Literature review to identify evidence of secondary transmission of pentavalent human-bovine reassortant rotavirus vaccine (RV5) strains to unvaccinated subjects.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea in infants and young children. Live attenuated vaccines can lead to horizontal transmission with the risk of vaccine-derived disease in contacts. Transmission of pentavalent human-bovine reassortant rotavirus vaccine (RV5) strains leading to clinical disease was not well evaluated in the pivotal clinical trials, and only a few case reports have been described in the literature. METHODS: We performed a systematic literature review to investigate secondary transmission of RV5 strains to unvaccinated subjects globally. We searched Embase, Medline for English papers, CNKI, Wan Fang for Chinese papers, and other resources (i.e., conference papers with full text) from January 2005 to June 2021. Eligibility criteria for inclusion were original articles based on non-interventional studies (case-control studies, cohort studies, cross-sectional studies) using RV5 strain transmission as outcomes. Other study or publication types were excluded, such as pre-clinical studies, interventional studies and case reports. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used, and study quality was assessed using the Newcastle-Ottawa Scale (NOS) for cohort studies and the JBI checklist for cross-sectional studies to assess the risk of bias. RESULTS: The search generated 2,089 articles in total. Seven articles met all inclusion criteria, including six cohort studies and one cross-sectional study. All studies underwent quality assessment and complied with the quality criteria of the NOS or JBI checklist, respectively. Overall, none of the seven studies identified RV5 vaccine-type transmission to an unvaccinated population, in either hospitals or nurseries under a close contact environment. One study reported that 1% of unvaccinated infants had gastrointestinal symptoms, but all symptoms were attributed to other clinical conditions. CONCLUSIONS: We found no evidence of horizontal transmission of RV5 strains to unvaccinated infants in a context of a limited amount and the descriptive nature of the identified studies.

High coverage and adherence to dose intervals of the national school-based HPV vaccination program in Sweden during 2012-2019.

Background: Close monitoring of vaccination coverage is important for cervical cancer prevention efforts. The study aims to describe the HPV vaccination coverage by dose in girls eligible for HPV vaccination within Sweden's childhood immunization program and provide an estimate on dose timing compliance. Methods: Vaccination records between 2012 and March 2019 were obtained for girls born in 2000-2006 from the vaccination registers in Sweden. The mid-time population counts for the respective birth cohorts were taken as the denominator. Full-dose coverage and coverage with at least one dose of the vaccine were calculated within the two-dose and three-dose regimen, by region. Dose compliance was calculated within the two-dose regimen. Results: Vaccination coverage with at least one dose of the vaccine was >80% within birth cohorts 2001-2006. Full-dose coverage within a two-dose and three-dose regimen were 73.4% in birth cohorts 2004-2005, and 56.3% in birth cohorts 2000-2001, respectively. Little variation was observed in vaccination coverage between regions. Dose completion was 91.8%, and 72.8% in girls that initiated a two-dose and three-dose regimen, respectively. Among girls receiving a two-dose regimen, 93.0% received the second dose 6-12 months after dose one. Discussion: In conclusion, high levels of HPV vaccination coverage were observed with little variation between regions. Dose timing compliance was particularly high in the two-dose regimen. To fully benefit from the impact of HPV vaccination, it will be important to further push the vaccination coverage and reach the girls that do not or partially engage with HPV vaccination.

The burden of rotavirus-associated acute gastroenteritis in the elderly: assessment of the epidemiology in the context of universal childhood vaccination programs.

INTRODUCTION: Rotaviruses (RVs) cause acute gastroenteritis (AGE) in infants and young children worldwide and also in older adults (≥60 years), however the burden among this age group is not well understood. Herd immunity through pediatric RV vaccination may reduce the burden of RVGE across all ages, however the impact of pediatric vaccination on burden in older adults is poorly understood. AREAS COVERED: This systematic review was undertaken to identify studies related to the following objectives: understand the burden of RV in older adults, RV seroprevalence, and the impact of pediatric vaccination on this burden and highlight evidence gaps to guide future research. Of studies identified, 59 studies from two databases were included in this analysis following a review by two reviewers. EXPERT OPINION: RV is an understudied disease in older adults. We found that 0-62% of patients with AGE tested positive for RV, with results varying by setting, country, and patient age. Results also suggest that pediatric vaccination benefits older adults through herd protection. Several studies showed a reduction in RV incidence after vaccination. However, there was variety in results and lack of consistency in outcomes reported. Further studies targeting older adults are needed to better characterize RV burden.

