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


METHODS
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.
Cusick
Sarah E
SE
Center for Human Nutrition, Department of International Health, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. scusick@cdc.gov
Tielsch
James M
JM
Ramsan
Mahdi
M
Jape
Jape K
JK
Sazawal
Sunil
S
Black
Robert E
RE
Stoltzfus
Rebecca J
RJ
D000740:Anemia / Q000097:blood*; D000962:Antimalarials / Q000494:pharmacology*; D002097:C-Reactive Protein / Q000032:analysis; D002675:Child, Preschool; D004338:Drug Combinations; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000096:biosynthesis; D005293:Ferritins / Q000097:blood; D006801:Humans; D007223:Infant; D011739:Pyrimethamine / Q000494:pharmacology*; D013413:Sulfadoxine / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology*
D000962:Antimalarials; D004338:Drug Combinations; D004921:Erythropoietin; D014801:Vitamin A; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D002097:C-Reactive Protein; D005293:Ferritins; D011739:Pyrimethamine