M. tuberculosis 16kDa, 38 kDa, ESAT-6

Background:BCG has low efficacy in tropical countries. We hypothesized that maternal latentMycobacterium tuberculosis (M.tb)infection (LTBI) results in fetal tolerance to mycobacterial antigens and impaired responses to BCG immunization. Methods:We enrolled 132 LTBI-positive and 150 LTBI-negative mothers and their babies in Entebbe, Uganda. Infants were BCG-immunized at birth. Cord blood and samples at weeks 1, 4, 6, 10, 14, 24, and 52 were analyzed for cytokine/chemokine responses toM.tbantigens by Luminex 17-plex assay in 6-day whole blood cultures and antibody responses by ELISA. Of the 17 Luminex analytes, seven (IL-2, IL-5, IL-10, IL-13, IL-17A, TNF, and IFN-gamma) were included in the main analysis as they were considered most likely to represent T cell responses. Immune sensitization was defined as a detectable cord blood cytokine response to PPD for any of the seven cytokines. Patterns of cytokine and antibody responses were compared between infants of mothers with and without LTBI using linear mixed models adjusting for confounders. Results:Most infants (73%) were sensitizedin uterotoM.tbantigens, with no overall difference seen between infants born to mothers with or without LTBI. Patterns of post-BCG cytokine and antibody responses to mycobacterial antigens were similar between the two infant groups. Conclusions:Our data do not support the hypothesis that maternal LTBI results in an impaired response to BCG immunization, in Ugandan infants. BCG vaccination at or shortly after birth is likely to be beneficial to all infants, irrespective of maternal LTBI status.

Introduction The definition of acute lower respiratory tract infection (LRTI) includes any infection involving the respiratory tract below the level of the larynx. In children, the most common acute LRTIs, and those with the greatest clinical relevance, are community-acquired pneumonia (CAP), bronchiolitis, bronchitis and tuberculosis (TB). The clinical relevance of LRTIs implies that they must be addressed with the most effective therapy. Antibiotics and antivirals play an essential role in this regard. Areas covered In this paper, the most recent advances in the drug treatment of LRTIs in children are discussed. Expert opinion Although LRTIs are extremely common and one of the most important causes of hospitalization and death in children, anti-infective therapy for these diseases remains unsatisfactory. For CAP and BR, the most important problem is the overuse and misuse of antibiotics; for BCL, the lack of drugs with demonstrated efficacy, safety and tolerability; for TB, the poor knowledge on the true efficacy and safety of the new drugs specifically planned to overcome the problem of MDR M. tuberculosis strains. There is still a long way to go for the therapy of pediatric LRTIs to be considered satisfactory.