Understanding barriers to vaccination against invasive meningococcal disease: a survey of the knowledge gap and potential solutions.

INTRODUCTION: Invasive meningococcal disease (IMD) is a leading cause of life-threatening bacterial meningitis and septicemia. Evidence points to a knowledge gap among parents, teenagers, and healthcare providers (HCPs) regarding IMD and available vaccines, including those against the highly prevalent serogroup B. AREAS COVERED: An online survey was conducted between March 27 and 12 April 2019, to gather insights into the knowledge that parents/guardians have about IMD vaccines. The children were aged 2 months to 10 years in Australia, Brazil, Germany, Greece, Italy, and Spain, 5-20 years in the UK, and 16-23 years in the USA. The findings were discussed in the context of the available literature and solutions were proposed to minimize the knowledge gap and the barriers to vaccination against IMD. EXPERT OPINION: The survey demonstrated that parents have a good understanding of IMD but a limited understanding of the different serogroups and vaccines. The available literature highlighted multiple barriers to IMD vaccine uptake; these may be reduced through education of HCPs, clear recommendations to parents by HCPs, the use of technology, and disease-awareness initiatives that engage parents through physical and digital channels. Further studies are warranted to assess the impact of the COVID-19 pandemic on IMD vaccination.

Pandemic's influence on parents' attitudes and behaviors toward meningococcal vaccination.

Invasive meningococcal disease is a life-threatening infection preventable through vaccination. Pediatric vaccination rates have declined during the coronavirus disease 2019 (COVID-19) pandemic. This survey aimed to understand how parents' attitudes and behaviors have changed during the pandemic with regard to immunization and, more specifically, meningococcal vaccination. An online survey was emailed to parents of eligible children 0-4 years, following the selection process from UK, France, Germany, Italy, Brazil, Argentina, and Australia; and of adolescents 11-18 years from US. Data collection took place 19 January-16 February 2021. Quotas were set to ensure a representative sample. Eleven questions relating to general perceptions around vaccination and attitudes and behaviors toward meningitis vaccination were displayed. On 4,962 parents (average 35 years) participating in the survey, most (83%) believed important for their child to continue receiving recommended vaccines during the COVID-19 pandemic. Nearly half of routine vaccine appointments were delayed or canceled due to the pandemic, and 61% of respondents were likely to have their children catch up once COVID-19 restrictions were lifted. 30% of meningitidis vaccination appointments were canceled or delayed during the pandemic, and 21% of parents did not intend to reschedule them because of lockdown/stay at home regulations, and fear of catching COVID-19 in public places. It is crucial to communicate clear instructions to health workers and the general population and to provide appropriate safety precautions in vaccination centers. This will help to maintain vaccination rates and limit infections to prevent future outbreaks.

What is the context? Invasive meningococcal disease (IMD) is an uncommon infection that can lead to permanent disabilities and even death.Meningitis vaccination can prevent IMDs caused by Neisseria meningitidis.Vaccination rates have declined during the coronavirus (COVID-19) pandemic.What is new? We collected opinion of parents from the UK, France, Germany, Italy, Brazil, Argentina, Australia, and the US, to understand their attitudes and behaviors toward meningitis vaccination during the COVID-19 pandemic.Results were reviewed by health care professional experts as well as by patient authors (IMD survivors).Most (83%) of the 4,962 parents believed that it is important for their child to continue receiving recommended vaccines during the COVID-19 pandemic.Half of the scheduled appointments for meningitis vaccination were canceled or delayed during the COVID-19 pandemic, mainly due to lockdown regulations and fear of catching COVID-19.Twenty-one percent of the parents who had their child's meningitis vaccination appointment canceled, did not intend to reschedule it.What is the impact? It is crucial that clear information is communicated by health care authorities and practitioners about the availability of vaccination during pandemic and the safety precautions that are taken.Collected opinions emphasize the importance of continuing vaccinations against infectious diseases during a pandemic.

Systematic review of the efficacy, effectiveness and impact of high-valency pneumococcal conjugate vaccines on otitis media.

