The Effect of α +-Thalassaemia on the Incidence of Malaria and Other Diseases in Children Living on the Coast of Kenya

Background: The α-thalassaemias are the commonest genetic disorders of humans. It is generally believed that this high frequency reflects selection through a survival advantage against death from malaria; nevertheless, the epidemiological description of the relationships between α-thalassaemia, malaria, and other common causes of child mortality remains incomplete. Methods and Findings: We studied the α+-thalassaemia-specific incidence of malaria and other common childhood diseases in two cohorts of children living on the coast of Kenya. We found no associations between α+-thalassaemia and the prevalence of symptomless Plasmodium falciparum parasitaemia, the incidence of uncomplicated P. falciparum disease, or parasite densities during mild or severe malaria episodes. However, we found significant negative associations between α+-thalassaemia and the incidence rates of severe malaria and severe anaemia (haemoglobin concentration 10,000 P. falciparum parasites/μl) and severe nonmalaria anaemia; the incidence rate ratios and 95% confidence intervals (CIs) for α+-thalassaemia heterozygotes and homozygotes combined compared to normal children were, for severe malaria anaemia, 0.33 (95% CI, 0.15,0.73; p = 0.006), and for severe nonmalaria anaemia, 0.26 (95% CI, 0.09,0.77; p = 0.015). Conclusions: Our observations suggest, first that selection for α+-thalassaemia might be mediated by a specific effect against severe anaemia, an observation that may lead to fresh insights into the aetiology of this important condition. Second, although α+-thalassaemia is strongly protective against severe and fatal malaria, its effects are not detectable at the level of any other malaria outcome; this result provides a cautionary example for studies aimed at testing malaria interventions or identifying new malaria-protective genes. A study of children from the coast of Kenya suggests that selection for α+-thalassemia in the population might be mediated by a specific effect against severe anemia. Background: Malaria is a very common disease in African children, although a number of factors influence how severe the disease is, including the age and genetic background of the child. Changes in the genes that code for the globin proteins (alpha and beta) that are an essential part of hemoglobin (the oxygen-carrying protein in the blood) are known to influence how people are affected by malaria. For example, one such change in the beta globin gene causes sickle hemoglobin; when individuals have two copies of the affected gene they can be severely affected with anemia and painful crises, but carrying just one copy seems to make people less susceptible to malaria. Other genetic variants, in the alpha globin gene, cause a condition called alpha-thalassaemia, which can also lead to anemia because of lower amounts of the alpha globin protein being present. People with alpha thalassaemia seem to have some protection against malaria. Why Was This Study Done?: Both sickle cell and alpha-thalassaemia are very common in Africa. These investigators wanted to investigate whether having alpha-thalassaemia protects against all types of malaria or just the severe type. What Did the Researchers Do and Find?: The authors studied two groups of children living on the coast of Kenya to find out whether they had alpha-thalassaemia. They assessed whether or not having alpha-thalassaemia led to any difference in whether the children were infected with the parasite that causes malaria, whether they had symptoms, and how severe the symptoms were. They found that having alpha-thalassaemia meant that the children were less likely to get severe malaria and severe malarial anemia. However, there was no effect on whether the children got mild malaria or not. What Do These Findings Mean?: These results suggest that over generations the genetic change that causes alpha-thalassaemia has become common in this population, because carrying it protects people against getting severe malaria, especially with anemia. However, the genetic change does not appear to make it more or less likely that children get mild malaria. This result may be important when designing studies to look at the relation between these genetic changes and malaria. Where Can I Get More Information Online?: Medline Plus has a page of links to malaria: