Cluster randomized evaluation of Adolescent Girls Empowerment Programme (AGEP): study protocol.

BACKGROUND: Adolescents in less developed countries such as Zambia often face multi-faceted challenges for achieving successful transitions through adolescence to early adulthood. The literature has noted the need to introduce interventions during this period, particularly for adolescent girls, with the perspective that such investments have significant economic, social and health returns to society. The Adolescent Girls Empowerment Programme (AGEP) was an intervention designed as a catalyst for change for adolescent girls through themselves, to their family and community. METHODS/DESIGN: AGEP was a multi-sectoral intervention targeting over 10,000 vulnerable adolescent girls ages 10-19 in rural and urban areas, in four of the ten provinces of Zambia. At the core of AGEP were mentor-led, weekly girls' group meetings of 20 to 30 adolescent girls participating over two years. Three curricula - sexual and reproductive health and lifeskills, financial literacy, and nutrition - guided the meetings. An engaging and participatory pedagogical approach was used. Two additional program components, a health voucher and a bank account, were offered to some girls to provide direct mechanisms to improve access to health and financial services. Embedded within AGEP was a rigorous multi-arm randomised cluster trial with randomization to different combinations of programme arms. The study was powered to assess the impact across a set of key longer-term outcomes, including early marriage and first birth, contraceptive use, educational attainment and acquisition of HIV and HSV-2. Baseline behavioural surveys and biological specimen collection were initiated in 2013. Impact was evaluated immediately after the program ended in 2015 and will be evaluated again after two additional years of follow-up in 2017. The primary analysis is intent-to-treat. Qualitative data are being collected in 2013, 2015 and 2017 to inform the programme implementation and the quantitative findings. An economic evaluation will evaluate the incremental cost-effectiveness of each component of the intervention. DISCUSSION: The AGEP program and embedded evaluation will provide detailed information regarding interventions for adolescent girls in developing country settings. It will provide a rich information and data source on adolescent girls and its related findings will inform policy-makers, health professionals, donors and other stakeholders. TRIAL REGISTRATION: ISRCTN29322231 . March 04 2016; retrospectively registered

Acquisition of pneumococci specific effector and regulatory Cd4+ T cells localising within human upper respiratory-tract mucosal lymphoid tissue

The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4(+) T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4(+) T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25(hi) T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4(+) T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines

Similar but different: Integrated phylogenetic analysis of Austrian and Swiss HIV-1 sequences reveal differences in transmission patterns of the local HIV-1 epidemics.

OBJECTIVES Phylogenetic analyses of two or more countries allow to detect differences in transmission dynamics of local HIV-1 epidemics beyond differences in demographic characteristics. METHODS A maximum-likelihood phylogenetic tree was built using pol-sequences of the Swiss HIV Cohort Study (SHCS) and the Austrian HIV Cohort Study (AHIVCOS), with international background sequences. Three types of phylogenetic cherries (clusters of size 2) were analyzed further: 1) Domestic cherries, 2) International cherries and 3) SHCS/AHIVCOS-cherries. Transmission group and ethnicities observed within the cherries were compared to the respective distribution expected from a random distribution of patients on the phylogeny. RESULTS The demographic characteristics of the AHIVCOS (included patients: 3'141) and the SHCS (included patients: 12'902) are very similar. In the AHIVCOS, 36.5% of the patients were in domestic cherries, 8.3% in international cherries, and 7.0% in SHCS/AHIVCOS cherries. Similarly, in the SHCS, 43.0% of the patients were in domestic cherries, 8.2% in international cherries, and 1.7% in SHCS/AHIVCOS cherries. While international cherries in the SHCS were dominated by heterosexuals (HET) with MSM being underrepresented, the opposite was the case for the AHIVCOS. In both cohorts, cherries with one patient belonging to the transmission group intravenous drug user (IDU) and the other one non-IDU were underrepresented. CONCLUSION In both cohorts, international HIV transmission plays a major role in the local epidemics, mostly driven by MSM in the AHIVOS, and by HET in the SHCS, highlighting the importance of international collaborations to understand global HIV transmission links on the way to eliminate HIV

Impact of Capsular Switch on Invasive Pneumococcal Disease Incidence in a Vaccinated Population

