Färnert Anna, Tengstam Karolin, Palme Ingela Berggren, Bronner Ulf, Lebbad Marianne, Swedberg Göte, Björkman Anders
Department of Medicine, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
Am J Trop Med Hyg. 2002 May;66(5):487-91. doi: 10.4269/ajtmh.2002.66.487.
The polymorphism of malaria parasites will greatly influence the efficiency of antimalarial drugs and vaccines. This study determined the genetic diversity of Plasmodium falciparum infections in 107 travelers and estimated the importance of mutations in the parasite dihydrofolate reductase (dhfr) gene for clinical breakthrough during proguanil prophylaxis. Genotyping with regards to the three highly polymorphic antigen-coding regions (merozoite surface protein-1 [msp-1], msp-2, and the glutamate-rich protein [glurp]) revealed multiple genotypes (up to five) in 64% of the patients. Single genotype infections were mainly associated with prior intake of antimalarial drugs, but also with a shorter stay in a malaria-endemic area and low parasite density. Malaria breakthrough despite proguanil prophylaxis was always associated with mutations in the dhfr gene; always the Asn-108 mutation and often the Ile-51 and Arg-59 mutations. The Leu-164 mutation was found in four travelers from Africa. Travelers with limited time in an endemic area were often infected with polyclonal P. falciparum infections, which suggests that single mosquito inoculations are often composed of several genetically diverse parasites. Chemoprophylaxis reduces the number of infecting clones and selects for resistant parasites as shown for proguanil through mutations in the dhfr gene.
疟原虫的多态性会极大地影响抗疟药物和疫苗的效力。本研究确定了107名旅行者中恶性疟原虫感染的遗传多样性，并评估了寄生虫二氢叶酸还原酶（dhfr）基因中的突变对于氯胍预防期间临床突破的重要性。针对三个高度多态的抗原编码区域（裂殖子表面蛋白-1 [msp-1]、msp-2和富含谷氨酸的蛋白 [glurp]）进行基因分型，结果显示64%的患者存在多种基因型（多达五种）。单一基因型感染主要与先前服用抗疟药物有关，但也与在疟疾流行地区停留时间较短以及寄生虫密度较低有关。尽管进行了氯胍预防仍出现疟疾突破，这总是与dhfr基因中的突变有关；总是出现Asn-108突变，并且常常出现Ile-51和Arg-59突变。在来自非洲的四名旅行者中发现了Leu-164突变。在流行地区停留时间有限的旅行者常常感染多克隆恶性疟原虫，这表明单次蚊虫叮咬通常由几种基因不同的寄生虫组成。化学预防减少了感染克隆的数量，并如氯胍通过dhfr基因中的突变所显示的那样，选择出耐药寄生虫。
