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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Special Emphasis Panel (ZAI1)
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New York University
New York
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Hoffmann, Angelika; Wassmer, Samuel C (2018) New Syndromes Identified by Neuroimaging during Cerebral Malaria. Am J Trop Med Hyg 98:349-350
Carlton, Jane M (2018) Malaria parasite evolution in a test tube. Science 359:159-160
Thomas, Shalu; Ravishankaran, Sangamithra; Asokan, Aswin et al. (2018) Socio-demographic and household attributes may not necessarily influence malaria: evidence from a cross sectional study of households in an urban slum setting of Chennai, India. Malar J 17:4
Thomas, Shalu; Ravishankaran, Sangamithra; Justin, N A Johnson Amala et al. (2018) Microclimate variables of the ambient environment deliver the actual estimates of the extrinsic incubation period of Plasmodium vivax and Plasmodium falciparum: a study from a malaria-endemic urban setting, Chennai in India. Malar J 17:201
Huijben, Silvie; Chan, Brian H K; Nelson, William A et al. (2018) The impact of within-host ecology on the fitness of a drug-resistant parasite. Evol Med Public Health 2018:127-137
Carlton, Jane M; Sullivan, Steven A (2017) A Feast of Malaria Parasite Genomes. Cell Host Microbe 21:310-312
Mohanty, Sanjib; Benjamin, Laura A; Majhi, Megharay et al. (2017) Magnetic Resonance Imaging of Cerebral Malaria Patients Reveals Distinct Pathogenetic Processes in Different Parts of the Brain. mSphere 2:
Waite, Jessica L; Swain, Sunita; Lynch, Penelope A et al. (2017) Increasing the potential for malaria elimination by targeting zoophilic vectors. Sci Rep 7:40551
Uplekar, Swapna; Rao, Pavitra Nagesh; Ramanathapuram, Lalitha et al. (2017) Characterizing Antibody Responses to Plasmodium vivax and Plasmodium falciparum Antigens in India Using Genome-Scale Protein Microarrays. PLoS Negl Trop Dis 11:e0005323
Mooney, Jason Paul; Wassmer, Samuel Crocodile; Hafalla, Julius Clemence (2017) Type I Interferon in Malaria: A Balancing Act. Trends Parasitol 33:257-260

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