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Causes for Increased Mortality of People With Increased Iron Stores in Areas of High Prevalence of Infectious Diseases

Eisenhut, Michael

JAIDS Journal of Acquired Immune Deficiency Syndromes: July 1st, 2008 - Volume 48 - Issue 3 - p 367-368
doi: 10.1097/QAI.0b013e3181776255
Letters to the Editor

Luton and Dunstable Hospital NHS Foundation Trust Luton, United Kingdom

To the Editor:

Recently a study was reported, which demonstrated that an elevated iron status predicted increased mortality in adults with HIV infection in the Gambia. The authors drew the conclusion that there may be negative implications in providing supplemental iron or transfusion therapy for anemia of unknown etiology in HIV infection. This and other studies did, however, not support an influence of iron status on the course of HIV infection.1 There was neither a relationship of iron status to CD4 count in this study nor an HIV viral load in previous studies.2,3

Studies of morbidity and mortality in populations undergoing trials of the effects of iron supplementation shed light on causes of increased mortality associated with increased iron stores. In a randomized placebo-controlled trial of iron supplementation in 24,076 children with and without anemia in Pemba (Tanzania), children who received iron supplements were 12% (95% confidence interval: 2 to 23, P = 0.02) more likely to die or to require hospital treatment. Apart from an increased risk of malaria-related complications, there was also independently an increased risk of deaths or admissions due to other infectious diseases, including pneumonia, sepsis, meningitis, measles, and pertussis.4 These findings led to the premature termination of this trial. Detailed analysis revealed that only the group of children with iron supplementation on a background of normal iron status was adversely affected by iron. Children with iron deficiency anemia, that is, low iron stores benefited from iron supplementation, and children with iron deficiency were not adversely affected. This illustrated that the effect of excessive iron stores on infectious causes of mortality is applicable to people without HIV. The causes of increased pathogenicity of bacteria in patients with increased iron stores have been investigated and include impaired chemotactic responses and phagocytic and bactericidal functions of mononuclear leukocytes in assays using Staphylococcus aureus and Escherichia coli strains.5-7

The findings of the authors are likely to be due to a general increase in mortality from infectious diseases unrelated to HIV infection and may apply to the general population. They illustrate that iron supplementation in areas with high prevalence of infectious diseases should only be given to people with iron deficiency anemia.

Michael Eisenhut

Luton and Dunstable Hospital NHS Foundation Trust Luton, United Kingdom

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1. McDermid JM, Jay A, Schim van der Loeff MF, et al. Elevated iron status strongly predicts mortality in West African adults with HIV infection. J Acquir Immune Defic Syndr. 2007;46:498-507.
2. Olsen A, Mwaniki D, Krarup H, et al. Low-dose iron supplementation does not increase HIV-1 load. J Acquir Immune Defic Syndr. 2004;36:637-638.
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6. Van Asbeck BS, Marx JJ, Struyvenberg A, et al. Functional defects in phagocytic cells from patients with iron overload. J Infect. 1984;8:232-240.
7. Cantinieaux B, Hariga C, Ferster A, et al. Neutrophil dysfunctions in thalassaemia major: the role of cell iron overload. Eur J Haematol. 1987;39:28-34.
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