ā288.
Laufer MK, Thesing PC, Eddington ND, Masonga R, Dzinjalamala FK, Takala SL, Taylor TE, Plowe CV, 2006. Return of chloroquine antimalarial efficacy in Malawi. N Engl J Med 355: 1959ā1966.
Tahar R, Ringwald P, Basco LK, 2009. Molecular epidemiology of malaria in Cameroon. XXVIII. In vitro activity of dihydroartemisinin against clinical isolates of Plasmodium falciparum and sequence analysis of the P. falciparum ATPase 6 gene. Am J Trop Med Hyg 81: 13ā18.
Dahlstrƶm S, Veiga MI, Ferreira P, MĆ„rtensson A, Kaneko A, Andersson B, Bjƶrkman A, Gil JP, 2008. Diversity of the sarco/endoplasmic reticulum Ca(2+)-ATPase orthologue of Plasmodium falciparum (PfATP6). Infect Genet Evol 8: 340ā345.
A-Elbasit IE, Alifrangis M, Khalil IF, Bygbjerg IC, Masuadi EM, Elbashir MI, Giha HA, 2007. The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics. Malar J 6: 108.
Mockenhaupt FP, Bousema JT, Eggelte TA, Ehrhardt S, Otchwemah RN, Sauerwein RW, Bienzle U, 2005. Concurrence of Plasmodium falciparum dhfr and crt mutations in northern Ghana. Malar J 4: 42.
Mockenhaupt FP, Eggelte TA, Till H, Bienzle U, 2001. Plasmodium falciparum pfcrt and pfmdr1 polymorphisms are associated with the pfdhfr N108 pyrimethamine-resistance mutation in isolates from Ghana. Trop Med Int Health 6: 749ā755.
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