A severe form of malaria, cerebral malaria (CM), causes coma and may cause death, though it is not clear how CM leads to coma. A biomarker that could guide therapy by discriminating between CM-related coma versus other causes of coma is urgently needed—especially in areas without access to neuroimaging and other sophisticated diagnostic tests.

In a study featured on the cover of the February 15, 2022, issue of the Journal of Infectious Diseases, Johanna Daily, M.D., M.S., and colleagues identified pipecolic acid (PA) as a potential cause of coma in patients with CM. PA is an amino acid produced by malaria parasites and is also associated with other neurologic diseases. The researchers used mass spectrometry to analyze plasma from Malawian children with either CM or mild malaria. PA was found to be abnormally elevated in CM plasma compared with normal levels in the plasma of patients with mild malaria. An experimental model of cerebral malaria supported those results: PA was present in significantly higher levels in the brains of mice that developed coma. The findings suggest that PA is not only responsible for causing coma in CM patients but that its level in blood could be a useful biomarker of coma caused by CM.

Dr. Daily is professor of medicine and of microbiology & immunology at Einstein.