Influence of maternal microbiota during pregnancy on infant immunity.

Microbiota from various maternal sites, including the gut, vagina and breast milk, are known to influence colonization in infants. However, emerging evidence suggests that these sites may exert their influence prior to delivery, in turn influencing fetal immune development. The dogma of a sterile womb continues to be challenged. Regardless, there is convincing evidence that the composition of the maternal gut prior to delivery influences neonatal immunity. Therefore, while the presence and function of placental microbiome is not clear, there is consensus that the gut microbiota during pregnancy is a critical determinant of offspring health. Data supporting the notion of bacterial translocation from the maternal gut to extra-intestinal sites during pregnancy are emerging, and potentially explain the presence of bacteria in breast milk. Much evidence suggests that the maternal gut microbiota during pregnancy potentially determines the development of atopy and autoimmune phenotypes in offspring. Here, we highlight the role of the maternal microbiota prior to delivery on infant immunity and predisposition to diseases. Moreover, we discuss potential mechanisms that underlie this phenomenon.

Immunogenicity of BCG in HIV-exposed and non-exposed infants following routine birth or delayed vaccination.

BACKGROUND: Human immunodeficiency virus (HIV) exposed infants are at high risk of Mycobacterium tuberculosis exposure, have high rates of progression to tuberculosis (TB) disease and are at significant risk of bacille Calmette-Guérin (BCG) induced adverse events. OBJECTIVE: To evaluate a delayed BCG vaccination strategy in HIV-exposed infants. DESIGN: A randomised trial of routine BCG vaccination given at birth compared to 14 weeks of age in HIV-exposed non-infected and non-HIV-exposed infants to investigate longitudinal BCG-induced immune responses using a 7-day whole blood interferon-gamma (IFN-γ) enzyme-linked immunosorbent assay. RESULTS: A significantly higher proportion of infants had positive responses to M. tuberculosis purified protein derivative (PPD) and BCG at 14 weeks in the birth vs. delayed vaccination groups (P = 0.001 for both). This difference was no longer apparent at weeks 24 or 52. Among infants vaccinated at birth, the 14-week IFN-γ response to M. tuberculosis PPD was lower among HIV-exposed than non-exposed infants (276.5 pg/ml vs. 790.2, P = 0.048). Among all infants, there were significant correlations between the magnitude of IFN-γ responses to BCG, M. tuberculosis PPD, TB 10.4 and culture filtrate protein 10/early secreted antigenic target 6. CONCLUSIONS: The timing of vaccination had limited effect on BCG-induced IFN-γ responses, which waned considerably over 1 year despite initial vigorous responses in both vaccination groups. The lower responses in HIV-exposed non-infected infants suggest potentially altered mycobacterial immunity early in life.

Positive futures: a qualitative study on the needs of adolescents on antiretroviral therapy in South Africa.

With the increasing availability of highly active antiretroviral therapy, vertically infected children have a better chance of surviving into adolescence and adulthood. Additionally, sexual transmission of human immunodeficiency virus (HIV) remains a problem, and incidence and prevalence among youth remain high. Therefore, HIV-infected adolescents are becoming a more prominent sub-group in the HIV/AIDS epidemic. Experience from the developed world indicates that providing effective care and treatment for adolescents poses unique challenges. This study aimed to identify the experiences and needs of adolescents growing up in care or on treatment for HIV in Cape Town, South Africa. Four focus groups interviews were conducted with a total of 26 young people attending an adolescent infectious diseases clinic at a tertiary hospital. Questions explored participant's perceptions on their present and future lives, and their self-identified needs. Focus groups revealed that adolescents viewed their illness negatively, but that social issues such as violence and poverty were also concerns. Despite these stressors, most respondents remained positive about the present and future, and wanted support for achieving their goals. As increasing numbers of HIV-infected children enter adolescence, healthcare providers and communities must find ways to support these young people to transition into adulthood.

A qualitative assessment of perspectives on the inclusion of adolescents in HIV vaccine trials in South Africa.

Adolescents are at high risk for HIV acquisition, and thus need to be included in HIV vaccine trials. In preparation for inclusion of adolescents in HIV vaccine trials in an urban community in Cape Town with a high antenatal HIV prevalence, the study assessed the attitudes towards the inclusion of adolescents in HIV vaccine trials. A total of 18 focus group discussions were conducted using a semistructured interview guide. The participants (n = 200) were adolescents, young adults, parents and other key informants. Participants from all groups welcomed the inclusion of adolescents in HIV vaccine trials due to their high-risk status. There were, however, concerns about sexual disinhibition, fear of side-effects, fear of HIV testing and disclosure of HIV status, mistrust of nurses and clinics. The study highlighted a number of ethical and social issues that need to be addressed before the trials.