Abstract
BackgroundWorldwide tuberculosis (TB) reports show a male bias in morbidity; however, the differences in pathogenesis between men and women with TB, as well as the mechanisms associated with such differences, are poorly investigated. We hypothesized that comparison of the degree of lung injury and clinical indices of well-matched men and women with newly diagnosed TB, and statistical analysis of the correlation between these indices and the extent of lung lesions, can provide insights into the mechanism of gender bias in TB.MethodsWe evaluated the acid-fast bacilli grading of sputum samples and compiled computed tomography (CT) data of the age-matched, newly diagnosed male and female TB patients without history of smoking or comorbidities. Inflammatory biomarker levels and routine haematological and coagulation-associated parameters were compared. Binary logistic regression analysis was used to define the association between the indices and lung lesions, and the influence of sex adjustment.ResultsWomen with TB have a longer delay in seeking healthcare than men after onset of the TB-associated symptoms. Men with TB have significantly more severe lung lesions (cavities and healing-associated features) and higher bacterial counts compared to women with TB. Scoring of the CT images before and after anti-TB treatment showed a faster response to therapy in women than in men. Coagulation- and platelet-associated indices were in models from multivariate regression analysis with groups of males or females with TB or in combination. In univariate regression analysis, lower lymphocyte counts were associated with both cavity and more bacterial counts, independent of sex, age and BMI. The association of international normalized ratios (INR), prothrombin times (PTs), mean platelet volumes (MPVs) and fibrinogen (FIB) level with lung lesions was mostly influenced by sex adjustment.ConclusionsSex influences the association between haemostasis and extent of TB lung lesions, which may be one mechanism involved in sex bias in TB pathogenesis.
Highlights
Worldwide tuberculosis (TB) reports show a male bias in morbidity; the differences in pathogenesis between men and women with TB, as well as the mechanisms associated with such differences, are poorly investigated
Higher sputum bacterial counts (3+ and 4+) were observed in 46.5% of male patients compared to 25.6% in female patients
The indices which were selected in the models were different in separate male or female groups, and in combination, we found that similar sets of coagulation and platelet indices were involved in association with severity of male (MPV, AT3, FIB with sputum bacterial grade, PCT with cavity) and female (PT with cavity) patients with TB, and in combination of the groups (APTT with sputum bacterial grade, PCT with cavity) (Tables 4 and 5)
Summary
Worldwide tuberculosis (TB) reports show a male bias in morbidity; the differences in pathogenesis between men and women with TB, as well as the mechanisms associated with such differences, are poorly investigated. While disagreement exists on whether socioeconomic and cultural factors may create barriers to accessing healthcare which cause undernotification in women, in developing countries [3,4,5], in recent years, increasing numbers of studies have indicated that biological mechanisms may account for a significant part of the difference between men and women in susceptibility to infection, including TB [6,7,8]. With C57BL/6 and Balb/c mouse models, previous researches have demonstrated that infection with Mtb. resulted in exacerbated pulmonary pathology and increased morbidity and mortality in male mice compared to females [9, 10]. Evidence for the sex bias in TB pathogenesis based on clinical observation is still scarce, and the underlying mechanisms are still little known
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