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-
1
Rønn AM, Msangeni HA, Mhina J, Wernsdorfer WH, Bygbjerg IC, 1996. High level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine in children in Tanzania. Trans R Soc Trop Med Hyg 90 :179–181.
-
2
Trigg JK, Mbwana H, Chambo O, Hills E, Watkins W, Curtis CF, 1997. Resistance to pyrimethamine/sulfadoxine in Plasmodium falciparum in 12 villages in north east Tanzania and a test of chlorproguanil/dapsone. Acta Trop 63 :185–189.
-
3
East African Network for Monitoring Antimalarial Treatment (EANMAT), 2003. The efficacy of antimalarial monotherapies, sulphadoxine-pyrimethamine and amodiaquine in East Africa: implications for sub-regional policy. Trop Med Int Health 8 :860–867.
-
4
Mugittu K, Ndejembi M, Malisa A, Lemnge M, Premji Z, Mwita A, Nkya W, Kataraihya J, Abdulla S, Beck HP, Mshinda H, 2004. Therapeutic efficacy of sulfadoxine-pyrimethamine and prevalence of resistance markers in Tanzania prior to revision of malaria treatment policy: Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase mutations in monitoring in vivo resistance. Am J Trop Med Hyg 71 :696–702.
-
5
Mutabingwa TK, Anthony D, Heller A, Hallett R, Ahmed J, Drakeley C, Greenwood BM, Whitty CJ, 2005. Amodiaquine alone, amodiaquine + sulfadoxine-pyrimethamine, amodiaquine + artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial. Lancet 365 :1474–1480.
-
6
Lemnge M, Alifrangis M, Kafuye MY, Segeja MD, Gesase S, Minja D, Massaga JJ, Ronn AM, Bygbjerg IC, 2006. High reinfection rate and treatment failures in children treated with amodiaquine for falciparum malaria in Muheza villages, northeastern Tanzania. Am J Trop Med Hyg 75 :188–193.
-
7
Cowman A, 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 :9109–9113.
-
8
Peterson DS, Walliker D, Wellems TE, 1988. Evidence that a point mutation in dihydrofolate reductase- thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc Natl Acad Sci USA 85 :9114–9118.
-
9
Brooks R, Wang P, Read M, Watkins MW, Sims PF, Hyde JE, 1994. Sequence variation of the hydroxymethyldihydropterin pyro-phosphokinase: dihydroptoate synthase gene lines of the human malaria parasite, Plasmodium falciparum, with differing resistance to sulfadoxine. J Biochem 224 :397–405.
-
10
Triglia T, Cowman A, 1994. Primary structure and expression of the dihydropteroate synthetase gene of Plasmodium falciparum. Proc Natl Acad Sci USA 91 :7149–7153.
-
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 :380–388.
-
12
Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LM, Sidhu AB, Naude B, Deitsch KW, Su XZ, Wootton JC, Roepe PD, Wellems TE, 2000. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell 6 :861–871.
-
13
Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, Coulibaly D, 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344 :257–263.
-
14
Holmgren G, Gil JP, Ferreira PM, Veiga MI, Obonyo CO, Bjorkman A, 2006. Amodiaquine resistant Plasmodium falciparum malaria in vivo is associated with selection of pfcrt 76T and pfmdr1 86Y. Infect Genet Evol 6 :309–314.
-
15
Warhurst DC, 2003. Polymorphism in the Plasmodium falciparum chloroquine-resistance transporter protein links verapamil enhancement of chloroquine sensitivity with the clinical efficacy of amodiaquine. Malar J 2 :31.
-
16
Alifrangis M, Dalgaard MB, Lusingu JP, Vestergaard LS, Staalsoe T, Jensen AT, Enevold A, Ronn AM, Khalil IF, Warhurst DC, Lemnge MM, Theander TG, Bygbjerg IC, 2006. Occurrence of the Southeast Asian/South American SVMNT haplotype of the chloroquine-resistance transporter gene in Plasmodium falciparum in Tanzania. J Infect Dis 193 :1738–1741.
-
17
Lusingu JP, Jensen AT, Vestergaard LS, Minja DT, Dalgaard MB, Gesase S, Mmbando BP, Kitua AY, Lemnge MM, Cavanagh D, Hviid L, Theander TG, 2006. Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes. Infect Immun 74 :2867–2875.
