Malaria Relapses Following Parasite-Free Blood Transfusions in the U.S. Army during the Korean War

Abstract

Latent Plasmodium vivax parasites in the liver known as hypnozoites activate causing malaria relapses months after the original infection. The putative initiation signal is unknown. Plasmodium falciparum infections appear to trigger P. vivax relapses and initiation of relapse may be triggered by hemolysis or fever. The U.S. Army hospital records from the Korean War (> 500,000 individual records) were used to determine whether there was an association between blood transfusion and vivax malaria relapse. Importantly, blood for transfusion was collected in the United States, so the risk of transmission of malaria parasites was minimal. Blood transfusion (largely for combat trauma) was a risk factor for subsequent vivax malaria (relative risk 2.54, 95% CI 2.15-2.99, P < 0.0001). As expected, blood transfusion was not a risk factor for subsequent dysentery, but transfusion was a risk factor for subsequent hepatitis. Blood transfusion causing an increased heme delivery to the liver and a subsequent redox signal within hepatocytes may partially explain hypnozoite activation leading to relapses of vivax malaria.