The online version of this article (doi:10.1186/1475-2875-11-100) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
AA: carried out the laboratory work, data collection and analysis of the results and wrote the manuscript. AMF: was involved in laboratory work. CT revised the manuscript. MB and AB contributed to reagents and helped the study. PB: was involved in laboratory work and revised the manuscript. All authors read and approved the final manuscript.
Drug resistance is a major problem to control Plasmodium falciparum infection in endemic countries. During last decade, African countries have changed first-line treatment to artemisinin-based combinations therapy (ACT); sulphadoxine-pyrimethamine (SP) is recommended for Intermittent Preventive Therapy (IPT). Molecular markers related to P falciparum resistance were analysed for the period of transition from SP to ACT, in isolates imported from Africa.
A first group of samples was taken in the period between June 2002 and June 2006 (n = 113); a second group in the period between November 2008 and August 2010 (n = 46). Several alleles were analysed by nested PCR-RFLP: 51, 59, 108, 164, in the pfdhfr gene; 436, 437, 540, 581, in the pfdhps gene; 86, 1246, in the pfmdr1 gene and 76, in the pfcrt gene. The prevalence of alleles in the groups was compared with the chi-squared or Fisher's exact tests.
The pfdhfr N51I, C59R and S108N were over to 90% in the two groups; all samples had the I164. In the pfdhps, 437 G and 581 G, increased up to 80% and 10.9% (p = 0.024), respectively in the second group. The 540 G decreases (24% to 16.%) and the 436A disappears at the end of the follow-up (p = 0.004) in the second group. The 76I-pfcrt stayed over 95% in the two groups. Prevalence of 86Y-pfmdr1 decreased over eight years.
Pharmacological pressure affects the resistance strains prevalence. As for SP, the disappearance of 436A and the decrease in 540 G suggest that these mutations are not fixed. On the other hand, studies carried out after ACT introduction show there was a selection of strains carrying the SNPs N86Y, D1246Y in pfmdr1. In this work, the prevalence of pfmdr1- D1246Y is increasing, perhaps as a result of selective pressure by ACT. Continued surveillance is essential to monitor the effectiveness of treatments.
Authors’ original file for figure 112936_2011_2101_MOESM1_ESM.pdf
Steketee R, Voltaire F, Hay SI, Alonso PL, Atta HY, Bassat Q, Bakyaita N, Clark JP, Doumbo OK, Drakeley C, Eckert EL, Eisele T, Gausi K, Guinovart C, Hayes N, Kilian A, Lama M, Meek S, Miller J, Nahlen B, Otten M, Ratcliffe A, López MH, Slutsker L, Greenwood B, Tanner M: A research agenda for malaria eradication: monitoring, evaluation, and surveillance. PLoS Med. 2011, 8: e1000400- CrossRef
Lehane AM, van Schalkwyk DA, Valderramos SG, Fidock DA, Kirk K: Differential drug efflux or accumulation does not explain variation in the chloroquine response of Plasmodium falciparu strains expressing the same isoform of mutant PfCRT. Antimicrob Agents Chemother. 2011, 55: 2310-2318. 10.1128/AAC.01167-10. PubMedCentralCrossRefPubMed
WHO: Global report on antimalarial drug efficacy and drug resistance: 2000-2010. 2010, Geneva, Switzerland: World Health Organization
Salgueiro P, Vicente JL, Ferreira C, Teófilo V, Galvao A, do Rosario VE, Cravo P, Pinto J: Tracing the origin and signatures of selection of antifolate resistance in island populations of Plasmodium falciparu. BMC Infect Dis. 2010, 10:
Vinayak S, Alam MT, Mixson-Hayden T, McCollum AM, Sem R, Shah NK, Lim P, Muth S, Rogers WO, Fandeur T, Barnwell JW, Escalante AA, Wongsrichanalai C, Ariey F, Meshnick SR, Udhayakumar V: Origin and evolution of sulphadoxine resistant Plasmodium falciparu. PLoS Pathog. 2010, 6: e1000830-10.1371/journal.ppat.1000830. PubMedCentralCrossRefPubMed
WHO African Region: Country antimalarial drug policies. 2010, Geneva, Switzerland: World Health Organization, [ http://www.who.in/malaria/am_drug_policies_by_region_afro/en/index.htlm]
