Job Cj Calis1, Kamija S Phiri2, E Brian Faragher3, Bernard J Brabin4, Imelda Bates3, Luis E Cuevas5, Rob J de Haan6, Ajib I Phiri2, Pelani Malange7, Mirriam Khoka7, Paul Jm Hulshof8, Lisette van Lieshout9, Marcel Ghm Beld10, Yik Y Teo11, Kirk A Rockett11, Anna Richardson11, Dominic P Kwiatkowski11, Malcolm E Molyneux12, Michaël Boele van Hensbroek13. 1. Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; College of Medicine, University of Malawi, Blantyre, Malawi; Emma Children's Hospital, the Global Child Health Group, Academic Medical Center, Amsterdam, The Netherlands. 2. Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; College of Medicine, University of Malawi, Blantyre, Malawi. 3. Liverpool School of Tropical Medicine, Liverpool, United Kingdom. 4. Emma Children's Hospital, the Global Child Health Group, Academic Medical Center, Amsterdam, The Netherlands; Child and Reproductive Health Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom. 5. Child and Reproductive Health Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom. 6. Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, Amsterdam, the Netherlands. 7. Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi. 8. Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands. 9. Department of Parasitology, Leiden University Medical Center, Leiden, the Netherlands. 10. Department of Medical Microbiology, Laboratory of Clinical Virology. 11. Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom. 12. Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; College of Medicine, University of Malawi, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, United Kingdom. 13. Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; College of Medicine, University of Malawi, Blantyre, Malawi; Emma Children's Hospital, the Global Child Health Group, Academic Medical Center, Amsterdam, The Netherlands; Child and Reproductive Health Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Abstract
BACKGROUND: Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied. METHODS: We conducted a case-control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling. RESULTS: Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9), malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD-202/-376 genetic disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B12 deficiency (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe anemia. Folate deficiency, sickle cell disease, and laboratory signs of an abnormal inflammatory response were uncommon. Iron deficiency was not prevalent in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was negatively associated with bacteremia. Malaria was associated with severe anemia in the urban site (with seasonal transmission) but not in the rural site (where malaria was holoendemic). Seventy-six percent of hookworm infections were found in children under 2 years of age. CONCLUSIONS: There are multiple causes of severe anemia in Malawian preschool children, but folate and iron deficiencies are not prominent among them. Even in the presence of malaria parasites, additional or alternative causes of severe anemia should be considered.
BACKGROUND: Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied. METHODS: We conducted a case-control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling. RESULTS:Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9), malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD-202/-376 genetic disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B12 deficiency (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe anemia. Folate deficiency, sickle cell disease, and laboratory signs of an abnormal inflammatory response were uncommon. Iron deficiency was not prevalent in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was negatively associated with bacteremia. Malaria was associated with severe anemia in the urban site (with seasonal transmission) but not in the rural site (where malaria was holoendemic). Seventy-six percent of hookworm infections were found in children under 2 years of age. CONCLUSIONS: There are multiple causes of severe anemia in Malawian preschool children, but folate and iron deficiencies are not prominent among them. Even in the presence of malaria parasites, additional or alternative causes of severe anemia should be considered.
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