-
18
Bodker R, Akida J, Shayo D, Kisinza W, Msangeni HA, Pedersen EM, Lindsay SW, 2003. Relationship between altitude and intensity of malaria transmission in the Usambara Mountains, Tanzania. J Med Entomol 40 :706–717.
-
19
Alifrangis M, Enosse S, Pearce R, Drakeley C, Roper C, Khalil IF, Nkya WM, Ronn AM, Theander TG, Bygbjerg IC, 2005. A simple high-throughput method to detect Plasmodium falciparum single nucleotide polymorphisms in the dihydrofolate reductase, dihydropteroate synthase, and P. falciparum cloroquine resistance transporter genes using polymerase chain reaction and enzyme linked immunosorbent assay-based technology. Am J Trop Med Hyg 72 :155–162.
-
20
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 :1–8.
-
21
Wang P, Lee C-S, Bayoumi R, Djimde A, Doumbo O, Swedberg G, Dao LD, Mshinda H, Tanner M, Watkins MW, Sims PF, Hyde JE, 1997. Resistance to antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthetase and dihydrofolate reductase alleles in a large number of field samples of diverse origins. Mol Biochem Parasitol 89 :161–177.
-
22
Enevold A, Nkya WM, Theisen M, Vestergaard LS, Jensen AT, Staalsoe T, Theander TG, Bygbjerg IC, Alifrangis M, 2007. Potential impact of host immunity on malaria treatment outcome in Tanzanian children infected with Plasmodium falciparum. Malar J 6 :153.
-
23
Pearce RJ, Drakeley C, Chandramohan D, Mosha F, Roper C, 2003. Molecular determination of point mutation haplotypes in the dihydrofolate reductase and dihydropteroate synthase of Plasmodium falciparum in three districts of northern Tanzania. Antimicrob Agents Chemother 47 :1347–1354.
-
24
Okiro EA, Hay SI, Gikandi PW, Sharif SK, Noor AM, Peshu N, Marsh K, Snow RW, 2007. The decline in paediatric malaria admissions on the coast of Kenya. Malar J 6 :151.
-
25
Bhattarai A, Ali AS, Kachur SP, Martensson A, Abbas AK, Khatib R, Al-Mafazy AW, Ramsan M, Rotllant G, Gerstenmaier JF, Molteni F, Abdulla S, Montgomery SM, Kaneko A, Bjorkman A, 2007. Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar. PLoS Med 4 :e309.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 527 | 493 | 32 |
| Full Text Views | 287 | 4 | 1 |
| PDF Downloads | 81 | 4 | 1 |
Five-Year Surveillance of Molecular Markers of Plasmodium falciparum Antimalarial Drug Resistance in Korogwe District, Tanzania: Accumulation of the 581G Mutation in the P. falciparum Dihydropteroate Synthase Gene
Michael Alifrangis
Michael Alifrangis
Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagem, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; National Institute for Medical Research, Tanga Centre, Tanga, Tanzania
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John P. Lusingu
John P. Lusingu
Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagem, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; National Institute for Medical Research, Tanga Centre, Tanga, Tanzania
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Bruno Mmbando
Bruno Mmbando
Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagem, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; National Institute for Medical Research, Tanga Centre, Tanga, Tanzania
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Michael B. Dalgaard
Michael B. Dalgaard
Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagem, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; National Institute for Medical Research, Tanga Centre, Tanga, Tanzania
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Lasse S. Vestergaard
Lasse S. Vestergaard
Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagem, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; National Institute for Medical Research, Tanga Centre, Tanga, Tanzania
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Deus Ishengoma
Deus Ishengoma
Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagem, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; National Institute for Medical Research, Tanga Centre, Tanga, Tanzania
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Insaf F. Khalil
Insaf F. Khalil
Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagem, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; National Institute for Medical Research, Tanga Centre, Tanga, Tanzania
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Thor G. Theander
Thor G. Theander
Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagem, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; National Institute for Medical Research, Tanga Centre, Tanga, Tanzania
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Martha M. Lemnge
Martha M. Lemnge
Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagem, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; National Institute for Medical Research, Tanga Centre, Tanga, Tanzania
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Ib C. Bygbjerg
Ib C. Bygbjerg
Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagem, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark; National Institute for Medical Research, Tanga Centre, Tanga, Tanzania
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In January 2007, Tanzania replaced sulfadoxine-pyrimethamine (SP) with artemether-lumefantrine for treatment of uncomplicated malaria. This study examined the impact of widespread SP use on molecular markers of Plasmodium falciparum drug resistance in blood samples from persons living in two villages in Korogwe District, Tanzania, from 2003 through 2007. The prevalence of the P. falciparum dihydropteroate synthase (Pfdhps) gene 581G mutation increased from 12% in 2003 to 56% in 2007 (P < 0.001), resulting in an increase in the triple mutant Pfdhps haplotype SGEGA from 8% to 32% (P < 0.001). In contrast, the chloroquine-sensitive P. falciparum chloroquine resistance transporter (Pfcrt) CVMNK haplotype increased from 6% to 30% (P < 0.001). The dramatic increase of the triple Pfdhps mutant SGEGA haplotype may endanger the continued use of SP for intermittent presumptive treatment of pregnant women (IPTp). Further studies are needed to determine the importance of Pfdhps SGEGA haplotype parasites on the efficacy of SP for IPTp.
