From Option B+ to Universal "Test and Treat" in Cameroon: Identification and Evaluation of District-level Factors Associated with Retention in Care.

Background and Objective: Retaining women in Option B+ services is crucial for eliminating new pediatric HIV infections. However, there are few studies on factors influencing retention at the district level. This study evaluates the factors associated with retention in two health districts of Cameroon. Methods: From September 1, 2015, to February 29, 2016, we reviewed the records of pregnant and breastfeeding women initiating Option B+, a lifelong approach to preventing mother-to-child transmission (PMTCT) of HIV, between October 2013 and July 2014. We abstracted sociodemographic and clinical data from registers in 22 health facilities in the Bamenda urban and Kumba rural districts into spreadsheets. Cox regression age-adjusted survival curves were used to compare retention probabilities at 6 and 12 months post-antiretroviral therapy (ART) initiation. Multivariable modified Poisson regressions were run to estimate adjusted relative risk (aRR) of factors associated with retention in PMTCT care at 12 months post-ART initiation. STATA software was used for the analyses. Results: Of the 560 files reviewed, majority, 62.7% (n=351), were above 24 years of age and married, 68.9% (n=386). From the multivariable analysis, enrolling early in antenatal care (ANC) (aRR: 1.50, 95% CIL: 1.17-1.93) and knowing the male partner's HIV-negative status (aRR: 1.16, 95% CI: 1.00-1.34) were significantly associated with higher retention in care, adjusting for maternal age, marital status, and distance from the health facility. By health district, knowing the male partner's HIV-negative status (aRR: 1.30, 95% CI: 1.13-1.50) in the Bamenda urban and enrolling early in ANC (aRR: 2.03, 95% CI" 1.21-3.41) in the Kumba rural district, had significantly higher retention rates after adjusting for the same covariates. Conclusion and Global Health Implications: Overall, factors influencing retention varied by urban or rural district. Therefore, tailored district-level interventions are needed to enhance early ANC enrollment in the rural and partner HIV status disclosure in the urban districts to improve retention in PMTCT care.

Measuring for Success: Evaluating Leadership Training Programs for Sustainable Impact.

Background: In an era of global health security challenges such as the COVID-19 pandemic, there is greater need for strong leadership. Over the past decades, significant investments have been made in global health leadership development programs by governments and philanthropic organizations to address this need. Evaluating the societal impact of these programs remains challenging, despite consensus on the importance of public health leadership. Objective: This article identifies the gaps and highlights the critical role of monitoring and evaluation approaches in assessing the impact of global health leadership programs. Importantly, we also propose the theory of change (TOC) as a common framework and identify a set of tools and indicators that leadership programs can adapt and use. Methods: We carried out an informal review of major global health leadership programs, including a literature review on leadership program evaluation approaches. Current practices in assessing the short- to long-term outcomes of leadership training programs were explored and synthesized. We also examined use of program theory frameworks, such as theory of change to guide the evaluation strategy. We find the TOC approach can be enhanced by integrating evaluation-specific frameworks and establishing broad stakeholder buy-in. We highlight measurement challenges, proposed outcome indicators and evaluation methodologies, and outline the future direction for such efforts. Findings: Most evaluation of current leadership programs is focused on short-term individual-level outcomes, while reports on long-term societal impact were limited. Reciprocal impacts on and benefits for the "host" organizations were not included in evaluation metrics. Most programs had program logic or result chains, but with no well-articulated program theories. Conclusion: Key stakeholders involved in leadership training programs benefit from the evidence of rigorous program evaluations to inform decisions that address barriers in fostering global health leadership and improving population health outcomes. Insight into reciprocal change in host organizations is important. Evaluation of global health leadership training must go beyond the individual trainee and encompass organizational and community-level impacts. Documentation of long-lasting organizational and societal impacts is essential for donors to appreciate the return on their investment. Key Takeaways: Evaluation plays an important role in understanding how leadership development takes place and how it contributes to improving public health outcomes.Making the case for investments in leadership development programs requires robust evidence from monitoring and evaluation strategies that link investments beyond the individual-level to longer-term societal impacts.The first critical step towards a strategy for success is for leadership programs to clearly build, articulate, share, and use their program theories or theories of change.Theories of change help identify the pathways (and potential tensions) through which leadership development programs effect change at the individual, organizational and community levels.Evaluation methods that examine outcomes of leadership programs should be multi-method, multi-level, and where possible include counterfactual outcomes.Allocation of funds to evaluate on-going and long-lasting societal impact of leadership programs should be a routine practice.

Known HIV status among adolescent women attending antenatal care services in Eswatini, Ethiopia and Mozambique.

