Plasmodium falciparum malaria is a major cause of morbidity and mortality and factors that determine the development of uncomplicated (UM) versus cerebral malaria (CM) are not fully understood. It is likely, however, that many different host, parasite, vectorial and circumstantial factors combine to determine the severity of each malarial illness. We showed that heterogeneity in TNF responsiveness does occur at the level of the vascular endothelial cell, a diversity that might influence the severity of the disease in patients with malaria. The main objective of this project is to decipher the different molecular mechanisms underlying the endothelial inter-individual variations in response to TNF in order to develop tools to identify patients at risks and develop new therapeutic approaches. For this, we will carry out an extensive analysis of the difference in responsiveness to TNF we described between UM (low responders) and CM (high responders) patients, using cells freshly isolated from patients admitted at Ispat General Hospital in Rourkela, India. We will analyze this variation and assess whether it is due to parameters that are

Public Health Relevance

Cerebral malaria (CM), the most severe complication of Plasmodium falciparum infection, is often fatal and represents a major public health burden. Our recent results show that patients who develop CM exhibit an over-reaction of their brain endothelium to systemic inflammation, which is not observed in patients who develop uncomplicated malaria. We aim to investigate the potential factors leading to this over-reaction and to determine whether the phenomenon can be blocked or reversed.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19AI089676-03S1
Application #
8472621
Study Section
Special Emphasis Panel (ZAI1-AWA-M (M1))
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$237,173
Indirect Cost
$13,500
Name
New York University
Department
Type
DUNS #
041968306
City
New York
State
NY
Country
United States
Zip Code
10012
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