Iron overload, either primary (eg, hereditary hemochromatosis) or secondary (eg, hemolysis/frequent transfusion states), may increase the risk of infections through at least 2 mechanisms: 1. Enhancement of the virulence of the pathogen; and 2. Interference with the body’s normal defense system.1-7
Excess iron has been reported to enhance the growth of numerous organisms, ranging from bacteria (eg, Yersinia, Shigella, Vibrio, Listeria, Legionella, Ehrlichia, many other Gram-negative bacteria, staphylococci, streptococci), mycobacteria, fungi (eg, Aspergillus, Rhizopus/Mucor, Cryptococcus, Pneumocystis), protozoa (eg, Entamaeba, Plasmodium, Toxoplasma) and viruses (HIV, hepatitis B/C, cytomegalovirus, parvovirus). 1-7
In addition to enhancing the growth of many pathogens, excess iron may also inhibit macrophage and lymphocyte function and neutrophil chemotaxis .1,2 Iron loading of macrophages results in the inhibition of interferon-gamma mediated pathways and loss of their ability to kill intracellular pathogens such as Legionella, Listeria and Ehrlichia. 2
Not surprisingly, there are numerous reports in the literature of infections in hemochromatosis, including Listeria monocytogenes meningitis, E. Coli septic shock, Yersinia enterocolitica sepsis/liver abscess, Vibrio vulnificus shock (attributed to ingestion of raw oysters) and mucormycosis causing periorbital cellulitis. 2
Bonus pearl: Did you know that the ascitic fluid of patients with cirrhosis has low transferrin levels compared to those with malignancy, potentially enhancing bacterial growth and increasing their susceptibility to spontaneous bacterial peritonitis? 8
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- Weinberg ED, Weinberg GA. The role of iron in infection. Curr Opin Infect Dis 1995;8:164-69. https://journals.lww.com/co-infectiousdiseases/abstract/1995/06000/the_role_of_iron_in_infection.4.aspx
- Khan FA, Fisher MA, Khakoo RA. Association of hemochromatosis with infectious diseases: expanding spectrum. Intern J Infect Dis 2007;11:482-87. https://www.sciencedirect.com/science/article/pii/S1201971207000811
- Thwaites PA, Woods ML. Sepsis and siderosis, Yersinia enterocolitica and hereditary haemochromatosis. BMJ Case Rep 2017. Doi:10.11336/bvr-206-218185. https://casereports.bmj.com/content/2017/bcr-2016-218185
- Weinberg ED. Iron loading and disease surveillance. Emerg Infect Dis 1999;5:346-52. https://wwwnc.cdc.gov/eid/article/5/3/99-0305-t3
- Matthaiou EI, Sass G, Stevens DA, et al. Iron: an essential nutrient for Aspergillus fumigatus and a fulcrum for pathogenesis. Curr Opin Infect Dis 2018;31:506-11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579532/
- Alexander J, Limaye AP, Ko CW, et al. Association of hepatic iron overload with invasive fungal infection in liver transplant recipients. Liver Transpl 12:1799-1804. https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/lt.20827
- Schmidt SM. The role of iron in viral infections. Front Biosci (Landmark Ed) 2020;25:893-911. https://pubmed.ncbi.nlm.nih.gov/31585922/
- Romero A, Perez-Aurellao JL, Gonzalez-Villaron L et al. Effect of transferrin concentration on bacterial growth in human ascetic fluid from cirrhotic and neoplastic patients. J Clin Invest 1993;23:699-705. https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1365-2362.1993.tb01289.x
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