title: Severe anemia in Malawian children.
abstract: 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.
  
  
  
  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.
  
  
  
  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), theG6PD-202/-376genetic 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 B12deficiency (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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Job Cj
authors.initials: JC
authors.lastname: Calis
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Kamija S
authors.initials: KS
authors.lastname: Phiri
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: E Brian
authors.initials: EB
authors.lastname: Faragher
authors.affiliation: 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.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Brabin
authors.affiliation: Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Imelda
authors.initials: I
authors.lastname: Bates
authors.affiliation: Child and Reproductive Health Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Cuevas
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: de Haan
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi; College of Medicine, University of Malawi, Blantyre, Malawi.
authors.forename: Ajib I
authors.initials: AI
authors.lastname: Phiri
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
authors.forename: Pelani
authors.initials: P
authors.lastname: Malange
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
authors.forename: Mirriam
authors.initials: M
authors.lastname: Khoka
authors.affiliation: Division of Human Nutrition, Wageningen University, Wageningen, the Netherlands.
authors.forename: Paul Jm
authors.initials: PJ
authors.lastname: Hulshof
authors.affiliation: Department of Parasitology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Lisette
authors.initials: L
authors.lastname: van Lieshout
authors.affiliation: Department of Medical Microbiology, Laboratory of Clinical Virology.
authors.forename: Marcel Ghm
authors.initials: MG
authors.lastname: Beld
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Yik Y
authors.initials: YY
authors.lastname: Teo
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Rockett
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Richardson
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Kwiatkowski
authors.affiliation: 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.
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
authors.affiliation: 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.
authors.forename: Michaël Boele
authors.initials: MB
authors.lastname: van Hensbroek