Multiplicity of Infection and Disease Severity in Plasmodium vivax.
Multiplicity of Infection and Disease Severity in Plasmodium vivax.
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DOI：
10.1371/journal.pntd.0004355
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发表时间：
2016-01
影响因子：
3.8
通讯作者：
Escalante AA
中科院分区：
文献类型：
--
作者：
Pacheco MA;Lopez-Perez M;Vallejo AF;Herrera S;Arévalo-Herrera M;Escalante AA
感染复数 (MOI) 是指同时感染患者的不同寄生虫基因型的平均数量。尽管有几项研究报告了恶性疟原虫的 MOI 和多克隆感染频率，但间日疟原虫的数据有限。在此，对南美洲地区的 MOI 和多克隆感染频率进行了研究，可以对间日疟原虫和恶性疟原虫进行比较。作为被动监测研究的一部分，2011 年至 2013 年间，哥伦比亚低传播地区招募了 1,328 名疟疾阳性患者。其中，在整个研究期间，只有 38 例间日疟原虫和 24 例恶性疟原虫临床复杂病例分散。将简单病例的样本与复杂病例的时间和地点进行匹配，以便比较这两类病例的循环基因型。总共对 92 例间日疟原虫和 57 例恶性疟原虫无并发症病例进行了随机二次抽样。所有样品均使用中性微卫星进行基因分型。间日疟原虫表现出比恶性疟原虫（14.8%）更多的多克隆感染（47.7%）。群体遗传学和单倍型网络分析没有检测到每种寄生虫的复杂和简单病例之间循环基因型的差异。然而，费舍尔精确检验发现多克隆间日疟原虫感染与复杂性疟疾之间存在显着关联。没有发现与恶性疟原虫感染之间的关联。间日疟原虫多克隆感染与疾病严重程度之间的关联与先前在啮齿动物疟疾中的观察结果一致。间日疟原虫和恶性疟原虫之间的对比模式可以至少部分地通过以下事实来解释：间日疟原虫感染的谱系比恶性疟原虫多克隆感染的谱系关系更远。未来的研究应该解决获得性免疫力和暴露对多克隆感染可能产生的作用及其与疾病严重程度的关系。先前对啮齿动物疟疾和数学模型的研究已经假设多克隆感染与疾病严重程度之间存在联系。这种关联已在主要在非洲的恶性疟原虫中进行了测试，有关间日疟原虫的信息有限。此外，来自传输率低的地区的信息也很少。在这里，我们使用了在南美洲哥伦比亚进行的被动监测中获得的样本。我们发现间日疟原虫的多克隆感染与疾病严重程度之间存在关联，但恶性疟原虫则不然。尽管复杂疟疾病例的数量很少，但这两个物种之间的对比模式强调了它们的流行病学差异。我们讨论了这种模式如何可能是由于同时感染患者的间日疟原虫谱系之间存在较高差异而导致的。我们假设低水平的获得性免疫可能在多克隆感染和疾病严重程度之间的关联中发挥作用。
Multiplicity of infection (MOI) refers to the average number of distinct parasite genotypes concurrently infecting a patient. Although several studies have reported on MOI and the frequency of multiclonal infections in Plasmodium falciparum, there is limited data on Plasmodium vivax. Here, MOI and the frequency of multiclonal infections were studied in areas from South America where P. vivax and P. falciparum can be compared. As part of a passive surveillance study, 1,328 positive malaria patients were recruited between 2011 and 2013 in low transmission areas from Colombia. Of those, there were only 38 P. vivax and 24 P. falciparum clinically complicated cases scattered throughout the time of the study. Samples from uncomplicated cases were matched in time and location with the complicated cases in order to compare the circulating genotypes for these two categories. A total of 92 P. vivax and 57 P. falciparum uncomplicated cases were randomly subsampled. All samples were genotyped by using neutral microsatellites. Plasmodium vivax showed more multiclonal infections (47.7%) than P. falciparum (14.8%). Population genetics and haplotype network analyses did not detect differences in the circulating genotypes between complicated and uncomplicated cases in each parasite. However, a Fisher exact test yielded a significant association between having multiclonal P. vivax infections and complicated malaria. No association was found for P. falciparum infections. The association between multiclonal infections and disease severity in P. vivax is consistent with previous observations made in rodent malaria. The contrasting pattern between P. vivax and P. falciparum could be explained, at least in part, by the fact that P. vivax infections have lineages that were more distantly related among them than in the case of the P. falciparum multiclonal infections. Future research should address the possible role that acquired immunity and exposure may have on multiclonal infections and their association with disease severity. Previous studies on rodent malarias and mathematical models have postulated a link between multiclonal infections and disease severity. This association has been tested in Plasmodium falciparum mostly in Africa with limited information on P. vivax. Furthermore, there is a paucity of information from areas with low transmission. Here, we used samples available from a passive surveillance carried out in Colombia, South America. We found an association between multiclonal infections and disease severity in P. vivax but not in P. falciparum. Although the number of complicated malaria cases is low, the contrasting pattern between these two species emphasizes their epidemiological differences. We discuss how this pattern could be the result of a higher divergence among the P. vivax lineages co-infecting a patient. We hypothesize that low levels of acquired immunity may play a role in the association between multiclonal infections and disease severity.