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Additional file 1: Figure S1. Flow chart for participants. Table S1. Interactions for the associations between serum vitamins and respiratory morbidity and mortality: P-values for effect modification by vitamin supplement use and smoking. Table S2. Associations between lower serum antioxidant vitamins and respiratory morbidity and mortality by use of vitamin supplements [NHANES III (1988–1994) and continuous NHANES (1999–2006)]. Table S3. Associations between lower serum antioxidant vitamins and respiratory morbidity and mortality by smoking status [NHANES III (1988–1994) and continuous NHANES (1999-2006)]. Table S4. Cohort specific estimates in models with significant heterogeneity. Table S5. Association of vitamin C deficiency and vitamin D (25-OHD) insufficiency with respiratory morbidity and mortality [NHANES III (1988–1994) and continuous NHANES (1999–2006)].

Background The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)-infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge. Methods We describe TB diagnosis and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries participated in the study. Results Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART included contact history in 41 sites (84%), symptom screening in 38 (88%), and chest Radiograph in 34 sites (79%). The use of diagnostic tools was examined among 146 children diagnosed with TB during the study period. Chest Radiograph was used in 125 (86%) children, sputum microscopy in 76 (52%), induced sputum microscopy in 38 (26%), gastric aspirate microscopy in 35 (24%), culture in 25 (17%), and Xpert MTB/RIF in 11 (8%) children. Conclusions Induced sputum and Xpert MTB/RIF were infrequently available to diagnose childhood TB, and screening was largely based on symptom identification. There is an urgent need to improve the capacity of ART programs in low- and middle-income countries to exclude and diagnose TB in HIV-infected children

Background: Based on clinical trial results, the World Health Organization recommends infant HIV testing at age 4-6 weeks and immediate antiretroviral therapy (ART) initiation in all HIV-infected infants. Little is known about the outcomes of HIV-infected infants diagnosed with HIV in the first weeks of life in resource-limited settings. We assessed ART initiation and mortality in the first year of life among infants diagnosed with HIV by 12 weeks of age. Methods: Cohort of HIV-infected infants in Kinshasa and Blantyre diagnosed before 12 weeks to estimate 12-month cumulative incidences of ART initiation and mortality, accounting for competing risks. Multivariate models were used to estimate associations between infant characteristics and timing of ART initiation. Results: One hundred and twenty-one infants were diagnosed at a median age of 7 weeks (interquartile range, 6-8). The cumulative incidence of ART initiation was 46% [ 95% confidence interval (CI), 36%, 55%] at 6 months and 70% (95% CI 60%, 78%) at 12 months. Only age at HIV diagnosis was associated with ART initiation by age 6 months, with a subdistribution hazard ratio of 0.70 (95% CI 0.52, 0.91) for each week increase in age at DNA polymerase chain reaction test. The 12-month cumulative incidence of mortality was 20% (95% CI 13%, 28%). Conclusions: Despite early diagnosis of HIV, ART initiation was slow and mortality remained high, underscoring the complexity in translating clinical trial findings and World Health Organization's guidance into real-life practice. Novel and creative health system interventions will be required to ensure that all HIV-infected infants achieve optimal treatment outcomes under routine care settings.

Socioeconomic disadvantage may contribute to poor health through immune-related biological mechanisms. We examined the associations between socioeconomic status, as measured by annual household income, and T-cell markers of aging, including the ratios of CD4 and CD8 effector cells to naïve cells (E:N ratio) and the CD4:CD8 T-cell ratio. We hypothesized that participants with a lower income would have higher E:N ratios and lower CD4:CD8 ratios compared to participants with a higher income, and that these associations would be partially mediated by elevated cytomegalovirus (CMV) IgG antibody levels, a virus implicated in aging and clonal expansion of T-cells.

BACKGROUND: The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)-infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge.METHODS: We describe TB diagnosis and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries participated in the study.RESULTS: Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART included contact history in 41 sites (84%), symptom screening in 38 (88%), and chest Radiograph in 34 sites (79%). The use of diagnostic tools was examined among 146 children diagnosed with TB during the study period. Chest Radiograph was used in 125 (86%) children, sputum microscopy in 76 (52%), induced sputum microscopy in 38 (26%), gastric aspirate microscopy in 35 (24%), culture in 25 (17%), and Xpert MTB/RIF in 11 (8%) children.CONCLUSIONS: Induced sputum and Xpert MTB/RIF were infrequently available to diagnose childhood TB, and screening was largely based on symptom identification. There is an urgent need to improve the capacity of ART programs in low- and middle-income countries to exclude and diagnose TB in HIV-infected children.

Outcomes of HIV-exposed infants remain inadequately studied, particularly in resource-deprived settings. We conducted an observational study of 1707 mother-infant pairs who received care in a comprehensive HIV program in Kinshasa, DR Congo during 2007-2013. The study resulted in two manuscripts, one which describes temporal changes in the outcomes of HIV-exposed infants and one that assesses the relationship between infant retention in care and the provision of combination antiretroviral therapy (cART) to their HIV-infected mothers. The first manuscript suggests there have been encouraging improvements over time in the outcomes of HIV-exposed infants but that continued efforts are needed. Accounting for competing risks (e.g. death), we estimated the cumulative incidences of having an initial specimen collected for HIV virologic testing, loss to follow-up (LTFU), HIV transmission, and death through age 18 months, as well as cART initiation among HIV-infected infants through age 24 months. The 18-month cumulative incidence of specimen collection increased from 73% (95% confidence limit [CL]: 68-78%) for infants enrolled in 2007-2008 to 99% (95% CL: 98-100%) for infants enrolled in 2011-2012. The 18-month cumulative incidence of HIV declined from 15% (95% CL: 11-21%) for infants enrolled in 2007-2008 to 8% (95% CL: 6-11%) for infants enrolled in 2011-2012 and death declined from 8% (95% CL: 5-11%) to 3% (95% CL: 2-5%). The 18-month cumulative incidence of LTFU did not improve, with 18-month cumulative incidences of 18% (95% CL: 14-22%) for infants enrolled in 2007-2008 and 18% (95% CL: 15-21%) for infants enrolled in 2011-2012. Among HIV-infected infants, the 24-month cumulative incidence of cART increased from 61% (95% CL: 43-75%) to 97% (95% CL: 82-100%); the median age at cART decreased from 17.9 to 9.3 months. In the second manuscript, we show that increasing access to cART for pregnant women could improve retention in care of their HIV-exposed infants. The 18-month cumulative incidence of LTFU was 9% among infants whose mothers had initiated cART by infant enrollment and 19% among infants whose mothers had not yet initiated cART (Gray's p-value