Long-term surveillance of rotavirus vaccination after implementation of a national immunization program in Finland (2008-2018).

BACKGROUND: Rotavirus (RV) vaccination was included in the Finnish National immunization Program (NIP) in 2009. RotaTeq (RV5) has been used exclusively with a national average vaccination coverage rate (VCR) of > 90%. While previous studies have demonstrated that inpatient rotavirus gastroenteritis (RVGE) admissions declined by as much as 96% in Finnish children ≤ 5 years old following RV vaccination introduction, no study has evaluated long-term protection after vaccination in Finland. In this study, we analyze incidence of hospital outpatient visits and inpatient admissions of gastroenteritis in children up to 7 years of age. METHODS: We first describe the incidence of RVGE, viral gastroenteritis (VGE), and acute gastroenteritis (AGE) for all Finnish children born during 2008-2011. Children were stratified by the year of birth into not-eligible, partially eligible and rotavirus vaccine-eligible (born in 2008, 2009, 2010 and 2011, respectively). Hospital inpatient and outpatient data was collected from the National Care Register for all children from birth until December 31st, 2018. We also studied RVGE incidence during 2014-2017 for children<3 years of age in municipalities with VCRs of 90% and above and municipalities with VCRs below 90%. RESULTS: RVGE incidence decreased significantly soon after implementation of RV vaccination in the NIP. In vaccine-eligible cohorts, no clear peak incidence in the youngest age groups could be observed, and no RVGE cases were observed beyond 6 years after vaccination, in contrast to vaccine ineligible and partially eligible cohorts. Despite an overall high VCR in Finland, regions with high VCR had lower incidence of RVGE than regions with lower VCR. CONCLUSION: Incidence of RVGE has remained low in all age groups during the 10 years following introduction of RV vaccine in the Finnish NIP. Differences in RVGE incidence were observed in regions with high as compared with lower VCR, highlighting the importance of maintaining high vaccination coverage.

Impact of a vaccination programme in children vaccinated with ProQuad, and ProQuad-specific effectiveness against varicella in the Veneto region of Italy.

BACKGROUND: Monovalent varicella vaccines have been available in the Veneto Region of Italy since 2004. In 2006, a single vaccine dose was added to the immunisation calendar for children aged 14 months. ProQuad®, a quadrivalent measles-mumps-rubella-varicella vaccine, was introduced in May 2007 and used, among other varicella vaccines, until October 2008. This study aimed to evaluate the effectiveness of a single dose of ProQuad, and the population impact of a vaccination program (VP) against varicella of any severity in children who received a first dose of ProQuad at 14 months of age in the Veneto Region, METHODS: All children born in 2006/2007, i.e., eligible for varicella vaccination after ProQuad was introduced, were retrospectively followed through individual-level data linkage between the Pedianet database (varicella cases) and the Regional Immunization Database (vaccination status). The direct effectiveness of ProQuad was estimated as the incidence rate of varicella in ProQuad-vaccinated children aged < 6 years compared to children with no varicella vaccination from the same birth cohort. The impact of the VP on varicella was measured by comparing children eligible for the VP to an unvaccinated historical cohort from 1997/1998. The vaccine impact measures were: total effect (the combined effect of ProQuad vaccination and being covered by the Veneto VP); indirect effect (the effect of the VP on unvaccinated individuals); and overall effect (the effect of the VP on varicella in the entire population of the Veneto Region, regardless of their vaccination status). RESULTS: The adjusted direct effectiveness of ProQuad was 94%. The vaccine impact measures total, indirect, and overall effect were 97%, 43%, and 90%, respectively. CONCLUSIONS: These are the first results on the effectiveness and impact of ProQuad against varicella; data confirmed its high effectiveness, based on immunological correlates for protection. Direct effectiveness is our only ProQuad-specific measure; all impact measures refer at least partially to the VP and should be interpreted in the context of high vaccine coverage and the use of various varicella vaccines in this region. The Veneto Region offered a unique opportunity for this study due to an individual data linkage between Pedianet and the Regional Immunization database.

Estimation of the burden of varicella in Europe before the introduction of universal childhood immunization.

