Department of Biochemistry, College of Medicine and Health Sciences, Sultan Qaboos University, Oman.
Infect Genet Evol. 2012 Aug;12(6):1253-9. doi: 10.1016/j.meegid.2012.03.011. Epub 2012 Mar 28.
A major challenge to the success of malaria control program in Saudi Arabia is the high influx of expatriates and holy visitors from malaria endemic countries. In the present study we examined whether drug resistant parasite genotypes reported in Jazan region, southwest of Saudi Arabia are imported or developed locally. We examined 178 Plasmodium falciparum isolates for alleles of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr), associated with Sulfadoxine-Pyrimethamine (SP) resistance, and three microsatellites flanking each gene. In addition, we examined a neutral polymorphic gene (Pfg377). We compared the dhfr and dhps haplotypes in Jazan, using network analysis, to an existing similar data set of 94 P. falciparum isolates from eastern Sudan. In Jazan, double mutant dhfr allele (51I, 108N) occurred with a prevalence of 33%. The vast majority (99%) of dhps were wild-type alleles. The mean expected heterozygosity (H(e)) of microsatellites around mutant dhfr alleles (H(e)=0.312; n=60) was lower (P ≤ 0.05) than that around the wild-type allele (H(e)=0.834; n=116). Also, the mutant dhfr isolates showed high H(e) for dhps (H(e)=0.80) and the non-drug resistance locus Pfg377 (H(e)=0.63) indicative of selection for mutant dhfr only. The predominant double mutant dhfr haplotype in Jazan (73%), was prevalent among P. falciparum in east Africa. Network analysis suggests the mutant haplotype of dhfr gene was possibly introduced into Jazan from East Africa. The absence of mutations in dhps as well as triple mutant dhfr haplotype associated with SP failure support the current use of SP as a partner with artesunate as a first line therapy in Saudi Arabia. However, the close relationship between the major mutant dhfr haplotype in Sudan and Saudi Arabia, favour the hypothesis of recent migration as a source of the major resistant dhfr lineage. Thus, regular monitoring of the dhfr and dhps haplotypes is of high priority to guard possible importation of high level SP resistant lineages.
沙特阿拉伯疟疾控制项目面临的主要挑战之一是大量来自疟疾流行国家的外国人和朝觐者涌入。在本研究中，我们研究了沙特阿拉伯西南部的吉赞地区报告的耐药寄生虫基因型是输入的还是当地产生的。我们检测了 178 株恶性疟原虫分离株的二氢叶酸合成酶（dhps）和二氢叶酸还原酶（dhfr）相关等位基因，这些等位基因与磺胺多辛-乙胺嘧啶（SP）耐药性有关，还检测了每个基因侧翼的三个微卫星。此外，我们还检查了一个中性多态基因（Pfg377）。我们使用网络分析将吉赞的 dhfr 和 dhps 单倍型与来自苏丹东部的 94 株恶性疟原虫的现有类似数据集进行了比较。在吉赞，双突变 dhfr 等位基因（51I，108N）的流行率为 33%。绝大多数（99%）的 dhps 为野生型等位基因。突变 dhfr 等位基因周围微卫星的平均预期杂合度（H(e)）（H(e)=0.312;n=60）较低（P≤0.05），而野生型等位基因周围的平均预期杂合度（H(e)=0.834;n=116）较高。此外，突变 dhfr 分离株的 dhps（H(e)=0.80）和非耐药基因 Pfg377（H(e)=0.63）的 H(e)较高，表明只有 dhfr 突变受到选择。吉赞流行的主要双突变 dhfr 单倍型（73%）在东非的恶性疟原虫中也很常见。网络分析表明，dhfr 基因的突变单倍型可能是从东非传入吉赞的。dhps 没有突变以及与 SP 失败相关的三重突变 dhfr 单倍型支持当前在沙特阿拉伯使用 SP 与青蒿琥酯联合作为一线治疗。然而，苏丹和沙特阿拉伯主要突变 dhfr 单倍型之间的密切关系支持最近移民是主要耐药 dhfr 谱系来源的假说。因此，定期监测 dhfr 和 dhps 单倍型对于防止高水平 SP 耐药谱系的可能输入至关重要。