Otitis media (OM) is a common disease of childhood and available pneumococcal conjugate vaccines (PCVs), with different compositions, could have different impact on OM reduction. This systematic literature review evaluated available data describing the efficacy, effectiveness, and impact of 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and 13-valent PCV (PCV13) on OM outcomes. Statistically significant reductions in all-cause and complicated OM, tympanostomy tube placement and OM-related hospitalizations were consistently observed after the introduction of PHiD-CV and PCV13. Impact studies with data in children <2 years of age using PCV13 report 47-51% and PHiD-CV 34-43% reduction of all-cause OM (primary care, outpatient, ambulatory, emergency department visits) compared to periods before PCV introduction. When the impact of both vaccines is assessed in comparable settings, some studies suggest PHiD-CV may offer better protection against some OM outcomes. Well-designed, head-to-head comparisons are needed to better understand the differences and guide vaccination policies.

Plain Language SummaryWhat is the context?Pneumococcal vaccines are highly effective in preventing pneumonia and meningitis in children. The two main pneumococcal vaccines are PHiD-CV (Synflorix, GSK) and PCV13 (Prevenar 13, Pfizer). Both vaccines have been shown to provide protection against otitis media despite differing in their composition.However, it is currently unknown if both vaccines confer similar level of protection against otitis media.What is new?We conducted a literature review to evaluate the effects of PHiD-CV and PCV13 on otitis media.From 33 articles, we found that:‡Both vaccines were effective in reducing doctor visits for otitis media as well as the number of severe cases and cases requiring hospitalization.‡Four studies suggested a higher level of protection provided by PHiD-CV compared to PCV13, although more data is needed to confirm this finding. What is the impact?Available information shows that PHiD-CV and PCV13 are effective in preventing a proportion of otitis media during childhood.Given the remaining substantial burden associated with the disease and the related significant usage of antibiotics, the development of improved vaccines with higher impact on otitis media would be welcome.

A systematic review of invasive pneumococcal disease vaccine failures and breakthrough with higher-valency pneumococcal conjugate vaccines in children.

INTRODUCTION: The pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV/PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) protect against vaccine-serotype invasive pneumococcal disease (VT IPD). However, VT IPD can still occur in fully or partially vaccinated children (vaccine failure or breakthrough). We performed a systematic review of vaccine failures and breakthrough IPD with PCV10 and PCV13 in ≤5-year-olds. AREAS COVERED: We searched Scopus/Medline/EMBASE to retrieve articles/abstracts published between 1/2008-7/2019. We excluded reports only including data from ≥6-year-olds, exclusively assessing PCV7-vaccinated children or children with comorbidities. Twenty-six reports (20 PCV13, 1 PCV10, 5 both), covering studies with various designs in six continents, using different schedules, were included. Collectively, they reported 469 VT IPD cases classified as vaccine failures and 403 as breakthrough. Vaccine failure and breakthrough rates were low: 8.4% and 9.3%, respectively, of all IPD in vaccinated children, consistent with the vaccines' high effectiveness. The main serotypes associated with vaccine failure/breakthrough were 19A, 3 and 19F for PCV13 and 14, 6B and vaccine-related 19A and 6A for PCV10. EXPERT OPINION: As we move to vaccines with more serotypes, it is not only important to consider which serotypes are added, but also monitor and address incomplete protection against specific serotypes.

PLAIN LANGUAGE SUMMARYWhat is the context?Pneumococcal conjugate vaccines have been given to children for over 20 years to prevent infections caused by the bacterium Streptococcus pneumoniae (such as pneumonia, meningitis and sepsis).At least 100 different types of S. pneumoniae, so called serotypes, exist, but a relatively small number causes most disease.Two current vaccines (Synflorix, GSK and Prevnar 13, Pfizer) protect against 10 to 13 serotypes and have significantly reduced pneumococcal disease caused by these serotypes.A rise in serotypes not targeted by these vaccines has lessened the vaccines' expected impact.As no vaccine is 100% protective, some serotypes targeted by the current vaccines continue to circulate.What is new?We performed a systematic literature review to evaluate which serotypes are most often associated with invasive disease occurring after receives all planned pneumococcal vaccine doses (vaccine failure) or after a child receives part of the planned vaccine doses (breakthrough).We found that vaccine failures and breakthrough disease were uncommon with both vaccines, irrespective of the administered schedule.A small number of serotypes were responsible for most vaccine failures and breakthrough disease with both vaccines.What is the impact?The low rate of vaccine failures and breakthrough disease observed with the current vaccines confirms their high effectiveness in preventing pneumococcal disease.The primary consideration in developing pneumococcal conjugate vaccines that include more than 13 serotypes will be how additional protection they can provide.Reduced protection against individual serotypes remains a risk.The evaluation of current vaccines demonstrates that incomplete protection against specific serotypes should also be addressed.

