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Blood, 1 July 2005, Vol. 106, No. 1, pp. 368-371. Prepublished online as a Blood First Edition Paper on March 15, 2005; DOI 10.1182/blood-2005-01-0313. This Article Full Text (PDF) All Versions of this Article: 2005-01-0313v1 106/1/368    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Williams, T. N Articles by Maitland, K. Search for Related Content PubMed PubMed Citation Articles by Williams, T. N Articles by Maitland, K. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 24, 2005 Accepted March 7, 2005 Both heterozygous and homozygous +thalassemia protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya Thomas N Williams*, Sammy Wambua, Sophie Uyoga, Alex Macharia, Jedidah K Mwacharo, Charles R Newton, and Kathryn Maitland Kenya Medical Research Institute, Centre for Geographic Medicine Research, Kilifi, Coast, Kenya; Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom; Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom Kenya Medical Research Institute, Centre for Geographic Medicine Research, Kilifi, Coast, Kenya Kenya Medical Research Institute, Centre for Geographic Medicine Research, Kilifi, Coast, Kenya; Neurosciences Unit, Institute of Child Health, University College, London, United Kingdom Kenya Medical Research Institute, Centre for Geographic Medicine Research, Kilifi, Coast, Kenya; Department of Paediatrics, Faculty of Medicine and the Wellcome Trust Centre for Clinical Tropical Medicine, Imperial College, London, United Kingdom * Corresponding author; email: twilliams{at}kilifi.mimcom.net. Although the +thalassemias almost certainly confer protection against death from malaria, this has not been formally documented. We have conducted a study involving 655 cases of rigorously defined severe malaria and 648 controls, frequency matched on area of residence and ethnic group. The prevalence of both heterozygous and homozygous +thalassemia was reduced in both severe malaria cases [adjusted ORs (95%ci; P) 0.73 (0.57-0.94; 0.013) and 0.57 (0.40-0.81; 0.002) respectively, compared to controls], and among the subgroup of children who died following admission with severe malaria [OR 0.60 (0.37-1.00; P=0.05) and 0.37 (0.16-0.87; 0.02) respectively compared to surviving cases]. The lowest ORs were seen for the forms of malaria associated with the highest mortality - coma and severe anemia complicated by deep, acidotic, breathing. Our study supports the conclusion that both heterozygotes and homozygotes enjoy a selective advantage against death from P. falciparum malaria. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Enevold, J. P. Lusingu, B. Mmbando, M. Alifrangis, M. M. Lemnge, I. C. Bygbjerg, T. G. Theander, and L. S. Vestergaard Reduced Risk of Uncomplicated Malaria Episodes in Children with Alpha+-Thalassemia in Northeastern Tanzania Am J Trop Med Hyg, May 1, 2008; 78(5): 714 - 720. [Abstract] [Full Text] [PDF] A. Navas, G. Cobas, M. Talavera, J. A. Ayala, J. A. Lopez, and J. L. Martinez Experimental validation of Haldane's hypothesis on the role of infection as an evolutionary force for Metazoans PNAS, August 21, 2007; 104(34): 13728 - 13731. [Abstract] [Full Text] [PDF] K. V. Patel, T. B. Harris, M. Faulhaber, S. B. Angleman, S. Connelly, D. C. Bauer, L. H. Kuller, A. B. Newman, J. M. Guralnik, and for the Health, Aging, and Body Composition Study Racial variation in the relationship of anemia with mortality and mobility disability among older adults Blood, June 1, 2007; 109(11): 4663 - 4670. [Abstract] [Full Text] [PDF] J. May, J. A. Evans, C. Timmann, C. Ehmen, W. Busch, T. Thye, T. Agbenyega, and R. D. Horstmann Hemoglobin Variants and Disease Manifestations in Severe Falciparum Malaria JAMA, May 23, 2007; 297(20): 2220 - 2226. [Abstract] [Full Text] [PDF] M. R. Clatworthy, L. Willcocks, B. Urban, J. Langhorne, T. N. Williams, N. Peshu, N. A. Watkins, R. A. Floto, and K. G. C. Smith Systemic lupus erythematosus-associated defects in the inhibitory receptor Fc{gamma}RIIb reduce susceptibility to malaria PNAS, April 24, 2007; 104(17): 7169 - 7174. [Abstract] [Full Text] [PDF] B. C. URBAN, M. J. SHAFI, D. V. CORDERY, A. MACHARIA, B. LOWE, K. MARSH, and T. N. WILLIAMS FREQUENCIES OF PERIPHERAL BLOOD MYELOID CELLS IN HEALTHY KENYAN CHILDREN WITH {alpha}+ THALASSEMIA AND THE SICKLE CELL TRAIT Am J Trop Med Hyg, April 1, 2006; 74(4): 578 - 584. [Abstract] [Full Text] [PDF]

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