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

• Published in: Malaria Journal
• Main Authors: Luis L. Fonseca, Chester J. Joyner, MaHPIC Consortium, Mary R. Galinski, Eberhard O. Voit
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2017
• Subjects: Host–pathogen interactions; Malaria; Mathematical model; Parasite dynamics; Plasmodium falciparum; Sequestration; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-017-2008-4; https://doaj.org/article/6a03934881ed4ede9c308189109782b3

Abstract Background 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. Methods 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. Results 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. Conclusions 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 ...