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Blood, 1 October 2004, Vol. 104, No. 7, pp. 2003-2006. Prepublished online as a Blood First Edition Paper on June 22, 2004June 15, 2004; DOI 10.1182/blood-2003-11-4090. This Article Full Text (PDF) All Versions of this Article: 2003-11-4090v1 2003-11-4090v2 104/7/2003    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 Mockenhaupt, F. P Articles by Bienzle, U. Search for Related Content PubMed PubMed Citation Articles by Mockenhaupt, F. P Articles by Bienzle, U. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 1, 2003 Accepted December 31, 1969 +-thalassemia protects from severe malaria in African children Frank P Mockenhaupt*, Stephan Ehrhardt, Sabine Gellert, Rowland N Otchwemah, Ekkehart Dietz, Sylvester D Anemana, and Ulrich Bienzle Institute of Tropical Medicine, Charite, Humboldt University, Berlin, Germany Institute of Tropical Medicine, Charite, Humboldt University, Berlin, Germany; Bernhardt Nocht Institute for Tropical Medicine, Hamburg, Germany Tamale Teaching Hospital, Tamale, Northern Region, Ghana School of Medicine and Health Sciences, University for Development Studies, Tamale, Northern Region, Ghana Institute for International Health, Free University & Humboldt University, Berlin, Germany Regional Health Administration, Takoradi, Western Region, Ghana * Corresponding author; email: frank.mockenhaupt{at}charite.de. The high frequency of +-thalassemia in malaria-endemic regions may reflect natural selection due to protection from potentially fatal severe malaria. In Africa, bearing 90% of global malaria morbidity and mortality, this has not been observed so far. We tested this hypothesis in an unmatched case-control study among 301 Ghanaian children with severe malaria and 2107 controls (62% parasitemic). In control children, +-thalassemia neither affected prevalence nor density of Plasmodium falciparum. However, heterozygous +-thalassemia was observed in 32.6% of controls but only in 26.2% of cases (OR, 0.74, 95%CI, 0.56-0.98). Protection against severe malaria was found to be pronounced comparing severe malaria patients to parasitemic controls (adjusted OR in children <5 years of age, 0.52; 95%CI, 0.34-0.78) and to wane with age. No protective effect was discernible for homozygous children. Our findings provide evidence for natural selection of +-thalassemia in Africa due to protection from severe malaria. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Raberg, A. L Graham, and A. F Read Decomposing health: tolerance and resistance to parasites in animals Phil Trans R Soc B, January 12, 2009; 364(1513): 37 - 49. [Abstract] [Full Text] [PDF] 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] 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] 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] F. P. Mockenhaupt, J. P. Cramer, L. Hamann, M. S. Stegemann, J. Eckert, N.-R. Oh, R. N. Otchwemah, E. Dietz, S. Ehrhardt, N. W. J. Schroder, et al. Toll-like receptor (TLR) polymorphisms in African children: Common TLR-4 variants predispose to severe malaria PNAS, January 3, 2006; 103(1): 177 - 182. [Abstract] [Full Text] [PDF] T. N. Williams, S. Wambua, S. Uyoga, A. Macharia, J. K. Mwacharo, C. R. J. C. Newton, and K. Maitland Both heterozygous and homozygous {alpha}+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya Blood, July 1, 2005; 106(1): 368 - 371. [Abstract] [Full Text] [PDF]

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