Reassessing potential economic value and health impact of effective Shigella vaccines.

The gram-negative bacterium Shigella is a leading cause of diarrheal morbidity and mortality in children in low- and middle-income countries. Several promising vaccine candidates are in late stages of clinical development against this increasingly antibiotic-resistant pathogen. However, considering the increasingly crowded and costly paediatric immunization schedule, and likely advent of other important new vaccines, it is unclear whether introduction of a Shigella vaccine would represent a high priority for international agencies or health ministries in low- and middle-income countries. To determine whether there is a compelling public health value proposition for a Shigella vaccine, we used the World Health Organization's Full Value of Vaccine Assessment analytic framework and formulated five broad scientific, policy, economic and commercial-related propositions regarding the development of a Shigella vaccine. We also explored the current regulatory, clinical, policy and commercial challenges to a Shigella-containing combination vaccine development and adoption. Through a series of literature reviews, expert consultations, social science field studies and model-based analyses, we addressed each of these propositions. As described in a series of separate publications that are synthesized here, we concluded that the economic and public health value of a Shigella vaccine may be greater than previously recognized, particularly if it is found to also be effective against less severe forms of diarrheal disease and childhood stunting. The decision by pharmaceutical companies to develop a standalone vaccine or a multipathogen combination will be a key factor in determining its relative prioritization by various stakeholders in low- and middle-income countries.

La bactérie à Gram négatif Shigella est l'une des principales causes de morbidité et de mortalité diarrhéiques chez les enfants des pays à revenu faible et intermédiaire. Plusieurs candidats vaccins prometteurs sont en phase avancée de conception clinique contre cet agent pathogène qui connaît une antibiorésistance croissante. Toutefois, compte tenu du calendrier de vaccination pédiatrique de plus en plus chargé et coûteux et de l'arrivée probable d'autres nouveaux vaccins importants, il n'est pas certain que la mise sur le marché d'un vaccin contre Shigella constitue une priorité élevée pour les agences internationales ou les ministères de la Santé des pays à revenu faible ou intermédiaire. Pour déterminer l'existence d'un intérêt convaincant en matière de santé publique pour un vaccin contre Shigella, nous avons utilisé le cadre analytique du cadre d'évaluation de la valeur totale des vaccins de l'Organisation mondiale de la santé et formulé cinq propositions scientifiques, politiques, économiques et commerciales générales concernant la conception d'un vaccin contre Shigella. Nous avons également étudié les défis en matière réglementaire, clinique, politique et commerciale qui se posent actuellement à la mise au point et à l'adoption d'un vaccin combiné contenant des Shigella. Nous avons abordé chacune de ces propositions au moyen d'une série d'analyses documentaires, de consultations d'experts, d'études de terrain en sciences sociales et d'analyses basées sur des modèles. Comme décrit dans une série de publications distinctes résumées ici, nous avons conclu que la valeur économique et sur le plan de la santé publique d'un vaccin contre Shigella pourrait être plus importante que ce qui était considéré précédemment, en particulier s'il s'avère que ce vaccin s'avère également efficace contre les formes moins sévères de maladies diarrhéiques et de retard de croissance chez l'enfant. La décision d'entreprises pharmaceutiques de mettre au point un vaccin autonome ou une combinaison de plusieurs agents pathogènes sera un facteur clé dans la détermination de sa priorité relative par les différentes parties prenantes dans les pays à revenu faible et intermédiaire.

La bacteria gramnegativa Shigella es una de las principales causas de morbilidad y mortalidad por diarrea en niños de países de ingresos bajos y medios. Varias vacunas candidatas y prometedoras se encuentran en las últimas fases de desarrollo clínico contra este patógeno cada vez más resistente a los antibióticos. Sin embargo, teniendo en cuenta el esquema de inmunización pediátrica, cada vez más saturado y costoso, y la probable llegada de otras vacunas nuevas importantes, no está claro si la introducción de una vacuna contra la Shigella representaría una alta prioridad para los organismos internacionales o los ministerios de salud de los países de ingresos bajos y medios. Para determinar si existe una propuesta de valor de salud pública convincente para una vacuna contra la Shigella, utilizamos el marco de análisis Full Value of Vaccine Assessment de la Organización Mundial de la Salud y formulamos cinco amplias propuestas científicas, políticas, económicas y comerciales relacionadas con el desarrollo de una vacuna contra la Shigella. También exploramos los actuales desafíos reglamentarios, clínicos, políticos y comerciales para el desarrollo y la adopción de una vacuna combinada que contenga Shigella. Mediante una serie de revisiones bibliográficas, consultas a expertos, estudios de campo de ciencias sociales y análisis basados en modelos, abordamos cada una de estas proposiciones. Como se describe en una serie de publicaciones separadas que se sintetizan aquí, llegamos a la conclusión de que el valor económico y de salud pública de una vacuna contra la Shigella puede ser mayor de lo que se reconocía anteriormente, en particular si se descubre que también es eficaz contra formas menos graves de enfermedad diarreica y retraso del crecimiento infantil. La decisión de las empresas farmacéuticas de desarrollar una vacuna independiente o una combinación multipatógena será un factor clave a la hora de determinar su prioridad relativa por parte de las diversas partes interesadas en los países de ingresos bajos y medios.