Humphreys GS, Merinopoulos I, Ahmed J, Whitty CJM, Mutabingwa TK, Sutherland CJ, Hallett RL: Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodiu alciparu mdr1 gene in Tanzanian children treated for uncomplicated malari. Antimicrob Agents Chemother. 2007, 51: 991-997. 10.1128/AAC.00875-06. PubMedCentralCrossRefPubMed
Somé AF, Seré YY, Dokomajilar C, Zongo I, Rouamba N, Greenhouse B, Ouédraogo JB, Rosenthal PJ: Selection of known Plasmodium falciparum res stance-mediating polymorphisms by artemether-lumefantrine and amodiaquine-sulfadoxinepyrimethamine but not dihydroartemisinin-piperaquine in Burkina Faso. Antimicrob Agents Chemother. 2010, 54: 1949-1954. 10.1128/AAC.01413-09. PubMedCentralCrossRefPubMed
Sisowath C, Petersen I, Veiga MI, Märtensson A, Premji Z, Björman A, Fidock DA, Gil JP: In vivo selection of Plasmodium falciparu parasites carrying the chloroquinesusceptible pfcrt K76 allele afte treatment with artemether-lumefantrine in Africa. J Infect Dis. 2009, 199: 750-757. 10.1086/596738. PubMedCentralCrossRefPubMed
PCR-allele-specific restriction analysis (ASRA): Protocols for Plasmodium falciparum drug resistance mutation analyses. 2002, University of Maryland School of Medicine, [ http://medschool.umaryland.edu/cvd/2002_pcr_asra.htm]
Picot S, Olliaro P, Monbrison F, Bienvenu AL, Price RN, Ringwald P: A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria. Malar J. 2009, 8: 89-10.1186/1475-2875-8-89. PubMedCentralCrossRefPubMed
Kapito-Tembo A, Meshnick SR, van Hesbroek MB, Phiri K, Fitzgerald M, Mwapasa V: Marked reduction in prevalence of malaria parasitaemia and anaemia in HIV-infected pregnant women taking cotrimoxazole with or without sulphadoxine-pyrimethamine intermittent preventive therapy during pregnancy in Malawi. J Infect Dis. 2011, 203: 464-472. 10.1093/infdis/jiq072. PubMedCentralCrossRefPubMed
Gasasira AF, Kamya MR, Ochonq EO, Vora N, Achan J, Charlebois E, Ruel T, Kateera F, Meva DN, Havlir D, Rosenthal PJ, Dorsey G: Effect of trimetroprim-sulphametoxazole on the risk of malaria in HIV-infected Ugandian children living in an area of widespread antifolate resistance. Malar J. 2010, 9: 17-10.1186/1475-2875-9-17. CrossRef
Gesase S, Gosling RD, Hashim R, Ord R, Naidoo I, Madebe R, Mosha JF, Joho A, Mandia V, Mrema H, Mapunda E, Savael Z, Lemnge M, Mosha F, Greenwood B, Roper C, Chandramohan D: High resistance of Plasmodium falciparu to sulphadoxine/pirymethamine in Northern Tanzania and the emergence of dhps resistance mutation at codon 581. PLoS ONE. 2009, 4: e4569-10.1371/journal.pone.0004569. PubMedCentralCrossRefPubMed
Harrington WE, Mutabingwa TK, Muehlenbachs A, Sorensen B, Bolla MC, Fried M, Duffy PE: Competitive facilitation of drug-resistant Plasmodium falciparu malaria parasites in pregnant women who receive preventive treatment. Proc Natl Acad Sci USA. 2009, 106: 9027-9032. 10.1073/pnas.0901415106. PubMedCentralCrossRefPubMed
Bertin G, Briand V, Bonaventure D, Carrieu A, Massougbodji A, Cot M, Deloron P: Molecular markers of resistance to sulphadoxine-pyrimethamine during intermittent preventive treatment of pregnant women in Benin. Malar J. 2011, 10: 169-10.1186/1475-2875-10-169. CrossRef
Kuile FO, Van Eijk AM, Scott JF: Effect of sulphadoxine-pyrimethamine resistance on the efficacy of intermittent preventive therapy for malaria control during pregnancy. J Am Med Ass. 2007, 297: 2603-2616. 10.1001/jama.297.23.2603. CrossRef
Dokomajilar C, Nsobya SL, Greenhouse B, Rosenthal PJ, Dorsey G: Selection of Plasmodium falciparum pfmdr alleles following therapy with artemether-lumefantrine in an area of Uganda where malaria is highly endemic. Antimicrob Agents Chemother. 2006, 50: 1893-1895. 10.1128/AAC.50.5.1893-1895.2006. PubMedCentralCrossRefPubMed
- Molecular markers in Plasmodium falciparum linked to resistance to anti-malarial drugs in samples imported from Africa over an eight-year period (2002-2010): impact of the introduction of artemisinin combination therapy
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