Frequency Distribution of Antimalarial Drug Resistance Alleles among Plasmodium falciparum Isolates from Gezira State, Central Sudan, and Gedarif State, Eastern Sudan

Michela Menegon Department of Infectious, Parasitic and Immunomediated Diseases and WHO Collaborating Centre for Research and Training in Tropical Diseases Control, Istituto Superiore di Sanità, Rome, Italy; Faculty of Medical Laboratory Sciences, University of Gezira, WadMedani, Sudan; Blue Nile Research National Institute for Communicable Diseases, University of Gezira, Wad Medani, Sudan; Directorate of Communicable Diseases Control-Federal Ministry of Health, Khartoum, Sudan; National Malaria Control Program Federal Ministry of Health, Khartoum, Sudan; Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University Vienna, Austria

Search for other papers by Michela Menegon in
Current site
Google Scholar
PubMed
Close
,
Albadawi A. Talha Department of Infectious, Parasitic and Immunomediated Diseases and WHO Collaborating Centre for Research and Training in Tropical Diseases Control, Istituto Superiore di Sanità, Rome, Italy; Faculty of Medical Laboratory Sciences, University of Gezira, WadMedani, Sudan; Blue Nile Research National Institute for Communicable Diseases, University of Gezira, Wad Medani, Sudan; Directorate of Communicable Diseases Control-Federal Ministry of Health, Khartoum, Sudan; National Malaria Control Program Federal Ministry of Health, Khartoum, Sudan; Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University Vienna, Austria

Search for other papers by Albadawi A. Talha in
Current site
Google Scholar
PubMed
Close
,
Carlo Severini Department of Infectious, Parasitic and Immunomediated Diseases and WHO Collaborating Centre for Research and Training in Tropical Diseases Control, Istituto Superiore di Sanità, Rome, Italy; Faculty of Medical Laboratory Sciences, University of Gezira, WadMedani, Sudan; Blue Nile Research National Institute for Communicable Diseases, University of Gezira, Wad Medani, Sudan; Directorate of Communicable Diseases Control-Federal Ministry of Health, Khartoum, Sudan; National Malaria Control Program Federal Ministry of Health, Khartoum, Sudan; Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University Vienna, Austria

Search for other papers by Carlo Severini in
Current site
Google Scholar
PubMed
Close
,
Sayed M. Elbushra Department of Infectious, Parasitic and Immunomediated Diseases and WHO Collaborating Centre for Research and Training in Tropical Diseases Control, Istituto Superiore di Sanità, Rome, Italy; Faculty of Medical Laboratory Sciences, University of Gezira, WadMedani, Sudan; Blue Nile Research National Institute for Communicable Diseases, University of Gezira, Wad Medani, Sudan; Directorate of Communicable Diseases Control-Federal Ministry of Health, Khartoum, Sudan; National Malaria Control Program Federal Ministry of Health, Khartoum, Sudan; Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University Vienna, Austria

Search for other papers by Sayed M. Elbushra in
Current site
Google Scholar
PubMed
Close
,
Ahmed A. Mohamedani Department of Infectious, Parasitic and Immunomediated Diseases and WHO Collaborating Centre for Research and Training in Tropical Diseases Control, Istituto Superiore di Sanità, Rome, Italy; Faculty of Medical Laboratory Sciences, University of Gezira, WadMedani, Sudan; Blue Nile Research National Institute for Communicable Diseases, University of Gezira, Wad Medani, Sudan; Directorate of Communicable Diseases Control-Federal Ministry of Health, Khartoum, Sudan; National Malaria Control Program Federal Ministry of Health, Khartoum, Sudan; Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University Vienna, Austria

Search for other papers by Ahmed A. Mohamedani in
Current site
Google Scholar
PubMed
Close
,
Elfatih M. Malik Department of Infectious, Parasitic and Immunomediated Diseases and WHO Collaborating Centre for Research and Training in Tropical Diseases Control, Istituto Superiore di Sanità, Rome, Italy; Faculty of Medical Laboratory Sciences, University of Gezira, WadMedani, Sudan; Blue Nile Research National Institute for Communicable Diseases, University of Gezira, Wad Medani, Sudan; Directorate of Communicable Diseases Control-Federal Ministry of Health, Khartoum, Sudan; National Malaria Control Program Federal Ministry of Health, Khartoum, Sudan; Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University Vienna, Austria

Search for other papers by Elfatih M. Malik in
Current site
Google Scholar
PubMed
Close
,
Tarig A. Mohamed Department of Infectious, Parasitic and Immunomediated Diseases and WHO Collaborating Centre for Research and Training in Tropical Diseases Control, Istituto Superiore di Sanità, Rome, Italy; Faculty of Medical Laboratory Sciences, University of Gezira, WadMedani, Sudan; Blue Nile Research National Institute for Communicable Diseases, University of Gezira, Wad Medani, Sudan; Directorate of Communicable Diseases Control-Federal Ministry of Health, Khartoum, Sudan; National Malaria Control Program Federal Ministry of Health, Khartoum, Sudan; Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University Vienna, Austria

