Global Meningococcal Initiative: Insights on antibiotic resistance, control strategies and advocacy efforts in Western Europe.

In Western Europe, many countries have robust and well-established surveillance systems and case reporting mechanisms. IMD incidence across Western Europe is low with a predominance of meningococcal serogroup B (MenB). Case confirmation and antimicrobial susceptibility testing is often standardised in this region, with many countries also having robust vaccination programmes in place.

Implications of Cross-Reactivity and Cross-Protection for Pneumococcal Vaccine Development.

Pneumococcal vaccines are a cornerstone for the prevention of pneumococcal diseases, reducing morbidity and mortality in children and adults worldwide. Pneumococcal vaccine composition is based on the polysaccharide capsule of , which is one of the most important identified contributors to the pathogen's virulence. Similarities in the structural composition of polysaccharides included in licensed pneumococcal vaccines may result in cross-reactivity of immune response against closely related serotypes, including serotypes not included in the vaccine.

The role of vaccines in reducing antimicrobial resistance: A review of potential impact of vaccines on AMR and insights across 16 vaccines and pathogens.

In 2019, an estimated 4.95 million deaths were linked to antimicrobial resistance (AMR). Vaccines can prevent many of these deaths by averting both drug-sensitive and resistant infections, reducing antibiotic usage, and lowering the likelihood of developing resistance genes.

Facilitating the development of urgently required combination vaccines.

The essence of a vaccine lies in its ability to elicit a set of immune responses specifically directed at a particular pathogen. Accordingly, vaccines were historically designed, developed, registered, recommended, procured, and administered as monopathogen formulations. Nonetheless, the control and elimination of an astonishing number of diseases was realised only after several once-separate vaccines were provided as combinations.

Lassa fever vaccine use cases and demand: Perspectives from select West African experts.

Lassa fever (LF) is a zoonotic viral hemorrhagic disease endemic to several West African countries. Approximately 300-500,000 cases occur annually across all ages with 10-20% case fatality rates. A LF vaccine is a recognized public health priority, with several candidates entering clinical trials.

Reassessing potential economic value and health impact of effective vaccines.

The gram-negative bacterium 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 vaccine would represent a high priority for international agencies or health ministries in low- and middle-income countries.

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.

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.

Vaccine value profile for enterotoxigenic Escherichia coli (ETEC).

Enterotoxigenic Escherichia coli (ETEC) is one of the leading bacterial causes of diarrhoea, especially among children in low-resource settings, and travellers and military personnel from high-income countries. WHO's primary strategic goal for ETEC vaccine development is to develop a safe, effective, and affordable ETEC vaccine that reduces mortality and morbidity due to moderate-to-severe diarrhoeal disease in infants and children under 5 years of age in LMICs, as well as the long-term negative health impact on infant physical and cognitive development resulting from infection with this enteric pathogen. An effective ETEC vaccine will also likely reduce the need for antibiotic treatment and help limit the further emergence of antimicrobial resistance bacterial pathogens.

Vaccine value profile for Shigella.

Shigella is the leading bacterial cause of diarrhoea and the second leading cause of diarrhoeal mortality among all ages. It also exhibits increasing levels of antibiotic resistance. The greatest burden is among children under five in low- and middle-income countries (LMICs).

Exploring vaccine priorities and preferences: Results from a mixed-methods study in low- and middle-income settings.

Background: is the leading bacterial cause of diarrheal mortality in children and can cause long-term effects on growth and development. No licensed vaccines currently exist but several promising candidates are in development and could be available in the next five years. Despite being a well-known public health target of the World Health Organization for decades, given current burden estimates and competing preventable disease priorities in low-income settings, whether the availability of an effective vaccine will lead to its prioritization and widespread introduction among countries at highest risk is unknown.

Projecting the long-term economic benefits of reducing Shigella-attributable linear growth faltering with a potential vaccine: a modelling study.

Background: Linear growth is an important outcome of child development with implications for economic productivity. Enteric infections, particularly Shigella, have been linked to linear growth faltering (LGF). However, benefits from potential reductions in LGF are rarely included in economic analyses of enteric infections.

Potential impact and cost-effectiveness of Shigella vaccination in 102 low-income and middle-income countries in children aged 5 years or younger: a modelling study.

Background: Vaccine impact and cost-effectiveness models have mostly focused on acute burden. Shigella-attributable moderate-to-severe diarrhoea has been shown to be associated with childhood linear growth faltering. Evidence also links less severe diarrhoea to linear growth faltering.

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.

The Challenges and Opportunities of Next-Generation Rotavirus Vaccines: Summary of an Expert Meeting with Vaccine Developers.

The 2nd Next Generation Rotavirus Vaccine Developers Meeting, sponsored by PATH and the Bill and Melinda Gates Foundation, was held in London, UK (7-8 June 2022), and attended by vaccine developers and researchers to discuss advancements in the development of next-generation rotavirus vaccines and to consider issues surrounding vaccine acceptability, introduction, and uptake. Presentations included updates on rotavirus disease burden, the impact of currently licensed oral vaccines, various platforms and approaches for next generation rotavirus vaccines, strategies for combination pediatric vaccines, and the value proposition for novel parenteral rotavirus vaccines. This report summarizes the information shared at the convening and poses various topics worthy of further exploration.

