1921
Volume 82, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Accumulation of mutations in dihydrofolate reductase () and dihydropteroate synthetase () is strongly associated with sulfadoxine-pyrimethamine (SP) treatment failure. Routine surveillance for these resistance markers was conducted annually at 26 sentinel sites in Maputo Province, Mozambique, before and after the phased deployment of artesunate plus SP (AS-SP), with 15,758 children sampled between 2004 and 2008. Mean asexual parasite prevalence, polymerase chain reaction (PCR) corrected, decreased from 44.2% in 2004 to 3.8% in 2008 ( < 0.0001). Among the 2,012 PCR-confirmed falciparum samples, the triple mutation remained close to fixation, whereas both double and “quintuple” mutations increased from 11.0% in 2004, to 75.0% by 2008 ( < 0.0001). Adding artesunate to SP did not retard the spread of SP-resistant parasites. The high “quintuple” mutation prevalence suggests a limited useful therapeutic lifespan of AS-SP for treating uncomplicated malaria, and may curb efficacy of SP-monotherapy for intermittent preventive treatment in Mozambique.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2010.09-0401
2010-05-01
2017-11-21
Loading full text...

Full text loading...

/deliver/fulltext/14761645/82/5/788.html?itemId=/content/journals/10.4269/ajtmh.2010.09-0401&mimeType=html&fmt=ahah

