Predicting Airborne Infection Risk: Association Between Personal Ambient Carbon Dioxide Level Monitoring and Incidence of Tuberculosis Infection in South African Health Workers

Ruvandhi R Nathavitharana, Hridesh Mishra, Amanda Sullivan, Shelley Hurwitz, Philip Lederer, Jack Meintjes, Edward Nardell, Grant Theron, Ruvandhi R Nathavitharana, Hridesh Mishra, Amanda Sullivan, Shelley Hurwitz, Philip Lederer, Jack Meintjes, Edward Nardell, Grant Theron

Abstract

Background: High rates of tuberculosis (TB) transmission occur in hospitals in high-incidence countries, yet there is no validated way to evaluate the impact of hospital design and function on airborne infection risk. We hypothesized that personal ambient carbon dioxide (CO2) monitoring could serve as a surrogate measure of rebreathed air exposure associated with TB infection risk in health workers (HWs).

Methods: We analyzed baseline and repeat (12-month) interferon-γ release assay (IGRA) results in 138 HWs in Cape Town, South Africa. A random subset of HWs with a baseline negative QuantiFERON Plus (QFT-Plus) underwent personal ambient CO2 monitoring.

Results: Annual incidence of TB infection (IGRA conversion) was high (34%). Junior doctors were less likely to have a positive baseline IGRA than other HWs (OR, 0.26; P = .005) but had similar IGRA conversion risk. IGRA converters experienced higher median CO2 levels compared to IGRA nonconverters using quantitative QFT-Plus thresholds of ≥0.35 IU/mL (P < .02) or ≥1 IU/mL (P < .01). Median CO2 levels were predictive of IGRA conversion (odds ratio [OR], 2.04; P = .04, ≥1 IU/mL threshold). Ordinal logistic regression demonstrated that the odds of a higher repeat quantitative IGRA result increased by almost 2-fold (OR, 1.81; P = .01) per 100 ppm unit increase in median CO2 levels, suggesting a dose-dependent response.

Conclusions: HWs face high occupational TB risk. Increasing median CO2 levels (indicative of poor ventilation and/or high occupancy) were associated with higher likelihood of HW TB infection. Personal ambient CO2 monitoring may help target interventions to decrease TB transmission in healthcare facilities and help HWs self-monitor occupational risk, with implications for other airborne infections including coronavirus disease 2019.

Keywords: IGRA; carbon dioxide monitoring; health workers; tuberculosis; tuberculosis infection control (TB-IC).

Conflict of interest statement

Potential conflicts of interest. R. R. N. and G. T. report collaboration on an NIH U01 grant evaluating TB diagnostics, outside the scope of this work, and R. R. N. is chair of the board for TB Proof, a TB advocacy organization based in South Africa. All other authors report no other conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.
Figure 1.
Study flow diagram. Abbreviations: CO2, carbon dioxide; QFT, QuantiFERON-Plus; TB, tuberculosis.
Figure 2.
Figure 2.
Comparison of quantitative baseline and repeat QuantiFERON-Plus TB1-nil and TB2-nil values. A and B, Results for all participants. C and D, Results for all interferon-γ release assay (IGRA) converters demonstrating significant differences in both TB1-nil and TB2-nil values. E and F, Results for all IGRA reverters.
Figure 3.
Figure 3.
Logistic regression probability plots. Probability of interferon-γ release assay (IGRA) conversion using median health worker (HW) carbon dioxide (CO2) levels comparing IGRA nonconverters to IGRA converters (A), IGRA nonconverters to IGRA converters whose TB1-nil or TB2-nil quantitative values are ≥0.7 IU/mL (B), and IGRA nonconverters to IGRA converters whose TB1-nil and TB2-nil quantitative values are ≥1 IU/mL (C).
Figure 4.
Figure 4.
Box plot illustrating median carbon dioxide (CO2) levels summarized according to interferon-γ release assay conversion group, based on repeat quantitative IGRA values. Line connects conversion level group medians; diamonds are group means. Negative: both TB1-nil and TB2-nil <0.35 IU/mL. Positive: both TB1-nil and TB2-nil ≥0.35 to 0.7 IU/mL; either TB1-nil or TB2-nil ≥0.7 IU/mL to 1 IU/mL; or both TB1-nil and TB2-nil ≥1.0 IU/mL.

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