The University of Georgia College of Veterinary Medicine

Georgia Veterinary Scholars Program

GVSP Summer 2011 Scholars

Georgia Veterinary Scholar	Faculty Mentor

Shannon Day UGA College of Veterinary Medicine Class of 2013	Dr. Julie Moore Department of Infectious Diseases UGA College of Veterinary Medicine

Neurological and Behavioral Changes Associated With Cerebral Malaria in a Laboratory Mouse Model

Shannon Day and Julie M. Moore

Background: Malaria remains a major public health concern in many parts of the developing world, with over 240 million cases diagnosed each year. Nearly one million people die each year from complications of the disease, with the majority of the fatalities occurring in children younger than five years of age. In the severest manifestation of Plasmodium falciparum infection, the intraerythrocytic parasite gains the ability to adhere to blood vessels via host endothelial receptors, leading to impaired blood flow and organ damage. When this occurs in the brain, a condition referred to as cerebral malaria, many patients succumb even with aggressive medical intervention. There is still much unknown about the pathogenesis of cerebral malaria, mainly because the disease is difficult to study in human subjects. P. berghei ANKA infection in laboratory mice has been most commonly used to study cerebral malaria, as it closely mimics the disease seen in humans. The aim of this study is to establish a recently published algorithm (using the SHIRPA protocol) that scores P.berghei ANKA infected mice based on a number of behavioral tests, neurological and physiologic assessments, and parasitemia. These resulting scores, when applied to the algorithm, predict not only which mice will develop cerebral malaria, but also when the mice will succumb to the disease. Once established, this algorithm can be used in further studies with genetically modified mice to investigate the possible role of coagulation in the pathogenesis of cerebral malaria.
Methods: Groups of 6-7 mice were evaluated on days 4, 5, and 6 post-infection using the SHIRPA protocol. Scores were calculated based on the published algorithm. Mice showing signs of cerebral malaria were immediately euthanized; those not exhibiting such signs were monitored daily and then euthanized on day 12.
Results: The evaluation and scoring methods have been optimized and 3 of the 5 total planned groups have been completed. Although data analysis is ongoing, the results thus far suggest that genetic background plays an important role in disease outcome. The algorithm may need to be modified to be reliably applied to genetically manipulated mice.