Differences Between RSV A and RSV B Subgroups and Implications for Pharmaceutical Preventive Measures.

INTRODUCTION: Understanding the differences between respiratory syncytial virus (RSV) subgroups A and B provides insights for the development of prevention strategies and public health interventions. We aimed to describe the structural differences of RSV subgroups, their epidemiology, and genomic diversity. The associated immune response and differences in clinical severity were also investigated. METHODS: A literature review from PubMed and Google Scholar (1985-2023) was performed and extended using snowballing from references in captured publications. RESULTS: RSV has two major antigenic subgroups, A and B, defined by the G glycoprotein. The RSV F fusion glycoprotein in the prefusion conformation is a major target of virus neutralizing antibodies and differs in surface exposed regions between RSV A and RSV B. The subgroups co-circulate annually, but there is considerable debate as to whether clinical severity is impacted by the subgroup of the infecting RSV strain. Large variations between the studies reporting RSV subgroup impact on clinical severity were observed. A tendency for higher disease severity may be attributed to RSV A but no consensus could be reached as to whether infection by one of the subgroup caused more severe outcomes. RSV genotype diversity decreased over the last two decades, and ON and BA have become the sole lineages detected for RSV A and RSV B, since 2014. No studies with data obtained after 2014 reported a difference in disease severity between the two subgroups. RSV F is relatively well conserved and highly similar between RSV A and B, but changes in the amino acid sequence have been observed. Some of these changes led to differences in F antigenic sites compared to reference F sequences (e.g., RSV/A Long strain), which are more pronounced in antigenic sites of the prefusion conformation of RSV B. Initial results from the second season after vaccination suggest specific RSV B efficacy wanes more rapidly than RSV A for RSV PreF-based monovalent vaccines. CONCLUSIONS: RSV A and RSV B both contribute substantially to the global RSV burden. Both RSV subgroups cause severe disease and none of the available evidence to date suggests any differences in clinical severity between the subgroups. Therefore, it is important to implement measures effective at preventing disease due to both RSV A and RSV B to ensure impactful public health interventions. Monitoring overtime will be needed to assess the impact of waning antibody levels on subgroup-specific efficacy.

Estimated Incidence of Hospitalizations Attributable to RSV Infection Among Adults in Ontario, Canada, Between 2013 and 2019.

INTRODUCTION: Adult respiratory syncytial virus (RSV) burden is underestimated due to non-specific symptoms, limited standard-of-care and delayed testing, reduced diagnostic test sensitivity-particularly when using single diagnostic specimen-when compared to children, and variable test sensitivity based on the upper airway specimen source. We estimated RSV-attributable hospitalization incidence among adults aged ≥ 18 years in Ontario, Canada, using a retrospective time-series model-based approach. METHODS: The Institute for Clinical Evaluative Sciences data repository provided weekly numbers of hospitalizations (from 2013 to 2019) for respiratory, cardiovascular, and cardiorespiratory disorders. The number of hospitalizations attributable to RSV was estimated using a quasi-Poisson regression model that considered probable overdispersion and was based on periodic and aperiodic time trends and viral activity. As proxies for viral activity, weekly counts of RSV and influenza hospitalizations in children under 2 years and adults aged 60 years and over, respectively, were employed. Models were stratified by age and risk group. RESULTS: In patients ≥ 60 years, RSV-attributable incidence rates were high for cardiorespiratory hospitalizations (range [mean] in 2013-2019: 186-246 [215] per 100,000 person-years, 3‒4% of all cardiorespiratory hospitalizations), and subgroups including respiratory hospitalizations (144-192 [167] per 100,000 person-years, 5‒7% of all respiratory hospitalizations) and cardiovascular hospitalizations (95-126 [110] per 100,000 person-years, 2‒3% of all cardiovascular hospitalizations). RSV-attributable cardiorespiratory hospitalization incidence increased with age, from 14-18 [17] hospitalizations per 100,000 person-years (18-49 years) to 317-411 [362] per 100,000 person-years (≥ 75 years). CONCLUSIONS: Estimated RSV-attributable respiratory hospitalization incidence among people ≥ 60 years in Ontario, Canada, is comparable to other incidence estimates from high-income countries, including model-based and pooled prospective estimates. Recently introduced RSV vaccines could have a substantial public health impact.

Evolution of Lyme Borreliosis Epidemiology in Primary Care and Hospital Settings in France During the COVID-19 Pandemic.

