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Case Western Reserve researchers discover the key to malaria susceptibility in children

July 28, 2009

Prenatal exposure to Plasmodium falciparum results in parasite tolerance in some babies

A team of researchers from Case Western Reserve University School of Medicine have solved the mystery of why some children are more susceptible to malaria infection and anemia. These novel findings suggest that some children who are exposed to Plasmodium falciparum (P. falciparum) malaria before birth become tolerant to the malaria parasites, or their soluble products. This tolerance, which persists into childhood, reduces the ability of the immune system to attack and destroy parasites and increases the susceptibility of these children to develop a malaria infection. It also increases their risk for anemia. The study, published in this week's issue of the open access journal, PLoS Medicine, is led by Indu Malhotra, Ph.D., and Christopher King, M.D., Ph.D., professor of international health, medicine, and pathology, with their colleagues at the Center for Global Health and Diseases at the Case Western Reserve University School of Medicine and their Kenyan colleagues at the Kenya Medical Research Institute and Division of Vector Borne Diseases.

"This is the first time it has been shown why some children are more susceptible to malaria and anemia than other children," says Dr. Indu Malhotra. "This study is timely given President Obama's Global Health Initiative to assist developing countries to control malaria, one of the 'big three' diseases."

The Case Western Reserve study, entitled, "Can Prenatal Malaria Exposure Produce an Immune Tolerant Phenotype?: A Prospective Birth Cohort Study in Kenya", investigated how prenatal malaria exposure affects anti-malaria immunity in young children and their susceptibility to subsequent malaria infections. Little is known about how immunity to malaria develops in infants, a process which researchers must understand in order to design effective vaccines for children. In particular, it is unclear how a mother's malaria infection affects a child's acquisition of anti-malaria immunity.

From a pool of 586 Kenyan newborn babies, the researchers identified those children who had been exposed to P. falciparum malaria in utero. The researchers looked for malaria-specific immune responses in T cells in the newborn babies' cord blood by measuring the production of cytokines, molecules that either activate or inhibit the immune system. Finally, they examined the infants biannually for three years to monitor the children's immune responses, susceptibility to malaria infection and risk for anemia..

"These findings could have important implications for the design of malaria vaccines for use in areas where children are often exposed to malaria before birth and for the design of strategies for the prevention of malaria during pregnancy," says Dr. Christopher King.

The babies were classified into three groups: "sensitized" - those babies whose cord blood cells produce activating cytokines in response to the malaria antigens; "exposed, not-sensitized'' - babies whose bodies did not produce activating cytokines but made an inhibitory cytokine; and "not-exposed''- babies born to mothers with no P. falciparum malaria infection at delivery.

In their first three years of life, the "exposed, not-sensitized" group had a 60 percent greater risk of malaria infection than the "not-exposed" group and a slightly higher risk of malaria infection than the "sensitized" group. They also had lower hemoglobulin levels, a sign of anemia, than the other babies. The T cells of "exposed, not-sensitized" children were less likely to make activating cytokines in response to malaria antigens.

In a PLoS Medicine Perspective article on this study, editorial board member, Lars Hviid, states that the research by Dr. King and colleagues "adds significantly to our understanding of prenatal exposure to P. falciparum antigens" and has "obvious clinical importance."

Case Western Reserve University