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Link between immune response and parasite synchronization in malaria.

TitleLink between immune response and parasite synchronization in malaria.
Publication TypeJournal Article
Year of Publication2003
AuthorsIM Rouzine, F McKenzie, E
JournalProc Natl Acad Sci U S A
Volume100
Issue6
Pagination3473-8
Date Published2003 Mar 18
ISSN0027-8424
KeywordsAnimals, Computer Simulation, Erythrocytes, Host-Parasite Interactions, Humans, Kinetics, Malaria, Falciparum, Models, Biological, Parasitemia, Periodicity, Plasmodium falciparum
Abstract

Anti-malaria vaccines and drugs could be greatly improved if we knew which phases of Plasmodium falciparum development in red blood cells are major inducers and which are major targets of natural immune responses. This information should focus attention on relevant immunogens and prove useful in developing immune-based therapies. Here we explore the hypothesis that innate immune responses mediate synchronization between the replication cycles of parasites in different red blood cells which is reflected in periodic fevers. Based on a recently developed, rather general mathematical model, we find that periodicity is highly sensitive to the position of both the inducing phase interval and the target phase interval in the parasite replication cycle. In addition, the degree of variability in the length of the replication cycle also strongly affects periodicity. To produce synchronization, the inducing and the target phase intervals must be developmentally distant from each other. We developed a computer program which prompts for information based on measurements of the numbers of erythrocytes in two replication cycle intervals chosen by the researcher, tests our model, and predicts the two phase intervals most critical to the synchronizing immune response. The program can be obtained from the authors.

DOI10.1073/pnas.262796299
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID12621156
PubMed Central IDPMC152317
Grant ListK25 AI001811 / AI / NIAID NIH HHS / United States
Z99 TW999999 / / Intramural NIH HHS / United States
K25 AI 01811 / AI / NIAID NIH HHS / United States