RIO DE JANEIRO, Brazil—Adding antioxidants to traditional antimalarial treatment may prevent cognitive dysfunction associated with cerebral malaria, according to a new study (PLoS Pathog. 2010;6(6):e1000963. DOI: 10.1371/journal.ppat.1000963). Cerebral malarial (CM) is the most severe neurological complication of infection with Plasmodium flaciparum, affecting more than 500,000 children in sub-Saharan Africa each year, killing around 20 percent; survivors often suffer long-term cognitive impairment.
A cohort of Brazilian researchers associated with the Oswaldo Cruz Foundation and an investigator from the University of Utah used several models of experimental malaria with differential features to investigate the cognitive effects and possible ways to prevent persistent neurological damage. Infecting C57BL/6 and Swiss mice with P. berghei ANKA or a lethal strain of P. yoelii XL resulted in documented CM and sustained persistent cognitive damage after cure of the disease with chloroquine therapy. However, other mouse strains infected with certain other Plasmodium parasites did not cause CM and the infection was cleared with chloroquine. The strains of mice that did show CM also had high levels of oxidative stress markers; treating the mice with antioxidants (desferoxamine and N-acetylcysteine) plus chloroquine at the first signs of CM prevented vascular and inflammatory changes in the animals’ brains.
In a statement, Guy A. Zimmerman M.D., professor and associate chair for research in the University of Utah School of Medicine’s Department of Internal Medicine and a contributor to the study, noted the neurological dysfunction seen in CM survivors poses a serious burden in many countries, and finding treatments to reduce or prevent the cognitive impairment could help ease that burden. “Although we believe that long-term cognitive dysfunction after cerebral malaria is initiated by injury to the brain during the initial period of untreated infection, it is possible that the mechanisms for persistent cognitive deficits are independent of those that cause neurological injury and death during acute cerebral malaria,” Zimmerman said. “Future research is aimed at clarifying this point. However, we have been able to demonstrate that oxidative stress is present in the brains of mice infected with cerebral malaria.”
