Genetic diversity of Plasmodium falciparum and distribution of drug resistance haplotypes in Yemen

Malaria Journal

Research

Zainab Al-Hashami¹  Hamza A Babiker²  Hissa Al-Farsi³  Salama Al-Hamidhi³  Mohamed A Idris³  Abdulsalam M Al-mekhlafi⁴  Mohammed AK Mahdy⁵  Albano Beja-Pereira⁶ 

[1] Department of Biochemistry, Faculty of Medicine and Health Sciences, Sultan Qaboos University, Alkhod, PO Box 35, Muscat, Oman;Department of Biochemistry, Faculty of Medicine and Health Sciences, Sultan Qaboos University, Alkhod, PO Box 35, Muscat, Oman;Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, EH9 3JT, Edinburgh, UK;Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman;Department of Parasitology, Faculty of Medicine, Sana’a University, Sana’a, Yemen;Department of Parasitology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia;Department of Parasitology, Faculty of Medicine, Sana’a University, Sana’a, Yemen;Research Centre in Biodiversity and Genetic Resources (CIBIO), University of Porto, Rua Padre Armando Quintas 7, Vairão, Portugal;

关键词: Malaria;    Yemen;    Arabian Peninsula;    Drug resistance;    Plasmodium falciparum;    Genetic diversity;   

DOI  :  10.1186/1475-2875-12-244

 received in 2013-03-02, accepted in 2013-07-11,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundDespite evident success of malaria control in many sites in the Arabian Peninsula, malaria remains endemic in a few spots, in Yemen and south-west of Saudi Arabia. In addition to local transmission, imported malaria sustains an extra source of parasites that can challenge the strengths of local control strategies. This study examined the genetic diversity of Plasmodium falciparum in Yemen and mutations of drug resistant genes, to elucidate parasite structure and distribution of drug resistance genotypes in the region.MethodsFive polymorphic loci (MSP-2, Pfg377 and three microsatellites on chromosome 8) not involved in anti-malarial drug resistance, and four drug resistant genes (pfcrt, pfmdr1, dhfr and dhps) were genotyped in 108 P. falciparum isolates collected in three sites in Yemen: Dhamar, Hodeidah and Taiz.ResultsHigh diversity was seen in non-drug genes, pfg377 (He = 0.66), msp-2 (He = 0.80) and three microsatellites on chr 8, 7.7 kb (He = 0.88), 4.3 kb (He = 0.77) and 0.8 kb (He = 0.71). There was a high level of mixed-genotype infections (57%), with an average 1.8 genotypes per patient. No linkage disequilibrium was seen between drug resistant genes and the non-drug markers (p < 0.05). Genetic differentiation between populations was low (most pair-wise FST values <0.03), indicating extensive gene flow between the parasites in the three sites.There was a high prevalence of mutations in pfmdr1, pfcrt and dhfr; with four mutant pfmdr1 genotypes (NFCDD[57%], NFSND[21%], YFCDD[13%] and YFSND[8% ]), two mutant pfcrt genotypes (CVIET[89%] and SVMNT[4%]) and one mutant dhfr genotype (ICNI[53.7%]). However, no dhps mutations were detected.ConclusionThe high diversity of P. falciparum in Yemen is indicative of a large parasite reservoir, which represents a challenge to control efforts. The presence of two distinct pfcrt genotype, CVIET and SVMNT, suggests that chloroquine resistance can possibly be related to a migratory path from Africa and Asia. The absence of the triple mutant dhfr genotype (IRN) and dhps mutations supports the use of artesunate + sulphadoxine-pyrimethamine as first-line therapy. However, the prevalent pfmdr1 genotype NFSND [21%] has previously been associated with tolerance/resistance response to artemisinin combination therapy (ACT). Regular surveys are, therefore, important to monitor spread of pfmdr1 and dhfr mutations and response to ACT.

【 授权许可】

Unknown   
© Al-Hamidhi et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.