Giuseppe
Emeritus
[Source: PLoS ONE, full page: (LINK). Abstract, edited.]
Research Article
Effects of Ascent to High Altitude on Human Antimycobacterial Immunity
Sarah Eisen, Louise Pealing, Robert W. Aldridge, Mark J. Siedner, Alejandro Necochea, Inna Leybell, Teresa Valencia, Beatriz Herrera, Siouxsie Wiles, Jon S. Friedland, Robert H. Gilman, Carlton A. Evans
Abstract
Background
Tuberculosis infection, disease and mortality are all less common at high than low altitude and ascent to high altitude was historically recommended for treatment. The immunological and mycobacterial mechanisms underlying the association between altitude and tuberculosis are unclear. We studied the effects of altitude on mycobacteria and antimycobacterial immunity.
Methods
Antimycobacterial immunity was assayed in 15 healthy adults residing at low altitude before and after they ascended to 3400 meters; and in 47 long-term high-altitude residents. Antimycobacterial immunity was assessed as the extent to which participants? whole blood supported or restricted growth of genetically modified luminescent Bacille Calmette-Gu?rin (BCG) mycobacteria during 96 hours incubation. We developed a simplified whole blood assay that could be used by a technician in a low-technology setting. We used this to compare mycobacterial growth in participants? whole blood versus positive-control culture broth and versus negative-control plasma.
Results
Measurements of mycobacterial luminescence predicted the number of mycobacterial colonies cultured six weeks later. At low altitude, mycobacteria grew in blood at similar rates to positive-control culture broth whereas ascent to high altitude was associated with restriction (p≤0.002) of mycobacterial growth to be 4-times less than in culture broth. At low altitude, mycobacteria grew in blood 25-times more than negative-control plasma whereas ascent to high altitude was associated with restriction (p≤0.01) of mycobacterial growth to be only 6-times more than in plasma. There was no evidence of differences in antimycobacterial immunity at high altitude between people who had recently ascended to high altitude versus long-term high-altitude residents.
Conclusions
An assay of luminescent mycobacterial growth in whole blood was adapted and found to be feasible in low-resource settings. This demonstrated that ascent to or residence at high altitude was associated with decreased mycobacterial growth in whole blood relative to controls, consistent with altitude-related augmentation of antimycobacterial cellular immunity.
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Citation: Eisen S, Pealing L, Aldridge RW, Siedner MJ, Necochea A, et al. (2013) Effects of Ascent to High Altitude on Human Antimycobacterial Immunity. PLoS ONE 8(9): e74220. doi:10.1371/journal.pone.0074220
Editor: Madhukar Pai, McGill University, Canada
Received: May 9, 2013; Accepted: July 29, 2013; Published: September 13, 2013
Copyright: ? 2013 Eisen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research was funded principally by the Wellcome Trust and the charity IFHAD: Innovation For Health And Development. Members of the project team and specific project activities were also funded by the Joint Global Health Trials consortium (MRC, DFID & Wellcome Trust), the World Health Organization, the Sir Halley Stewart Trust, the Foundation for Innovative New Diagnostics and the Bill & Melinda Gates Foundation. JSF acknowledges support from the Imperial College Biomedical Research Centre. SE and LP gratefully acknowledge multiple donors for supporting their medical student elective travel and subsistence for this research project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The corresponding author is an academic editor for PLOS Medicine but has not communicated with anyone associated with PLOS in relation to this manuscript and therefore does not consider that this represents any conflict of interest. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
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Research Article
Effects of Ascent to High Altitude on Human Antimycobacterial Immunity
Sarah Eisen, Louise Pealing, Robert W. Aldridge, Mark J. Siedner, Alejandro Necochea, Inna Leybell, Teresa Valencia, Beatriz Herrera, Siouxsie Wiles, Jon S. Friedland, Robert H. Gilman, Carlton A. Evans
Abstract
Background
Tuberculosis infection, disease and mortality are all less common at high than low altitude and ascent to high altitude was historically recommended for treatment. The immunological and mycobacterial mechanisms underlying the association between altitude and tuberculosis are unclear. We studied the effects of altitude on mycobacteria and antimycobacterial immunity.
Methods
Antimycobacterial immunity was assayed in 15 healthy adults residing at low altitude before and after they ascended to 3400 meters; and in 47 long-term high-altitude residents. Antimycobacterial immunity was assessed as the extent to which participants? whole blood supported or restricted growth of genetically modified luminescent Bacille Calmette-Gu?rin (BCG) mycobacteria during 96 hours incubation. We developed a simplified whole blood assay that could be used by a technician in a low-technology setting. We used this to compare mycobacterial growth in participants? whole blood versus positive-control culture broth and versus negative-control plasma.
Results
Measurements of mycobacterial luminescence predicted the number of mycobacterial colonies cultured six weeks later. At low altitude, mycobacteria grew in blood at similar rates to positive-control culture broth whereas ascent to high altitude was associated with restriction (p≤0.002) of mycobacterial growth to be 4-times less than in culture broth. At low altitude, mycobacteria grew in blood 25-times more than negative-control plasma whereas ascent to high altitude was associated with restriction (p≤0.01) of mycobacterial growth to be only 6-times more than in plasma. There was no evidence of differences in antimycobacterial immunity at high altitude between people who had recently ascended to high altitude versus long-term high-altitude residents.
Conclusions
An assay of luminescent mycobacterial growth in whole blood was adapted and found to be feasible in low-resource settings. This demonstrated that ascent to or residence at high altitude was associated with decreased mycobacterial growth in whole blood relative to controls, consistent with altitude-related augmentation of antimycobacterial cellular immunity.
____
Citation: Eisen S, Pealing L, Aldridge RW, Siedner MJ, Necochea A, et al. (2013) Effects of Ascent to High Altitude on Human Antimycobacterial Immunity. PLoS ONE 8(9): e74220. doi:10.1371/journal.pone.0074220
Editor: Madhukar Pai, McGill University, Canada
Received: May 9, 2013; Accepted: July 29, 2013; Published: September 13, 2013
Copyright: ? 2013 Eisen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research was funded principally by the Wellcome Trust and the charity IFHAD: Innovation For Health And Development. Members of the project team and specific project activities were also funded by the Joint Global Health Trials consortium (MRC, DFID & Wellcome Trust), the World Health Organization, the Sir Halley Stewart Trust, the Foundation for Innovative New Diagnostics and the Bill & Melinda Gates Foundation. JSF acknowledges support from the Imperial College Biomedical Research Centre. SE and LP gratefully acknowledge multiple donors for supporting their medical student elective travel and subsistence for this research project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The corresponding author is an academic editor for PLOS Medicine but has not communicated with anyone associated with PLOS in relation to this manuscript and therefore does not consider that this represents any conflict of interest. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
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