Sex Differences in the Presentation of Tuberculosis in Uganda

Tuberculosis is a global disease that threatens both individual and public health. Tuberculosis, however, is a disease of disparities. Worldwide, it is more common in countries with low socioeconomic status or in settings overwhelmed by the HIV epidemic. But there is another disparity with tuberculosis that is not fully appreciated nor well understood: that is the disparity of tuberculosis between men and women. The World Health Organization, among others, has highlighted the untoward effects of tuberculosis on women, largely attributed to access to care and treatment, effects of pregnancy, and gender roles which diminish their social capital. Yet men have a higher incidence and prevalence of disease and may have worse outcomes with treatment compared to women. Biologic mechanisms may underlie some of these differences between men and women with tuberculosis. A complex interplay of endocrine, metabolic, and immune interactions likely affect the expression of M. tuberculosis. We hypothesize that total body energy stores, and the balance of that energy, determine the outcomes of tuberculosis, whether treated or not. Since the balance of fat and lean tissue differ in men and women, we further hypothesize that there will be differences in total energy stores between men and women at the time of diagnosis of tuberculosis. Finally, we hypothesize that the immune activation cause by infection with M. tuberculosis is modified by the hormonal milieu to affect metabolism of fat and protein in patients. We proposed to compare metabolic, immune, and hormonal profiles between men and women at the time of tuberculosis diagnosis. This study will lay the groundwork for future studies that can assess the effect of these differences on tuberculosis mortality and other treatment outcomes. The Specific Aims of the supplement are: 1. Compare immune and metabolic measures between men and women and relate them to total body energy as measured by body composition. 2. Discover new biomarkers by comparing RNA expression profiles between men and women presenting with tuberculosis.