A Decade of Fighting Invasive Meningococcal Disease: A Narrative Review of Clinical and Real-World Experience with the MenACWY-CRM Conjugate Vaccine.

The quadrivalent A, C, W and Y meningococcal vaccine conjugated to nontoxic mutant of diphtheria toxin (MenACWY-CRM) has been licensed since 2010 for the prevention of invasive meningococcal disease (IMD), an uncommon but life-threatening condition. Here, we summarize the experience accrued with MenACWY-CRM during the first decade since its licensure, by providing an overview of clinical trials investigating the safety, immunogenicity and co-administration of MenACWY-CRM with other vaccines as well as presenting real-world evidence regarding the impact of MenACWY-CRM vaccination on carriage and IMD incidence. MenACWY-CRM has demonstrated an acceptable clinical safety profile across a wide range of age groups; no safety concerns have been reported in special populations, such as immunocompromised infants and toddlers, or pregnant women. MenACWY-CRM has also been proven to be immunogenic in various age groups and geographic settings, and a booster dose has been shown to elicit strong anamnestic responses in all studied populations, irrespective of the vaccine used for priming. With no clinically relevant vaccine interactions reported, MenACWY-CRM is being conveniently integrated into existing vaccination programs for various age and risk groups; this possibility of co-administration helps improving vaccine coverage and streamlining the healthcare process of fighting preventable infectious diseases. Vaccination of adolescents and adults has been proven to reduce nasopharyngeal carriage for serogroups C, W and Y, which is an important element in reducing transmission. Real-world evidence indicates that MenACWY-CRM can reduce IMD incidence even in high-exposure groups. When combined with vaccines against serogroup B meningococci, MenACWY-CRM can offer protection against five of the most common serogroups responsible for IMD, which is an important advantage in the continuously evolving landscape of meningococcal serogroup epidemiology.

Invasive meningococcal disease is an uncommon but life-threatening infection that appears as meningitis and/or sepsis. It is caused by Neisseria meningitidis, a bacteria commonly present in the throat or nose. Vaccination with MenACWY-CRM (Menveo, GSK) helps to prevent invasive meningococcal disease caused by four of the most common N. meningitidis serogroups (A, C, W and Y). This vaccine has been licensed for 10 years: we summarized here all available evidence gathered since the vaccine has been available in general practice, from clinical development to real-world experience. Information gained during clinical trials of MenACWY-CRM confirms that vaccination is well tolerated, has an acceptable safety profile and would induce significant protection when given to individuals of various ages such as infants, toddlers, children, adolescents and adults, and when administered at the same time as routine or traveler vaccinations as well as vaccines against serogroup B meningococci (4CMenB). Vaccination with MenACWY-CRM has been shown to decrease the number of serogroup C, W and Y meningococci found in the nose and throat in adolescents and adults as well as the occurrence of invasive meningococcal disease in a high-exposure population from a real-world setting. MenACWY-CRM can conveniently be integrated into most of the existing vaccination schedules for various age and risk groups. When combined with vaccination against serogroup B meningococci, MenACWY-CRM can contribute to providing protection against five of the most common serogroups responsible for invasive meningococcal disease.

Public health perspective of a pentavalent meningococcal vaccine combining antigens of MenACWY-CRM and 4CMenB.

OBJECTIVES: Invasive meningococcal disease (IMD) is a life-threatening disease that can rapidly progress to death or leave survivors with severe, life-long sequelae. Five meningococcal serogroups (A, B, C, W and Y) account for nearly all IMD. Meningococcal serogroup distribution fluctuates over time across the world and age groups. Here, we consider the potential public health impact of a pentavalent MenABCWY vaccine developed to help further control meningococcal disease and improve immunisation rates. RESULTS: The GSK MenABCWY vaccine combines the antigenic components of MenACWY-CRM (Menveo®) and 4CMenB (Bexsero®), building on a wide body of clinical experience and real-world evidence. Both approved vaccines have acceptable safety profiles, demonstrate immunogenicity, and are broadly used, including in national immunisation programmes in several countries. Since the advent of quadrivalent vaccines, public health in relation to IMD has improved, with a decline in the overall incidence of IMD and an increase in vaccine coverage. CONCLUSION: A pentavalent MenABCWY has the potential to provide further public health benefits through practical, broad IMD protection programmes encompassing serogroups A, B, C, W and Y, and is currently in late-stage development.

Invasive Pneumococcal Disease burden and PCV coverage in children under five in Southeast Asia: implications for India.