Healthcare provider perspectives on delivering next generation rotavirus vaccines in five low-to-middle-income countries.

Background: Live oral rotavirus vaccines (LORVs) have significantly reduced rotavirus hospitalizations and deaths worldwide. However, LORVs are less effective in low- and middle-income countries (LMICs). Next-generation rotavirus vaccines (NGRVs) may be more effective but require administration by injection or a neonatal oral dose, adding operational complexity.

Potential impact and cost-effectiveness of injectable next-generation rotavirus vaccines in 137 LMICs: a modelling study.

While current live, oral rotavirus vaccines (LORVs) are reducing severe diarrhea everywhere, their effectiveness is lower in high burden settings. Alternative approaches are in advanced stages of clinical development, including injectable next-generation rotavirus vaccine (iNGRV) candidates, which have the potential to better protect children, be combined with existing routine immunizations and be more affordable than current LORVs. In an effort to better understand the real public health value of iNGRVs and to help inform decisions by international agencies, funders, and vaccine manufacturers, we conducted an impact and cost-effectiveness analysis examining 20 rotavirus vaccine use cases.

What Drives the Value of a Vaccine?

The development and licensure of a safe and highly efficacious vaccine has been a priority in international public health circles for decades and would represent a great scientific achievement. Nonetheless, in the context of increasingly crowded and costly childhood immunization programs, and with a myriad of other new and improved vaccines currently or soon on the market, there is no guarantee that even a highly effective vaccine would become a priority for adoption and introduction by the low- and middle-income countries that could benefit from it the most. We discuss here some of the major determinants and questions regarding the introduction of vaccines and the importance of developing a succinct, compelling public health value proposition.

Does Anybody Want an Injectable Rotavirus Vaccine, and Why? Understanding the Public Health Value Proposition of Next-Generation Rotavirus Vaccines.

Routine infant immunization with live, oral rotavirus vaccines (LORVs) has had a major impact on severe gastroenteritis disease. Nevertheless, in high morbidity and mortality settings rotavirus remains an important cause of disease, partly attributable to the sub-optimal clinical efficacy of LORVs in those settings. Regardless of the precise immunological mechanism(s) underlying the diminished efficacy, the introduction of injectable next-generation rotavirus vaccines (iNGRV), currently in clinical development, could offer a potent remedy.

National stakeholder preferences for next-generation rotavirus vaccines: Results from a six-country study.

Background: Currently available live, oral rotavirus vaccines (LORVs) have significantly reduced severe rotavirus hospitalizations and deaths worldwide. However, LORVs are not as effective in low- and middle-income countries (LMIC) where rotavirus disease burden is highest. Next-generation rotavirus vaccine (NGRV) candidates in development may have a greater public health impact where they are needed most.

Antimicrobial resistance in paediatric isolates amid global implementation of pneumococcal conjugate vaccines: a systematic review and meta-regression analysis.

Background: Pneumococcal diseases are a leading cause of morbidity and mortality among children globally, and the burden of these diseases might be worsened by antimicrobial resistance. To understand the effect of pneumococcal conjugate vaccine (PCV) deployment on antimicrobial resistance in pneumococci, we assessed the susceptibility of paediatric pneumococcal isolates to various antimicrobial drugs before and after PCV implementation.

Methods: We did a systematic review of studies reporting antimicrobial susceptibility profiles of paediatric pneumococcal isolates between 2000 and 2020 using PubMed and the Antimicrobial Testing Leadership and Surveillance database (ATLAS; Pfizer).

Leveraging Vaccines to Reduce Antibiotic Use and Prevent Antimicrobial Resistance: A World Health Organization Action Framework.

This Action Framework identifies priority actions to prevent antimicrobial-resistant (AMR) through expanding the use of licensed vaccines, developing new vaccines that contribute to the prevention and control of AMR, and expanding knowledge about the impact of vaccines on AMR.

Low-dose and oral exposure to SARS-CoV-2 may help us understand and prevent severe COVID-19.

Background: The effectiveness and sustainability of current public health interventions designed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission remain of great concern in many settings, especially in the absence of a transmission-preventing vaccine.

Hypothesis: It was hypothesized that a more targeted set of interventions focusing on preventing severe coronavirus disease 2019 (COVID-19), rather than SARS-CoV-2 transmission, would be less disruptive to society. To identify these, it would be helpful to better understand how the infecting dose of SARS-CoV-2 and its route of infection influence the clinical outcome, immunological protection, and likelihood of onward transmission.

High levels of inherent variability in microbiological assessment of bronchoalveolar lavage samples from children with persistent bacterial bronchitis and healthy controls.

Bronchoalveolar lavage (BAL) is widely regarded as providing "gold standard" samples for infective lower respiratory tract disease. Current approaches have been adopted empirically without robust assessment and hence carry many assumptions that have not been tested. Many of these uncertainties were highlighted in the ATS pediatric bronchoscopy guidelines.