Malaria continues to cause marked morbidity and mortality worldwide. Infection can result in severe life threatening disease, mild symptoms or an asymptomatic carriage state. Protection from severe disease outcomes naturally occurs in residents high Plasmodium falciparum transmission regions. This protection is related to repeated malaria exposures which result in mild to asymptomatic carriage rather than devastating complications which occur in non-immune individuals. The basis of this clinical observation made decades ago remains poorly characterized. Our group and others have identified a role for type I INF response during malarial infection. Type I INF is known as a powerful immunomodulatory molecule that can promote activation, differentiation or even apoptosis of effector cells such as NK and T lymphocytes and favor cross-priming by DCs. Thus, our working hypothesis proposes that a stronger type I IFN response in malaria infections is associated with a more protective host innate and adaptive immune responses. We will examine the role of type IINF during mild malaria and whether this response changes during repeated infections in one individual, alters the risk of re-infection and is associated with transmission intensity. This proposal brings Dr. Lauvau's expertise in studying immune responses against microbial pathogens, Dr. Daily's expertise in transcriptional analysis with the Malawi ICEMR program to characterize innate and subsequent adaptive immune responses in children with mild disease in a longitudinal study. This proposal will enhance the Malawi ICEMR goals of understanding the determinants of malarial disease. Host immune responses alter the development of malarial disease and thus this proposal will provide a further characterization of host responses to inform disease models. We will also address how changes in transmission intensity through malaria control interventions in the parent study may alter host response and disease presentation. Finally, this proposal will further the training mission of the Malawi ICEMR by training Malawian scientists and building in-country laboratory and scientific capacity in malaria immunology.

Public Health Relevance

This project investigates specific aspects of the immune response associated with malaria infections in humans, a leading cause of morbidity and mortality worldwide. We will examine the role of type I interferon, a powerful immunomodulatory molecule during infection and whether this response changes during repeated infections in one individual, alters the risk of re-infection and is associated with transmission intensity. Studies ill inform vaccine and adjunctive therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19AI089683-03S1
Application #
8412100
Study Section
Special Emphasis Panel (ZAI1-AWA-M (M1))
Program Officer
Rao, Malla R
Project Start
2010-07-01
Project End
2017-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$249,671
Indirect Cost
$15,551
Name
Michigan State University
Department
Internal Medicine/Medicine
Type
Schools of Osteopathic Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Mzilahowa, Themba; Chiumia, Martin; Mbewe, Rex B et al. (2016) Increasing insecticide resistance in Anopheles funestus and Anopheles arabiensis in Malawi, 2011-2015. Malar J 15:563
Buchwald, Andrea G; Walldorf, Jenny A; Cohee, Lauren M et al. (2016) Bed net use among school-aged children after a universal bed net campaign in Malawi. Malar J 15:127
Coalson, Jenna E; Walldorf, Jenny A; Cohee, Lauren M et al. (2016) High prevalence of Plasmodium falciparum gametocyte infections in school-age children using molecular detection: patterns and predictors of risk from a cross-sectional study in southern Malawi. Malar J 15:527
Mathanga, Don P; Tembo, Atupele Kapito; Mzilahowa, Themba et al. (2016) Patterns and determinants of malaria risk in urban and peri-urban areas of Blantyre, Malawi. Malar J 15:590
Artimovich, Elena; Schneider, Kristan; Taylor, Terrie E et al. (2015) Persistence of Sulfadoxine-Pyrimethamine Resistance Despite Reduction of Drug Pressure in Malawi. J Infect Dis 212:694-701
Sisya, Tamika J; Kamn'gona, Raphael M; Vareta, Jimmy A et al. (2015) Subtle changes in Plasmodium falciparum infection complexity following enhanced intervention in Malawi. Acta Trop 142:108-14
Kobayashi, Tamaki; Gamboa, Dionicia; Ndiaye, Daouda et al. (2015) Malaria Diagnosis Across the International Centers of Excellence for Malaria Research: Platforms, Performance, and Standardization. Am J Trop Med Hyg 93:99-109
Cui, Liwang; Mharakurwa, Sungano; Ndiaye, Daouda et al. (2015) Antimalarial Drug Resistance: Literature Review and Activities and Findings of the ICEMR Network. Am J Trop Med Hyg 93:57-68
Wassmer, Samuel C; Taylor, Terrie E; Rathod, Pradipsinh K et al. (2015) Investigating the Pathogenesis of Severe Malaria: A Multidisciplinary and Cross-Geographical Approach. Am J Trop Med Hyg 93:42-56
Artimovich, Elena; Kapito-Tembo, Atupele; Pensulo, Paul et al. (2015) The effect of local variation in malaria transmission on the prevalence of sulfadoxine-pyrimethamine resistant haplotypes and selective sweep characteristics in Malawi. Malar J 14:387

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