BACKGROUND: Varicella is generally considered a mild disease. Disease burden is not well known and country-level estimation is challenging. As varicella disease is not notifiable, notification criteria and rates vary between countries. In general, existing surveillance systems do not capture cases that do not seek medical care, and most are affected by underreporting and underascertainment. We aimed to estimate the overall varicella disease burden in Europe to provide critical information to support decision-making regarding varicella vaccination. METHODS: We conducted a systematic literature review to identify all available epidemiological data on varicella IgG antibody seroprevalence, primary care and hospitalisation incidence, and mortality. We then developed methods to estimate age-specific varicella incidence and annual number of cases by different levels of severity (cases in the community, health care seekers in primary care and hospitals, and deaths) for all countries belonging to the European Medicines Agency (EMA) region and Switzerland. RESULTS: In the absence of universal varicella immunization, the burden of varicella would be substantial with a total of 5.5 million (95% CI: 4.7-6.4) varicella cases occurring annually across Europe. Variation exists between countries but overall the majority of cases (3 million; 95% CI: 2.7-3.3) would occur in children <5 years. Annually, 3-3.9 million patients would consult a primary care physician, 18,200-23,500 patients would be hospitalised, and 80 varicella-related deaths would occur (95% CI: 19-822). CONCLUSIONS: Varicella disease burden is substantial. Most cases occur in children <5 years old but adults require hospitalisation more often and are at higher risk of death. This information should be considered when planning and evaluating varicella control strategies. A better understanding of the driving factors of country-specific differences in varicella transmission and health care utilization is needed. Improving and standardizing varicella surveillance in Europe, as initiated by the European Centre for Disease Prevention and Control (ECDC), is important to improve data quality to facilitate inter-country comparison.

Estimation of the overall burden of cancers, precancerous lesions, and genital warts attributable to 9-valent HPV vaccine types in women and men in Europe.

BACKGROUND: In addition to cervical cancer, human papillomavirus (HPV) is responsible for a significant proportion of cancers and precancerous lesions of the vulva, vagina, anus, penis, head and neck, as well as genital warts. We estimated the annual number of new cases of these diseases attributable to 9-valent HPV vaccine types in women and men in Europe. METHODS: The annual number of new cancers of the cervix, vulva, vagina, anus, penis, and selected head and neck sites in the population of the European Medicines Agency territory was estimated based on age-specific incidence rates extracted from Cancer Incidence in 5 Continents, Volume X and Eurostat population data for 2015. The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated by applying the HPV attributable fraction from reference publications based on a large European multicenter study. For non-cervical cancers, HPV attributable fractions were based on oncogenically-active HPV infections only (i.e., detection of HPV DNA and either mRNA and/or p16 positivity). For precancerous lesions of the cervix, vulva, vagina, and anus, and for genital warts, previously published estimations were updated for the 2015 population. RESULTS: The annual number of new cancers attributable to 9-valent HPV vaccine types was estimated at 47,992 (95% bound: 39,785-58,511). Cervical cancer showed the highest burden (31,130 cases), followed by head and neck cancer (6,786 cases), anal cancer (6,137 cases), vulvar cancer (1,466 cases), vaginal cancer (1,360 cases), and penile cancer (1,113 cases). About 81% were estimated to occur in women and 19% in men. The annual number of new precancerous lesions (CIN2+, VIN2/3, VaIN2/3, and AIN2/3) and genital warts attributable to 9-valent HPV vaccine types was estimated at 232,103 to 442,347 and 680,344 to 844,391, respectively. CONCLUSIONS: The burden of cancers associated with 9-valent HPV vaccine types in Europe is substantial in both sexes. Head and neck cancers constitute a heavy burden, particularly in men. Overall, about 90% of HPV-related cancers, 80% of precancerous lesions, and 90% of genital warts are expected to be attributable to 9-valent HPV vaccine types each year, demonstrating the important preventive potential of the 9-valent HPV vaccine in Europe.

Sustained High Effectiveness of RotaTeq on Hospitalizations Attributable to Rotavirus-Associated Gastroenteritis During 4 Years in Finland.

