Using a microarray-based approach, Michael Levin and colleagues develop a disease risk score to distinguish active from latent tuberculosis, as well as tuberculosis from other diseases, using whole blood samples. Please see later in the article for the Editors' Summary

Background The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. Methods We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. Results Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of −1.4 percentage points (90% confidence interval [CI], −4.9 to 2.2; 95% CI, −5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P = 0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). Conclusions Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927.)

Globally, tuberculosis (TB) continues to exact an unacceptably high toll of disease and death among children, particularly in the wake of the HIV epidemic. Increased international travel and immigration have seen childhood TB rates increase even in traditionally low burden, industrialised settings, and threaten to facilitate the emergence and spread of multi-drug resistant strains. While intense scientific and clinical research efforts into novel diagnostic, therapeutic and preventative interventions have focused on TB in adults, childhood TB has been relatively neglected. However, children are particularly vulnerable to severe disease and death following infection, and those with latent infection become the reservoir of disease reactivation in adulthood, fueling the future epidemic. Further research into the epidemiology, immune mechanisms, diagnosis, treatment and prevention of childhood TB is urgently needed. Advances in our understanding of TB in children would provide wider insights and opportunities to facilitate efforts to control this ancient disease.