Understanding supplement use: an application of temporal self-regulation theory.

Vitamin and mineral supplement use is increasing worldwide. As evidence of the effects of these practices are equivocal at best, it is important to determine why individuals engage in vitamin and mineral supplement use through the application of a theoretical framework. The aim of this study was to employ temporal self-regulation theory (TST) to establish the determinants of supplement use. A cross-sectional design was used with a sample of 121 individuals who consume vitamins or minerals as dietary supplements. Hierarchical regression analyses were conducted to determine the influence of intention, habit, self-control, and the interaction between intention and habit and self-control on the frequency of supplement use. The model accounted for a significant proportion of variance in behaviour (R2 = .44) with intention and habit significantly related to supplement use. Self-control moderated the relationship between intention and behaviour indicating that intention was not related to behaviour when self-control was low. The TST model offers a satisfactory account of supplement use and provides avenues for interventions aimed at increasing safe and beneficial supplement use and decreasing potentially harmful supplement use.

The 2022 Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference: Summary of breakout workshops.

The global public health nonprofit organization PATH hosted the third Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Washington, DC, from November 29 to December 1, 2022. This international gathering focused on cutting-edge research related to the development of vaccines against neglected diarrheal pathogens including Shigella, enterotoxigenic Escherichia coli (ETEC), Campylobacter, and non-typhoidal Salmonella. In addition to the conference's plenary content, the agenda featured ten breakout workshops on topics of importance to the enteric vaccine field. This unique aspect of VASE Conferences allows focused groups of attendees to engage in in-depth discussions on subjects of interest to the enteric vaccine development community. In 2022, the workshops covered a range of topics. Two focused on the public health value of enteric vaccines, with one examining how to translate evidence into policy and the other on the value proposition of potential combination vaccines against bacterial enteric pathogens. Two more workshops explored new tools for the development and evaluation of vaccines, with the first on integrating antigen/antibody technologies for mucosal vaccine and immunoprophylactic development, and the second on adjuvants specifically for Shigella vaccines for children in low- and middle-income countries. Another pair of workshops covered the status of vaccines against two emerging enteric pathogens, Campylobacter and invasive non-typhoidal Salmonella. The remaining four workshops examined the assessment of vaccine impact on acute and long-term morbidity. These included discussions on the nature and severity of intestinal inflammation; cellular immunity and immunological memory in ETEC and Shigella infections; clinical and microbiologic endpoints for Shigella vaccine efficacy studies in children; and intricacies of protective immunity to enteric pathogens. This article provides a brief summary of the presentations and discussions at each workshop in order to share these sessions with the broader enteric vaccine field.

The 2022 Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference: Summary of abstract-based presentations.

The global nonprofit organization PATH hosted the third Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Washington, DC, on November 29 to December 1, 2022. With a combination of plenary sessions and posters, keynote presentations, and breakout workshops, the 2022 VASE Conference featured key updates on research related to the development of vaccines against neglected diarrheal pathogens including Shigella, enterotoxigenic Escherichia coli (ETEC), Campylobacter, and Salmonella. The presentations and discussions highlighted the significant impact of these diarrheal pathogens, particularly on the health of infants and young children in low- and middle-income countries, reflecting the urgent need for the development and licensure of new enteric vaccines. Oral and poster presentations at the VASE Conference explored a range of topics, including: the global burden and clinical presentation of disease, epidemiology, and the impact of interventions; the assessment of the value of vaccines against enteric pathogens; preclinical evaluations of vaccine candidates and models of enteric diseases; vaccine candidates in clinical trials and human challenge models; host parameters and genomics that predict responses to infection and disease; the application of new omics technologies for characterization of emerging pathogens and host responses; novel adjuvants, vaccine delivery platforms, and immunization strategies; and strategies for combination/co-administered vaccines. The conference agenda also featured ten breakout workshop sessions on topics of importance to the enteric vaccine field, which are summarized separately. This article reviews key points and highlighted research presented in each of the plenary conference sessions and poster presentations at the 2022 VASE Conference.

