Nicastri Emanuele, Paglia Maria Grazia, Severini Carlo, Ghirga Piero, Bevilacqua Nazario, Narciso Pasquale
Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani, IRCCS, Rome, Italy.
Travel Med Infect Dis. 2008 Jul;6(4):205-9. doi: 10.1016/j.tmaid.2008.01.001. Epub 2008 Mar 4.
The pathogenesis of malaria is the result of complex interactions between parasites, host and environment. Several studies have assessed the role of genetic characteristics of Plasmodium falciparum infection in the clinical severity of malaria infection comparing different genotypic determinants in mild and severe cases. The genes encoding the polymorphic merozoite surface proteins 1 (msp-1) and 2 (msp-2) and the dihydrofolate reductase (dhfr) of malaria parasites have been extensively used as markers to investigate the genetic diversity and the population structure of P. falciparum. The aim of this study was to assess the epidemiological, clinical, host- and parasite-related determinant factor of the genetic diversity of P. falciparum infections in travellers returning to Italy.
Between 1998 and 2001, we have retrospectively studied 64 inpatients all returning from African malaria-endemic countries. Designation of severe malaria was determined by using the World Health Organization (WHO) definition. P. falciparum infections detected by species-specific PCR were genotyped at the msp-1 and msp-2 loci and clones were determined. PCR and enzyme-digestion methods were used to screen the mutation occurring at codon 108.
Multiple P. falciparum genotypes were detected in 32 patients (50%). The number of genotypes was correlated to different host characteristics. No association was found between allelic number of msp-1 or msp-2 and season of travel, absence of antimalarial prophylaxis, length of stay or blood parasitemia. At multiple analysis adjusted for few confounding variables, two variables showed a significant association with multiplicity of P. falciparum genotypes: male gender (p=0.018) and severity of disease (p=0.044).
In our study all but one patients with severe malaria had a infection with a multiplicity of P. falciparum clones. At multivariate analysis the male gender, and the occurrence of severe malaria were significantly more commonly detected in patients affected by imported malaria with multiple clones.
疟疾的发病机制是寄生虫、宿主和环境之间复杂相互作用的结果。多项研究评估了恶性疟原虫感染的遗传特征在疟疾感染临床严重程度中的作用,比较了轻症和重症病例中不同的基因型决定因素。编码多态性裂殖子表面蛋白1(msp-1)和2(msp-2)以及疟原虫二氢叶酸还原酶(dhfr)的基因已被广泛用作标记,以研究恶性疟原虫的遗传多样性和种群结构。本研究的目的是评估返回意大利的旅行者中恶性疟原虫感染遗传多样性的流行病学、临床、宿主和寄生虫相关决定因素。
1998年至2001年期间,我们对64名均从非洲疟疾流行国家返回的住院患者进行了回顾性研究。重症疟疾的诊断采用世界卫生组织(WHO)的定义。通过种特异性PCR检测到的恶性疟原虫感染在msp-1和msp-2位点进行基因分型并确定克隆。采用PCR和酶切方法筛选108密码子处发生的突变。
32例患者(50%)检测到多种恶性疟原虫基因型。基因型数量与不同的宿主特征相关。未发现msp-1或msp-2等位基因数量与旅行季节、未进行抗疟预防、停留时间或血中疟原虫血症之间存在关联。在对少数混杂变量进行校正的多因素分析中,有两个变量与恶性疟原虫基因型的多样性显著相关:男性(p=0.018)和疾病严重程度(p=0.044)。
在我们的研究中,除1例患者外,所有重症疟疾患者均感染了多种恶性疟原虫克隆。在多变量分析中,男性以及重症疟疾在感染多种克隆的输入性疟疾患者中明显更为常见。