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Iron supplementation in areas of high malaria transmission
The role of iron in the prevention and treatment of anemia in high malaria transmission areas
remains a controversial issue. There are concerns that the administration of iron may exacerbate
malaria and other illnesses in otherwise healthy, iron sufficient children. A large-scale randomized,
double-blind, placebo-controlled trial conducted in Pemba, Zanzibar was recently published in the
Lancet ; researchers found that under certain conditions, supplementation may be associated with
adverse effects including increased risk of hospitalization and mortality, primarily due to malaria
and other infectious diseases (1). These findings raise concerns about the safety of current WHO
guidelines for universal iron and folic acid supplementation. As a result, WHO released a statement
suggesting that "�caution should be exercised in settings where the prevalence of malaria and other
infectious diseases is high" (2) when providing iron and folic acid supplementation to young children in
malaria endemic regions (3). However "�at the present time WHO policy with regard to prevention and
treatment of iron deficiency anaemia remains unchanged". Briefly, the statement advises that,
"�until the WHO recommendations are revised it is advised that iron and folic acid supplementation
be targeted to those who are anaemia and at risk of iron deficiency." In addition, it recommends
that these children "�should receive concurrent protection from malaria and other infectious
diseases through prevention and effective case management". Furthermore, the WHO advised that
"�these conclusions should not be extrapolated to fortification or food-based interventions for
delivering iron, where the patterns of iron absorption and metabolism may be substantially different".
Implications for using Sprinkles
Sprinkles is a food-based intervention since the micronutrient powder is added directly to foods (4).
From research in West Africa, it has been determined that the iron from Sprinkles is well absorbed
from a maize-based food and that infants have the capacity to regulate
the amount that is absorbed according to needs (5). The current INACG/WHO/UNICEF recommendation is
to provide daily iron supplementation to all infants 6-24 months where the prevalence of anemia is
at least 40% (6). From previous studies to date on the Sprinkles intervention, there is evidence that
the administration of 60 Sprinkles sachets is adequate to rapidly improve hemoglobin concentrations
and iron stores in a large proportion of young children . After the ingestion of 60 sachets, the
hematologic benefits were sustained over a period of at least 6 months. Thus, Sprinkles may not be
required for a prolonged period of time thus potentially lowering the risk of adverse effects.
Recommendations
Considering the evidence to date, Sprinkles distribution programs in high malaria transmission areas
should be integrated with malaria control programs such as the use of insecticide treated bed-nets
or the treatment of detected cases of malaria. When implementing a Sprinkles program and wherever
feasible, it is recommended to monitor for safety and adverse effects. Considering the conflicting
results to date and the possibility that iron delivery may exacerbate malaria and other infectious
diseases, it is crucial to ensure that iron interventions are safe for young children in all regions,
especially where malaria is present. From both a biological and practical standpoint and until more
data becomes available on the safety of the long-term delivery of iron to young children, we
recommend the provision of Sprinkles for a shorter rather than longer period of time. A
short-course regimen (e.g. 60 sachets) would ensure higher compliance and acceptability as compared
to a longer-course regimen, would be provided at a relatively low cost and would most likely
minimize any negative adverse effects on health. Until evidence is available, it would be prudent
to withhold giving any iron intervention (including Sprinkles) to a child presenting with fever to
minimize the potential that iron could exacerbate the infection.
Further research and evaluation of programs should be conducted to develop the most effective
strategies for controlling iron deficiency and anemia in regions where malaria transmission is high.
The optimal dose, duration and delivery of iron need to be established to ensure that children in
these regions gain the benefits of iron during the first years of life without increased risk to
malaria or other infectious diseases. The WHO is planning a consultation which will set a research
agenda in this area. The Sprinkles Global Health Initiative will continue to seek direction from the
WHO on recommendations for iron delivery to children and pursue research to establish the safety of
Sprinkles among populations where there is a high prevalence of malaria and infectious diseases.
References
(1) Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ, Dutta A, Dhingra U, Kabole I, Deb S,
Othman MK, Kabole FM. Effects of routine prophylactic supplementation with iron and folic acid
on admission to hospital and mortality in preschool children in a high malaria transmission
setting: community-based, randomised, placebo-controlled trial. Lancet 2006;367:133-43.
View Abstract.
(2) World Health Organization. Iron supplementation of young children in regions where malaria
transmission is intense and infectious disease highly prevalent. WHO Statement, 2006.
View Report.
(3) de Benoist B, Darnton-Hill I, Lynch S, Allen L, Savioli L. Zinc and iron supplementation trials in
Nepal and Tanzania. Lancet 2006;367:816.
(4) Zlotkin SH, Christofides AL, Hyder SMZ, Schauer CS, Tondeur MC, Sharieff W. Controlling iron
deficiency anemia through the use of home-fortified complementary foods. Indian J Pediatr
2004;71(11):1015-1019.
View Abstract.
(5) Tondeur MC, Schauer CS, Christofides AL, Asante KP, Newton S, Serfass RE, Zlotkin SH.
Determination of iron absorption from intrinsically labeled microencapsulated ferrous fumarate
(sprinkles) in infants with different iron and hematologic status by using a dual-stable-isotope
method. Am J Clin Nutr 2004;80(5):1436-44. View Full Article.
(6) Stoltzfus RJ, Dreyfuss ML. (1998) Guidelines for the Use of Iron Supplements to Prevent and Treat
Iron Deficiency Anemia. INACG/WHO/UNICEF. International Life Sciences Institute, USA.
View Report.
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