Journal article
Modelling pathogen load dynamics to elucidate mechanistic determinants of host–Plasmodium falciparum interactions
A Georgiadou, HJ Lee, M Walther, AE van Beek, F Fitriani, D Wouters, TW Kuijpers, D Nwakanma, U D’Alessandro, EM Riley, TD Otto, A Ghani, M Levin, LJ Coin, DJ Conway, MT Bretscher, AJ Cunnington
Nature Microbiology | NATURE PUBLISHING GROUP | Published : 2019
Abstract
During infection, increasing pathogen load stimulates both protective and harmful aspects of the host response. The dynamics of this interaction are hard to quantify in humans, but doing so could improve understanding of the mechanisms of disease and protection. We sought to model the contributions of the parasite multiplication rate and host response to observed parasite load in individual subjects infected with Plasmodium falciparum malaria, using only data obtained at the time of clinical presentation, and then to identify their mechanistic correlates. We predicted higher parasite multiplication rates and lower host responsiveness in cases of severe malaria, with severe anaemia being more..
View full abstractGrants
Awarded by Wellcome Trust
Funding Acknowledgements
We are grateful to K. Dietz for providing the original data and parameter estimates from malariatherapy patients, and his model, and to the St. Mary's NHLI FACS core facility and Y. Guo for support and instrumentation. This work was supported by the Medical Research Council (MRC) UK via core funding to the malaria research programme at the MRC Unit, The Gambia; the UK MRC and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement that is also part of the EDCTP2 program supported by the European Union (MR/L006529/1 to A.J.C.); a Wellcome Trust Value In People Award to A.J.C. and the European Union's seventh Framework program under EC-GA no. 279185 (EUCLIDS; www.euclids-project.eu).