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

Abstract

BackgroundThe 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 FindingsWe 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 < 50 g/l). The strongest associations were for severe malaria anaemia (> 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). ConclusionsOur 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.

Minimal Association of Common Red Blood Cell Polymorphisms with Plasmodium falciparum Infection and Uncomplicated Malaria in Papua New Guinean School Children

“…4,8,11,31,32 The absence of protection against P. falciparum infection or complicated disease in our study is thus consistent with these reports. The mechanisms of protection, however, remain unclear.…”

“…The lack of a protection against uncomplicated P. falciparum malaria is in line with both earlier studies in Africa 6,8 and observations in children > 5 years of age in Vanuatu, 10 but contradicts a more recent study from Tanzania that did find a significant decreased risk in children > 5 years of age. 9 Given the lack of protection against disease and LM-diagnosed infections, the finding of a significant reduction in risk of PCR-diagnosed infection is surprising.…”

“…[6][7][8][9] Interestingly, in the later study protective effects were most prominent in children > 5 years of age. 9 In Melanesia, where both P. falciparum and Plasmodium vivax are common and where both humans and parasite populations have different genetic backgrounds to Africa, the influence of α-globin polymorphisms on malaria outcomes is more varied.…”

Potential Immune Mechanisms Associated with Anemia in Plasmodium vivax Malaria: a Puzzling Question

“…The reasons why individuals with thalassemias may be more prone to malaria are related to their ineffective erythropoiesis as well as to the shortened survival of their RBCs, which leads to a high cell turnover, increasing their reticulocyte counts and favoring the infection of these cells by P. vivax (76)(77)(78). Interestingly, a different association, in which thalassemia would decrease the susceptibility to P. falciparum, conferring protection against severe diseases such as anemia, was observed in falciparum malaria (79). This protection appears to be related to the higher levels of antibodies (Abs) that bind to parasitized erythrocytes (80), allowing their phagocytosis by blood monocytes (81).…”

Spatial heterogeneity of haemoglobin concentration in preschool-age children in sub-Saharan Africa

“…Steptococcus pneumoniae, non-typhi Salmonella species and Haemophilus influenzae type b); neglected tropical diseases (especially those caused by Schistosoma haematobium -the cause of urinary schistosomiasis -hookworm and, to a lesser extent, Trichuris trichiura and Schistosoma mansoni), and inherited haemoglobinopathies and thalassemias. 1,[9][10][11][12][13][14][15][16][17][18] Currently, the planning of resources required for anaemia control is based on prevalence data from field surveys within a country, which are then extrapolated to the country as a whole. 3 However, efficient allocation of health interventions to control anaemia may require more targeted approaches based on information on the geographical distribution of high-risk communities and on an understanding of the relative contribution of major causes of anaemia.…”