Malaria Protection Provided By Inherited Blood Disorder

An inherited childrens’ blood disorder called alpha thalassemia can protect children against malaria, according to a new study.

"We made the surprising finding that packaging your hemoglobin in smaller amounts in more cells is an advantage against malaria," says Karen Day, Ph.D., Professor and Chairman of the Department of Medical Parasitology at NYU School of Medicine, who led the research with colleagues at the University of Oxford. Hemoglobin is the oxygen-carrying protein in red blood cells.The study, published in the March issue of the journal PLoS Medicine, proposes an answer to a biological puzzle that first emerged more than 50 years ago.

The study was conducted in Papua, New Guinea, where malaria is endemic, with 800 children participating. 68% of children there have alpha thalassemia. Dr. Day and her then-Ph D. student Freya J.I. Fowkes, and colleagues from the University of Oxford, Papua New Guinea Institute of Medical Research, and Swansea University showed that a severe attack of malaria caused the loss of one third to one half of the total number of red blood cells. However, children with mild thalassemia started with 10% –20% more red blood cells than unaffected children, and could therefore withstand this huge loss.

"It is really remarkable and so simple. Children with alpha thalassemia have adapted to the loss of red blood cells associated with malarial disease by making more of these cells with less hemoglobin," says Dr. Day. "So, these children do better because they end up with more hemoglobin overall when they have a malaria attack compared to normal children," says Dr. Day.
Malaria afflicts hundreds of millions of people, causing up to 2 million deaths every year in Africa and Asia. Many of its victims are young children. In regions of the world where malaria is endemic, mutations have arisen in human populations that allow people to survive. Sickle cell trait, for example, protects against malaria.

Nearly sixty years ago the renowned evolutionary biologist J.B.S.Haldane postulated that the thalassemias were common in human populations because they protected against malaria. Alpha thalassemia is common in Asia, the Mediterranean and Melanesia where malaria is or was prevalent. In the mid 1990s researchers working on the north coast of Papua New Guinea proved that children with mild alpha thalassemia, who inherit mutations in the "alpha" part of hemoglobin genes from each parent, were protected against malaria. These children were 60 percent less likely to get severe malarial anemia than normal children, however the mechanism of such protection was unclear.

Dr. Day and colleagues based their new study on this same population of children. "We are proposing an unexpected mechanism of protection against severe malarial anemia" says Dr. Day. "We show that alpha thalassemia is giving the child a hematological advantage by making more red blood cells.

Source: New York University Medical Center

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