Abstract
BackgroundWhile WHO guidelines recommend iron supplements to only iron-deficient children in high infection pressure areas, these are rarely implemented. One of the reasons for this is the commonly held view that iron supplementation increases the susceptibility to some infectious diseases including malaria. Secondly, currently used markers to diagnose iron deficiency are also modified by infections. With the objective of improving iron deficiency diagnosis and thus, its management, we evaluated the performance of iron markers in children exposed to high infection pressure.Methodology/Principal FindingsIron markers were compared to bone marrow findings in 180 anaemic children attending a rural hospital in southern Mozambique. Eighty percent (144/180) of the children had iron deficiency by bone marrow examination, 88% (155/176) had an inflammatory process, 66% (119/180) had moderate anaemia, 25% (45/180) severe anaemia and 9% (16/180) very severe anaemia. Mean cell haemoglobin concentration had a sensitivity of 51% and specificity of 71% for detecting iron deficiency. Soluble transferrin receptor (sTfR) and soluble transferrin receptor/log ferritin (TfR-F) index (adjusted by C reactive protein) showed the highest areas under the ROC curve (AUCROC) (0.75 and 0.76, respectively), and were the most sensitive markers in detecting iron deficiency (83% and 75%, respectively), but with moderate specificities (50% and 56%, respectively).Conclusions/SignificanceIron deficiency by bone marrow examination was extremely frequent in these children exposed to high prevalence of infections. However, even the best markers of bone marrow iron deficiency did not identify around a quarter of iron-deficient children. Tough not directly extrapolated to the community, these findings urge for more reliable, affordable and easy to measure iron indicators to reduce the burden of iron deficiency anaemia in resource-poor settings where it is most prevalent.
Highlights
Iron deficiency (ID) is the most common and widespread nutrient deficiency, affecting approximately two billion people worldwide and resulting in over 500 million cases of anaemia [1,2]
This is the first study on the evaluation of iron markers to identify ID in a high infection pressure setting among anaemic children with any degree of anaemia
The low sensitivity of ferritin is explained for being an acute phase reactant [19], and its plasma concentration may not reflect the actual iron status in the presence of inflammation, which was very prevalent in the study population (88%) [19,48]
Summary
Iron deficiency (ID) is the most common and widespread nutrient deficiency, affecting approximately two billion people worldwide and resulting in over 500 million cases of anaemia [1,2]. In sub-Saharan Africa, the prevalence of iron-deficiency anaemia (IDA) is estimated around 60% [1,2], with 40 to 50% of children under five years of age in developing countries being iron deficient [3]. If the infant’s diet does not provide enough iron, there is a significant risk to develop IDA. This physiological iron deficiency is often exacerbated by the early introduction of weaning foods [4], that frequently contain iron absorption inhibitors [5]. Iron deficiency may be worsened by intestinal chronic blood loss from intestinal parasitic infections [3,6] All these determinants are frequent in developing countries, leading to a prevalence of ID that may reach more than 30% by 12 months of age [7]. With the objective of improving iron deficiency diagnosis and its management, we evaluated the performance of iron markers in children exposed to high infection pressure
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