Background: Lyme borreliosis (LB) remains a public health concern in France despite improved patient management and medical care. Stay-at-home restrictions during the COVID-19 pandemic, which affected participation in outdoor recreational activities and disrupted access to health care services, may have impacted the risk of developing LB. Methods: We analyzed data from two general practitioner networks in France (Sentinel Network and an electronic medical records database [EMR]) and the national hospital discharge database to describe LB epidemiology in 2020-2021 and compare it to previous years. Google Trends' search volume was used to evaluate the association between the population's interest in LB and the evolving epidemiology. Results: Annual LB incidence rates in primary care decreased from 104 cases/100,000 population in 2018 to 71/100,000 in 2021 and from 82/100,000 to 60/100,000 according to Sentinel Network and EMR, respectively. Google Trends' search volume for "Lyme" followed a similar trend, one year earlier. Annual hospitalizations were stable from 2012-2019 (1.6/100,000 on average) and declined to 1.3/100,000 in 2020 and 1.1/100,000 in 2021. This decline was observed primarily in adults (e.g., 3.4/100,000 in 2017-2019 to 1.8/100,000 in 2020-2021 for 70-79 years of age). Changes in regional incidence rates in primary care from 2017-2019 to 2020-2021 ranged from -75% to 208%. Hospitalizations decreased in all regions except in Bretagne. Conclusions: The estimated LB incidence decreased in 2020 and 2021 compared with previous years but this change may not be related to COVID-19. The incidence decrease observed in primary care could result from reduced population interest in LB, leading to lower care-seeking behavior. The decrease in LB hospitalizations may be explained by changes in clinical practice. Surveillance systems are critical to understand the evolution of LB epidemiology. However, external factors impacting incidence estimates should be considered.

Estimation of Symptomatic Respiratory Syncytial Virus Infection Incidence in Adults in Multiple Countries: A Time-Series Model-Based Analysis Protocol.

INTRODUCTION: Estimating respiratory syncytial virus (RSV) burden in adults is challenging because of non-specific symptoms, infrequent standard-of-care testing, resolution of viral shedding before seeking medical care, test positivity that varies by specimen site in the upper airway and lower diagnostic test sensitivity compared to children. Conducting prospective observational studies to assess RSV burden in adults is time- and resource-intensive. Thus, model-based approaches can be applied using existing data to obtain more accurate estimates of RSV burden. This protocol establishes essential elements for estimating RSV incidence rate in adults using a time series model-based approach. It can be tailored to specific databases and applied globally across countries, enabling estimation of local RSV disease burden to inform public health decision-making, including immunization policy. METHODS: Data are analysed using a quasi-Poisson regression model, considering the effect of baseline trends and pathogen co-circulation, stratified by age and risk status. Pathogen co-circulation is represented by viral proxies defined based on ICD code groupings indicating RSV and influenza-specific hospitalizations, lagged 0 up to 4 weeks based on the model selection. A final model is constructed in two steps: optimization of the time trend (using p-values) and selection of the viral proxy lag time (using test statistics, to prioritize the most biologically plausible option). The yearly incidence rate and percentage of events attributable to RSV are estimated from the final model. Confidence intervals are calculated using residual bootstrapping. PLANNED OUTCOMES: Outcomes to be modelled are based on administrative ICD code groupings and include the number of cardiorespiratory, respiratory and cardiovascular events in a specific care setting (e.g., general practitioner visit, emergency department visit, hospitalization and death). Cardiovascular events are limited to those for which existing evidence suggests an association with RSV infection. Additional secondary outcomes are constructed as a subset of the primary outcomes based on specific ICD code groups.

Estimated Incidence of Hospitalizations and Deaths Attributable to Respiratory Syncytial Virus Infections Among Adults in Germany Between 2015 and 2019.

INTRODUCTION: Respiratory syncytial virus (RSV) burden in adults is underestimated mainly due to unspecific symptoms and limited standard-of-care testing. We estimated the population-based incidence of hospitalization and mortality attributable to RSV among adults with and without risk factors in Germany. METHODS: Weekly counts of hospitalizations and deaths for respiratory, cardiovascular, and cardiorespiratory diseases were obtained (Statutory Health Insurance database, 2015-2019). A quasi-Poisson regression model was fitted to estimate the number of hospitalizations and deaths attributable to RSV as a function of periodic and aperiodic time trends, and viral activity while allowing for potential overdispersion. Weekly counts of RSV and influenza hospitalizations in children < 2 years and adults ≥ 60 years, respectively, were used as viral activity indicators. Models were stratified by age group and risk status (defined as presence of selected comorbidities). RESULTS: Population-based RSV-attributable hospitalization incidence rates were high among adults ≥ 60 years: respiratory hospitalizations (236-363 per 100,000 person-years) and cardiorespiratory hospitalizations (584-912 per 100,000 person-years). RSV accounted for 2-3% of all cardiorespiratory hospitalizations in this age group. The increase in cardiorespiratory hospitalization risk associated with underlying risk factors was greater in 18-44 year old persons (five to sixfold higher) than in ≥ 75 year old persons (two to threefold higher). CONCLUSIONS: This is a first model-based study to comprehensively assess adult RSV burden in Germany. Estimated cardiorespiratory RSV hospitalization rates increased with age and were substantially higher in people with risk factors compared to those without risk factors. Our study indicates that RSV, like other respiratory viruses, contributes to both respiratory and cardiovascular hospitalizations. Effective prevention strategies are needed, especially among older adults ≥ 60 years and among adults with underlying risk factors.

