Effect of mature blood-stage Plasmodium parasite sequestration on pathogen biomass in mathematical and in vivo models of malaria

Khoury, David S., Cromer, Deborah, Best, Shannon E., James, Kylie R., Kim, Peter S., Engwerda, Christian R., Haque, Ashraful and Davenport, Miles P. (2014) Effect of mature blood-stage Plasmodium parasite sequestration on pathogen biomass in mathematical and in vivo models of malaria. Infection and Immunity, 82 1: 212-220. doi:10.1128/IAI.00705-13

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Author Khoury, David S.
Cromer, Deborah
Best, Shannon E.
James, Kylie R.
Kim, Peter S.
Engwerda, Christian R.
Haque, Ashraful
Davenport, Miles P.
Title Effect of mature blood-stage Plasmodium parasite sequestration on pathogen biomass in mathematical and in vivo models of malaria
Formatted title
Effect of mature blood-stage Plasmodium parasite sequestration on pathogen biomass in mathematical and in vivo models of malaria
Journal name Infection and Immunity   Check publisher's open access policy
ISSN 0019-9567
1098-5522
Publication date 2014-01-01
Sub-type Article (original research)
DOI 10.1128/IAI.00705-13
Open Access Status File (Publisher version)
Volume 82
Issue 1
Start page 212
End page 220
Total pages 9
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Formatted abstract
Parasite biomass and microvasculature obstruction are strongly associated with disease severity and death in Plasmodium falciparum- infected humans. This is related to sequestration of mature, blood-stage parasites (schizonts) in peripheral tissue. The prevailing view is that schizont sequestration leads to an increase in pathogen biomass, yet direct experimental data to support this are lacking. Here, we first studied parasite population dynamics in inbred wild-type (WT) mice infected with the rodent species of malaria, Plasmodium berghei ANKA. As is commonly reported, these mice became moribund due to large numbers of parasites in multiple tissues. We then studied infection dynamics in a genetically targeted line of mice, which displayed minimal tissue accumulation of parasites. We constructed a mathematical model of parasite biomass dynamics, incorporating schizontspecific host clearance, both with and without schizont sequestration. Combined use of mathematical and in vivo modeling indicated, first, that the slowing of parasite growth in the genetically targeted mice can be attributed to specific clearance of schizonts from the circulation and, second, that persistent parasite growth in WT mice can be explained solely as a result of schizont sequestration. Our work provides evidence that schizont sequestration could be a major biological process driving rapid, early increases in parasite biomass during blood-stage Plasmodium infection.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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