A model of Plasmodium vivax concealment based on Plasmodium cynomolgi infections in Macaca mulatta.
A model of Plasmodium vivax concealment based on Plasmodium cynomolgi infections in Macaca mulatta.
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DOI：
10.1186/s12936-017-2008-4
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发表时间：
2017-09-18
期刊：
影响因子：
3
通讯作者：
Voit EO
中科院分区：
文献类型：
--
作者：
Fonseca LL;Joyner CJ;MaHPIC Consortium;Galinski MR;Voit EO
间日疟原虫可引起严重的疟疾。感染期间的总寄生虫生物量与疾病的严重程度相关，但不一定通过显微镜准确定量。这一发现提出了一个问题，即是否存在在外周血涂片中未观察到的寄生虫亚群，但继续导致寄生虫数量增加，从而导致发病。利用密切相关的猴疟疾寄生虫食蟹猴疟原虫的非人灵长类动物感染模型具有量化可能未观察到的受感染红细胞（iRBC）群体的大小并确定这种隐藏水库的存在如何与疾病严重程度相关的潜力。使用追踪感染食蟹猴疟原虫的五只猕猴中寄生虫血症的纵向发展的时间序列数据来设计计算模型，该计算模型定量在血液中循环的iRBC与不可检测的iRBC，并且在此称为“隐藏的”iRBC。提出该术语是为了将这些观察结果与恶性疟原虫iRBC的深血管和广泛的“隔离”区分开来，后者由明显不同的分子机制控制。本文提供的计算模型清楚地表明，观察到的iRBC群体的生长数据与食蟹猴附红细胞的已知生物学和血液阶段周期不一致。然而，当考虑到隐藏的iRBC的亚群时，可以解决差异。该模型表明，隐藏的寄生虫亚群的早期增长有可能导致疾病。作为一种替代方案，这些数据可以通过裂殖子在数天内从肝脏连续释放来解释，但这种情况似乎不太可能。食蟹猴疟原虫感染M. mulatta是这种成功的宿主-病原体关系的一个重要方面。数据还支持间日疟原虫iRBC亚群具有相当的从外周循环中退出的手段的可能性。这一推论对理解间日疟生物学和发病机制具有重要意义，并强调了考虑间日疟流行病学和间日疟感染的量化和治疗方面的隐藏寄生虫水库的重要性。本文的在线版本（doi：10.1186/s12936-017-2008-4）包含补充材料，可供授权用户使用。
Plasmodium vivax can cause severe malaria. The total parasite biomass during infections is correlated with the severity of disease but not necessarily quantified accurately by microscopy. This finding has raised the question whether there could be sub-populations of parasites that are not observed in peripheral blood smears but continue to contribute to the increase in parasite numbers that drive pathogenesis. Non-human primate infection models utilizing the closely related simian malaria parasite Plasmodium cynomolgi hold the potential for quantifying the magnitude of possibly unobserved infected red blood cell (iRBC) populations and determining how the presence of this hidden reservoir correlates with disease severity. Time series data tracking the longitudinal development of parasitaemia in five Macaca mulatta infected with P. cynomolgi were used to design a computational model quantifying iRBCs that circulate in the blood versus those that are not detectable and are termed here as ‘concealed’. This terminology is proposed to distinguish such observations from the deep vascular and widespread ‘sequestration’ of Plasmodium falciparum iRBCs, which is governed by distinctly different molecular mechanisms. The computational model presented here clearly demonstrates that the observed growth data of iRBC populations are not consistent with the known biology and blood-stage cycle of P. cynomolgi. However, the discrepancies can be resolved when a sub-population of concealed iRBCs is taken into account. The model suggests that the early growth of a hidden parasite sub-population has the potential to drive disease. As an alternative, the data could be explained by the sequential release of merozoites from the liver over a number of days, but this scenario seems less likely. Concealment of a non-circulating iRBC sub-population during P. cynomolgi infection of M. mulatta is an important aspect of this successful host–pathogen relationship. The data also support the likelihood that a sub-population of iRBCs of P. vivax has a comparable means to become withdrawn from the peripheral circulation. This inference has implications for understanding vivax biology and pathogenesis and stresses the importance of considering a concealed parasite reservoir with regard to vivax epidemiology and the quantification and treatment of P. vivax infections. The online version of this article (doi:10.1186/s12936-017-2008-4) contains supplementary material, which is available to authorized users.
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影响因子：
6.4
作者：
Carvalho, Bruna O.;Lopes, Stefanie C. P.;Costa, Fabio T. M.
通讯作者：
Costa, Fabio T. M.
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影响因子：
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作者：
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影响因子：
3
作者：
Fonseca, Luis L.;Alezi, Harnel S.;Voit, Eberhard O.
通讯作者：
Voit, Eberhard O.
影响因子：
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作者：
Auburn, Sarah;Bohme, Ulrike;Otto, Thomas D
通讯作者：
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