Estimated Respiratory Syncytial Virus-Related Hospitalizations and Deaths Among Children and Adults in Spain, 2016-2019.

INTRODUCTION: Respiratory syncytial virus (RSV) causes a substantial disease burden among infants. In older children and adults, incidence is underestimated due to nonspecific symptoms and limited standard-of-care testing. We aimed to estimate RSV-attributable hospitalizations and deaths in Spain during 2016-2019. METHODS: Nationally representative hospitalization and mortality databases were obtained from the Ministry of Health and the National Statistical Office. A quasi-Poisson regression model was fitted to estimate the number of hospitalizations and deaths attributable to RSV as a function of periodic and aperiodic time trends and viral activity, while allowing for potential overdispersion. RESULTS: In children, the RSV-attributable respiratory hospitalization incidence was highest among infants aged 0-5 months (3998-5453 cases/100,000 person-years, representing 72% of all respiratory hospitalizations) and decreased with age. In 2019, estimated rates in children 0-5, 6-11, 12-23 months and 6-17 years were approximately 1.3, 1.4, 1.5, and 6.5 times higher than those based on standard-of-care RSV-specific codes. In adults, the RSV-attributable cardiorespiratory hospitalization rate increased with age and was highest among persons ≥ 80 years (1325-1506 cases/100,000, 6.5% of all cardiorespiratory hospitalizations). In 2019, for persons aged 18-49, 50-59, 60-79, and ≥ 80 years, estimated rates were approximately 8, 6, 8, and 16 times higher than those based on standard-of-care RSV-specific codes. The RSV-attributable cardiorespiratory mortality rate was highest among ≥ 80 age group (126-150 deaths/100,000, 3.5-4.1% of all cardiorespiratory deaths), when reported mortality rate ranged between 0 and 0.5/100,000. CONCLUSIONS: When accounting for under-ascertainment, estimated RSV-attributable hospitalizations were higher than those reported based on standard-of-care RSV-specific codes in all age groups but particularly among older children and older adults. Like other respiratory viruses, RSV contributes to both respiratory and cardiovascular complications. Efficacious RSV vaccines could have a high public health impact in these age and risk groups.

Epidemiology of Lyme Borreliosis in France in Primary Care and Hospital Settings, 2010-2019.

Introduction: Lyme borreliosis (LB) is a growing public health concern requiring accurate and comprehensive epidemiological knowledge to inform health care interventions. This study compared the epidemiology of LB in primary care and hospital settings, using for the first time in France three sources of data, and highlighted specific populations at higher risk of developing LB. Methods: This study analyzed data from general practitioner networks (i.e., Sentinel network, Electronic Medical Records [EMR]) and the national hospital discharge database to describe the LB epidemiology from 2010 to 2019. Results: The average annual incidence rates of LB in primary care increased from 42.3 cases/100,000 population in 2010-2012 to 83.0/100,000 in 2017-2019 for the Sentinel Network and 42.7/100,000 to 74.6/100,000 for the EMR, following a marked rise in 2016. The annual hospitalization rate remained stable from 2012 to 2019 fluctuating between 1.6 and 1.8 hospitalizations/100,000. Women were more likely to present with LB in primary care setting compared with men (male-to-female incidence rate ratio [IRR] = 0.92), whereas men were predominant among hospitalizations (IRR = 1.4), with the largest discordance among adolescents aged 10-14 years (IRR = 1.8) and adults aged 80 years and older (IRR = 2.5). In 2017-2019, the average annual incidence rate peaked among persons aged 60-69 years in primary care (>125/100,000) and aged 70-79 years among hospitalized patients (3.4/100,000). A second peak occurred in children aged 0-4 or 5-9 years depending on sources. Incidence rates in Limousin and the north-eastern regions were the highest for both primary care and hospital settings. Conclusions: Analyses showed disparities in the evolution of incidence, sex-specific incidence rates, and predominant age groups between primary care and hospital settings that merit further exploration.

Evolution of invasive meningococcal disease epidemiology in Europe, 2008 to 2017.

