1921
Volume 75, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Sulfadoxine-pyrimethamine (SP) is still a useful drug to combat chloroquine-resistant malaria in Cameroon. Because of several disadvantages of the test and drug sensitivity assays, molecular assays are an alternative laboratory tool to monitor the evolution of antifolate resistance, especially over the entire country that is characterized by several epidemiologic strata and malaria transmission patterns. In this study, 1,430 blood samples from either symptomatic children or asymptomatic carriers were collected from 14 sites throughout the country between 1999 and 2003 for the analysis of dihydrofolate reductase () sequence. Of 1,368 samples (95.7%) that were successfully amplified, 1,180 were analyzed by direct sequencing of the polymerase chain reaction product, and 188 were analyzed by restriction enzymes. The prevalences of the wild-type, single Asn-108 mutation, double Arg-59/Asn-108 mutations, double Ile-51/Asn-108 mutations, triple Ile-51/Arg-59/Asn-108 mutations, and mixed alleles were 20.8%, 2.8%, 5.7%, 0.8%, 62.2%, and 7.6%, respectively. The proportions of triple mutations were > 60% at all study sites, with the exception of the eastern province (42% triple mutants in Bertoua in 1999) and the northern provinces (11–35% triple mutants in Ngaoundere, Garoua, and Maroua). In these two provinces, the proportion of mutant parasites increased significantly ( < 0.05) over the period of 2–4 years. Furthermore, there was a higher proportion ( < 0.05) of wild-type parasites in the northern provinces, compared with the rest of the country. The geographic mapping of molecular markers offers a novel tool for monitoring the epidemiology of drug-resistant malaria.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2006.75.396
2006-09-01
2017-09-24
Loading full text...

Full text loading...

/deliver/fulltext/14761645/75/3/0750396.html?itemId=/content/journals/10.4269/ajtmh.2006.75.396&mimeType=html&fmt=ahah

