title: Pathophysiological mechanisms of severe anaemia in Malawian children.
abstract: BACKGROUND
  Severe anaemia is a major cause of morbidity and mortality in African children. The aetiology is multi-factorial, but interventions have often targeted only one or a few causal factors, with limited success.
  
  
  RESULTS
  We assessed the contribution of different pathophysiological mechanisms (red cell production failure [RCPF], haemolysis and blood loss) to severe anaemia in Malawian children in whom etiological factors have been described previously. More complex associations between etiological factors and the mechanisms were explored using structural equation modelling. In 235 children with severe anaemia (haemoglobin<3.2 mMol/L [5.0 g/dl]) studied, RCPF, haemolysis and blood loss were found in 48.1%, 21.7% and 6.9%, respectively. The RCPF figure increased to 86% when a less stringent definition of RCPF was applied. RCPF was the most common mechanism in each of the major etiological subgroups (39.7-59.7%). Multiple aetiologies were common in children with severe anaemia. In the final model, nutritional and infectious factors, including malaria, were directly or indirectly associated with RCPF, but not with haemolysis.
  
  
  CONCLUSIONS
  RCPF was the most common pathway leading to severe anaemia, from a variety of etiological factors, often found in combination. Unlike haemolysis or blood loss, RCPF is a defect that is likely to persist to a significant degree unless all of its contributing aetiologies are corrected. This provides a further explanation for the limited success of the single factor interventions that have commonly been applied to the prevention or treatment of severe anaemia. Our findings underline the need for a package of measures directed against all of the local aetiologies of this often fatal paediatric syndrome.
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi. MBVH04@Gmail.com
authors.forename: Michaël
authors.initials: M
authors.lastname: Boele van Hensbroek
authors.forename: Job C J
authors.initials: JC
authors.lastname: Calis
authors.forename: Kamija S
authors.initials: KS
authors.lastname: Phiri
authors.forename: Raymond
authors.initials: R
authors.lastname: Vet
authors.forename: Francis
authors.initials: F
authors.lastname: Munthali
authors.forename: Rob
authors.initials: R
authors.lastname: Kraaijenhagen
authors.forename: Henk
authors.initials: H
authors.lastname: van den Berg
authors.forename: Brian
authors.initials: B
authors.lastname: Faragher
authors.forename: Imelda
authors.initials: I
authors.lastname: Bates
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Molyneux
mesh_terms: D000740:Anemia / Q000378:metabolism / Q000503:physiopathology*; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D007223:Infant; D008295:Malawi; D008297:Male
chemical_list: D006454:Hemoglobins