Lifting non-pharmaceutical interventions following the COVID-19 pandemic - the quiet before the storm?

INTRODUCTION: In the first months of the novel coronavirus (COVID-19) pandemic that begun in 2020, non-pharmaceutical interventions (NPIs) have been adopted worldwide. However, the effects of NPI implementation go beyond slowing the spread of COVID-19. Here, we review the non-intended effects that may have arisen from prolonged application of NPIs. AREAS COVERED: NPIs also affected the epidemiology of other infectious diseases, with unprecedentedly low circulation of several respiratory and gastrointestinal viruses being observed worldwide in 2020. While this was a welcome effect for already strained health-care systems, prolonged low exposure to pathogens may result in an increased pool of individuals susceptible to certain diseases. Out-of-season or unusually intense outbreaks of non-vaccine preventable diseases have already been documented as NPIs were gradually eased. In the context of widespread and important disruptions in national vaccination programs during the early phase of the pandemic, the risk of vaccine-preventable disease resurgence after NPIs are lifted cannot be excluded either. EXPERT OPINION: Awareness must be raised of the risk of vaccine-preventable disease resurgence, and efforts need to be made to mitigate this risk, where possible, by increasing vaccination coverage. Research and regulatory opportunities brought on by the COVID-19 pandemic should be seized.

In the first months of the COVID-19 pandemic, the only methods available to slow the spread of the disease were non-pharmaceutical interventions, such as lockdowns, mask wearing, social distancing, school closures, and travel bans. Even after vaccines against COVID-19 became available, combinations of non-pharmaceutical interventions continued to be implemented by most countries, to various extents. Although these measures lowered the number of people who got sick before vaccines and therapies against COVID-19 were available, they also had other consequences for public health. The non-pharmaceutical interventions implemented worldwide have slowed or even stopped the spread of several infectious diseases: since 2020, fewer cases of flu, bronchiolitis, gastroenteritis, and other diseases were recorded compared to pre-pandemic times. This relatively long 2-year period during which people, especially children, were exposed to fewer infections might mean that their immune systems are less prepared to fight these diseases. In addition, vaccination against diseases other than COVID-19 dropped in the early months of the pandemic, meaning that the number of children and adults who are not protected against vaccine-preventable disease has potentially increased. Easing of COVID-19 restrictions has caused a comeback of some diseases against which no vaccine is available, sometimes with more cases than during the pre-pandemic years; there is a risk that this might happen with vaccine-preventable diseases as well. To prevent outbreaks, routine and catch-up vaccinations against other diseases besides COVID-19 should be encouraged and promoted.

Recommendations for the ethical conduct of vaccination awareness campaigns by biopharmaceutical companies.

Health awareness campaigns educate and inform the public about particular health conditions with the aim of either changing behavior or enhancing uptake of appropriate healthcare, such as vaccination or screening. The campaigns may be run by governments and public health bodies but are also deployed by biopharmaceutical companies. Industry-sponsored disease awareness (DA) campaigns intend to provide information about diseases and their prevention or treatment, without mentioning specific products. In most countries, DA campaigns fall outside of the laws and regulations that apply to promotion of medicines. Currently, guidance for industry is limited and only exists at national level. This article provides an overview of existing guidance on DA campaigns, discusses benefits and risks, and proposes recommendations for industry-sponsored vaccination awareness campaigns.

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.

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.

PLAIN LANGUAGE SUMMARYThe diseaseRotaviruses are a leading cause of acute diarrhea, also called gastroenterities, among young children. They can lead to servere dehydration, hospitilization, and even death.Several vaccines against rotavirus disease have been developed. Their design is based on:weakened human rotavirus that mimic natural infection without causing disease, such as Rotarix, Rotavin-M1, Rotavac and RV3-BB (not yet marketed)non-infective animal viruses such as RotaTeq, Rotasiil or LLR.new concepts, such as inactivated vaccinesWhat is new?We reviewed the current, recently launched and soon-to-be-launched rotavirus vaccines and found that:Rotarix and RotaTeq have been used globally for more than a decade with demonstrated impact and favourable safety profileLimited data on the impact and safety profile are available to date for:Rotavin-M1 and LLR vaccines, locally marketed in Vietnam and China, respectivelyRotavac and Rotasiil, licensed in indiaNew vaccine concepts have been mainly investigated animal models with encouraging resultsWhat is the impact?Despite their different designs, the current rotavirus vaccines demonstrate effectiveness in protecting against rotairus gastroenterits.Data for most recent vacciness are currently limited, for which additional data are needed to demonstrate how they will perform on a larger scale, their added value in a real setting and ther safety profile.

Measles, mumps, rubella prevention: how can we do better?