Search for other papers by Tarig A. Mohamed in
Current site
Google Scholar
PubMed
Close
,
Walther H. Wernsdorfer Department of Infectious, Parasitic and Immunomediated Diseases and WHO Collaborating Centre for Research and Training in Tropical Diseases Control, Istituto Superiore di Sanità, Rome, Italy; Faculty of Medical Laboratory Sciences, University of Gezira, WadMedani, Sudan; Blue Nile Research National Institute for Communicable Diseases, University of Gezira, Wad Medani, Sudan; Directorate of Communicable Diseases Control-Federal Ministry of Health, Khartoum, Sudan; National Malaria Control Program Federal Ministry of Health, Khartoum, Sudan; Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University Vienna, Austria

Search for other papers by Walther H. Wernsdorfer in
Current site
Google Scholar
PubMed
Close
,
Giancarlo Majori Department of Infectious, Parasitic and Immunomediated Diseases and WHO Collaborating Centre for Research and Training in Tropical Diseases Control, Istituto Superiore di Sanità, Rome, Italy; Faculty of Medical Laboratory Sciences, University of Gezira, WadMedani, Sudan; Blue Nile Research National Institute for Communicable Diseases, University of Gezira, Wad Medani, Sudan; Directorate of Communicable Diseases Control-Federal Ministry of Health, Khartoum, Sudan; National Malaria Control Program Federal Ministry of Health, Khartoum, Sudan; Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University Vienna, Austria

Search for other papers by Giancarlo Majori in
Current site
Google Scholar
PubMed
Close
, and
Bakri Y. M. Nour Department of Infectious, Parasitic and Immunomediated Diseases and WHO Collaborating Centre for Research and Training in Tropical Diseases Control, Istituto Superiore di Sanità, Rome, Italy; Faculty of Medical Laboratory Sciences, University of Gezira, WadMedani, Sudan; Blue Nile Research National Institute for Communicable Diseases, University of Gezira, Wad Medani, Sudan; Directorate of Communicable Diseases Control-Federal Ministry of Health, Khartoum, Sudan; National Malaria Control Program Federal Ministry of Health, Khartoum, Sudan; Institute of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University Vienna, Austria

Search for other papers by Bakri Y. M. Nour in
Current site
Google Scholar
PubMed
Close
Restricted access

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.

Author Notes

*Address correspondence to Michela Menegon, Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, viale Regina Elena, 299, 00161, Rome, Italy. E-mail: michela.menegon@iss.it

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 Sanità, 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 Sanità, 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 Control–Federal Ministry of Health, Khartoum, Sudan, E-mail: fatihmmalik@hotmail.com. Tarig A. Mohamed, National Malaria Control Program–Federal Ministry of Health, Khartoum, Sudan, E-mail: tarigmohmed_ali@hotmail.com. Walther H. Wernsdorfer, National Malaria Control Program–Federal 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.

  • 1.

    Wellems T, Plowe C, 2001. Chloroquine-resistant malaria. J Infect Dis 184: 770776.

  • 2.

    White NJ, 2004. Antimalarial drug resistance. J Clin Invest 113: 10841092.

  • 3.

    Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR, 2002. Epidemiology of drug-resistant malaria. Lancet Infect Dis 2: 209218.

  • 4.

    Hayton K, Su XZ, 2004. Genetic and biochemical aspects of drug resistance in malaria parasites. Curr Drug Targets Infect Disord 4: 110.

  • 5.

    Sisowath C, Stromberg J, Martensson A, Msellem M, Obondo C, Björkman A, Gil JP, 2005. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis 191: 10141017.

    • Search Google Scholar
    • Export Citation
  • 6.

    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: 18111844.

    • Search Google Scholar
    • Export Citation
  • 7.

    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: 91099113.

    • Search Google Scholar
    • Export Citation
  • 8.

    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: 181182.

    • Search Google Scholar
    • Export Citation
  • 9.

    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: 565568.

    • Search Google Scholar
    • Export Citation
  • 10.

    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: 582588.

    • Search Google Scholar
    • Export Citation
  • 11.

    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: 380388.

    • Search Google Scholar
    • Export Citation
  • 12.

    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: 396401.

    • Search Google Scholar
    • Export Citation
  • 13.

    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: 991996.

    • Search Google Scholar
    • Export Citation
  • 14.

    Balint GA, 2001. Artemisinin and its derivatives: an important new class of antimalarial agents. Pharmacol Ther 90: 261265.

  • 15.

    World Health Organization, 2001. Antimalarial Drug Combination Therapy. Geneva: World Health Organization, WHO/CDS/RBM/2001.35.

  • 16.

    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: 26192620.

