Skip to main content

Advertisement

Log in

Prevalence of molecular markers of Plasmodium falciparum resistance to sulfadoxine–pyrimethamine during the intermittent preventive treatment in infants coupled with the expanded program immunization in Senegal

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Several studies have shown the efficacy of the intermittent preventive treatment (IPT) using sulfadoxine–pyrimethamine (SP) coupled with the expanded program of immunization (EPI) in infants. However, its adoption as a strategy is conditioned by the long-term efficacy of SP. The impact of IPT–SP coupled with the EPI on the prevalence of markers of resistance to SP was evaluated during this study conducted in Southern Senegal. Three cross-sectional surveys in two health districts (IPT+) were conducted prior to the implementation, 1 year, and 2 years after. A third district located between the two districts served as a test zone (IPT−). PCR tests were carried out from filter papers collected in children under five for the two first measures and from positive rapid diagnostic tests in the same population for the third measure. Mutations in codons 51, 59, and 108 of the DHFR gene and in codons 437 and 540 of the DHPS were analyzed. The results showed that the prevalence of DHFR triple mutation was more frequent after 2 years in IPT+ areas. Regarding quadruple mutation, DHFR (51, 59, and 108) and DHPS (437), no difference was noted between the two areas. The quintuple mutation was not observed after 2 years of implementation in both areas. However, an individual analysis showed significant differences in the individual mutation points 51, 59, 108, and 437. This study reveals that despite an increase in the prevalence of individual mutations, the IPT-SP coupled with the EPI has no major impact on DHFR and DHPS combined mutations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aponte JJ, Schellenberg D, Egan A, Breckenridge A, Carneiro I, Critchley J, Danquah I, Dodoo A, Kobbe R, Lell B, May J, Premji Z, Sanz S, Sevene E, Soulaymani-Becheikh R, Winstanley P, Adjei S, Anemana S, Chandramohan D, Issifou S, Mockenhaupt F, Owusu-Agyei S, Greenwood B, Grobusch MP, Kremsner PG, Macete E, Mshinda H, Newman RD, Slutsker L, Tanner M, Alonso P, Menendez C (2009) Efficacy and safety of intermittent preventive treatment with sulfadoxine–pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials. Lancet 374(9700):1533–1542

    Article  PubMed  CAS  Google Scholar 

  • Chandramohan D, Owusu-Agyei S, Carneiro I, Awine T, Amponsa-Achiano K, Mensah N, Jaffar S, Baiden R, Hodgson A, Binka F, Greenwood B (2005) Cluster randomised trial of intermittent preventive treatment for malaria in infants in area of high, seasonal transmission in Ghana. BMJ 331(7519):727–733

    Article  PubMed  Google Scholar 

  • Cissé B, Sokhna C, Boulanger D, Milet J, Bâ el H, Richardson K, Hallett R, Sutherland C, Simondon K, Simondon F, Alexander N, Gaye O, Targett G, Lines J, Greenwood B, Trape JF (2006) Seasonal intermittent preventive treatment with artesunate and sulfadoxine–pyrimethamine for prevention of malaria in Senegalese children: a randomised, placebo-controlled, double-blind trial. Lancet 367(9511):659–667

    Article  PubMed  Google Scholar 

  • Dicko A, Sagara I, Djimdé AA, Touré SO, Traore M, Dama S, Diallo AI, Barry A, Dicko M, Coulibaly OM, Rogier C, de Sousa A, Doumbo OK (2010) Molecular markers of resistance to sulphadoxine–pyrimethamine one year after implementation of intermittent preventive treatment of malaria in infants in Mali. Malar J 9:9. doi:10.1186/1475-2875-9-9

    Article  PubMed  Google Scholar 

  • Doumbo OK, Kayentao K, Djimde A, Cortese JF, Diourte Y, Konaré A, Kublin JG, Plowe CV (2000) Rapid selection of Plasmodium falciparum dihydrofolate reductase mutants by pyrimethamine prophylaxis. J Infect Dis 182(3):993–996

    Article  PubMed  CAS  Google Scholar 

  • Eboumbou Moukoko EC, Bogreau H, Briolant S, Pradines B, Rogier C (2009) Molecular markers of Plasmodium falciparum drug resistance. Med Trop 69:606–612

    CAS  Google Scholar 

  • Enosse S, Magnussen P, Abacassamo F, Gómez-Olivé X, Rønn 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. doi:10.1186/1475-2875-7-115

    Article  PubMed  Google Scholar 

  • Etard JF, Delaunay V, Le Hesran JY, Ndiaye JL, Diallo JP (2004) Childhood mortality and probable causes of death using verbal autopsy in Niakhar, Senegal, 1989–2000. Int J Epidemiol 33(6):1286–1292

