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-Guérin (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.