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HAPTOGLOBIN LEVELS ARE ASSOCIATED WITH HAPTOGLOBIN GENOTYPE AND α+-THALASSEMIA IN A MALARIA-ENDEMIC AREA

HEATHER IMRIEPeter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, Oxford, United Kingdom; Papua New Guinea Institute of Medical Research, PO Box 378, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, PO Box 60, Goroka, EHP 441, Papua New Guinea; Department of Medical Parasitology, New York University School of Medicine, New York, New York

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FREYA J.I. FOWKESPeter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, Oxford, United Kingdom; Papua New Guinea Institute of Medical Research, PO Box 378, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, PO Box 60, Goroka, EHP 441, Papua New Guinea; Department of Medical Parasitology, New York University School of Medicine, New York, New York

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PASCAL MICHONPeter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, Oxford, United Kingdom; Papua New Guinea Institute of Medical Research, PO Box 378, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, PO Box 60, Goroka, EHP 441, Papua New Guinea; Department of Medical Parasitology, New York University School of Medicine, New York, New York

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LIVINGSTONE TAVULPeter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, Oxford, United Kingdom; Papua New Guinea Institute of Medical Research, PO Box 378, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, PO Box 60, Goroka, EHP 441, Papua New Guinea; Department of Medical Parasitology, New York University School of Medicine, New York, New York

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JENNIFER C.C. HUMEPeter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, Oxford, United Kingdom; Papua New Guinea Institute of Medical Research, PO Box 378, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, PO Box 60, Goroka, EHP 441, Papua New Guinea; Department of Medical Parasitology, New York University School of Medicine, New York, New York

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KAREN P. PIPERPeter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, Oxford, United Kingdom; Papua New Guinea Institute of Medical Research, PO Box 378, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, PO Box 60, Goroka, EHP 441, Papua New Guinea; Department of Medical Parasitology, New York University School of Medicine, New York, New York

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JOHN C. REEDERPeter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, Oxford, United Kingdom; Papua New Guinea Institute of Medical Research, PO Box 378, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, PO Box 60, Goroka, EHP 441, Papua New Guinea; Department of Medical Parasitology, New York University School of Medicine, New York, New York

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KAREN P. DAYPeter Medawar Building for Pathogen Research and Department of Zoology, University of Oxford, Oxford, United Kingdom; Papua New Guinea Institute of Medical Research, PO Box 378, Madang, Papua New Guinea; Papua New Guinea Institute of Medical Research, PO Box 60, Goroka, EHP 441, Papua New Guinea; Department of Medical Parasitology, New York University School of Medicine, New York, New York

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Haptoglobin (Hp) is an acute phase protein that removes free hemoglobin (Hb) released during hemolysis. Hp has also been shown to be toxic for malaria parasites. α+-Thalassemia is a hemoglobinopathy that results in subclinical hemolytic anemia. α+-Thassemia homozygosity confers protection against severe malarial disease by an as yet unidentified mechanism. Hp levels were measured in a serial cross-sectional survey of children in Madang Province, Papua New Guinea (PNG). Hp levels were related to age, Hp genotype, Hb levels, parasitemia, splenomegaly, and α+-thalassemia genotype. Surprisingly, children who were homozygous for α+ -thalassemia had significantly higher levels of Hp than did heterozygotes, after controlling for relevant confounders. We suggest that this is the result of either reduced mean cell Hb associated with α+ -thalassemia homozygosity or an elevated IL-6–dependent acute phase response.

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