Identification and quantification of biomarkers of malaria infection.
EMSL Project ID
44592
Abstract
This application is for the continuation of the currently closed proposal 8211 "Membrane proteins of placental parasites". We have a joint grant proposal between Richard D. Smith and Michal Fried to further investigate these biomarkers of infection. EMSL receives funding from this grant to perform the mass spectrometry of these samples. P. falciparum causes severe syndromes by adhering to endothelium and sequestering in deep vascular beds, where it elicits an inflammatory response. Pregnancy malaria is the best-understood malaria syndrome because the placenta provides accessible, abundant material for detailed studies of the sequestered parasites and local immune responses. Parasites infecting the human placenta are a distinct form, defined by their ability to adhere to the placental receptor chondroitin sulfate A (CSA) and to react with sera from multigravid women but not men. Women in endemic areas uniformly develop resistance to pregnancy malaria over 1-2 pregnancies as they acquire antibodies against placental parasites, and immune sera from multigravid women are cross-reactive with placental parasites collected in Africa and Asia. In a similar fashion, naturally exposed children develop immunity that prevents severe malaria relatively quickly, suggesting that the parasite forms that are targeted by protective immunity have limited diversity. This project aims to use proteomics tools to identify surface antigens expressed by parasites causing severe malaria syndromes similar to the approach we have used to study the parasites associated with pregnancy malaria. Immune responses to severe malaria have been associated with various mediators like cytokines and chemokines. However factors associated with a specific syndrome are unknown. Proteomics studies are a nonbiased approach to discover global protein expression, and will identify previously unrecognized factors that may influence disease outcome and will elucidate pathological changes associated with the development of severe malaria in children and pregnant women. Overall in this project we will identify parasite and host biomarkers that will guide the development of anti-parasite vaccine and disease-specific biomarkers that will provide a new tool to develop diagnostics.
Project Details
Start Date
2011-06-29
End Date
2014-05-06
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members