BACKGROUND: Antenatal care (ANC) clinics remain important entry points to HIV care for pregnant women living with HIV-including adolescents. Prior knowledge of their HIV status at ANC enrollment is crucial to providing services for prevention of mother-to-child transmission (PMTCT) of HIV. We examined known HIV status of pregnant adolescents and women in other age groups at ANC enrollment. METHODS: A descriptive study of routinely reported PMTCT data from 419 facilities in Eswatini, Ethiopia, and Mozambique, from January through December 2018 was conducted. We assessed knowledge of HIV status by country for three age groups: adolescents aged 15-19 years, young women aged 20-24 years, and older women aged 25-49 years. We report HIV prevalence and proportions of known and newly diagnosed HIV infections in women, by age group and country. The data were summarized by frequencies and proportions, including their 95% confidence intervals. RESULTS: Among the facilities examined, 52 (12.4%) were in Eswatini, 63 (15.0%) in Ethiopia, and 304 (72.6%) in Mozambique. Across three countries, 488,121 women attended a first ANC visit and 23,917 (4.9%) were HIV-positive. Adolescents constituted 22% of all ANC attendees, whereas young and older women represented 33% and 45%, respectively. HIV prevalence was lowest among adolescents than in other age groups in Eswatini (adolescents 11.9%, young 24.2% and older 47.3%), but comparable to young women in Ethiopia (adolescents 1.6%, young 1.6% and older 2.2%) and Mozambique (adolescents 2.5%, young 2.5% and older 5.8%), However, in each of the three countries, lower proportions of adolescents knew their HIV-positive status before ANC enrollment compared to other age groups: in Eswatini (adolescents 51.3%, young 59.9% and older 79.2%), in Ethiopia (adolescents 42.9%, young 63.7% and older 75.2%), and in Mozambique (adolescents 16.4%, young 33.2% and older 45.6%). CONCLUSION: Overall, adolescents made up nearly one-quarter of the women examined and had the least knowledge of their HIV status at ANC enrollment. Their HIV prevalence and known HIV-positive status varied widely across the countries examined. Adolescent-friendly sexual and reproductive health, and PMTCT services, before pregnancy, are needed to improve knowledge of HIV status and support pregnant adolescents and their infants. Antenatal care (ANC) clinics are important for HIV testing of pregnant adolescents, who may not know their HIV-positive status at the first ANC visit. We describe data on pregnant adolescents and women in other age groups in ANC services to examine their prior HIV status at ANC enrollment across three African countries. We examined data from 419 PMTCT sites in Eswatini, Ethiopia, and Mozambique from January-December 2018, to evaluate HIV testing results for adolescents, young and older women aged 15-19, 20-24 and 25-49 years, respectively. We report the number of women living with HIV and the proportions of known and newly identified women living with HIV, by age-group and country. Across three countries, 488,121 women attended ANC and 23,917 (4.9%) were living with HIV. Adolescents constituted 22% of all ANC attendees, whereas young and older women represented 33% and 45%, respectively. HIV prevalence in each country compared to other age groups was lowest and varied among adolescents from 11.9% in Eswatini, to 1.6% in Ethiopia and to 2.5% in Mozambique. Also, fewer adolescents knew their HIV-positive status before ANC enrollment compared to young and older women from 51.3% in Eswatini, 42.9% in Ethiopia to only 16.4% in Mozambique. Pregnant adolescents made up nearly one-quarter of all ANC attendees; a majority of them had no previously known HIV-positive status. Adolescent-friendly, sexual and reproductive health services, before pregnancy and in PMTCT services, are needed to support pregnant adolescents and their infants.

Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs.

Mesenchymal stem cells (MSCs) and macrophages are fundamental components of the stem cell niche and function coordinately to regulate haematopoietic stem cell self-renewal and mobilization. Recent studies indicate that mitophagy and healthy mitochondrial function are critical to the survival of stem cells, but how these processes are regulated in MSCs is unknown. Here we show that MSCs manage intracellular oxidative stress by targeting depolarized mitochondria to the plasma membrane via arrestin domain-containing protein 1-mediated microvesicles. The vesicles are then engulfed and re-utilized via a process involving fusion by macrophages, resulting in enhanced bioenergetics. Furthermore, we show that MSCs simultaneously shed micro RNA-containing exosomes that inhibit macrophage activation by suppressing Toll-like receptor signalling, thereby de-sensitizing macrophages to the ingested mitochondria. Collectively, these studies mechanistically link mitophagy and MSC survival with macrophage function, thereby providing a physiologically relevant context for the innate immunomodulatory activity of MSCs.

TNFR1/phox interaction and TNFR1 mitochondrial translocation Thwart silica-induced pulmonary fibrosis.

Macrophages play a fundamental role in innate immunity and the pathogenesis of silicosis. Phagocytosis of silica particles is associated with the generation of reactive oxygen species (ROS), secretion of cytokines, such as TNF, and cell death that contribute to silica-induced lung disease. In macrophages, ROS production is executed primarily by activation of the NADPH oxidase (Phox) and by generation of mitochondrial ROS (mtROS); however, the relative contribution is unclear, and the effects on macrophage function and fate are unknown. In this study, we used primary human and mouse macrophages (C57BL/6, BALB/c, and p47(phox-/-)) and macrophage cell lines (RAW 264.7 and IC21) to investigate the contribution of Phox and mtROS to silica-induced lung injury. We demonstrate that reduced p47(phox) expression in IC21 macrophages is linked to enhanced mtROS generation, cardiolipin oxidation, and accumulation of cardiolipin hydrolysis products, culminating in cell death. mtROS production is also observed in p47(phox-/-) macrophages, and p47(phox-/-) mice exhibit increased inflammation and fibrosis in the lung following silica exposure. Silica induces interaction between TNFR1 and Phox in RAW 264.7 macrophages. Moreover, TNFR1 expression in mitochondria decreased mtROS production and increased RAW 264.7 macrophage survival to silica. These results identify TNFR1/Phox interaction as a key event in the pathogenesis of silicosis that prevents mtROS formation and reduces macrophage apoptosis.