Genetic Variation Protects Against 2 Types of Malaria

Children who possess a gene that allows them to produce high levels of nitric oxide are protected from two of the deadliest forms of malaria, according to a report published today in the international medical journal, The Lancet.

The discovery was made by an international team of researchers led by Maurine R. Hobbs, Ph.D., and Donald L. Granger, M.D., at the University of Utah, Brice Weinberg, M.D., Duke University, Nick Antsey, Menzies School of Health Research, Australia, and malaria experts in Atlanta, Tanzania, and Kenya.

"This is a major advance in understanding how and why children get the deadliest forms of malaria," Weinberg said.

The findings may lead to new treatments for more than 1 million children--most of them African--who die every year from cerebral malaria and severe malarial anemia, according to Hobbs, research assistant professor of internal medicine at the U of U School of Medicine and the study's first author.

"This is exciting because it confirms the importance of nitric oxide in the immune response to malaria, and could lead to new therapies to protect against the devastating effects of malaria infection," Hobbs said.

Nitric oxide is a tiny molecule, yet it performs numerous functions in the human body, ranging from assisting blood flow to killing bacteria, viruses, and other germs. The amount of nitric oxide the body makes during infection is regulated by the gene for nitric oxide synthase (NOS2), a protein produced by white blood cells.

The researchers studied 179 children in coastal Tanzania, with and without cerebral malaria, one of the deadliest forms of the disease.

"Children with the variant of NOS2 that allowed them to make greater amounts of nitric oxide were 88 percent less likely to develop cerebral malaria than were those without the variant," Hobbs said.

The researchers then examined DNA collected through a U.S. Centers for Disease Control study of 1,106 children in Kenya. Using the DNA from the Kenyan children, they assayed the NOS2 gene and found that the same variant protected them from severe malarial anemia, also one of the most lethal forms of the disease.

Malaria, caused by parasites transmitted through mosquito bites, affects more than half a billion people each year, killing more than 1 million small children. An increasing number of adults also are dying from this disease as global drug resistance worsens.

"Targeted interventions to increase NO delivery or production may provide new strategies to treat and prevent this major cause of death in children," the researchers wrote.

Along with the University of Utah and Duke University, institutions involved in the study include the Veterans Affairs Medical Centers in Salt Lake City and Durham, N.C.; Centers for Disease Control, Atlanta; World Health Organization, Geneva, Switzerland; Hubert Kairuki Memorial University, Dar es Salaam, Tanzania; and Menzies School of Health Research, Darwin, Australia. The research was supported by the NIH, the U.S. Veterans Affairs, the U.S. Agency for International Development, and the U.S. Centers for Disease Control.