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

Malaria Journal

Research

Carlos Toro¹  Aranzazu Amor¹  Margarita Baquero¹  Pedro Berzosa²  Amalia Fernández-Martínez²  Agustín Benito² 

[1] Department of Microbiology and Parasitology, Hospital Carlos III, C/Sinesio Delgado 10, 28029, Madrid, Spain;Malaria Laboratory, National Centre of Tropical Medicine, Carlos III Institute of Health, C/Melchor Fernández Almagro 3, pabellón 13, 28029, Madrid, Spain;

关键词: Malaria;    Chloroquine;    Artemisinin Combination Therapy;    Artemisinin Combination Therapy;    Amodiaquine;   

DOI  :  10.1186/1475-2875-11-100

 received in 2011-11-21, accepted in 2012-03-30,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundDrug 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.MethodsA 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.ResultsThe 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.ConclusionsPharmacological 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.

【 授权许可】

CC BY   
© Amor et al; licensee BioMed Central Ltd. 2012