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, mala...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Public Library of Science
2006
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| _version_ | 1826263332932288512 |
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| author | Wambua, S Mwangi, T Kortok, M Uyoga, S Macharia, A Mwacharo, J Weatherall, D Snow, R Marsh, K Williams, T |
| author_facet | Wambua, S Mwangi, T Kortok, M Uyoga, S Macharia, A Mwacharo, J Weatherall, D Snow, R Marsh, K Williams, T |
| author_sort | Wambua, S |
| collection | OXFORD |
| description | 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 <em>Plasmodium falciparum</em> parasitaemia, the incidence of uncomplicated <em>P. falciparum</em> 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 <em>P. falciparum</em> 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 ¼ 0.006), and for severe nonmalaria anaemia, 0.26 (95% CI, 0.09,0.77; p ¼ 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. |
| first_indexed | 2024-03-06T19:50:04Z |
| format | Journal article |
| id | oxford-uuid:23ac4a77-4117-4794-a0a2-729e9a9732fb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:50:04Z |
| publishDate | 2006 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:23ac4a77-4117-4794-a0a2-729e9a9732fb2022-03-26T11:45:32ZThe effect of α (^+) - thalassaemia on the incidence of malaria and other diseases in children living on the coast of KenyaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:23ac4a77-4117-4794-a0a2-729e9a9732fbPaediatricsMalariaEnglishOxford University Research Archive - ValetPublic Library of Science2006Wambua, SMwangi, TKortok, MUyoga, SMacharia, AMwacharo, JWeatherall, DSnow, RMarsh, KWilliams, TBackground: 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 <em>Plasmodium falciparum</em> parasitaemia, the incidence of uncomplicated <em>P. falciparum</em> 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 <em>P. falciparum</em> 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 ¼ 0.006), and for severe nonmalaria anaemia, 0.26 (95% CI, 0.09,0.77; p ¼ 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. |
| spellingShingle | Paediatrics Malaria Wambua, S Mwangi, T Kortok, M Uyoga, S Macharia, A Mwacharo, J Weatherall, D Snow, R Marsh, K Williams, T The effect of α (^+) - thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya |
| title | The effect of α (^+) - thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya |
| title_full | The effect of α (^+) - thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya |
| title_fullStr | The effect of α (^+) - thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya |
| title_full_unstemmed | The effect of α (^+) - thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya |
| title_short | The effect of α (^+) - thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya |
| title_sort | effect of α thalassaemia on the incidence of malaria and other diseases in children living on the coast of kenya |
| topic | Paediatrics Malaria |
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