BACKGROUND: Despite the dramatic decline in the incidence of invasive pneumococcal disease (IPD) observed since the introduction of conjugate vaccination, it is feared that several factors may undermine the future effectiveness of the vaccines. In particular, pathogenic pneumococci may switch their capsular types and evade vaccine-conferred immunity. METHODOLOGY/PRINCIPAL FINDINGS: Here, we first review the literature and summarize the available epidemiological data on capsular switch for S. pneumoniae. We estimate the weekly probability that a persistently carried strain may switch its capsule from four studies, totalling 516 children and 6 years of follow-up, at 1.5x10(-3)/week [4.6x10(-5)-4.8x10(-3)/week]. There is not enough power to assess an increase in this frequency in vaccinated individuals. Then, we use a mathematical model of pneumococcal transmission to quantify the impact of capsular switch on the incidence of IPD in a vaccinated population. In this model, we investigate a wide range of values for the frequency of vaccine-selected capsular switch. Predictions show that, with vaccine-independent switching only, IPD incidence in children should be down by 48% 5 years after the introduction of the vaccine with high coverage. Introducing vaccine-selected capsular switch at a frequency up to 0.01/week shows little effect on this decrease; yearly, at most 3 excess cases of IPD per 10(6) children might occur due to switched pneumococcal strains. CONCLUSIONS: Based on all available data and model predictions, the existence of capsular switch by itself should not impact significantly the efficacy of pneumococcal conjugate vaccination on IPD incidence. This optimistic result should be tempered by the fact that the selective pressure induced by the vaccine is currently increasing along with vaccine coverage worldwide; continued surveillance of pneumococcal populations remains of the utmost importance, in particular during clinical trials of the new conjugate vaccines

Technology transfer model for Austrian higher education institutions

The aim of this paper is to present the findings of a PhD research (Heinzl 2007, Unpublished PhD Thesis) conducted on the Universities of Applied Sciences in Austria. Four of the models that emerge from this research are: Generic Technology Transfer Model (Sect. 5.1); Idiosyncrasies Model for the Austrian Universities of Applied Sciences (Sect. 5.2); Idiosyncrasies-Technology Transfer Effects Model (Sect. 5.3); Idiosyncrasies-Technology Transfer Cumulated Effects Model (Sect. 5.3). The primary and secondary research methods employed for this study are: literature survey, focus groups, participant observation, and interviews. The findings of the research contribute to a conceptual design of a technology transfer system which aims to enhance the higher education institutions' technology transfer performance. © 2012 Springer Science+Business Media, LLC

Pneumococcal Serotypes and Mortality following Invasive Pneumococcal Disease: A Population-Based Cohort Study

Analyzing population-based data collected over 30 years in more than 18,000 patients with invasive pneumococcal infection, Zitta Harboe and colleagues find specific pneumococcal serotypes to be associated with increased mortality

Pneumococcal Capsular Polysaccharide Structure Predicts Serotype Prevalence

There are 91 known capsular serotypes of Streptococcus pneumoniae. The nasopharyngeal carriage prevalence of particular serotypes is relatively stable worldwide, but the host and bacterial factors that maintain these patterns are poorly understood. Given the possibility of serotype replacement following vaccination against seven clinically important serotypes, it is increasingly important to understand these factors. We hypothesized that the biochemical structure of the capsular polysaccharides could influence the degree of encapsulation of different serotypes, their susceptibility to killing by neutrophils, and ultimately their success during nasopharyngeal carriage. We sought to measure biological differences among capsular serotypes that may account for epidemiological patterns. Using an in vitro assay with both isogenic capsule-switch variants and clinical carriage isolates, we found an association between increased carriage prevalence and resistance to non-opsonic neutrophil-mediated killing, and serotypes that were resistant to neutrophil-mediated killing tended to be more heavily encapsulated, as determined by FITC-dextran exclusion. Next, we identified a link between polysaccharide structure and carriage prevalence. Significantly, non-vaccine serotypes that have become common in vaccinated populations tend to be those with fewer carbons per repeat unit and low energy expended per repeat unit, suggesting a novel biological principle to explain patterns of serotype replacement. More prevalent serotypes are more heavily encapsulated and more resistant to neutrophil-mediated killing, and these phenotypes are associated with the structure of the capsular polysaccharide, suggesting a direct relationship between polysaccharide biochemistry and the success of a serotype during nasopharyngeal carriage and potentially providing a method for predicting serotype replacement