Short-term effects of vitamin A and antimalarial treatment on erythropoiesis in severely anemic Zanzibari preschool children

Am J Clin Nutr. 2005 Aug;82(2):406-12. doi: 10.1093/ajcn.82.2.406.

Abstract

Background: The pathophysiology of anemia in coastal East Africa is complex. Impaired erythropoietin production is one possible mechanism. Plasmodium falciparum malaria has been found to blunt erythropoietin production, whereas vitamin A stimulates erythropoietin production in vitro.

Objective: We investigated the 72-h effects of vitamin A and the antimalarial drug sulfadoxine pyramethamine (SP) on erythropoietin production in severely anemic (hemoglobin < or = 70 g/L) preschool children in Zanzibar, a region of known vitamin A deficiency. We hypothesized that both treatments would stimulate erythropoietin production directly, within 72 h, before a change in hemoglobin would occur.

Design: One hundred forty-one severely anemic children were identified during the baseline assessment of a morbidity substudy of a community-based micronutrient supplementation trial. All severely anemic children were randomly assigned to receive either vitamin A (100,000 or 200,000 IU depending on age) or SP at baseline; 72 h later they received the opposite treatment plus daily hematinic syrup for 90 d. Erythropoietic and parasitic indicators were assessed at baseline and again after 72 h.

Results: After 72 h, SP reduced the malaria parasite density (by 5029 parasites/microL; P < 0.001), CRP concentrations (by 10.6 mg/L; P = 0.001), and the proportion of children infected with malaria (by 32.4%; P < 0.001). Vitamin A reduced CRP (by 9.6 mg/L; P = 0.011), serum ferritin (by 18.1 microg/L; P = 0.042), and erythropoietin (by 194.7 mIU/mL; P = 0.011) concentrations and increased the reticulocyte production index (by 0.40; P = 0.041).

Conclusions: Contrary to our hypothesis, vitamin A significantly decreased erythropoietin concentration. The most important effect of both vitamin A and SP was the rapid reduction of inflammation. Vitamin A also mobilized iron from stores and stimulated the production of new erythrocytes.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anemia / blood*
  • Antimalarials / pharmacology*
  • C-Reactive Protein / analysis
  • Child, Preschool
  • Drug Combinations
  • Erythropoiesis / drug effects*
  • Erythropoietin / biosynthesis
  • Ferritins / blood
  • Humans
  • Infant
  • Pyrimethamine / pharmacology*
  • Sulfadoxine / pharmacology*
  • Vitamin A / pharmacology*

Substances

  • Antimalarials
  • Drug Combinations
  • Erythropoietin
  • Vitamin A
  • fanasil, pyrimethamine drug combination
  • Sulfadoxine
  • C-Reactive Protein
  • Ferritins
  • Pyrimethamine