Challenges and opportunities in developing a Shigella-containing combination vaccine for children in low- and middle-income countries: Report of an expert convening.

The gram-negative bacterium Shigella is an enteric pathogen responsible for significant morbidity and mortality due primarily to severe diarrhea and dysentery, mainly among children younger than five years of age living in low- and middle-income countries (LMICs). Long considered a priority target for vaccine development, recent scientific advances have led to a number of promising Shigella vaccine candidates now entering advanced stages of clinical testing. Yet, there is no guarantee that even a highly efficacious Shigella vaccine will be recommended, prioritized, purchased, and widely adopted-especially if it requires additional doses in the immunization schedule and/or visits within the immunization program. This uncertainty is due to a variety of factors, including continuing declines in Shigella-specific and overall diarrheal disease mortality rates, the increasing complexity and cost of infant immunization programs in LMICs, and the recent availability of other high-priority vaccines. Since combining a Shigella vaccine with an existing infant vaccine would conceivably increase its attractiveness, there is a need to systematically consider the challenges determining the public health value, clinical development, manufacturing, licensure, policy recommendations, and financing for a Shigella-containing combination vaccine. The international non-governmental health organization PATH convened an independent panel of 34 subject matter experts across academic, industry, philanthropic, and global health sectors to discuss hypothetical combinations of a notional parenteral Shigella vaccine with three existing vaccines in order to begin exploring the challenges associated with their development. The resulting insights and recommendations from this meeting contribute to PATH's broader effort to evaluate the public health value of potential Shigella vaccines. They may also help guide future combination vaccine development efforts more broadly.

Recommendations regarding the development of combined enterotoxigenic Eschericha coli and Shigella vaccines for infants.

PATH hosted a workshop on October 14 and 15, 2013 in Washington, DC to solicit expert opinions on the potential merits and challenges of developing combined enterotoxigenic Escherichia coli (ETEC) and Shigella vaccine products to benefit children in developing countries. This article summarizes the key issues raised during the workshop and provides an analysis of the recommendations regarding the strategic, clinical and regulatory, and manufacturing considerations for the development of a combined enteric vaccine, which aim to guide future vaccine development efforts and donor investment strategies in this area. Notwithstanding the potential technical, legal, financial, and other constraints that would be faced in developing a combined ETEC/Shigella vaccine, it is clear that this is the preferred approach over standalone products. There are many advantages to a combined vaccine, such as the potential cost-effectiveness and easier logistics of introducing a combined vaccine instead of two standalone vaccines in low-resource, endemic countries.

Inflammatory disease of the aorta: patterns and classification of giant cell aortitis, Takayasu arteritis, and nonsyndromic aortitis.

OBJECTIVE: Inflammatory diseases of the aorta, other than those of known infective etiology, are poorly understood. We analyzed a large series of affected patients who had histologic diagnoses with a view to improving the classification of the extent of aortitis to enable a more targeted approach of treatment. METHODS: Between 1996 and 2012, we operated on 7551 patients with ascending or aortic arch disease, of whom 279 had clinically diagnosed inflammatory disease. Of these, 156 (2%) were found to have aortitis on histologic examination. RESULTS: Patients were divided into 4 histologically based groups: giant cell aortitis, 31% (49/156); Takayasu arteritis, 5.1% (8/156); isolated aortitis, 59% (92/156); and other, 4.5% (7/156). Patterns of anatomic extent were also analyzed, and in particular it was noted that giant cell aortitis and isolated aortitis had more extensive disease. In addition, specimen analysis suggested early indications of unrecognized preexistent infections. Death after surgery occurred in 3.2% (5/156), and stroke in 1.9% (3/156). Kaplan-Meier survival at 8 years was 55%. We present a classification for disease extent and management. CONCLUSIONS: Aortitis continues to be a conundrum; however, good results are achievable with surgery. Intervention should be based on a clearer understanding of the histologic pattern and extent of disease, which helps in subsequent targeted disease management.