Author Notes
ProCite
RefWorks
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BibTeX
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-
1
Rønn AM, Msangeni HA, Mhina J, Wernsdorfer WH, Bygbjerg IC, 1996. High level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine in children in Tanzania. Trans R Soc Trop Med Hyg 90 :179–181.
-
2
Trigg JK, Mbwana H, Chambo O, Hills E, Watkins W, Curtis CF, 1997. Resistance to pyrimethamine/sulfadoxine in Plasmodium falciparum in 12 villages in north east Tanzania and a test of chlorproguanil/dapsone. Acta Trop 63 :185–189.
-
3
East African Network for Monitoring Antimalarial Treatment (EANMAT), 2003. The efficacy of antimalarial monotherapies, sulphadoxine-pyrimethamine and amodiaquine in East Africa: implications for sub-regional policy. Trop Med Int Health 8 :860–867.
-
4
Mugittu K, Ndejembi M, Malisa A, Lemnge M, Premji Z, Mwita A, Nkya W, Kataraihya J, Abdulla S, Beck HP, Mshinda H, 2004. Therapeutic efficacy of sulfadoxine-pyrimethamine and prevalence of resistance markers in Tanzania prior to revision of malaria treatment policy: Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase mutations in monitoring in vivo resistance. Am J Trop Med Hyg 71 :696–702.
-
5
Mutabingwa TK, Anthony D, Heller A, Hallett R, Ahmed J, Drakeley C, Greenwood BM, Whitty CJ, 2005. Amodiaquine alone, amodiaquine + sulfadoxine-pyrimethamine, amodiaquine + artesunate, and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian children: a four-arm randomised effectiveness trial. Lancet 365 :1474–1480.
-
6
Lemnge M, Alifrangis M, Kafuye MY, Segeja MD, Gesase S, Minja D, Massaga JJ, Ronn AM, Bygbjerg IC, 2006. High reinfection rate and treatment failures in children treated with amodiaquine for falciparum malaria in Muheza villages, northeastern Tanzania. Am J Trop Med Hyg 75 :188–193.
-
7
Cowman A, 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 :9109–9113.
-
8
Peterson DS, Walliker D, Wellems TE, 1988. Evidence that a point mutation in dihydrofolate reductase- thymidylate synthase confers resistance to pyrimethamine in falciparum malaria. Proc Natl Acad Sci USA 85 :9114–9118.
-
9
Brooks R, Wang P, Read M, Watkins MW, Sims PF, Hyde JE, 1994. Sequence variation of the hydroxymethyldihydropterin pyro-phosphokinase: dihydroptoate synthase gene lines of the human malaria parasite, Plasmodium falciparum, with differing resistance to sulfadoxine. J Biochem 224 :397–405.
-
10
Triglia T, Cowman A, 1994. Primary structure and expression of the dihydropteroate synthetase gene of Plasmodium falciparum. Proc Natl Acad Sci USA 91 :7149–7153.
-
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 :380–388.
-
12
Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LM, Sidhu AB, Naude B, Deitsch KW, Su XZ, Wootton JC, Roepe PD, Wellems TE, 2000. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell 6 :861–871.