INTRODUCTION: Measles, mumps, and rubella incidence decreased drastically following vaccination programs' implementation. However, measles and mumps' resurgence was recently reported, outbreaks still occur, and challenges remain to control these diseases. AREAS COVERED: This qualitative narrative review provides an objective appraisal of the literature regarding current challenges in controlling measles, mumps, rubella infections, and interventions to address them. EXPERT OPINION: While vaccines against measles, mumps, and rubella (including trivalent vaccines) are widely used and effective, challenges to control these diseases are mainly related to insufficient immunization coverage and changing vaccination needs owing to new global environment (e.g. traveling, migration, population density). By understanding disease transmission peculiarities by setting, initiatives are needed to optimize vaccination policies and increase vaccination coverage, which was further negatively impacted by COVID-19 pandemic. Also, awareness of the potential severity of infections and the role of vaccines should increase. Reminder systems, vaccination of disadvantaged, high-risk and difficult-to-reach populations, accessibility of vaccination, healthcare infrastructure, and vaccination services management should improve. Outbreak preparedness should be strengthened, including implementation of high-quality surveillance systems to monitor epidemiology. While the main focus should be on these public health initiatives to increase vaccination coverage, slightly more benefits could come from evolution of current vaccines.

PLAIN LANGUAGE SUMMARYWhat is the context?Measles, mumps, and rubella are highly contagious diseases associated with significant medical and societal burden. Effective vaccines against these diseases are available, and the implementation of vaccination programs drastically reduced disease incidence globally. However, reports of measles and mumps outbreaks in the last few years highlight remaining challenges to eliminate these diseases.What does the review highlight?We conducted a literature review to identify challenges associated with controlling measles, mumps, and rubella infections, and interventions needed to address them. We identified 11 challenges mainly related to low immunization coverage and vaccine characteristics. Societal challenges could be addressed by increasing awareness of disease severity and vaccines impact, targeting high-risk, unvaccinated, and under-vaccinated populations, improving vaccination access, setting up clear outbreak preparedness plans, and implementing country-specific vaccination policies. System weaknesses could be addressed through improving vaccination services and health infrastructure, implementing high-quality surveillance, patient invite, and reminder systems, ensuring vaccine implementation and long-term supply. Interventions related to vaccine characteristic challenges could include adaptation of vaccination schedules (shorter interval between doses, administration of a third dose) and development of vaccines against emerging strains.What is the take-home message?Policymakers should support the following strategies to increase vaccination coverage and reach elimination of measles, mumps, and rubella: strengthening health systems and vaccination access; raising awareness of disease severity and vaccination impact; limiting disease propagation owing to global changing environment and population dynamics (traveling, migration); improving surveillance systems to rapidly address the immunity gaps against disease resurgence.

Association between rotavirus gastroenteritis and intussusception: suggested evidence from a retrospective study in claims databases in the United States.

The etiology of intussusception (IS), a serious gastrointestinal obstruction, remains unclear. Limited evidence suggests a role for viral infection. We investigated the risk of IS after rotavirus gastroenteritis (RV GE) in the first year of life. In this retrospective, self-controlled case series (SCCS), we assessed the risk of IS after RV GE using data from United States administrative claims databases. Incidence rate ratios (IRR) of IS were calculated for the 7- and 21-day risk periods after RV GE (main analysis) or after fracture (sensitivity analysis). A total of 290,912,068 subjects were screened; 42 presented claims for RV GE and IS, and 66 for fracture and IS. The IRRs of IS after RV GE were 79.6 (95% confidence interval, CI: 38.6-164.4) and 25.5 (95% CI: 13.2-49.2) in the 7- and 21-day risk periods. The sensitivity analysis showed an association between IS and fracture for both periods, suggesting potential confounding. Post-hoc analyses did not confirm the association between fracture and IS but suggested a potential association between RV GE and IS. A temporal association between RV GE and IS was detected using claims databases. Due to some limitations of the data sources, this association should be further investigated.

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.

Fifteen years of experience with the oral live-attenuated human rotavirus vaccine: reflections on lessons learned.

INTRODUCTION: Rotavirus (RV) disease remains a prominent cause of disease burden in children <5 years of age worldwide. However, implementation of RV vaccination has led to significant reductions in RV mortality, compared to the pre-vaccination era. This review presents 15 years of real-world experience with the oral live-attenuated human RV vaccine (HRV; Rotarix). HRV is currently introduced in ≥80 national immunization programs (NIPs), as 2 doses starting from 6 weeks of age. AREAS COVERED: The clinical development of HRV and post-marketing experience indicating the impact of HRV vaccination on RV disease was reviewed. EXPERT OPINION: In clinical trials, HRV displayed an acceptable safety profile and efficacy against RV-gastroenteritis, providing broad protection against heterotypic RV strains by reducing the consequences of severe RV disease in infants. Real-world evidence shows substantial, rapid reduction in the number of RV infections and associated hospitalizations following introduction of HRV in NIPs, regardless of economic setting. Indirect effects against RV disease are also observed, such as herd protection, decrease in nosocomial infections incidence, and a reduction of disease-related societal/healthcare costs. However, not all countries have implemented RV vaccination. Coverage remains suboptimal and should be improved to maximize the benefits 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.