    Article  PubMed  Google Scholar 

  • Grobusch MP, Lell B, Schwarz NG, Gabor J, Dornemann J, Potschke M, Oyakhirome S, Kiessling GC, Necek M, Langin MU, Klein Klouwenberg P, Klopfer A, Naumann B, Altun H, Agnandji ST, Goesch J, Decker M, Salazar CL, Supan C, Kombila DU, Borchert L, Koster KB, Pongratz P, Adegnika AA, Glasenapp I, Issifou S, Kremsner PG (2007) Intermittent preventive treatment against malaria in infants in Gabon—a randomized, double-blind, placebo-controlled trial. J Infect Dis 196(11):1595–1602

    Article  PubMed  CAS  Google Scholar 

  • Henderson RH, Sundundarset T (1982) Cluster sampling to assess immunization coverage. A review experience with a simplified method. Bull World Health Org 60:253–260

    PubMed  CAS  Google Scholar 

  • 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(3):380–388

    Article  PubMed  CAS  Google Scholar 

  • Macete E, Aide P, Aponte JJ, Sanz S, Mandomando I, Espasa M, Sigauque B, Dobaño C, Mabunda S, DgeDge M, Alonso P, Menendez C (2006) Intermittent preventive treatment for malaria control administered at the time of routine vaccinations in Mozambican infants: a randomized, placebo-controlled trial. J Infect Dis 194(3):276–285

    Article  PubMed  Google Scholar 

  • Mayor A, Serra-Casas E, Sanz S, Aponte JJ, Macete E, Mandomando I, Puyol L, Berzosa P, Dobaño C, Aide P, Sacarlal J, Benito A, Alonso P, Menéndez C (2008) Molecular markers of resistance to sulfadoxine–pyrimethamine during intermittent preventive treatment for malaria in Mozambican infants. J Infect Dis 197(12):1737–1742

    Article  PubMed  Google Scholar 

  • Ministère de la Santé et de la Prévention Médicale. (2006). Centre de Recherche pour le Développement Humain Dakar, Sénégal Enquête Démographique et de Santé Sénégal 2005 (EDS IV)

  • Mockenhaupt FP, Bedu-Addo G, Eggelte TA, Hommerich L, Holmberg V, von Oertzen C, Bienzle U (2008) Rapid increase in the prevalence of sulfadoxine–pyrimethamine resistance among Plasmodium falciparum isolated from pregnant women in Ghana. J Infect Dis 198(10):1545–1549

    Article  PubMed  Google Scholar 

  • Ndiaye D, Daily JP, Sarr O, Ndir O, Gaye O, Mboup S, Wirth DF (2005) Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase genes in Senegal. Trop Med Int Health 10(11):1176–1179. doi:10.1111/j.1365-3156

    Article  PubMed  CAS  Google Scholar 

  • Ndiaye D, Daily JP, Sarr O, Ndir O, Gaye O, Mboup S, Roper C, Wirth DF (2006) Defining the origin of Plasmodium falciparum resistant dhfr isolates in Senegal. Acta Trop 99(1):106–111

    Article  PubMed  CAS  Google Scholar 

  • O'Meara WP, Smith DL, McKenzie FE (2006) Potential impact of intermittent preventive treatment (IPT) on spread of drug-resistant malaria. PLoS Med 3(5):e141

    Article  PubMed  Google Scholar 

  • Picot S, Olliaro P, de Monbrison F, Bienvenu AL, Price RN, Ringwald P (2009) A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria. Malar J 8:89. doi:10.1186/1475-2875-8-89

    Article  PubMed  Google Scholar 

  • 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(6):565–568

    PubMed  CAS  Google Scholar 

  • Schellenberg D, Menendez C, Kahigwa E, Aponte J, Vidal J, Tanner M, Mshinda H, Alonso P (2001) Intermittent treatment for malaria and anaemia control at time of routine vaccinations in infants: a randomised, placebo-controlled trial. Lancet 357:1471–1477

    Article  PubMed  CAS  Google Scholar 

  • Sendagire H, Kyabayinze D, Swedberg G, Kironde F (2005) Plasmodium falciparum: higher incidence of molecular resistance markers for sulphadoxine than for pyrimethamine in Kasangati, Uganda. Trop Med Int Health 10(6):537–543

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the populations of Kedougou, Velingara, and Tambacounda regions and the Health staff of Kédougou, Velingara, and Tambacounda medical districts.

This study was funded by the Bill and Melinda Gates Foundation through UNICEF.

Conflict of interest

None declared.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Babacar Faye.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Faye, B., Ndiaye, M., Ndiaye, J.L. et al. Prevalence of molecular markers of Plasmodium falciparum resistance to sulfadoxine–pyrimethamine during the intermittent preventive treatment in infants coupled with the expanded program immunization in Senegal. Parasitol Res 109, 133–138 (2011). https://doi.org/10.1007/s00436-010-2236-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-010-2236-9

Keywords

Navigation