1921
Volume 75, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

We evaluated associations between key polymorphisms in target genes and responses to treatment with sulfadoxine-pyrimethamine (SP) or amodiaquine (AQ) for uncomplicated malaria in Bobo-Dioulasso, Burkina Faso. Presence of the dihydrofolate reductase () 108N or 59R mutations (but not 51I or dihydropteroate synthetase [] 437G) and chloroquine resistance transporter () 76T or multidrug resistance 1 () 86Y or 1246Y mutations (but not 184F) predicted recrudescence after treatment with SP and AQ, respectively. Treatment led to significant increases in the prevalence of the same mutations (except 1246Y) in new infections that presented after therapy. The 164L and 540E mutations were not seen in any isolates. These results clarify the key roles of a small number of mutations in resistance to SP and AQ in west Africa.

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2006-07-01
2017-09-24
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References

  1. Mockenhaupt FP, Ehrhardt S, Dzisi SY, Teun Bousema J, Wassilew N, Schreiber J, Anemana SD, Cramer JP, Otchwemah RN, Sauerwein RW, Eggelte TA, Bienzle U, 2005. A randomized, placebo-controlled, double-blind trial on sulfadoxine-pyrimethamine alone or combined with artesunate or amodiaquine in uncomplicated malaria. Trop Med Int Health 10 : 512–520.
  2. Yeka A, Banek K, Bakyaita N, Staedke SG, Kamya MR, Talisuna A, Kironde F, Nsobya SL, Kilian A, Slater M, Reingold A, Rosenthal PJ, Wabwire-Mangen F, Dorsey G, 2005. Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in Uganda. PLoS Med 2 : e190.
  3. Shulman CE, Dorman EK, Cutts F, Kawuondo K, Bulmer JN, Peshu N, Marsh K, 1999. Intermittent sulphadoxine-pyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial. Lancet 353 : 632–636.
  4. Schellenberg D, Menendez C, Aponte JJ, Kahigwa E, Tanner M, Mshinda H, Alonso P, 2005. Intermittent preventive antimalarial treatment for Tanzanian infants: follow-up to age 2 years of a randomised, placebo-controlled trial. Lancet 365 : 1481–1483.
  5. 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 : 582–588.
  6. Roper C, Pearce R, Bredenkamp B, Gumede J, Drakeley C, Mosha F, Chandramohan D, Sharp B, 2003. Antifolate anti-malarial resistance in southeast Africa: a population-based analysis. Lancet 361 : 1174–1181.
  7. 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.
  8. Reed MB, Saliba KJ, Caruana SR, Kirk K, Cowman AF, 2000. Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum. Nature 403 : 906–909.
  9. Pickard AL, Wongsrichanalai C, Purfield A, Kamwendo D, Emery K, Zalewski C, Kawamoto F, Miller RS, Meshnick SR, 2003. Resistance to antimalarials in southeast Asia and genetic polymorphisms in pfmdr1. Antimicrob Agents Chemother 47 : 2418–2423.
  10. Zongo I, Dorsey G, Rouamba N, Dokomajilar C, Lankoande M, Ouedraogo JB, Rosenthal PJ, 2005. Amodiaquine, sulfadoxine-pyrimethamine, and combination therapy for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso. Am J Trop Med Hyg 73 : 826–832.
  11. Cattamanchi A, Kyabayinze D, Hubbard A, Rosenthal PJ, Dorsey G, 2003. Distinguishing recrudescence from reinfection in a longitudinal antimalarial drug efficacy study: comparison of results based on genotyping of msp-1, msp-2, and glurp. Am J Trop Med Hyg 68 : 133–139.
  12. Anderson TJ, Su XZ, Bockarie M, Lagog M, Day KP, 1999. Twelve microsatellite markers for characterization of Plasmodium falciparum from finger-prick blood samples. Parasitology 119 : 113–125.
  13. 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 : 565–568.
  14. 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.
  15. Kyabayinze D, Cattamanchi A, Kamya MR, Rosenthal PJ, Dorsey G, 2003. Validation of a simplified method for using molecular markers to predict sulfadoxine-pyrimethamine treatment failure in African children with falciparum malaria. Am J Trop Med Hyg 69 : 247–252.
  16. Wongsrichanalai C, Pickard AL, Wernsdorfer WH, Meshnick SR, 2002. Epidemiology of drug-resistant malaria. Lancet Infect Dis 2 : 209–218.
  17. Marks F, Evans J, Meyer CG, Browne EN, Flessner C, von Kalckreuth V, Eggelte TA, Horstmann RD, May J, 2005. High prevalence of markers for sulfadoxine and pyrimethamine resistance in Plasmodium falciparum in the absence of drug pressure in the Ashanti region of Ghana. Antimicrob Agents Chemother 49 : 1101–1105.
  18. Dorsey G, Dokomajilar C, Kiggundu M, Staedke SG, Kamya MR, Rosenthal PJ, 2004. Principal role of dihydropteroate synthase mutations in mediating resistance to sulfadoxine-pyrimethamine in single-drug and combination therapy of uncomplicated malaria in Uganda. Am J Trop Med Hyg 71 : 758–763.
  19. Ochong EO, van den Broek IV, Keus K, Nzila A, 2003. Short report: association between chloroquine and amodiaquine resistance and allelic variation in the Plasmodium falciparum multiple drug resistance 1 gene and the chloroquine resistance transporter gene in isolates from the upper Nile in southern Sudan. Am J Trop Med Hyg 69 : 184–187.
  20. 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 : 309–314.
  21. Hawley SR, Bray PG, Park BK, Ward SA, 1996. Amodiaquine accumulation in Plasmodium falciparum as a possible explanation for its superior antimalarial activity over chloroquine. Mol Biochem Parasitol 80 : 15–25.
  22. Sisowath C, Stromberg J, Martensson A, Msellem M, Obondo C, Bjorkman A, Gil JP, 2005. In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem). J Infect Dis 191 : 1014–1017.
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  • Received : 10 Feb 2006
  • Accepted : 19 Feb 2006

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