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Investigating the role of cerebral vasoconstriction in cerebral malaria

Award Number: R21AI142472
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/12/2019
PERIOD OF PERFORMANCE END DATE: 01/31/2021

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Investigating the role of cerebral vasoconstriction in cerebral malaria - Plasmodium falciparum malaria is a major cause of mortality and morbidity in the developing world and cerebral malaria (CM), its most severe form, accounts for the majority of malaria-associated deaths. The pathophysiology and the molecular mechanisms underlying this complex neurologic syndrome are still poorly understood, which has hindered the development of effective adjunct therapies. For this exploratory project, we will leverage our International Center of Excellence for Malaria Research in India to expand the unique ongoing MRI investigations in both adults and pediatric CM patients admitted at Ispat General Hospital (IGH) in Rourkela, and apply advanced magnetic resonance imaging techniques in the first comprehensive vascular imaging analysis of its kind. Novel findings suggest that reversible cerebral vasoconstriction syndrome (RCVS) alone or in combination with posterior reversible encephalopathy syndrome (PRES) may play a role in the pathophysiology of CM. Here, we propose to investigate the occurrence, frequency and amplitude of cerebral vasoconstriction in CM patients at IGH by combining for the first time serial vascular imaging including time-of-flight and phase-contrast magnetic resonance angiography , as well as cerebral perfusion measurements and assessment of subtle blood-brain barrier disruption. By comparing our imaging results with plasma levels of endothelin-1 (ET-1), angiopoietin-1(Ang-1), Ang-2 and free heme in our patients, we will evaluate their clinical relevance as biomarkers of RCVS in CM. The primary outcome of this project will be a better understanding of the different pathogenetic processes involved in pediatric and adult CM, which will guide the development of new adjunct therapies.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2021 ( Subtotal = -$21,253 )
2021	2020	LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE	KEPPEL ST	LONDON				GBR	Allergy and Infectious Diseases Research	000	2	9/9/2021	NON-COMPETING CONTINUATION	-$21,253
														Subtotal = -$21,253

Issue Date FY: 2020 ( Subtotal = $143,309 )
2020	2020	LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE	KEPPEL ST	LONDON		WC1E 7HT		GBR	Allergy and Infectious Diseases Research	000	2	1/27/2020	NON-COMPETING CONTINUATION	$143,309
														Subtotal = $143,309

Issue Date FY: 2019 ( Subtotal = $147,053 )
2019	2019	LONDON SCHOOL OF HYGIENE & TROPICAL MEDICINE	KEPPEL ST	LONDON		WC1E 7HT		GBR	Allergy and Infectious Diseases Research	000	1	2/11/2019	NEW	$147,053
														Subtotal = $147,053

Grand Total All Awards = $269,109

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Investigating the role of cerebral vasoconstriction in cerebral malaria

Award Number: R21AI142472

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/12/2019

PERIOD OF PERFORMANCE END DATE: 01/31/2021

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