Increased expression levels of the pvcrt-o and pvmdr1 genes in a patient with severe Plasmodium vivax malaria.

Increased expression levels of the pvcrt-o and pvmdr1 genes in a patient with severe Plasmodium vivax malaria.
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患有严重间日疟原虫疟疾的患者中 pvcrt-o 和 pvmdr1 基因的表达水平增加。

DOI:
10.1186/1475-2875-8-55
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发表时间:
2009-04-02
期刊:
影响因子:
3
通讯作者:
Gascón J
Gascón J
中科院分区:
医学3区
文献类型:
--
作者:
Fernández-Becerra C;Pinazo MJ;González A;Alonso PL;del Portillo HA;Gascón J

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有越来越多的报告严重的临床病例完全与间日疟原虫感染。值得注意的是,这种严重性最近被认为与氯喹抗性有关。两名不同的患者在巴塞罗那医院诊所就诊,患有间日疟。一名患者症状严重,另一名症状轻微。这两名患者于2007年穿越巴西亚马逊(马瑙斯)。对这两名患者来说,目前的疟疾诊断是第一次。另外两名症状轻微的病人于2000年也在巴西亚马逊(朗)的“热带医学研究中心”就诊。为了排除患者的严重症状是由于恶性疟原虫的可能性,进行了巢式PCR。使用磁性方法纯化不含人白细胞的间日疟原虫。进行定量实时PCR以比较可能参与间日疟原虫氯喹抗性的两种主要转运蛋白的转录水平,即间日疟原虫氯喹抗性转运蛋白pvcrt-o和间日疟原虫多药抗性转运蛋白pvmdr 1。结果表明,严重的临床症状完全是由于间日疟原虫。患者出现急性呼吸道疾病,需要入住重症监护室。磁性方法显示高度纯化的感染网织红细胞具有成熟阶段。此外,发现与来自具有轻度症状的其他患者的寄生虫的表达水平相比,从重度患者获得的寄生虫具有高达2.9倍的pvmdr 1水平增加和高达21.9倍的pvcrt-o水平增加。这是西班牙首例完全与间日疟有关的严重疾病临床病例。此外,这些研究结果表明,临床严重程度可能与氯喹抗性可能涉及的寄生虫基因的表达水平增加有关。有必要进一步探讨pvmdr 1,特别是pvcrt-o表达水平作为间日疟原虫严重疾病分子标志物的潜力。
There are increasing reports of severe clinical cases exclusively associated with Plasmodium vivax infections. Notably, this severity has been recently suggested to be associated with chloroquine resistance. Two different patients presented at the Hospital Clinic in Barcelona with P. vivax malaria episodes. One patient had severe symptoms and the other mild symptoms. Both patients traveled through the Brazilian Amazon (Manaus) in 2007. For both patients the current diagnosis of malaria was the first. Two other patients with mild symptoms presented to the "Centro de Pesquisa em Medicina Tropical", also in the Brazilian Amazon (Rondônia) in 2000. To exclude the possibility that the patient's severe symptoms were due to Plasmodium falciparum, a nested PCR was performed. A magnetic method was used to purify P. vivax free of human leukocytes. Quantitative real-time PCR was performed to compare the transcript levels of two main transporters likely to be involved in chloroquine resistance in P. vivax, namely the P. vivax chloroquine resistance transporter, pvcrt-o, and the P. vivax multidrug resistance transporter, pvmdr 1. Results demonstrated that the severe clinical symptoms were exclusively due to P. vivax. The patient presented acute respiratory conditions requiring admission to the intensive care unit. The magnetic method showed highly purified infected-reticulocytes with mature stages. In addition, it was found that parasites obtained from the severe patient had up to 2.9-fold increase in pvmdr1 levels and up to 21.9-fold increase in pvcrt-o levels compared to expression levels of parasites from the other patients with mild symptoms. This is the first clinical case of severe disease exclusively associated with vivax malaria in Spain. Moreover, these findings suggest that clinical severity could be associated with increased expression levels of parasite genes likely involved in chloroquine resistance. It is necessary to further explore the potential of pvmdr1 and particularly pvcrt-o expression levels as molecular markers of severe disease in P. vivax.
DOI: 10.1086/510756
发表时间: 2007-02-15
期刊: The Journal of infectious diseases
影响因子: --
作者:
Anstey NM;Handojo T;Pain MC;Kenangalem E;Tjitra E;Price RN;Maguire GP
通讯作者: Maguire GP
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发表时间: 2007-10-31
期刊: PloS one
影响因子: 3.7
作者:
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通讯作者: Price RN
DOI: 10.1016/j.actatropica.2003.12.001
发表时间: 2004-04-01
期刊: ACTA TROPICA
影响因子: 2.7
作者:
Lacerda, MVG;Alexandre, MAA;Alecrim, MGC
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DOI: 10.1186/1475-2875-3-7
发表时间: 2004-03-01
期刊: MALARIA JOURNAL
影响因子: 3
作者:
Trang, DTX;Huy, NT;Kamei, K
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DOI: 10.4269/ajtmh.2009.80.194
发表时间: 2009-02-01
影响因子: 3.3
作者:
Kochar, Dhanpat K.;Das, Ashish;Gupta, Vikas
通讯作者: Gupta, Vikas