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Details of talk

TitleDirect quantification of host removal in Plasmodium infection and the effects of antimalarial drugs on removal of parasites
PresenterRosemary Aogo (University of New South Wales)
Author(s)Rosemary Aogo, David S. Khoury, Deborah Cromer, Trish Elliott, Jasmin Akter, Lily G. Fogg, Arya Sheela Nair, Urijah N. Liligeto, Megan S. F. Soon, Bryce S. Thomas, Ashraful Haque, Miles P. Davenport
SessionMathematical Biology
Time11:30:00 2017-09-25
Abstract


The mononuclear phagocytic system (MPS) is thought to play a pivotal role in the
removal of malaria parasites from circulation. Artesunate causes a rapid
reduction in parasitemia compared to other drugs, such as mefloquine, and it has
been suggested that artesunate treated parasites are rapidly ‘cleared’ by the
host phagocytic system. However, a direct comparison of the removal of
artesunate-treated parasites relative to untreated parasites, or parasites
treated with different drugs is still lacking.
Here we combine experimental data and mathematical modelling. Using a novel
experimental system, we track the loss and replication of Plasmodium berghei
(PbA) infected cells in mice. Our novel mathematical modelling approach directly
estimate the host rate of removal and the replication rate of parasitized red
blood cells (pRBCs). Our analysis showed that in untreated mice pRBCs were
removed from circulation by the host with a half-life of around 14.7 hours. The
effect of antimalarial drugs on the host removal of pRBCs was also explored by
treating the mice with either artesunate or mefloquine. High dose
artesunate-treated parasites were removed from circulation approximately twice
as fast as in an untreated infection (half-life of 8.7 hours), while the
half-life of circulating parasites after mefloquine treatment was not
significantly different from that in untreated infection. Finally, we used
clodronate-containing liposomes to demonstrate a key role for phagocytes in the
removal of pRBCs in the murine PbA infections.