Epidemiology of rotavirus gastroenteritis and need of high rotavirus vaccine coverage with early completion of vaccination schedule for protection against rotavirus diarrhea in India: A narrative review.

Rotavirus is a leading cause of severe pediatric diarrhea worldwide, with about 199,000 childhood deaths in 2015, of which 90% in low-income countries. India alone accounts for 22% of the global rotavirus gastroenteritis (RVGE)-related deaths among children below 5 years of age. The World Health Organization recommends introducing rotavirus vaccines (RVVs) as a priority in developing countries where high rates of RVGE are observed. To have the desired impact, RVV should be administered the earliest possible, ideally before the first episode of RVGE. In India, four RVVs are available for use in infants ≥6 weeks of age: the single-strain, two-dose, live-attenuated human RVV Rotarix; the five-strain, three-dose, human-bovine reassortant RVV Rotateq; the single-strain, three-dose, naturally reassortant human-bovine RVV Rotavac; and the five-strain, three-dose, human-bovine RVV Rotasiil; all of them proven to be efficacious and well tolerated. Whereas Rotarix and Rotateq have shown high efficacy/effectiveness against severe RVGE in developed countries (≥90%), they have been observed to be lower in developing countries (~40%-70%). Rotavac and Rotasiil have shown similar efficacy in low-income settings, but further studies are needed to assess their effectiveness. Rotarix and Rotateq have not shown increased intussusception (IS) risk in clinical trials. Postmarketing surveillances were able to show a very tiny increased risk of IS after the first dose of vaccine, but the extensive benefits of rotavirus vaccination far outweigh the low-level risk of IS. In India, where the disease is a major problem and occurs in very early months of life, RVVs should have high coverage and vaccination schedule should be completed as early as possible (≥6 weeks of age) to maximize the vaccine impact.

Impact of history of febrile convulsions on the risk difference of febrile convulsions with the tetravalent measles-mumps-rubella-varicella vaccine: Post-hoc exploratory analysis of results from a matched-cohort study.

This post-hoc analysis of data from a matched cohort study investigated the risk of febrile convulsions (FC) 5-12 days post-first dose of measles-mumps-rubella-varicella vaccine (MMRV) in a low-risk population, compared to measles-mumps-rubella (MMR) and varicella (V) vaccines administered separately. The low-risk population excluded children with personal history of FC (Scenario 1) and children with personal or/and family history (≥1 parent/sibling) of FC (Scenario 2). Incidence of FC post-MMRV in Scenario 2 (excluding at risk children) (36.3-49.5/100,000) and post-MMR+V in the whole cohort including children with personal/family history of FC (43.6/100,000) were similar. The risk difference of FC increased by 0.2 case/100,000 in Scenario 1 and decreased by 5.3-8.6 cases/100,000 of vaccinated children in Scenario 2, compared to the whole cohort. The overall risk of FC post-first dose MMRV vaccination could be lowered by administering MMRV only to children with no personal or family history of FC.

Understanding modern-day vaccines: what you need to know.

Vaccines are considered to be one of the greatest public health achievements of the last century. Depending on the biology of the infection, the disease to be prevented, and the targeted population, a vaccine may require the induction of different adaptive immune mechanisms to be effective. Understanding the basic concepts of different vaccines is therefore crucial to understand their mode of action, benefits, risks, and their potential real-life impact on protection. This review aims to provide healthcare professionals with background information about the main vaccine designs and concepts of protection in a simplified way to improve their knowledge and understanding, and increase their confidence in the science of vaccination ( Supplementary Material ). KEY MESSAGE Different vaccine designs, each with different advantages and limitations, can be applied for protection against a particular disease. Vaccines may contain live-attenuated pathogens, inactivated pathogens, or only parts of pathogens and may also contain adjuvants to stimulate the immune responses. This review explains the mode of action, benefits, risks and real-life impact of vaccines by highlighting key vaccine concepts. An improved knowledge and understanding of the main vaccine designs and concepts of protection will help support the appropriate use and expectations of vaccines, increase confidence in the science of vaccination, and help reduce vaccine hesitancy.

Pain caused by measles, mumps, and rubella vaccines: A systematic literature review.