-
13
Djimde A, Doumbo OK, Cortese JF, Kayentao K, Doumbo S, Diourte Y, Dicko A, Su XZ, Nomura T, Fidock DA, Wellems TE, Plowe CV, Coulibaly D, 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344 :257–263.
-
14
Holmgren G, Gil JP, Ferreira PM, Veiga MI, Obonyo CO, Bjorkman A, 2006. Amodiaquine resistant Plasmodium falciparum malaria in vivo is associated with selection of pfcrt 76T and pfmdr1 86Y. Infect Genet Evol 6 :309–314.
-
15
Warhurst DC, 2003. Polymorphism in the Plasmodium falciparum chloroquine-resistance transporter protein links verapamil enhancement of chloroquine sensitivity with the clinical efficacy of amodiaquine. Malar J 2 :31.
-
16
Alifrangis M, Dalgaard MB, Lusingu JP, Vestergaard LS, Staalsoe T, Jensen AT, Enevold A, Ronn AM, Khalil IF, Warhurst DC, Lemnge MM, Theander TG, Bygbjerg IC, 2006. Occurrence of the Southeast Asian/South American SVMNT haplotype of the chloroquine-resistance transporter gene in Plasmodium falciparum in Tanzania. J Infect Dis 193 :1738–1741.
-
17
Lusingu JP, Jensen AT, Vestergaard LS, Minja DT, Dalgaard MB, Gesase S, Mmbando BP, Kitua AY, Lemnge MM, Cavanagh D, Hviid L, Theander TG, 2006. Levels of plasma immunoglobulin G with specificity against the cysteine-rich interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane protein 1, VAR4, predict protection against malarial anemia and febrile episodes. Infect Immun 74 :2867–2875.
-
18
Bodker R, Akida J, Shayo D, Kisinza W, Msangeni HA, Pedersen EM, Lindsay SW, 2003. Relationship between altitude and intensity of malaria transmission in the Usambara Mountains, Tanzania. J Med Entomol 40 :706–717.
-
19
Alifrangis M, Enosse S, Pearce R, Drakeley C, Roper C, Khalil IF, Nkya WM, Ronn AM, Theander TG, Bygbjerg IC, 2005. A simple high-throughput method to detect Plasmodium falciparum single nucleotide polymorphisms in the dihydrofolate reductase, dihydropteroate synthase, and P. falciparum cloroquine resistance transporter genes using polymerase chain reaction and enzyme linked immunosorbent assay-based technology. Am J Trop Med Hyg 72 :155–162.
-
20
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 :1–8.
-
21
Wang P, Lee C-S, Bayoumi R, Djimde A, Doumbo O, Swedberg G, Dao LD, Mshinda H, Tanner M, Watkins MW, Sims PF, Hyde JE, 1997. Resistance to antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthetase and dihydrofolate reductase alleles in a large number of field samples of diverse origins. Mol Biochem Parasitol 89 :161–177.
-
22
Enevold A, Nkya WM, Theisen M, Vestergaard LS, Jensen AT, Staalsoe T, Theander TG, Bygbjerg IC, Alifrangis M, 2007. Potential impact of host immunity on malaria treatment outcome in Tanzanian children infected with Plasmodium falciparum. Malar J 6 :153.
-
23
Pearce RJ, Drakeley C, Chandramohan D, Mosha F, Roper C, 2003. Molecular determination of point mutation haplotypes in the dihydrofolate reductase and dihydropteroate synthase of Plasmodium falciparum in three districts of northern Tanzania. Antimicrob Agents Chemother 47 :1347–1354.
-
24
Okiro EA, Hay SI, Gikandi PW, Sharif SK, Noor AM, Peshu N, Marsh K, Snow RW, 2007. The decline in paediatric malaria admissions on the coast of Kenya. Malar J 6 :151.
-
25
Bhattarai A, Ali AS, Kachur SP, Martensson A, Abbas AK, Khatib R, Al-Mafazy AW, Ramsan M, Rotllant G, Gerstenmaier JF, Molteni F, Abdulla S, Montgomery SM, Kaneko A, Bjorkman A, 2007. Impact of artemisinin-based combination therapy and insecticide-treated nets on malaria burden in Zanzibar. PLoS Med 4 :e309.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 527 | 493 | 32 |
| Full Text Views | 287 | 4 | 1 |
| PDF Downloads | 81 | 4 | 1 |