KEY POINTS: The effectiveness of pentavalent rotavirus vaccine against rotavirus-associated hospitalization was more than 90% 4 years after introduction into the national immunization program in Finland. A major impact on hospitalization for all-cause gastroenteritis was observed also. BACKGROUND: Rotavirus vaccination with exclusive use of RotaTeq was added to the National Immunization Programme (NIP) of Finland in September 2009. The objective of our study was to estimate the effectiveness and impact of RotaTeq after 4 years of follow-up. METHODS: Between 2009 and 2013, we conducted a prospective surveillance study of children aged <16 years with acute gastroenteritis (AGE) and admitted in 2 hospitals in Finland. Rotavirus and other gastroenteritis viruses were detected in stool samples by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assays. The effectiveness of RotaTeq was investigated by using a case-control design; wild-type rotavirus-positive children were classified as "cases" and rotavirus-negative children as "controls." Hospital discharge records were used to estimate the impact of RotaTeq on rotavirus-associated AGE (RV-AGE) and all-cause AGE (AC-AGE) hospitalizations of age-eligible children in the NIP by comparing the prevaccination (2001-2006) and post-NIP seasons (2009-2013). RESULTS: The crude estimate of the effectiveness of RotaTeq to prevent RV-AGE hospitalization in NIP age-eligible children was 94.4% (95% confidence interval, 79.8%-98.4%). No change in prevalent wild-type rotavirus genotypes was observed. Vaccine-derived rotaviruses were detected in 8% of the children with RV-AGE, with a probable causal association in 2 children. Hospital discharge records revealed that RV-AGE and AC-AGE hospitalizations in children aged <16 years decreased in the two post-NIP seasons by 79% and 58%, respectively, compared to those in the prevaccination seasons. CONCLUSIONS: Over 4 years of follow-up, high rotavirus vaccine coverage in the NIP (>95%) has led to a major reduction in RV-AGE and AC-AGE hospitalizations without a resurgence of rotavirus activity. However, rotavirus continues to circulate in older unvaccinated children.

Hospital bed occupancy for rotavirus and all cause acute gastroenteritis in two Finnish hospitals before and after the implementation of the national rotavirus vaccination program with RotaTeq®.

BACKGROUND: Vaccination-impact studies of the live-attenuated pentavalent oral vaccine Rotateq® have demonstrated that the burden of rotavirus gastroenteritis has been reduced significantly after the introduction of RotaTeq® vaccination, but less is known about the benefit of this vaccination on hospital overcrowding. METHODS: As part of an observational surveillance conducted during the RV seasons 2000/2001 to 2011/2012, we analysed hospital discharge data collected retrospectively from two Finnish hospitals (Oulu and Tampere), concerning ICD 10 codes A00-09 (acute gastroenteritis, AGE) and A08.0 (rotaviral acute gastroenteritis RV AGE). We estimated the reduction in the number of beds occupied and analysed the bed occupancy rate, for RV AGE and all cause AGE, among 0-16 year-old children, before and after the implementation of the RV immunisation program. RESULTS: The rate of bed days occupied for RV AGE was reduced by 86% (95% CI 66%-94%) in Tampere and 79% (95% CI 47%-92%) in Oulu after RV vaccination implementation. For all cause AGE, reduction was 50% (95% CI 29% to 65%) in Tampere and 70% (95% CI 58% to 79%) in Oulu. Results were similar among 0-2 year-old children. This effect was also observed on overcrowding in both hospitals, with a bed occupancy rate for all cause AGE >25% in only 1% of the time in Tampere and 9% in Oulu after the implementation of the immunisation program, compared to 13% and 48% in the pre-vaccination period respectively. After extrapolation to the whole country, the annual number of prevented hospitalizations for all cause AGE in the post-vaccination period in Finland was estimated at 1,646 and 2,303 admissions for 0-2 and 0-16 year-old children respectively. CONCLUSIONS: This study demonstrated that universal RV vaccination is associated with a clear decrease in the number of bed days and occupancy rates for RV AGE and all cause AGE. Positive consequences include increase in quality of care and a better healthcare management during winter epidemics.

Factors associated with early adherence to tiotropium in chronic obstructive pulmonary disease.

