Immunometabolic signatures predict risk of progression to active tuberculosis and disease outcome

Data Availability: All datasets generated for this study are included in the manuscript with the exception of the rhesus macaque metabolics data which is included as Table S6 [https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00527/full#SM14].Supplementary Material is available online at: https://www.frontiersin.org/articles/10.3389/fimmu.2019.00527/full#supplementary-material .There remains a pressing need for biomarkers that can predict who will progress to active tuberculosis (TB) after exposure to Mycobacterium tuberculosis (MTB) bacterium. By analyzing cohorts of household contacts of TB index cases (HHCs) and a stringent non-human primate (NHP) challenge model, we evaluated whether integration of blood transcriptional profiling with serum metabolomic profiling can provide new understanding of disease processes and enable improved prediction of TB progression. Compared to either alone, the combined application of pre-existing transcriptome- and metabolome-based signatures more accurately predicted TB progression in the HHC cohorts and more accurately predicted disease severity in the NHPs. Pathway and data-driven correlation analyses of the integrated transcriptional and metabolomic datasets further identified novel immunometabolomic signatures significantly associated with TB progression in HHCs and NHPs, implicating cortisol, tryptophan, glutathione, and tRNA acylation networks. These results demonstrate the power of multi-omics analysis to provide new insights into complex disease processes.This work was supported by the Bill & Melinda Gates Foundation (BMGF) Grand Challenges in Global Health (GC6-74 grant 37772, OPP1055806 and OPP1087783 in conjunction with AERAS). This work was also supported by a Strategic Health Innovation Partnership grant from the South African Medical Research Council and Department of Science and Technology/South African Tuberculosis Bioinformatics Initiative. Additional support was provided by the European Union FP7 (ADITEC, 280873 and TBVAC2020, 643381) and the National Institutes of Health [U19 AI106761 and U19 AI135976]. FD was supported by the NCDIR (National Institutes of Health [P41 GM109824]). DT and GT were supported by South African Medical Research Council SHIP funding for the South African Tuberculosis Bioinformatics Initiative to GW

Positive Impact of a Shelter-based Hepatitis B Vaccine Program in Homeless Baltimore Children and Adolescents

Homeless youth are at increased risk for hepatitis B virus (HBV) infection and HBV vaccine coverage is poor in this group. The purpose of our study was to determine if a shelter-based HBV vaccine program in children and adolescents 2–18 years of age with a randomized controlled trial using a culturally appropriate HBV video could increase HBV vaccine coverage rates. Subjects were randomized to an 8 min HBV video or a control, smoking prevention video. Before exposure to the videos, HBV knowledge, and demographics were assessed in caregivers and adolescents. HBV vaccine no. 1 was offered to all subjects who did not produce a vaccine record; subsequently, an accurate HBV vaccine history was obtained from medical providers. Subjects were asked to return 1 and 3 months after visit 1, HBV vaccine was offered to all with incomplete coverage, and HBV knowledge was reassessed. There were 328 children and adolescents cared for by 170 caregivers enrolled in the study. One hundred and four had incomplete HBV vaccine coverage. Data are reported for all family units with at least one subject needing vaccine. There were 53 children and adolescents randomized to the HBV video vs. 51 to the smoking video. HBV knowledge scores of caregivers improved at Visit no. 2 vs. no. 1 in the HBV video group (p = 0.01) but not in the smoking group (p = 0.82). Similar results were observed for adolescents in the HBV video group (p = 0.05) but not in the smoking group (p = 0.40). Exposure to the HBV video vs the smoking video had a significant effect on return rates for vaccine at Visit no. 2 (59 vs. 31%; p = 0.05) but not at Visit no. 3 (47 vs. 18%, p = 0.06). The shelter-based vaccine program was very effective in increasing HBV coverage rates in the entire group of 328 children and adolescents enrolled in the study, from 68% coverage at baseline to 85% at the conclusion of the study. We conclude that shelter-based HBV vaccine programs can be highly effective in increasing vaccine coverage rates in older children and adolescents. A brief exposure to a culturally appropriate HBV video improves HBV knowledge and may improve return rates for vaccine