    • Search Google Scholar
    • Export Citation
  • 17.

    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: 19601963.

    • Search Google Scholar
    • Export Citation
  • 18.

    Legrand E, Volney B, Meynard JB, Esterre P, Mercereau-Puijalon O, 2007. Resistance to dihydroartemisinin. Emerg Infect Dis 13: 808809.

  • 19.

    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: 628629.

    • Search Google Scholar
    • Export Citation
  • 20.

    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: 957961.

    • Search Google Scholar
    • Export Citation
  • 21.

    Sudan, Country Profile. Available at: http://rbm.who.int/wmr2005/profiles/sudan.pdf. Accessed April 28, 2005.

  • 22.

    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: 8590.

    • Search Google Scholar
    • Export Citation
  • 23.

    Yousif MA, Adeel AA, 2000. Antimalarials prescribing pattern in Gazera State: precepts and practices. East Mediterr Health J 6: 939947.

  • 24.

    Omer AH, 1978. Response of Plasmodium falciparum in Sudan to oral chloroquine. Am J Trop Med Hyg 27: 853857.

  • 25.

    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: 785789.

    • Search Google Scholar
    • Export Citation
  • 26.

    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: 162166.

    • Search Google Scholar
    • Export Citation
  • 27.

    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: 808812.

    • Search Google Scholar
    • Export Citation
  • 28.

    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: 157165.

    • Search Google Scholar
    • Export Citation
  • 29.

    Babiker HA, Satti G, Ferguson H, Bayoumi R, Walliker D, 2005. Drug resistant Plasmodium falciparum in an area of seasonal transmission. Acta Trop 94: 260268.

    • Search Google Scholar
    • Export Citation
  • 30.

    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.

    • Search Google Scholar
    • Export Citation
  • 31.

    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: 725732.

    • Search Google Scholar
    • Export Citation
  • 32.

    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: 604612.

    • Search Google Scholar
    • Export Citation
  • 33.

    Alifrangis M, Enosse S, Khalil IF, Tarimo DS, Lemnge MM, Thompson R, Bygbjerg IC, Rønn 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: 601606.

    • Search Google Scholar
    • Export Citation
  • 34.

    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: 10681073.

    • Search Google Scholar
    • Export Citation
  • 35.

    National Malaria Control Program, 2004. The National Protocol for Treatment of Malaria. Khartoum, Sudan: Federal Ministry of Health.

  • 36.

    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: 29242929.

    • Search Google Scholar
    • Export Citation
  • 37.

    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: 97106.

    • Search Google Scholar
    • Export Citation
  • 38.

    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: 1323.

    • Search Google Scholar
    • Export Citation
  • 39.

    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: 18.

    • Search Google Scholar
    • Export Citation
  • 40.

    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: 233235.

    • Search Google Scholar
    • Export Citation
  • 41.

    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.

    • Search Google Scholar
    • Export Citation
  • 42.

    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.

    • Search Google Scholar
    • Export Citation
  • 43.

    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: 5259.

    • Search Google Scholar
    • Export Citation
  • 44.

    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: 15351538.

    • Search Google Scholar
    • Export Citation
  • 45.

    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: 660663.

    • Search Google Scholar
    • Export Citation
  • 46.

    Noedl H, Wongsrichanalai C, Wernsdorfer WH, 2003. Malaria drug-sensitivity testing: new assays, new perspectives. Trends Parasitol 19: 175181.

    • Search Google Scholar
    • Export Citation
  • 47.

    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: 401405.

    • Search Google Scholar
    • Export Citation
  • 48.

    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: 474480.

    • Search Google Scholar
    • Export Citation
  • 49.

    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: 405407.

    • Search Google Scholar
    • Export Citation
  • 50.

    Laufer MK, Plowe CV, 2004. Withdrawing antimalarial drugs: impact on parasite resistance and implications for malaria treatment policies. Drug Resist Updat 7: 279288.

    • Search Google Scholar
    • Export Citation
  • 51.

    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: 19591966.

    • Search Google Scholar
    • Export Citation
  • 52.

    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: 1318.

    • Search Google Scholar
    • Export Citation
  • 53.

    Dahlström S, Veiga MI, Ferreira P, Mårtensson A, Kaneko A, Andersson B, Björkman A, Gil JP, 2008. Diversity of the sarco/endoplasmic reticulum Ca(2+)-ATPase orthologue of Plasmodium falciparum (PfATP6). Infect Genet Evol 8: 340345.

    • Search Google Scholar
    • Export Citation
  • 54.

    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.

    • Search Google Scholar
    • Export Citation
  • 55.

    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.

    • Search Google Scholar
    • Export Citation
  • 56.

    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: 749755.

    • Search Google Scholar
    • Export Citation
  • 57.

    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: 427433.

    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 25 25 9
Full Text Views 294 115 0
PDF Downloads 68 35 0
 
Membership Banner
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save