Defining the Recipe for an Optimal Rotavirus Vaccine Introduction in a High-Income Country in Europe

Observational data over 15 years of rotavirus vaccine introduction in Belgium have indicated that rotavirus hospitalisations in children aged <5 years plateaued at a higher level than expected, and was followed by biennial disease peaks. The research objective was to identify factors influencing these real-world vaccine impact data. We constructed mathematical models simulating rotavirus-related hospitalisations by age group and year for those children. Two periods were defined using different model constructs. First, the vaccine uptake period encompassed the years required to cover the whole at-risk population. Second, the post-uptake period covered the years in which a new infection/disease equilibrium was reached. The models were fitted to the observational data using optimisation programmes with regression and differential equations. Modifying parameter values identified factors affecting the pattern of hospitalisations. Results indicated that starting vaccination well before the peak disease season in the first year and rapidly achieving high coverage was critical in maximising early herd effect and minimising secondary sources of infection. This, in turn, would maximise the reduction in hospitalisations and minimise the size and frequency of subsequent disease peaks. The analysis and results identified key elements to consider for countries initiating an optimal rotavirus vaccine launch programme

Letter to the editor concerning the article ‘Association between rotavirus vaccination and risk of intussusception among neonates and infants: a systematic review and meta-analysis’ (JAMA Netw Open. 2019;2(10):e1912458)

A recent meta-analysis investigating the association between intussusception (IS) and rotavirus (RV) vaccination demonstrated an absence of risk up to 2 years after vaccination. Meta-analyses including only randomized clinical trials are inadequate to identify a potential increased risk of rare adverse events such as IS. The study conducted failed to discuss relevant limitations. Additionally, the safety profiles of newer RV vaccines, evaluated in clinical studies with limited sample size, were considered comparable with that of the well-established and widely used RV vaccines, RotaTeq and Rotarix. We, therefore, re-emphasize that extensive and updated evidence from post-marketing surveillance indicates a slight increased risk of IS, mostly within 7 days of RV vaccination, with a benefit/risk profile assessment in favor of RV vaccination

Role of healthcare practitioners in rotavirus disease awareness and vaccination – insights from a survey among caregivers

An online survey was designed to assess awareness and understanding of Rotavirus (RV) gastroenteritis (RVGE), and knowledge and attitudes towards RV vaccination in Germany, Poland, Turkey, Indonesia, the Philippines and Thailand. Survey participants (n = 1500) comprised parents, expectant parents and guardians of children ≤5 years of age who have sole or joint responsibility for health and well-being decisions relating to their child, who were recruited from an online panel and provided their consent for study participation. Participants from most countries had a high level of awareness of RV infections (mean: 82%) and of those aware of RV, a mean of 61% participants were aware that RV was the most common cause of GE, however the majority (mean: 59%) were unaware that nearly every child would be infected with RVGE by the age of 5 years. Healthcare professional (HCP) recommendation was identified as the key driver for participants seeking vaccination (48%–75% of participants stated this reason, with results differing by country) followed by availability of RV vaccine in the national immunization program. Despite a high level of awareness of RVGE among participants, fostering knowledge regarding the difficulty of RVGE prevention, the risk of RV contraction and the associated serious consequences like dehydration is imperative to improve RV vaccination uptake. HCPs, being the primary influence on participants’ decision on vaccination, are best suited to bridge existing knowledge gaps and recommend parents to vaccinate their children against RVGE

Human rotavirus vaccine (Rotarix): Focus on effectiveness and impact 6 years after first introduction in Africa

Artículo de publicación ISIA decade after licensure of the human rotavirus vaccine (HRV), a wealth of evidence supports a reduction of rotavirus (RV) gastroenteritis-associated mortality and hospitalizations following HRV inclusion in national immunization programs. Nevertheless, the majority of real-world data has been generated in high-or middle-income settings. Clinical efficacy trials previously indicated RV vaccine performance may be lower in less-developed countries compared with wealthier counterparts. Using recently published data from Africa, we examine the effectiveness and impact of HRV in resource-deprived areas, exploring whether vaccine performance differs by socioeconomic setting and the potential underlying factors. HRV vaccine effectiveness in early adopting African countries has proven to be similar or even superior to the efficacy results observed in pre-licensure studies

Rotavirus vaccination and intussusception: a paradigm shift?

Rotavirus (RV) is one of the leading causes of severe childhood gastroenteritis in children <5 years of age. Several countries have successfully implemented vaccination against RV disease; however, hesitancy to include RV vaccination in the national immunization program exists and relates, among other reasons, to the results of international post-licensure studies of RV vaccines that established an increased risk of intussusception (IS) in infants following immunization. IS is one of the major causes of bowel obstruction in infants between 4 and 10 months of age. Some studies have investigated the etiology of IS, including the role of natural RV infection and available evidence suggests that RV disease may be an independent risk factor for IS. In this regard, the benefit-risk profile of RV vaccination, which is recognized as positive, could potentially turn out to be even more favorable in preventing IS cases triggered by RV disease. However, further research is prompted to quantify the IS risk attributable to RV disease

Systematic literature review on the safety and immunogenicity of rotavirus vaccines when co-administered with meningococcal vaccines

