A model of Plasmodium vivax concealment based on Plasmodium cynomolgi infections in Macaca mulatta

Malaria Journal

Research

Mary R. Galinski¹  Chester J. Joyner²  Luis L. Fonseca³  Eberhard O. Voit³ 

[1] International Center for Malaria Research, Education and Development, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, 30329, Atlanta, GA, USA;Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, GA, USA;Malaria Host-Pathogen Interaction Center, Atlanta, GA, USA;International Center for Malaria Research, Education and Development, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, 30329, Atlanta, GA, USA;Malaria Host-Pathogen Interaction Center, Atlanta, GA, USA;The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 950 Atlantic Drive, Suite 2115, 30332-2000, Atlanta, GA, USA;Malaria Host-Pathogen Interaction Center, Atlanta, GA, USA;

关键词: Host–pathogen interactions;    Malaria;    Mathematical model;    Parasite dynamics;    Plasmodium falciparum;    Sequestration;    Systems biology;   

DOI  :  10.1186/s12936-017-2008-4

 received in 2017-04-07, accepted in 2017-09-02,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundPlasmodium 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.MethodsTime 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.ResultsThe 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.ConclusionsConcealment 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.

【 授权许可】

CC BY   
© The Author(s) 2017