Association of severe malaria with a specific Plasmodium falciparum genotype in French Guiana

Association of severe malaria with a specific Plasmodium falciparum genotype in French Guiana
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DOI:
10.1086/322012
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发表时间:
2001-07-15
影响因子:
6.4
通讯作者:
Mercereau-Puijalon, O
Mercereau-Puijalon, O
中科院分区:
医学2区
文献类型:
--
作者:
Ariey, F;Hommel, D;Mercereau-Puijalon, O

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为什么只有一小部分患者发生严重的恶性疟原虫疟疾尚不清楚。在法属圭亚那,一个低流行区,寄生虫多样性低,所有严重病例的患者都被转诊到一个重症监护室,研究了特定寄生虫特征导致严重程度的可能性。在地理和时间上匹配的轻度和重度疾病患者中进行的寄生虫基因分型显示,在重度和轻度疾病患者中,特定msp-1等位基因(B-K1)与特定var基因(var-D)的相关性过高(分别为47%和3%; P <0.001)。此外,在最严重的临床病例中始终观察到这种基因型组合。逆转录聚合酶链反应证实了var-D在体内的程序性表达,这与其在严重疾病中的潜在意义一致。这些结果提供了严重疟疾与寄生虫特定遗传特征相关的现场证据,并为针对寄生虫关键毒力因子的干预策略开辟了道路。
Why severe Plasmodium falciparum malaria occurs in only a small percentage of patients is unclear. The possibility that specific parasite characteristics contribute to severity has been investigated in French Guiana, a hypoendemic area, where parasite diversity is low and all patients with severe cases are referred to a single intensive care unit. Parasite genotyping in geographically and temporally matched patients with mild and severe disease showed that the association of a specific msp-1 allele (B-K1) with a specific var gene (var-D) was overrepresented among patients with severe versus mild disease (47% vs. 3%, respectively; P < .001). Moreover, this genotype combination was consistently observed in the most severe clinical cases. Reverse-transcription polymerase chain reaction demonstrated programmed expression of var-D in vivo, which is consistent with its potential implication in severe disease. These results provide field evidence of an association of severe malaria with specific genetic characteristics of parasites and open the way for intervention strategies targeting key virulence factors of parasites.