The Murine Model of Cerebral Malaria–Colin MacKichan

According to the World Health Organization, about 3.2 billion people, or half the world’s population, are at risk for malaria, which is directly linked to poverty. Countries with the highest poverty rates have also been shown to have the highest malaria infection rates. An estimated one percent of victims of malaria develop cerebral malaria (CM), which results in swelling and hemorrhaging in white matter in the corpus collosum and the subcortical rim leading to a thirty percent mortality rate. Of the seventy percent of patients that do survive, about ten to twenty percent have lasting physical and cognitive dysfunction.

Although CM still imposes a large threat to the world’s population, funding for research is largely nonexistent due to the fact that the wealthiest countries are no longer affected. Ideally human research experiments could be conducted, but developing countries rarely have the funds for MRI, MRS, and CT scans needed to properly trace and research the development of CM. It has also been found that peripheral blood information is incomplete and inconclusive and clinical trial networks are largely too time consuming and costly for developing countries.

With no efficient human research model, researchers have focused on the use of mice to study CM. Overall, the murine model is inexpensive and mice brains are relatively comparable to human brains in respect to physiological, parasitological, and immunological features. Most murine model CM papers end with a statement of relevance in regards to cerebral malaria in humans, or fail to differentiate murine CM from human CM.

Unfortunately, it was found that ninety-two percent of successful treatments found using the murine model failed in treatment of humans, because there exists major histopathological differences between human and mouse CM. Murine CM has little or no intracerebral sequestration of parasitized erythrocytes, while human CM has intense intracerebal sequestration. Murine CM has accumulation of leukocytes and platelets and inflammation in the brain, while human CM has neither. These two major differences show that cerebral malaria does not act the same in mice as it does in humans. Also, the treatments proposed in mice are given before the mice develop any symptoms, which is nearly impossible to do with humans.

The failure of the murine model to deliver any conclusive results should lead to the questioning of the effectiveness of it. However, several reasons contribute to the continuing use and validation of the murine model. First, many research institutions already have existing murine laboratory programs, making it an independent and self-sustaining discipline. It also uses genetically homogenous hosts and parasites, and provides high quality histopathology on all subjects. Lastly, it produces positive results, which appeal to a substantial lab based immunological audience.