Viral-vectored boosting of OmcB- or CPAF-specific T-cell responses fail to enhance protection from Chlamydia muridarum in infection-immune mice and elicits a non-protective CD8-dominant response in naïve mice.

A vaccine is needed to combat the Chlamydia epidemic. Replication-deficient viral vectors are safe and induce antigen-specific T-cell memory. We tested the ability of intramuscular immunization with modified vaccinia Ankara (MVA) virus or chimpanzee adenovirus (ChAd) expressing chlamydial outer membrane protein (OmcB) or the secreted protein, chlamydial protease-like activating factor (CPAF), to enhance T-cell immunity and protection in mice previously infected with plasmid-deficient Chlamydia muridarum CM972 and elicit protection in naïve mice. MVA.OmcB or MVA.CPAF increased antigen-specific T cells in CM972-immune mice ∼150 and 50-fold, respectively, but failed to improve bacterial clearance. ChAd.OmcB/MVA.OmcB prime-boost immunization of naïve mice elicited a cluster of differentiation (CD) 8-dominant T-cell response dominated by cluster of differentiation (CD)8 T cells that failed to protect. ChAd.CPAF/ChAd.CPAF prime-boost also induced a CD8-dominant response with a marginal reduction in burden. Challenge of ChAd.CPAF-immunized mice genetically deficient in CD4 or CD8 T cells showed that protection was entirely CD4-dependent. CD4-deficient mice had prolonged infection, whereas CD8-deficient mice had higher frequencies of CPAF-specific CD4 T cells, earlier clearance, and reduced burden than wild-type controls. These data reinforce the essential nature of the CD4 T-cell response in protection from chlamydial genital infection in mice and the need for vaccine platforms that drive CD4-dominant responses.

A Platform for Sustainable Scale: The Challenge Initiative's Innovative Approach to Scaling Proven Interventions.

INTRODUCTION: The global health community continues to face barriers in scaling up evidence-based interventions for widespread adoption. Although many effective interventions have been developed over the years, expanding their reach to benefit broader populations has happened slowly or not at all. OVERVIEW: The Challenge Initiative (TCI) is a nontraditional development platform that supports local urban governments to rapidly scale up proven family planning (FP) and adolescent and youth sexual and reproductive health (AYSRH) interventions for the urban poor. TCI prioritizes sustainability and local ownership and uses a health systems approach when planning for and managing scale. TCI strengthens urban health systems with seed funding, coaching, and technical assistance (TA), and TCI University houses "how-to" guidance and tools for implementing the interventions. In turn, local governments commit political will and financial and human resources while using TCI coaching to integrate interventions into routine practice and systems to achieve widespread and sustained impact at scale. RESULTS: As of June 2021, TCI has supported 104 local governments across 11 countries in scaling up effective FP and AYSRH interventions, while also mobilizing about US$28 million from those local governments to facilitate their implementation. TCI has increased capacity and bolstered urban health systems, with 39 local governments "graduating" from TCI support and 2.02 million additional FP clients across 4 regional TA hubs. CONCLUSION: TCI aims to change how local governments coordinate, finance, and implement proven interventions to improve access to quality FP information and services. With built-in incentives for local governments, partners, and donors to participate, TCI is generating significant learning on how local governments can realize sustainable scale and demonstrating how organizations like TCI that facilitate governments to scale up effective interventions can accelerate the scale-up of these interventions across multiple geographies.

Boosting Contraceptive Uptake in Urban Uganda: Older Women Benefit When Layering Adolescent and Youth Interventions Onto Existing Family Planning Programming.

INTRODUCTION: Uganda has a large young population with a high unmet need for family planning (FP). Although there have been many efforts to improve access to and uptake of contraception, improvements have been slow. The Ministry of Health Uganda partnered with The Challenge Initiative (TCI) to implement a novel multipronged approach layering adolescent and youth sexual reproductive health (AYSRH) onto a functioning general FP program for women of reproductive age in 3 local governments of Buikwe, Mukono, and Iganga. We describe the approach and aim to determine whether layering AYSRH interventions onto an existing program resulted in increased contraceptive uptake among adolescents and youth aged 10-24 years and among women aged 25-49 years. METHODS: We analyzed service statistics from the Uganda Health Management Information System to assess contraceptive uptake for adolescents and youth (aged 10-24 years) and older women (aged 25-49 years) before and after the implementation of the AYSRH approach in 3 areas (Buikwe, Iganga, and Mukono) compared to 11 areas where only the general FP program was implemented and the Uganda country total. RESULTS: This analysis showed that before the start of TCI's support, levels of contraceptive uptake were similar in all local governments. However, after implementation, there was an increase in uptake for general FP program only areas (1.7-point advantage over country total) and an even greater increase in general FP+AYSRH areas (2.4-point advantage over FP only programming). This was observed in both adolescents and youth aged 10-24 years and among women aged 25-49 years. CONCLUSION: The layering of TCI's AYSRH interventions onto a well-functioning FP platform not only increased contraceptive uptake among adolescents and youth aged 10-24 years but also boosted uptake among women older than age 25 years.

Generating and capitalizing on the demographic dividend potential in sub-Saharan Africa: a conceptual framework from a systematic literature review.

Background: Africa will double its population by 2050 and more than half will be below age 25. The continent has a unique opportunity to boost its socioeconomic welfare. This systematic literature review aims to develop a conceptual framework that identifies policies and programs that have provided a favorable environment for generating and harnessing a demographic dividend. This framework can facilitate sub-Saharan African countries' understanding of needed actions to accelerate their demographic transition and capitalize on their demographic dividend potential. Methods: The search strategy was structured around three concepts: economic development, fertility, and sub-Saharan Africa. Databases used included PubMed and EconLit. An inductive approach was employed to expand the reference base further. Data were extracted using literature records following a checklist of items to include when reporting a systematic review suggested in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Results: The final review consisted of 78 peer-reviewed articles, ten reports from the gray literature, and one book. Data were categorized according to relevant demographic dividend typology: pre-dividend and early-dividend. The results from the literature review were synthesized into a framework consisting of five sectors for pre-dividend countries, namely 1) Governance and Economic Institutions, 2) Family Planning, 3) Maternal and Child Health, 4) Education, and 5) Women's Empowerment. An additional sector, 6) Labor Market, is added for early-dividend countries. These sectors must work together to attain a demographic dividend. Conclusions: A country's demographic transition stage must guide policy and programs. Most sub-Saharan African countries have prioritized job creation and employment for youth, yet their efforts to secure a productive labor market require preliminary and complementary investments in governance, family planning, maternal and child health, education, and women's empowerment. Creating a favorable policy environment for generating and capitalizing on a demographic dividend can support their stated goals for development.