Tiotropium is an innovative intervention in chronic obstructive pulmonary disease (COPD). Early adherence to tiotropium remains inadequately explored, notably time from initiation to discontinuation (persistence). In patients with COPD, the factors associated with the risk of discontinuing the treatment with tiotropium within 12 months following initiation were identified (12-month persistence). Claim databases from the French Social Security were used. A random sample of patients (aged 50-80 years) who initiated tiotropium soon after launch was selected. Factors associated with the persistence were investigated (Log-rank test and multivariate Cox model). Of the 1147 newly treated patients (mean age 68 years, 33% women), 64% remained in the treatment of tiotropium for over a period of 12 months following initiation. More than 10% of the patients interrupted therapy after a single dispensing, most often those with mild COPD. Lower risks of discontinuing tiotropium within 12 months following initiation were observed when it was initiated by a private sector specialist (hazard ratio (HR) = 0.65, 95% confidence interval (CI) = (0.52-0.82)), by hospital-based physician (HR = 0.58, 95% CI = (0.42-0.78)), when ≥ 2 other respiratory drugs were associated (HR = 0.74, 95% CI = (0.58-0.95)) and in case of long-term disease status (HR = 0.78, 95% CI = (0.63-0.97)). Conversely, no clear effect appeared according to age or gender. In this population of patients with COPD, fewer early discontinuations of tiotropium were observed in patients having a severe condition.

Estimation of the epidemiological burden of human papillomavirus-related cancers and non-malignant diseases in men in Europe: a review.

BACKGROUND: The role of human papillomavirus (HPV) in malignant and non-malignant genital diseases in women is well known and the corresponding epidemiological burden has been widely described. However, less is known about the role of HPV in anal, penile and head and neck cancer, and the burden of malignant and non-malignant HPV-related diseases in men. The objective of this review is to estimate the epidemiological burden of HPV-related cancers and non-malignant diseases in men in Europe. METHODS: The annual number of new HPV-related cancers in men in Europe was estimated using Eurostat population data and applying cancer incidence rates published by the International Agency for Research on Cancer. The number of cancer cases attributable to HPV, and specifically to HPV16/18, was calculated based on the most relevant prevalence estimates. The annual number of new cases of genital warts was calculated from the most robust European studies; and latest HPV6/11 prevalence estimates were then applied. A literature review was also performed to retrieve exhaustive data on HPV infection at all anatomical sites under study, as well as incidence and prevalence of external genital warts, recurrent respiratory papillomatosis and HPV-related cancer trends in men in Europe. RESULTS: A total of 72, 694 new cancer cases at HPV-related anatomical sites were estimated to occur each year in men in Europe. 17,403 of these cancer cases could be attributable to HPV, with 15,497 of them specifically attributable to HPV16/18. In addition, between 286,682 and 325,722 new cases of genital warts attributable to HPV6/11were estimated to occur annually in men in Europe. CONCLUSIONS: The overall estimated epidemiological burden of HPV-related cancers and non-malignant diseases is high in men in Europe. Approximately 30% of all new cancer cases attributable to HPV16/18 that occur yearly in Europe were estimated to occur in men. As in women, the vast majority of HPV-positive cancer in men is related to HPV16/18, while almost all HPV-related non-malignant diseases are due to HPV6/11. A substantial number of these malignant and non-malignant diseases may potentially be prevented by quadrivalent HPV vaccination.

Viral and bacterial pathogens identification in children hospitalised for severe pneumonia and parapneumonic empyema.

Pneumonia is caused by respiratory bacteria and/or viruses. Little is known if co-infections are an aggravating factor in hospitalised children with severe pneumonia. We studied the impact of respiratory pathogens on the severity of pneumonia. Between 2007 and 2009, 52 children hospitalised with a well-documented diagnosis of community-acquired pneumonia (CAP), with or without parapneumonic empyema (PPE), were enrolled in the study. The patients were classified into 2 groups: CAP + PPE (n = 28) and CAP (n = 24). The identification of respiratory viruses and bacteria in nasopharyngeal aspirates and pleural effusion samples were performed using conventional bacterial techniques and molecular assays. Using real-time multiplex PCR and antigen detection, Streptococcus pneumoniae was the main agent identified in 76% of the cases by molecular tests and BinaxNOW® in pleural fluid. A total of 8% of pleural fluid samples remained undiagnosed. In nasopharyngeal aspirates, rhinovirus, parainfluenza viruses, human metapneumovirus, and respiratory syncytial virus were detected in both CAP and CAP + PPE populations; however, the percentage of viral co-detection was significantly higher in nasopharyngeal aspirates from CAP + PPE patients (35%) compared with CAP patients (5%). In conclusion, viral co-detection was observed mainly in patients with more severe pneumonia. Molecular biology assays improved the pathogens detection in pneumonia and confirmed the S. pneumoniae detection by BinaxNOW® in pleural effusion samples. Interestingly, the main S. pneumoniae serotypes found in PPE are not the ones targeted by the heptavalent pneumococcal conjugate vaccine.