This study is aimed to review the published evidence on safety, immunogenicity, and efficacy of rotavirus vaccines when co-administered with meningococcal vaccines in infants. A systematic literature search was performed in four databases containing peer-reviewed articles and conference abstracts. In total, twelve articles were included in the review; 11 provided information on safety and five on the immunogenicity of rotavirus vaccines following co-administration. No paper was found on efficacy. Additional routine vaccines were administered in all studies. The safety analysis was mainly focused on fever, vomiting, diarrhea, intussusception, and changes in eating habits. Overall, safety profiles and immune responses associated with rotavirus vaccination were comparable between infants co-administered with rotavirus and meningococcal vaccines and infants receiving rotavirus vaccines without meningococcal vaccines. Although data are limited, co-administration of rotavirus and meningococcal vaccines does not appear to interfere with the safety or immunogenicity of rotavirus vaccines

Established and new rotavirus vaccines: a comprehensive review for healthcare professionals

Robust scientific evidence related to two rotavirus (RV) vaccines available worldwide demonstrates their significant impact on RV disease burden. Improving RV vaccination coverage may result in better RV disease control. To make RV vaccination accessible to all eligible children worldwide and improve vaccine effectiveness in high-mortality settings, research into new RV vaccines continues. Although current and in-development RV vaccines differ in vaccine design, their common goal is the reduction of RV disease risk in children <5 years old for whom disease burden is the most significant. Given the range of RV vaccines available, informed decision-making is essential regarding the choice of vaccine for immunization. This review aims to describe the landscape of current and new RV vaccines, providing context for the assessment of their similarities and differences. As data for new vaccines are limited, future investigations will be required to evaluate their performance/added value in a real-world setting

The impact of childhood varicella vaccination on the incidence of herpes zoster in the general population: modelling the effect of exogenous and endogenous varicella-zoster virus immunity boosting

Background A controversy exists about the potential effect of childhood varicella vaccination on Herpes Zoster (HZ) incidence. Mathematical models projected temporary HZ incidence increase after vaccine introduction that was not confirmed by real-world evidence. These models assume that absence of contacts with infected children would prevent exogenous boosting of Varicella-Zoster-Virus (VZV) immunity and they do not include an endogenous VZV immunity-boosting mechanism following asymptomatic VZV reactivation. This study aims to explore the effect of various assumptions on exogenous and endogenous VZV immunity-boosting on HZ incidence in the general population after introduction of routine childhood varicella vaccination. Methods An age-structured dynamic transmission model was adapted and fitted to the seroprevalence of varicella in France in absence of vaccination using the empirical contact matrix. A two-dose childhood varicella vaccination schedule was introduced at 12 and 18 months. Vaccine efficacy was assumed at 65%/95% (dose 1/dose 2), and coverage at 90%/80% (dose 1/dose 2). Exogenous boosting intensity was based on assumptions regarding HZ-immunity duration, age-dependent boosting effect, and HZ reactivation rates fitted to observed HZ incidence. Endogenous boosting was the same as pre-vaccination exogenous boosting but constant over time, whilst exogenous boosting depended on the force of infection. Five scenarios were tested with different weightings of exogenous (Exo) - endogenous (Endo) boosting: 100%Exo–0%Endo, 75%Exo–25%Endo, 50%Exo–50%Endo, 25%Exo–75%Endo, 0%Exo–100%Endo. Results HZ incidence before varicella vaccination, all ages combined, was estimated at 3.96 per 1000 person-years; it decreased by 64% by year 80 post vaccine introduction, for all boosting assumptions. The 100%Exo-0%Endo boosting scenario, predicted an increase in HZ incidence for the first 21 years post vaccine introduction with a maximum increase of 3.7% (4.1/1000) at year 9. However, with 0%Exo-100%Endo boosting scenario an immediate HZ decline was projected. The maximum HZ incidence increases at 10, 3, and 2 years post vaccination were 1.8% (75%Exo-25%Endo), 0.8% (50%Exo-50%Endo) and 0.2% (25%Exo-75%Endo), respectively. Conclusions Assuming modest levels of endogenous boosting, the increase in HZ incidence following childhood varicella vaccination was smaller and lasted for a shorter period compared with 100%Exo-0%Endo boosting assumption. Endogenous boosting mechanism could partly explain the divergence between previous HZ-incidence projections and real-world evidence

Pertussis knowledge, attitude and practices among European health care professionals in charge of adult vaccination

Despite successful infant vaccination program, pertussis remains endemic in many countries. Waning immunity leaves adolescents and adults susceptible to disease and potential reservoirs of infection allowing transmission to vulnerable infants. Misdiagnosis leads to significant underestimation of disease burden and inappropriate treatment. This online survey of 517 European health care professionals (HCP) examined their knowledge, attitudes and practices regarding pertussis and adult vaccination. Compared with other vaccine-preventable diseases, HCPs did not perceive pertussis as a serious disease in adults and there was a low perceived need for adult vaccination; only 17% mentioned pertussis as a disease they would usually vaccinate adults against. Pertussis incidence was considered to be low. Although the majority of HCPs agreed that vaccination is useful to prevent pertussis transmission from adults to susceptible infants, respondents discussed pertussis vaccination with ≤5% of patients; 58% respondents had never prescribed a pertussis vaccine to adults. The perceived low incidence of pertussis in adults and the lack of official guidelines/recommendations were cited as key reasons for not administering pertussis boosters. Despite only taking place in four countries, our results suggest that the incidence and burden of adult pertussis is not reflected in the attitudes of European HCP s to the disease. Awareness of adult pertussis, its diagnosis and guidance on pertussis boosters should be raised to protect adults and vulnerable infants and to manage the consequences of waning pertussis immunity