Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria.

Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria.
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DOI:
10.1186/1475-2875-11-276
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发表时间:
2012-08-16
期刊:
影响因子:
3
通讯作者:
Woodrow CJ
Woodrow CJ
中科院分区:
医学3区
文献类型:
--
作者:
Ramutton T;Hendriksen IC;Mwanga-Amumpaire J;Mtove G;Olaosebikan R;Tshefu AK;Onyamboko MA;Karema C;Maitland K;Gomes E;Gesase S;Reyburn H;Silamut K;Chotivanich K;Promnares K;Fanello CI;von Seidlein L;Day NP;White NJ;Dondorp AM;Imwong M;Woodrow CJ

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恶性疟原虫富组氨酸蛋白PFHRP2测量被广泛用于诊断,最近用于恶性疟疾的严重性评估。Pfhrp2基因具有高度多态性,在实验室和田间分离株中均报告了整个基因的缺失。这些问题可能混淆PFHRP2测量的解释。研究旨在检测Pfhrp2及其parabolic Pfhrp3的缺失进行了从七个国家的患者样本有助于最大的医院为基础的严重疟疾试验(AQUAMAT)。序列多态性和PFHRP 2血浆浓度之间的定量关系进行了研究,在莫桑比克和坦桑尼亚的选定地点的样品。在7个国家的77份PFHRP 2血浆浓度最低的样本中,没有证据表明Pfhrp2或Pfhrp3缺失。Pfhrp2序列的多样性非常高,没有单倍型之间共享66测序样品。Pfhrp2序列长度和重复类型与PFHRP2血浆浓度无相关性。这些发现表明,序列多态性不是非洲儿童血浆样本中PFHRP2浓度变化的重要原因。这证明进一步开发血浆PFHRP 2浓度作为评估可能患有严重恶性疟疾的非洲儿童的方法是合理的。这些数据也增加了现有的证据基础,支持使用基于PFHRP2检测的快速诊断测试。
Plasmodium falciparum histidine-rich protein PFHRP2 measurement is used widely for diagnosis, and more recently for severity assessment in falciparum malaria. The Pfhrp2 gene is highly polymorphic, with deletion of the entire gene reported in both laboratory and field isolates. These issues potentially confound the interpretation of PFHRP2 measurements. Studies designed to detect deletion of Pfhrp2 and its paralog Pfhrp3 were undertaken with samples from patients in seven countries contributing to the largest hospital-based severe malaria trial (AQUAMAT). The quantitative relationship between sequence polymorphism and PFHRP2 plasma concentration was examined in samples from selected sites in Mozambique and Tanzania. There was no evidence for deletion of either Pfhrp2 or Pfhrp3 in the 77 samples with lowest PFHRP2 plasma concentrations across the seven countries. Pfhrp2 sequence diversity was very high with no haplotypes shared among 66 samples sequenced. There was no correlation between Pfhrp2 sequence length or repeat type and PFHRP2 plasma concentration. These findings indicate that sequence polymorphism is not a significant cause of variation in PFHRP2 concentration in plasma samples from African children. This justifies the further development of plasma PFHRP2 concentration as a method for assessing African children who may have severe falciparum malaria. The data also add to the existing evidence base supporting the use of rapid diagnostic tests based on PFHRP2 detection.
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