title: Erythropoietin levels are not independently associated with malaria-attributable severe disease in Mozambican children.
abstract: BACKGROUND
  Severe malaria is difficult to differentiate from other forms of malaria or other infections with similar symptoms. Any parameter associated to malaria-attributable severe disease could help to improve severe malaria diagnosis.
  
  
  METHODS
  This study assessed the relation between erythropoietin (EPO) and malaria-attributable severe disease in an area of Mozambique with moderate malaria transmission. 211 children <5 years, recruited at Manhiça District Hospital or in the surrounding villages, were included in one of the following groups: severe malaria (SM, n = 44), hospital malaria without severity (HM, n = 49), uncomplicated malaria (UM, n = 47), invasive bacterial infection without malaria parasites (IBI, n = 39) and healthy community controls (C, n = 32). Malaria was diagnosed by microscopy and IBI by blood/cerebrospinal fluid culture.
  
  
  RESULTS
  Mean EPO concentration in the control group was 20.95 U/l (SD = 2.96 U/l). Values in this group were lower when compared to each of the clinical groups (p = 0.026 C versus UM, p<0.001 C vs HM, p<0.001 C vs SM and p<0.001 C vs IBI). In the 3 malaria groups, values increased with severity [mean = 40.82 U/l (SD = 4.07 U/l), 125.91 U/l (SD = 4.99U/l) and 320.87 U/l (SD = 5.91U/l) for UM, HM and SM, respectively, p<0.001]. The IBI group [mean = 101.75 U/l (SD = 4.12 U/l)] presented lower values than the SM one (p = 0.002). In spite of the differences, values overlapped between study groups and EPO levels were only associated to hemoglobin. Hemoglobin means of the clinical groups were 93.98 g/dl (SD = 14.77 g/dl) for UM, 75.96 g/dl (SD = 16.48 g/dl) for HM, 64.34 g/dl (SD = 22.99 g/dl) for SM and 75.67 g/dl (SD = 16.58 g/dl) for IBI.
  
  
  CONCLUSIONS
  Although EPO levels increase according to malaria severity and are higher in severe malaria than in bacteremia, the utility of EPO to distinguish malaria-attributable severe disease is limited due to the overlap of values between the study groups and the main role of hemoglobin in the expression of EPO.
authors.affiliation: Centre de Recerca en Salut Internacional de Barcelona, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Díez-Padrisa
authors.forename: Ruth
authors.initials: R
authors.lastname: Aguilar
authors.forename: Sonia
authors.initials: S
authors.lastname: Machevo
authors.forename: Luis
authors.initials: L
authors.lastname: Morais
authors.forename: Tacilta
authors.initials: T
authors.lastname: Nhampossa
authors.forename: Cristina
authors.initials: C
authors.lastname: O'Callaghan-Gordo
authors.forename: Delino
authors.initials: D
authors.lastname: Nhalungo
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
authors.forename: Anna
authors.initials: A
authors.lastname: Roca
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Alonso
authors.forename: Quique
authors.initials: Q
authors.lastname: Bassat
mesh_terms: D016470:Bacteremia / Q000175:diagnosis / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D007223:Infant; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008288:Malaria / Q000097:blood / Q000175:diagnosis / Q000378:metabolism* / Q000635:transmission; D008297:Male; D009073:Mozambique
chemical_list: D006454:Hemoglobins; D004921:Erythropoietin; D007770:L-Lactate Dehydrogenase; D001663:Bilirubin