PURPOSE: The risk of post-vaccination adverse events (AEs) is a primary public health concern. Among the AEs, pain is a significant source of anxiety for both children and their parents. This review describes and assesses the intensity of pain experienced by children post-vaccination with widely used Measles-Mumps-Rubella (MMR) vaccines. METHODS: A systematic literature search was conducted in Pubmed, Embase and Cochrane to identify publications describing immediate pain at injection site (primary objective) or pain within days (secondary objective) after 2 specific MMR vaccines. Immediate pain ('acute pain' according to the Brighton Collaboration case definition) was defined as pain occurring at the time or within 5min of injection. RESULTS: Four studies, which compared the intensity of immediate injection site pain experienced by children after MMR vaccination, were identified. Various pain assessment tools and methods were used to quantify the intensity of pain, including the median difference in Visual Analog Scale scores between vaccine groups. All four studies showed significantly less immediate pain caused by Priorix (GSK Vaccines) compared with M-M-R II (Merck & Co., Inc.). CONCLUSIONS: To our knowledge, this review summarizes for the first time the available scientific evidence on the intensity of pain following different MMR vaccines. It highlights that MMR vaccines can differ in terms of immediate pain. Further research may be needed to better understand the underlying reason for this observation. In this context, it is very important to understand which physicochemical properties are most relevant for the immediate pain profile of a vaccine to thereby support the development of vaccines with the best possible immediate pain profile.

Parents' insights after pediatric hospitalization due to rotavirus gastroenteritis in Italy.

Most of the severe cases of acute gastroenteritis in infants and children under 5 globally are caused by rotavirus infection. There are nearly 15,000 rotavirus gastroenteritis (RVGE) hospitalizations in Italy each year, which could be reduced by available rotavirus vaccines. In addition to the economic and societal burden, RVGE hospitalization could impact families negatively. The aim of this survey was to obtain parents' insights after hospitalization of their child for RVGE. Parents, of 500 children aged 0-5 years, were interviewed about their experience of RVGE hospitalization and asked to rate their stress on different items and overall. Most children (32.6%) were hospitalized aged 12-23 months, and 6.8% were <6 months old. Family pediatricians referred 56.2% of cases to hospital, and 25.8% went based on their parents' decision. During hospitalization, mean parental stress scores (out of 10, with 10 as highest stress) ranged from 6.6 to 8.4. The highest scores were for child malaise (8.42, SD 1.00), vomiting/diarrhea (8.07, SD 0.97), stress for the family in general (7.82, SD 0.90), parental stress (7.68, SD 0.93) and child dehydration (7.18, SD 1.02). The overall stress for the family was graded as 'high' by 67.2% of parents. Geographical areas and stress level were related (p = 0.0071), being the "high" stress score not an evenly distributed variable (p < 0.0001). Most children (91.8%) were not vaccinated against rotavirus, as most parents (74.5%) were not aware of vaccination availability. Parental distress due to RVGE hospitalization appears to be significant (93.6% reporting high/medium stress) and there is an important lack of awareness among parents about rotavirus vaccination. More education on RVGE for families in Italy should be warranted.

Routinely vaccinating adolescents against meningococcus: targeting transmission & disease.

Adolescents have the highest rates of meningococcal carriage and transmission. Interrupting the adolescent habitat in order to reduce carriage and transmission within adolescents and to other age groups could help to control meningococcal disease at a population level. Compared to immunization strategies restricted to young children, a strategy focused on adolescents may have more profound and long-lasting indirect impacts, and may be more cost effective. Despite challenges in reaching this age-group, experience with other vaccines show that high vaccine coverage of adolescents is attainable.

Identification and characterization of the bacterial etiology of clinically problematic acute otitis media after tympanocentesis or spontaneous otorrhea in German children.

BACKGROUND: Acute Otitis Media (AOM) is an important and common disease of childhood. Bacteria isolated from cases of clinically problematic AOM in German children were identified and characterized. METHODS: In a prospective non-interventional study in German children between 3 months and less than 60 months of age with Ear, Nose and Throat Specialist -confirmed AOM, middle ear fluid was obtained by tympanocentesis (when clinically indicated) or by careful sampling of otorrhea through/at an existing perforation. RESULTS: In 100 children with severe AOM, Haemophilus influenzae was identified in 21% (18/21, 85.7% were non-typeable [NTHi]), Streptococcus pneumoniae in 10%, S. pyogenes in 13% and Moraxella catarrhalis in 1%. H. influenzae was the most frequently identified pathogen in children from 12 months of age. H. influenzae and S. pneumoniae were equally prevalent in children aged 3-11 months, but S. pyogenes was most frequently isolated in this age group. NTHi AOM disease appeared prevalent in all ages. CONCLUSIONS: NTHi, S. pneumoniae and S. pyogenes are implicated as important causes of complicated AOM in children in Germany. NTHi disease appears prevalent in all ages. The impact of vaccination to prevent NTHi and S. pneumoniae AOM may be substantial in this population and is worth investigating.