Bilirubin protects against the most serious effects of malaria

Bilirubin, a pigment that causes jaundice, or yellowing of the skin, may help protect people from the most serious consequences of malaria.

A study published in the journal ' Science ' suggests that bilirubin could be a future target for drugs that increase its production to prevent the most lethal or debilitating effects of malaria.

Although bilirubin is one of the most frequently measured metabolites in the blood, its functions in the body are only just beginning to be understood.

These findings may indicate that bilirubin could help protect people against other infectious diseases.

Jaundice, or yellowing of the skin, is a common presentation of malaria, with 2.5% to 50% of malaria patients experiencing jaundice, according to two studies published in The New England Journal of Medicine and Clinical Infectious Disease .

In an attempt to determine the role of bilirubin, the study authors analyzed blood samples from a group of 42 volunteer patients who were infected with the malaria parasite P. falciparum, which causes the deadliest form of the disease, according to the World Health Organization .

Using techniques to measure bilirubin and its precursor, biliverdin, the scientists measured the amount of bilirubin not yet processed by the liver in blood samples from asymptomatic and symptomatic malaria patients. They found that, on average, people with asymptomatic malaria had ten times more unprocessed bilirubin in their blood than symptomatic people, and suspected that the accumulation of the pigment might have helped protect them from malaria.

The researchers then exposed normal mice and mice genetically engineered to lack BVRA, a protein that helps produce bilirubin, to a form of malaria that infects rodents.

The researchers analyzed the rate at which the malaria parasite died in both bilirubin-deficient and normal mice.

In normal mice, the concentration of unprocessed bilirubin in their systems increased significantly after malaria infection , and all mice survived. In mice without BVRA, the parasite spread vigorously, and all mice died.

The scientists then set out to test whether bilirubin could help mice without BVRA overcome the infection or whether it contributed to worsening symptoms. They administered bilirubin to malaria-infected mice that also lacked BVRA and observed that giving them higher doses of bilirubin resulted in survival rates similar to those of normal mice.

"Bilirubin was previously considered a waste product," says Bindu Paul of Johns Hopkins Medicine. "This study confirms that it could be a crucial protective measure against infectious diseases and, potentially, neurodegenerative diseases."