Tuberculosis case fatality is higher in male than female patients in Europe: a systematic review and meta-analysis

Epidemiological TB data indicate differences in infection prevalence, progression rates, and clinical disease incidence between sexes. In contrast, evidence on sex-specific differential (post) TB case fatality in Europe has not been synthesized systematically.

We searched electronic databases and grey literature up to December 2020 for studies reporting sex-stratified TB death data for Europe. The JBI critical appraisal tools served for bias risk assessment and subgroup analyses for studying heterogeneity. Random-effects models meta-analyses enabled estimating pooled relative risks of sex-associated TB fatality. Considering associations of comorbidities and risk factors on fatality differences, we applied relative risk meta-regression.

Based on 17,400 records screened, 117 studies entered quantitative analyses. Seventy-five studies providing absolute participant data with moderate quality and limited sex stratification reported 33 to 235,000 TB cases and 7 to 27,108 deaths. The pooled male-to-female TB fatality risk ratio was 1.4 [1.3-1.5]. Heterogeneity was high between studies and subgroups. Study time, concurrent comorbidities (e.g., HIV, diabetes, cancers), and mean participant ages showed no effect modification. We identified higher male TB fatality in studies with higher homelessness (coefficient 3.18, 95% CI [-0.59 to 6.94], p-value 0.10) and lower migrants proportion (coefficient - 0.24, 95% CI [- 0.5 to 0.04], p-value 0.09).

We found 30-50% higher TB case fatality for males in Europe. Except for homelessness, migration, and a trend for some comorbidities, assessing effect modification could not reduce our meta-analysis' high heterogeneity. Public health authorities should take heed of this higher risk of dying in male patients' treatment services.