Additional file 1: of Investments in tuberculosis research – what are the gaps?

Response to reviewers. (DOCX 120 kb

RAW_DATA

Data from: Human cytomegalovirus epidemiology and relationship to tuberculosis and cardiovascular disease risk factors in a rural Ugandan cohor

Human cytomegalovirus epidemiology and relationship to tuberculosis and cardiovascular disease risk factors in a rural Ugandan cohort

<div><p>Human cytomegalovirus (HCMV) infection has been associated with increased mortality, specifically cardiovascular disease (CVD), in high-income countries (HICs). There is a paucity of data in low- and middle-income countries (LMICs) where HCMV seropositivity is higher. Serum samples from 2,174 Ugandan individuals were investigated for HCMV antibodies and data linked to demographic information, co-infections and a variety of CVD measurements. HCMV seropositivity was 83% by one year of age, increasing to 95% by five years. Female sex, HIV positivity and active pulmonary tuberculosis (TB) were associated with an increase in HCMV IgG levels in adjusted analyses. There was no evidence of any associations with risk factors for CVD after adjusting for age and sex. HCMV infection is ubiquitous in this rural Ugandan cohort from a young age. The association between TB disease and high HCMV IgG levels merits further research. Known CVD risk factors do not appear to be associated with higher HCMV antibody levels in this Ugandan cohort.</p></div

General population cohort characteristics of individuals included in this study.

<p>General population cohort characteristics of individuals included in this study.</p

Bar graphs showing unadjusted mean CVD risk factors by HCMV IgG OD level.

<p><b>HIV positive individuals were excluded from this analysis. Mean and 99% CI with p value from linear regression or logistic regression (for hypertension). p values shown are from age- and sex-adjusted likelihood ratio tests.</b> CI—confidence interval, CVD—cardiovascular disease, HCMV—human cytomegalovirus, HIV—human immunodeficiency virus.</p

Age and sex-adjusted regression for CVD risk factors cholesterol, HbA1c, HDL, LDL and BMI and hypertension showing mean difference (or Odds Ratio), p value from likelihood ratio test and 99% CI.

<p>Age and sex-adjusted regression for CVD risk factors cholesterol, HbA1c, HDL, LDL and BMI and hypertension showing mean difference (or Odds Ratio), p value from likelihood ratio test and 99% CI.</p

Unadjusted and fully adjusted mean differences (values obtained using a multivariable model including age, quadratic age, sex, HIV and TB status) in HCMV IgG OD with p value (t test for unadjusted values, regression for adjusted values) and 99% confidence intervals.

<p>Unadjusted and fully adjusted mean differences (values obtained using a multivariable model including age, quadratic age, sex, HIV and TB status) in HCMV IgG OD with p value (t test for unadjusted values, regression for adjusted values) and 99% confidence intervals.</p

Number of active TB cases by HCMV IgG tertile.

<p>Numbers above bars show number of active TB cases (n = 27 total active TB cases).</p

Percent HCMV seropositive by age group (years).

<p>Vertical lines show 99% CI for each mean data point. CI—confidence interval, HCMV—human cytomegalovirus.</p

Low responders make a stronger regulatory response to vaccination with MVA85A.

<p>To further explore the relationship between Treg marlers and IFN-γ ELISpot response identified through the microarray, flow cytometry of Treg markers was done of cells from the same volunteers taken on day of vaccination (day 0) and 1 week later (day 7). - A. mRNA levels as measured by microarray for several Treg markers show an inverse correlation with the IFN-γ ELISpot response. B. The Treg population (CD4+ CD25+ Foxp3+) is increased in low but not high responders during the first week following vaccination (paired t-test, p=0.009) C. STAT5B expression on day 0 correlates with frequency of Tregs (CD25+ Foxp3+, % CD4+) and there is a trend between expression of CTLA4 on day 2 and Tregs on day 7. Treg absolute counts: mean: 1687, median: 1631, interquartile range: 740-2882.</p