Sex Differences in Mortality After Tuberculosis Treatment

Doctor checking coronavirus patient chest x-ray film at ward hospital.
Researchers studied patients with pulmonary tuberculosis to better understand the impact of sex on mortality and sputum microbiological status after treatment initiation.

All-cause mortality was found to be higher in men vs women after treatment for tuberculosis (TB), according to results from a retrospective cohort study and a meta-analysis published in Clinical Infectious Diseases.

To assess sex differences in clinical and microbiological outcomes in TB, researchers conducted a retrospective cohort study comprising 2894 patients with drug-susceptible pulmonary TB enrolled at the National Taiwan University Hospital in Taipei from 2000 to 2016. Primary outcomes were all-cause mortality and infection-related mortality (including mortality due to pneumonia, sepsis, and TB) 9 months after TB treatment. Secondary outcomes were sputum culture and sputum smear positivity 2 months after TB treatment.

The researchers also performed a systematic review and meta-analysis of 398 observational studies from 81 countries over the past 10 years to determine whether men had increased mortality compared with women following TB treatment.

Of the 2894 patients in the retrospective cohort study, 68.2% were men and 31.8% were women. Men were older than women (median age, 68.9 vs 58.2 years; P <.001), had higher rates of cavitary disease (15.7% vs 11.1%; P <.001), and had a greater proportion of comorbidities, history of smoking, and alcohol abuse. 

At 9 months following treatment, men were found to have higher all-cause mortality (hazard ratio [HR], 1.75; 95% CI, 1.42-2.14) and infection-related mortality (HR, 1.52; 95% CI, 1.17-1.99). After adjusting for body mass index, Charlson Comorbidity Index, hypertension, transplant status, alcoholism, smoking, cavitary disease, and baseline acid-fast bacilli (AFB), the association remained for all-cause mortality (adjusted HR, 1.53; 95% CI, 1.08-2.17) and infection-related mortality (adjusted HR, 1.81; 95% CI, 1.11-2.93).

At 2 months after treatment, men had higher sputum culture (18.4% vs 11.6%; P =.003) and AFB smear (8.3% vs 5.0%; P =.015) positivity than women. After adjusting for confounders, the associations remained for both sputum culture positivity (adjusted odds ratio (aOR), 1.67; 95% CI, 1.06-2.63) and sputum smear positivity (aOR, 1.30; 95% CI, 0.67-2.55). Sensitivity analysis adjusting for age yielded similar results.

Findings from the meta-analysis also yielded similar results. All-cause mortality was higher in men than women with a pooled OR of 1.26 (95% CI, 1.19-1.34) from 135 studies (I2=77.9%) and a pooled HR of 1.17 (95% CI, 1.07-1.27) from 44 studies (I2=63.59%). Of the 82 studies that had adjustments for at least 1 confounder, the pooled adjusted OR was 1.31 (95% CI, 1.18-1.45) among 52 studies (I2=74.80%), and the pooled adjusted HR was 1.19 (95% CI, 1.05-1.67) among 30 studies (I2=82.5%).

With respect to sputum culture and sputum smear positivity, the meta-analysis showed higher pooled unadjusted and adjusted odds for both following TB treatment.

The associations did not significantly change when accounting for diabetes, hypertension, alcohol abuse, smoking, cardiovascular events, chronic obstructive pulmonary disease, and HIV.

The findings “should inform medical decision-making in TB treatment programs and motivate further focused research into the biological (immunological and genetic) basis of these sex-based differences,” concluded the researchers.


Chidambaram V, Tun NL, Majella MG, et al. Male sex is associated with worse microbiological and clinical outcomes following tuberculosis treatment: a retrospective cohort study, a systematic review of the literature, and meta-analysis. Clin Infect Dis. Published online June 8, 2021. doi:10.1093/cid/ciab527

This article originally appeared on Infectious Disease Advisor