BackgroundInvasive meningococcal disease (IMD) epidemiology has fluctuated over the past 25 years and varies among serogroups, age groups and geographical locations.AimThis study analysed the evolution of European IMD epidemiology from 2008 to 2017 to identify trends.MethodsReported number of IMD cases and associated incidence were extracted from the European Centre for Disease Prevention and Control Surveillance Atlas for Infectious Diseases for individual European countries. Epidemiology and its evolution were analysed by serogroup and age group.ResultsOverall IMD incidence decreased by 34.4% between 2008 and 2017. Serogroup B remained predominant in 2017; despite a 56.1% decrease over the 10-year period, the rate of decrease has slowed in recent years and varies by age group. Serogroup C was the second most prevalent serogroup until 2016. Its incidence decreased among individuals aged 1-24 years, the main population targeted by MenC vaccination campaigns, but increases have occurred in other age groups. Incidences of serogroups W and Y were low but increased by > 500% and > 130% (to 0.10 and 0.07/100,000) respectively, from 2008 to 2017. Considering all serogroups, a marked modification of the evolution trends by age group has occurred, with increases in incidence mainly affecting older age groups.ConclusionAlthough the overall IMD incidence decreased in Europe between 2008 and 2017, increases were observed for serogroups W and Y, and in the older population when considering all serogroups. It may be necessary to adapt current vaccination strategies to reflect epidemiological changes and their likely future evolution.

Introduction of a second MenB vaccine into Europe - needs and opportunities for public health.

INTRODUCTION: Invasive meningococcal disease (IMD) can be devastating; it is associated with high case fatality rates and long-term sequelae among many survivors. Five serogroups (A, B, C, W, and Y) cause nearly all IMD cases worldwide, and serogroup B (MenB) is the most prevalent in Europe. The European Medicines Agency approved the use of MenB-fHbp (Trumenba®; Pfizer Ltd, Sandwich, UK) in individuals ≥10 years of age for the prevention of MenB IMD in May 2017. MenB-fHbp contains two lipidated recombinant fHbp variants from two different fHbp subfamilies that help provide broad coverage against circulating meningococcal strains and may also improve antibody response compared to a nonlipidated antigen. AREAS COVERED: This review summarizes the latest epidemiology evaluating the disease burden of MenB in Europe, introduces MenB-fHbp (the vaccine most recently approved in the European Union for the prevention of MenB IMD), and provides an overview of its development. EXPERT OPINION: MenB is by far the most prevalent meningococcal serogroup in Europe, and its epidemiology is not currently addressed by European immunization recommendations. New strategies to prevent MenB IMD in Europe will continue to develop with the growing use of vaccines to prevent MenB disease, with increasing support through national immunization programs.

Meningococcal disease in adolescents and young adults: a review of the rationale for prevention through vaccination.

Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is characterized by high mortality and morbidity. While IMD incidence peaks in both infants and adolescents/young adults, carriage rates are often highest in the latter age groups, increasing IMD risk and the likelihood of transmission. Effective vaccines are available for 5 of 6 disease-causing serogroups. Because adolescents/young adults represent a significant proportion of cases, often have the highest carriage rate, and have characteristically low vaccination adherence, efforts should be focused on educating this population regarding long-term consequences of infection and the importance of meningococcal vaccination in prevention. This review describes the role of adolescents/young adults in meningococcal transmission and the clinical consequences and characteristics of IMD in this population. With a focus on countries with advanced economies that have specific meningococcal vaccination recommendations, the epidemiology of meningococcal disease and vaccination recommendations in adolescents/young adults will also be discussed.

Critical Role for Skin-Derived Migratory DCs and Langerhans Cells in TFH and GC Responses after Intradermal Immunization.

Intradermal delivery of antigen represents a potent route of immunization that involves multiple blood- and skin-derived dendritic cell subpopulations endowed with specialized functions and dynamics in their ability to prime naïve CD4+ T cells in the draining lymph nodes. However, their individual contributions to the generation of CD4+ T follicular helper (TFH) cells and germinal centers (GCs) remain to be understood. We found that intradermal immunization of mice with a particle-based vaccine induced robust TFH and germinal center B-cell responses in skin draining lymph nodes, which were completely abrogated when skin cell emigration was prevented. However, in this later condition, both lymph node-resident and blood-derived inflammatory cells access the antigen in the draining lymph nodes but are not able to induce TFH cell differentiation. Rather, only skin-derived dendritic cells up-regulated key genes related to TFH cell development in the draining lymph nodes. Depletion of Langerhans cells partially abrogated TFH and germinal center B-cell responses. Thus, after intradermal immunization, only skin-derived migratory dendritic cells, including Langerhans cells, permit the generation of TFH cells and germinal centers. Identifying the relative contributions of tissue and lymphoid organ dendritic cell subsets in generating humoral immune responses is of great importance for the development of tailored vaccines.