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Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study
BACKGROUND: Identifying people at higher risk of developing tuberculosis with human immunodeficiency virus (HIV) infection may improve clinical management of co-infections. Iron influences tuberculosis (TB) pathogenesis, but understanding the exact mechanisms of how and timing of when iron is involv...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568026/ https://www.ncbi.nlm.nih.gov/pubmed/23360117 http://dx.doi.org/10.1186/1471-2334-13-48 |
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author | McDermid, Joann M Hennig, Branwen J van der Sande, Marianne Hill, Adrian VS Whittle, Hilton C Jaye, Assan Prentice, Andrew M |
author_facet | McDermid, Joann M Hennig, Branwen J van der Sande, Marianne Hill, Adrian VS Whittle, Hilton C Jaye, Assan Prentice, Andrew M |
author_sort | McDermid, Joann M |
collection | PubMed |
description | BACKGROUND: Identifying people at higher risk of developing tuberculosis with human immunodeficiency virus (HIV) infection may improve clinical management of co-infections. Iron influences tuberculosis (TB) pathogenesis, but understanding the exact mechanisms of how and timing of when iron is involved remains challenging since biological samples are rarely available from the disease susceptibility period due to the difficulty in predicting in who and when, if ever, TB will develop. The objective of this research was to determine how host iron status measured at HIV diagnosis and genotypes related to host iron metabolism were associated with incident TB. METHODS: Archived clinical data, plasma and DNA were analyzed from 1139 adult participants in a large HIV-1, HIV-2 and dual seroprevalent cohort based at the Medical Research Council Laboratories in The Gambia. Incident pulmonary and/or extrapulmonary TB diagnoses a minimum of 28 days after HIV diagnosis were independently re-confirmed using available evidence (n=152). Multiple host iron status biomarkers, Haptoglobin and solute carrier family 11, member 1 (SLC11A1) genotypes were modeled to characterize how indicators of host iron metabolism were associated with TB susceptibility. RESULTS: Hemoglobin (incidence rate ratio, IRR=0.88, 95% CI=0.79-0.98), plasma transferrin (IRR=0.53, 0.33-0.84) and ferritin (IRR=1.26, 1.05-1.51) were significantly associated with TB after adjusting for TB susceptibility factors. While genotype associations were not statistically significant, SLC11A1 associations replicated similar directions as reported in HIV-seronegative meta-analyses. CONCLUSIONS: Evidence of host iron redistribution at HIV diagnosis was associated with incident TB, and genetic influences on iron homeostasis may be involved. Low hemoglobin was associated with subsequent diagnosis of TB, but when considered in combination with additional iron status biomarkers, the collective findings point to a mechanism whereby anemia and iron redistribution are likely due to viral and/or bacteria-driven processes and the host immune response to infection. As a result, iron supplementation may not be efficacious or safe under these circumstances. Clinical and nutritional management of HIV and Mycobacterium tuberculosis co-infected individuals, especially in regions where food insecurity and malnutrition co-exist, may be further improved when the iron-related TB risk factors identified here are better understood and managed to favor host rather than pathogen outcomes. |
format | Online Article Text |
id | pubmed-3568026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35680262013-02-12 Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study McDermid, Joann M Hennig, Branwen J van der Sande, Marianne Hill, Adrian VS Whittle, Hilton C Jaye, Assan Prentice, Andrew M BMC Infect Dis Research Article BACKGROUND: Identifying people at higher risk of developing tuberculosis with human immunodeficiency virus (HIV) infection may improve clinical management of co-infections. Iron influences tuberculosis (TB) pathogenesis, but understanding the exact mechanisms of how and timing of when iron is involved remains challenging since biological samples are rarely available from the disease susceptibility period due to the difficulty in predicting in who and when, if ever, TB will develop. The objective of this research was to determine how host iron status measured at HIV diagnosis and genotypes related to host iron metabolism were associated with incident TB. METHODS: Archived clinical data, plasma and DNA were analyzed from 1139 adult participants in a large HIV-1, HIV-2 and dual seroprevalent cohort based at the Medical Research Council Laboratories in The Gambia. Incident pulmonary and/or extrapulmonary TB diagnoses a minimum of 28 days after HIV diagnosis were independently re-confirmed using available evidence (n=152). Multiple host iron status biomarkers, Haptoglobin and solute carrier family 11, member 1 (SLC11A1) genotypes were modeled to characterize how indicators of host iron metabolism were associated with TB susceptibility. RESULTS: Hemoglobin (incidence rate ratio, IRR=0.88, 95% CI=0.79-0.98), plasma transferrin (IRR=0.53, 0.33-0.84) and ferritin (IRR=1.26, 1.05-1.51) were significantly associated with TB after adjusting for TB susceptibility factors. While genotype associations were not statistically significant, SLC11A1 associations replicated similar directions as reported in HIV-seronegative meta-analyses. CONCLUSIONS: Evidence of host iron redistribution at HIV diagnosis was associated with incident TB, and genetic influences on iron homeostasis may be involved. Low hemoglobin was associated with subsequent diagnosis of TB, but when considered in combination with additional iron status biomarkers, the collective findings point to a mechanism whereby anemia and iron redistribution are likely due to viral and/or bacteria-driven processes and the host immune response to infection. As a result, iron supplementation may not be efficacious or safe under these circumstances. Clinical and nutritional management of HIV and Mycobacterium tuberculosis co-infected individuals, especially in regions where food insecurity and malnutrition co-exist, may be further improved when the iron-related TB risk factors identified here are better understood and managed to favor host rather than pathogen outcomes. BioMed Central 2013-01-29 /pmc/articles/PMC3568026/ /pubmed/23360117 http://dx.doi.org/10.1186/1471-2334-13-48 Text en Copyright ©2013 McDermid et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article McDermid, Joann M Hennig, Branwen J van der Sande, Marianne Hill, Adrian VS Whittle, Hilton C Jaye, Assan Prentice, Andrew M Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study |
title | Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study |
title_full | Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study |
title_fullStr | Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study |
title_full_unstemmed | Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study |
title_short | Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study |
title_sort | host iron redistribution as a risk factor for incident tuberculosis in hiv infection: an 11-year retrospective cohort study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568026/ https://www.ncbi.nlm.nih.gov/pubmed/23360117 http://dx.doi.org/10.1186/1471-2334-13-48 |
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