INTRODUCTION: Pneumococcal diseases, though preventable, are a major public health problem in Southeast Asia and particularly in India. Pneumococcal conjugate vaccines (PCVs) are used in the region for over a decade, but to understand their impact, invasive pneumococcal diseases (IPD) burden and PCV coverage data in the region are needed. METHODOLOGY: A literature search was conducted to identify i) key evidence published between February 2008 and February 2018 on IPD burden, serotype prevalence and antibiotic resistance in Southeast Asia, and ii) PCV serotype and vaccination coverage in Southeast Asia. RESULTS: 49 relevant articles were included in the final analysis. Mortality in children under 5 years remains high in Southeast Asian countries, with around 25% of deaths due to IPD in India and Pakistan. There was a lack of recent data on IPD incidence. Antibiotic resistance to IPD isolates is increasing, with high resistance rates especially for meningeal isolates. Based on serotype distribution data, primarily for India, available PCVs would cover around 70-80% of IPD-causing serotypes. Vaccine coverage was around 15-20% in India to 98% in South Korea. CONCLUSIONS: Widespread PCV use could successfully reduce IPD burden in the region due to high serotype coverage by available PCVs; emphasis should be placed on increasing vaccination uptake, for every child, particularly in India. Reducing health system barriers and improving surveillance and awareness is essential to improve coverage and effectively prevent IPD morbidity and mortality particularly in at risk regions.

Meningococcal Disease Outbreaks: A Moving Target and a Case for Routine Preventative Vaccination.

Outbreaks of invasive meningococcal disease (IMD) are unpredictable, can be sudden and have devastating consequences. We conducted a non-systematic review of the literature in PubMed (1997-2020) to assess outbreak response strategies and the impact of vaccine interventions. Since 1997, IMD outbreaks due to serogroups A, B, C, W, Y and X have occurred globally. Reactive emergency mass vaccination campaigns have encompassed single institutions (schools, universities) through to whole sections of the population at regional/national levels (e.g. serogroup B outbreaks in Saguenay-Lac-Saint-Jean region, Canada and New Zealand). Emergency vaccination responses to IMD outbreaks consistently incurred substantial costs (expenditure on vaccine supplies, personnel costs and interruption of other programmes). Impediments included the limited pace of transmission of information to parents/communities/healthcare workers; issues around collection of informed consents; poor vaccine uptake by older adolescents/young adults, often a target age group; issues of reimbursement, particularly in the USA; and difficulties in swift supply of large quantities of vaccines. For serogroup B outbreaks, the need for two doses was a significant issue that contributed substantially to costs, delayed onset of protection and non-compliance with dose 2. Real-world descriptions of outbreak control strategies and the associated challenges systematically show that reactive outbreak management is administratively, logistically and financially costly, and that its impact can be difficult to measure. In view of the unpredictability, fast pace and potential lethality of outbreak-associated IMD, prevention through routine vaccination appears the most effective mitigation tool. Highly effective vaccines covering five of six disease-causing serogroups are available. Preparedness through routine vaccination programmes will enhance the speed and effectiveness of outbreak responses, should they be needed (ready access to vaccines and need for a single booster dose rather than a primary series).

Ten years of experience with the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (Synflorix) in children.

Introduction: Pneumococcal diseases (including pneumonia, meningitis and sepsis) are among the leading vaccine-preventable causes of death in under-5-year-olds. Pneumococci are also one of the main bacterial pathogens associated with acute otitis media (AOM). Infant immunization programs with pneumococcal conjugate vaccines (PCVs) have led to stark reductions in pneumococcal disease rates.Areas covered: We summarized the development of the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and evidence of its protective effect in children, since its licensure one decade ago. We highlighted the most recent data from post-licensure studies on invasive pneumococcal disease (IPD), pneumonia and AOM and from health economic evaluations. We present results from a model estimating PHiD-CV's impact on pneumococcal-related deaths.Expert opinion: Recent data from post-licensure studies confirm the previously demonstrated positive impact of PHiD-CV on IPD, pneumonia, AOM and AOM-related interventions (e.g., antibiotic use). Despite the success of infant PHiD-CV (and other PCV) programs, pneumococcal diseases still pose a substantial public health burden. Further reducing this burden will require improving access to currently available PCVs, increasing vaccination coverage and addressing the remaining burden due to non-vaccine serotypes. Future availability of lower-cost PCVs, PCVs with a broader serotype coverage and serotype-independent vaccines may contribute to this.