Severe malaria (SM) places a disproportionate burden of nriortality and death on the children of Sub-Saharan Africa. Death, as a result of SM, is not a direct consequence of parasite load but is associated with excessive inflammatory response(s) in the brain and lungs of SM patients. Parasite-derived activators of the innate immune response, together with inflammatory monocytes, have been implicated in mediating this tissue damage. However, the activation pathways responsible for localized inflammation and compromising the blood brain barrier (BBB) remain to be determined. We propose elucidating the mechanism(s) by: 1. Defining the transcriptional profiles at the sites of damage in tissues from pediatric SM. We propose assembling a transcriptional

Public Health Relevance

90% of the deaths caused by severe malaria occur in children in Sub-Saharan Africa. Death, most frequently, is the result of an inappropriate level of inflammation in the microvasculature of the brain or the lungs of the SM patient. This project proposes determination of the role of parasite pigment-loaded monocytes in mediating or exacerbating this pathology, and the identification of chemotherapeutic approaches to de-activate the damaging cellular response. the identification of chemotherapeutic

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI089683-04
Application #
8502238
Study Section
Special Emphasis Panel (ZAI1-AWA-M)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$205,952
Indirect Cost
$4,747
Name
Michigan State University
Department
Type
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Mohanty, Sanjib; Taylor, Terrie E; Kampondeni, Sam et al. (2014) Magnetic resonance imaging during life: the key to unlock cerebral malaria pathogenesis? Malar J 13:276
Mathanga, Don P; Walker, Edward D; Wilson, Mark L et al. (2012) Malaria control in Malawi: current status and directions for the future. Acta Trop 121:212-7
Wilson, Mark L; Walker, Edward D; Mzilahowa, Themba et al. (2012) Malaria elimination in Malawi: research needs in highly endemic, poverty-stricken contexts. Acta Trop 121:218-26