References

  1. Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI, , 2004. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434: 214217.[Crossref]
  2. Olliaro P, , 2005. Drug resistance hampers our capacity to roll back malaria. Clin Infect Dis 41 (Suppl 4): S247S257.[Crossref]
  3. World Health Organization, 2003. Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. Available at: http://www.who.int/malaria/docs/ProtocolWHO.pdf.
  4. White NJ, , 1999. Antimalarial drug resistance and chemotherapy. Philos Trans R Soc Lond B Biol Sci 354: 739749.[Crossref]
  5. Adjuik M, Babiker A, Garner P, Olliaro P, Taylor W, White N, , 2004. Artesunate combinations for the treatment of malaria: meta-analysis. Lancet 363: 917.[Crossref]
  6. Sutherland CJ, Ord R, Dunyo S, Jawara M, Drakeley CJ, Alexander N, Coleman R, Pinder M, Walraven G, Targett GAT, , 2005. Reduction of malaria transmission to Anopheles mosquitoes with a six dose regimen of co-artmether. PLoS Med 2: e92.[Crossref]
  7. World Health Organization, 2006. Guidelines for the treatment of malaria. Available at: http://www.who.int/malaria/docs/TreatmentGuidelines2006.pdf.
  8. World Health Organization, 2008. World Malaria Report. Available at: http://www.who.int/malaria/wmr2008.
  9. Enosse S, Magnussen P, Abacassamo F, Gomez-Olive X, Ronn AM, Thompson R, Alifrangis M, , 2008. Rapid increase of Plasmodium falciparum dhfr/dhps resistant haplotypes after the adoption of sulphadoxine-pyrimethamine as first line treatment in 2002, in southern Mozambique. Malar J 7: 115.[Crossref]
  10. Bwijo B, Kaneko A, Takechi M, Zungu IL, Moriyama Y, Lum JK, Tsukahara T, Mita T, Takahashi N, Bergqvist Y, Bjorkman A, Kobayakawa T, , 2003. High prevalence of quintuple mutant dhps/dhfr genes in Plasmodium falicaparum infections seven years after introduction of sulfadoxine and pyrimethamine as first line treatment in Malawi. Acta Trop 85: 363373.[Crossref]
  11. Roper C, Pearce R, Bredenkamp B, Gumede J, Drakeley C, Mosha F, Chandramohan D, Sharp B, , 2003. Antifolate antimalarial resistance in southeast Africa: a population-based analysis. Lancet 361: 11741181.[Crossref]
  12. Nkhoma S, Molyneux M, Ward S, , 2007. Molecular surveillance for drug-resistant Plasmodium falciparum malaria in Malawi. Acta Trop 102: 138142.[Crossref]
  13. Mlambo G, Sullivan D, Mutambu SL, Soko W, Mbedzi J, Chivenga J, Gemperli A, Kumar N, , 2007. High prevalence of molecular markers for resistance to choloroquine and pyrimethamine in Plasmodium falciparum from Zimbabwe. Parasitol Res 101: 11471151.[Crossref]
  14. O'Meara WP, Smith DL, McKenzie FE, , 2006. Potential impact of intermittent preventive treatment on the spread of drug resistant malaria. PLoS Med 3: e141.[Crossref]
  15. Sharp BL, Kleinschmidt I, Streat E, Maharaj R, Barnes KI, Durrheim DN, Ridl FC, Morris N, Seocharan I, Kunene S, La Granga JJP, Mthembu JD, Maartens F, Martin CL, Barreto A, , 2007. Seven years of regional malaria control collaboration–Mozambique, South Africa and Swaziland. Am J Trop Med Hyg 76: 4272.
  16. Allen EN, Little F, Camba T, Cassam Y, Raman J, Boulle A, Barnes KI, , 2009. Efficacy of sulphadoxine-pyrimethamine with or without artesunate for the treatment of uncomplicated Plasmodium falciparum malaria in southern Mozambique: a randomized controlled trial. Malar J 8: 141.[Crossref]
  17. The LSDI Annual Report, 2009. Lubombo Spatial Development Initiataive, Mapato Province, Annual Report, 2009. Available at: http://www.malaria.org.za/lsdi/Reports/2009/LSDIMaputoAnnualReport2009.pdf.
  18. Price RN, Uhlemann AC, Brockman A, McGready R, Ashley E, Phaipun L, Laing K, Looareesuwan S, White NJ, Nosten F, Krishna S, , 2004. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet 364: 438447.[Crossref]
  19. Shah NK, Alker AP, Sem R, Susanti AI, Muth S, Maguire JD, Duong S, Areiy F, Meshnick SR, Wongsrichanalai C, , 2008. Molecular surveillance for multidrug-resistant Plasmodium falciparum, Cambodia. Emerg Infect Dis 14: 16371640.[Crossref]
  20. Talisuna AO, Nalunkuma-Kazibwe A, Langi P, Mutabingwa TK, Watkins WW, Van Marck E, Egwang TG, D'Alsessandro U, , 2004. Two mutations in dihydrofolate reductase combined with one in the dihydropteroate sunthase gene predict sulphadoxine-pryimethamine parasitological failure in Ugandan children with uncomplicated falciparum malaria. Infect Genet Evol 4: 321327.[Crossref]
  21. Raman J, Sharp B, Kleinschmidt I, Roper C, Streat E, Kelly V, Barnes KI, , 2008. Differential effect of regional drug pressure on dihydrofolate reductase and dihydropteroate synthetase mutations in southern Mozambique. Am J Trop Med Hyg 78: 256261.
  22. Wooden J, Keyes S, Sibley CH, , 1993. PCR and strain identification in Plasmodium falciparum . Parasitol Today 9: 303305.[Crossref]
  23. Snounou G, Viriyakosol S, Zhu XP, Jarra W, Pinheiro L, do Rosario VE, Thaithong S, Brown KN, , 1993. High sensitivity to detection of human malaria parasites by the use of nested polymerase chain reaction. Mol Biol Parasitol 61: 315320.[Crossref]