References

  1. World Health Organization, 2003. Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. World Health Organization: Geneva, WHO/HTM/RBM/2003.50.
  2. White NJ, 2004. Antimalarial drug resistance. J Clin Invest 113 : 1084–1092.
  3. Ringwald P, Basco LK, 1999. Comparison of in vivo and in vitro tests of resistance in patients treated with chloroquine in Yaoundé, Cameroon. Bull World Health Org 77 : 34–43.
  4. Duraisingh MT, Roper C, Walliker D, Warhurst DC, 2000. Increased sensitivity to the antimalarials mefloquine and artemisinin is conferred by mutations in the pfmdr1 gene of Plasmodium falciparum. Mol Microbiol 36 : 955–961.
  5. 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.
  6. Ringwald P, Same Ekobo A, Keundjian A, Kedy Mangamba D, Basco LK, 2000. Chimiorésistance de P. falciparum en milieu urbain à Yaoundé, Cameroun. Part I: Surveillance in vitro et in vivo de la résistance de Plasmodium falciparum à la chloroquine entre 1994 et 1999 à Yaoundé, Cameroun. Trop Med Int Health 5 : 612–619.
  7. Basco LK, Foumane Ngane V, Ndounga M, Same-Ekobo A, Youmba JC, Okalla Abodo RT, Soula G, 2006. Molecular epidemiology of malaria in Cameroon. XXI Baseline therapeutic efficacy of chloroquine, amodiaquine, and sulfadoxine-pyrimethamine monotherapies in children before national drug policy change. Am J Trop Med Hyg. 75 : 388–395.
  8. Basco LK, 2004. Molecular epidemiology of malaria in Cameroon. XIX. Quality of antimalarial drugs used for self-medication. Am J Trop Med Hyg 70 : 245–250.
  9. 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 : 1811–1814.
  10. Basco LK, Ringwald P, 2000. Molecular epidemiology of malaria in Yaoundé, Cameroon. VI. Sequence variations in the Plasmodium falciparum dihydrofolate reductase-thymidylate synthase gene and in vitro resistance to pyrimethamine and cycloguanil. Am J Trop Med Hyg 62 : 271–276.
  11. Basco LK, Tahar R, Keundjian A, Ringwald P, 2000. Sequence variations in the genes encoding dihydropteroate synthase and dihydrofolate reductase and clinical response to sulfadoxine-pyrimethamine in patients with acute uncomplicated falciparum malaria. J Infect Dis 182 : 624–628.
  12. Bonnet S, Paul REI, Gouagna C, Safeukui I, Meunier JY, Gounoue R, Boudin C, 2002. Level and dynamics of malaria transmission and morbidity in an equatorial area of South Cameroon. Trop Med Int Health 7 : 249–256.
  13. Henning L, Felger I, Beck HP, 1999. Rapid DNA extraction for molecular epidemiological studies of malaria. Acta Trop 72 : 149–155.
  14. Basco LK, Ndounga M, Tejiokem M, Foumane Ngane V, Youmba JC, Ringwald P, Soula G, 2002. Molecular epidemiology of malaria in Cameroon. XI. Geographic distribution of Plasmodium falciparum isolates with dihydrofolate reductase gene mutations in southern and central Cameroon. Am J Trop Med Hyg 67 : 378–382.
  15. Eldin de Pécoulas P, Basco LK, Abdallah B, Djé MK, Le Bras J, Mazabraud A, 1995. Plasmodium falciparum: Detection of antifolate resistance by mutation-specific restriction enzyme digestion. Exp Parasitol 80 : 483–487.
  16. Hyde JE, 1990. The dihydrofolate reductase-thymidylate synthetase gene in the drug resistance of malaria parasites. Pharmacol Ther 48 : 45–59.
  17. Foote SJ, Galatas D, Cowman AF, 1990. Amino acids in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum involved in cycloguanil resistance differ from those involved in pyrimethamine resistance. Proc Natl Acad Sci U S A 87 : 3014–3017.
  18. Peterson DS, Milhous WK, Wellems TE, 1990. Molecular basis of differential resistance to cycloguanil and pyrimethamine in Plasmodium falciparum malaria. Proc Natl Acad Sci U S A 87 : 3018–3022.
  19. Ringwald P, Keundjian A, Same Ekobo A, Basco LK, 2000. Chimiorésistance de P. falciparum en milieu urbain à Yaoundé, Cameroun. Part 2: Evaluation de l’efficacité de l’amodiaquine et de l’association sulfadoxine-pyriméthamine pour le traitement de l’accès palustre simple à Plasmodium falciparum à Yaoundé, Cameroun. Trop Med Int Health 5 : 620–627.
  20. Ndounga M, Basco LK, Ringwald P, 2001. Evaluation of a new sulfadoxine sensitivity assay in vitro for field isolates of Plasmodium falciparum. Trans R Soc Trop Med Hyg 95 : 55–57.
  21. Basco LK, Ringwald P, 1999. Molecular epidemiology of malaria in Yaoundé, Cameroon. IV. Evolution of pyrimethamine resistance between 1994 and 1998. Am J Trop Med Hyg 61 : 802–806.
  22. Basco LK, 2003. Molecular epidemiology of malaria in Cameroon. XVI. Longitudinal surveillance of in vitro pyrimethamine resistance. Am J Trop Med Hyg 69 : 174–178.
  23. 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 : 991–996.
  24. Mockenhaupt FP, Bousema JT, Eggelte TA, Schreiber J, Ehrhardt S, Wassilew N, Otchwemah RN, Sauerwein RW, Bienzle U, 2005. Plasmodium falciparum dhfr but not dhps mutations associated with sulphadoxine-pyrimethamine treatment failure and gametocyte carriage in northern Ghana. Trop Med Int Health 10 : 901–908.
  25. Kublin JG, Dzinjalamala FK, Kamwendo DD, Malkin EM, Cortese JF, Martino LM, Mukadam RAG, 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.
  26. 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.
  27. 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.
  28. 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.
  29. Talisuna AO, Nalunkuma-Kazibwe A, Langi P, Mutabingwa TK, Watkins WW, Van Marck E, Egwang TG, D’Alessandro U, 2004. Two mutations in dihydrofolate reductase combined with one in the dihydropteroate synthase gene predict sulphadoxine-pyrimethamine parasitological failure in Ugandan children with uncomplicated falciparum malaria. Infect Genet Evol 4 : 321–327.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2006.75.396
Loading
/content/journals/10.4269/ajtmh.2006.75.396
Loading

Data & Media loading...

  • Received : 24 Oct 2005
  • Accepted : 03 May 2006

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error