  24. Plowe CV, Cortese JF, Djimde A, Nwanyanwu OC, Watkins WM, Winstanley PA, Estrada-France JG, Mollinedo R, Avila JC, Cespedes JL, Carter D, Doumbo OK, , 1997. Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance. J Infect Dis 176: 15901596.[Crossref]
  25. Rabe-Hesketh S, Skrondal A, , 2005. Multilevel and Longitudinal Modelling Using Stata. College Station, TX: StataCorp LP.
  26. Hopkins H, Kambale W, Kamya MR, Staedke SG, Dorsey G, Rosenthal PJ, , 2007. Comparison HRP2- and pLDH-based rapid diagnostic tests for malaria with longitudinal follow-up in Kampala, Uganda. Am J Trop Med Hyg 78: 256261.
  27. Nosten F, van Vugt M, Price R, Luxemburger C, Thway KL, Broackman A, McGready R, ter Kuile F, Looareesuwan S, White NJ, , 2000. Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand. Lancet 356: 297302.[Crossref]
  28. Brockman A, Price RN, van Vugt M, Heppner DG, Walsh D, Sookto P, Wimonwattrawatee T, Looareesuwan S, White NJ, Nosten F, , 2000. Plasmodium falciparum antimalarial drug susceptibility on the north-western border of Thailand during five years of extensive use of artesunate-mefloquine. Trans R Soc Trop Med Hyg 94: 537544.[Crossref]
  29. Watkins WM, Mosobo M, , 1993. Treatment of Plasmodium falciparum malaria with pyrimethamine-sulfadoxine: selective pressure for resistance is a function of long elimination half live. Trans R Soc Trop Med Hyg 87: 7578.[Crossref]
  30. Zongo I, Dorsey G, Rouamba N, Tinto H, Dokomajilar C, Guiguemde RT, Rosenthal PJ, Ouedraogo JB, , 2007. Artemether-lumefantrine versus amodiaquine plus sufaldoxine-pyrimethamine for uncomplicated malaria in Burkina Faso: a randomised non-inferiority trial. Lancet 369: 491498.[Crossref]
  31. Bell DJ, Nyirongo SK, Mukaka M, Zijlstra EE, Plowe CV, Molyneux ME, Ward SA, Winstanley PA, , 2008. Sulfadoxine-pyrimethamine-based combinations for malaria: a randomised blinded trial to compare efficacy, safety and selection of resistance in Malawi. PLoS One 3: e1578.[Crossref]
  32. Uhlemann A-C, McGready R, Ashley EA, Brockman A, Singhasivanon P, Krishna S, White NJ, Nosten F, Price RN, , 2007. Intrahost selection of Plasmodium falciparum pfmdr1 alleles after antimalarial treatment on the northwestern border of Thailand. J Infect Dis 195: 134141.[Crossref]
  33. Barnes KI, Little F, Mabuza A, Mngomezulu N, Govere J, Durrheim D, Roper C, Watkins B, White NJ, , 2008. Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria. J Infect Dis 197: 16051613.[Crossref]
  34. Mabuza A, Govere J, La Grange K, Mngomezulu N, Allen E, Zitha A, Mbokazi F, Durrheim D, Barnes K, , 2005. Therapeutic efficacy of sulfadoxine-pyrimethamine for Plasmodium falciparum malaria. S Afr Med J 95: 346349.
  35. Adjuik M, Babiker A, Garner P, Olliaro P, Taylor W, White N, , 2004. Artesunate combinations for treatment of malaria: meta-analysis. International Artemisinin Study Group. Lancet 363: 1822.[Crossref]
  36. Targett G, Drakeley C, Jawara M, von Seidlein L, Coleman R, Deen J, Pinder M, Doherty T, Sutherland C, Walraven G, Milligan P, , 2001. Artesunate reduces but does not prevent posttreatment transmission of Plasmodium falciparum to Anopheles gambiae . J Infect Dis 183: 12541259.[Crossref]
  37. Barnes KI, Little F, Smith PJ, Evans A, Watkins WM, White NJ, , 2006. Sulfadoxine-pyrimethamine pharmacokinetics in malaria: pediatric dosing implications. Clin Pharmacol Ther 80: 582596.[Crossref]
  38. Noedl H, Se Y, Schaecher K, Smith BL, Socheat D, Fukuda MM, , 2008. Artemisinin resistance in Cambodia 1 (ARC1) study consortium. N Engl J Med 359: 26192620.[Crossref]
  39. Dondorp AM, Nosten F, Poravuth P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ, , 2009. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361: 455467.[Crossref]
  40. World Health Organization, 2008. World Malaria Report. Available at: http://www.who.int/malaria/wmr2008.
  41. World Health Organization, 2008. Technical expert group meeting on intermittent preventive treatment in pregnancy (IPTp). Available at: http://apps.who.int/malaria/docs/IPTp/TechnicalExpertMtgIPTpReport.pdf.
  42. Dorsey G, Njama D, Kamya MR, Cattamanchi A, Kyabayinze D, Staedke SG, Gasasira A, Rosenthal PJ, , 2002. Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial. Lancet 360: 20312038.[Crossref]
  43. Rwagacondo CE, Niyitegeka F, Sarushi J, Karema C, Mugisha V, Dujardin JC, Van Overmeir C, van den Ende J, D'Alessandro U, , 2003. Efficacy of amodiaquine alone and combined with sulfadoxine-pyrimethamine and of sulfadoxine-pyrimethamine combined with artesunate. Am J Trop Med Hyg 68: 743747.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2010.09-0401
Loading
/content/journals/10.4269/ajtmh.2010.09-0401
Loading

Data & Media loading...

Supplementary Data

Supplementary appendix

  • Received : 15 Jul 2009
  • Accepted : 06 Feb 2010

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