Impact of five years of rotavirus vaccination in Finland – And the associated cost savings in secondary healthcare

IntroductionThis study aimed to estimate the impact of the national rotavirus (RV) vaccination programme, starting 2009, on the total hospital-treated acute gastroenteritis (AGE) and severe RV disease burden in Finland during the first five years of the programme. This study also evaluated the costs saved in secondary healthcare by the RV vaccination programme.MethodsThe RV related outcome definitions were based on ICD10 diagnostic codes recorded in the Care Register for Health Care. Incidences of hospitalised and hospital outpatient cases of AGE (A00-A09, R11) and RVGE (A08.0) were compared prior (1999–2005) and after (2010–2014) the start of the programme among children less than five years of age.ResultsThe reduction in disease burden in 2014, when all children under five years of age have been eligible for RV vaccination, was 92.9% (95%CI: 91.0%–94.5%) in hospitalised RVGE and 68.5% (66.6%–70.3%) in the total hospitalised AGE among children less than five years of age. For the corresponding hospital outpatient cases, there was a reduction of 91.4% (82.4%–96.6%) in the RVGE incidence, but an increase of 6.3% (2.7%–9.9%) in the AGE incidence. The RV vaccination programme prevented 2206 secondary healthcare AGE cases costing €4.5 million annually. As the RV immunisation costs were €2.3 million, the total net savings just in secondary healthcare costs were €2.2 million, i.e. €33 per vaccinated child.DiscussionThe RV vaccination programme clearly controlled the severe, hospital-treated forms of RVGE. The total disease burden is a more valuable end point than mere specifically diagnosed cases as laboratory confirmation practises usually change after vaccine introduction. The RV vaccination programme annually pays for itself at least two times over.     

Reduction in HPV 16/18 prevalence in sexually active young women following the introduction of HPV immunisation in England

Background

Reduction in the prevalence of vaccine type HPV infection in young women is an early indication of the impact of the HPV immunisation programme and a necessary outcome if the subsequent impact on cervical cancer is to be realised.

Methods

Residual vulva-vaginal swab (VVS) specimens from young women aged 16–24 years undergoing chlamydia screening in community sexual health services (formerly known as family planning clinics), general practice (GP), and youth clinics in 2010–2012 were submitted from 10 laboratories in seven regions around England. These specimens were linked to demographic and sexual behaviour data reported with the chlamydia test, anonymised, and tested for type-specific HPV DNA using a multiplex PCR and Luminex-based genotyping test. Estimated immunisation coverage was calculated and findings were compared to a baseline survey conducted prior to the introduction of HPV immunisation in 2008.

Results

A total of 4664 eligible specimens were collected and 4178 had a valid test result. The post-immunisation prevalence of HPV 16/18 infection was lowest in this youngest age group (16–18 years) and increased with age. This increase with age was a reversal of the pattern seen prior to immunisation and was inversely associated with estimates of age-specific immunisation coverage (65% for 16–18 year olds). The prevalence of HPV 16/18 infection in the post-immunisation survey was 6.5% amongst 16–18 year olds, compared to 19.1% in the similar survey conducted prior to the introduction of HPV immunisation.

Conclusions

These findings are the first indication that the national HPV immunisation programme is successfully preventing HPV 16/18 infection in sexually active young women in England. The reductions seen suggest, for the estimated coverage, high vaccine effectiveness and some herd-protection benefits. Continued surveillance is needed to determine the effects of immunisation on non-vaccine HPV types.     

Acute gastroenteritis hospitalizations after implementation of universal mass vaccination against rotavirus

BackgroundEstonia implemented rotavirus universal mass vaccination (RV UMV) in July 2014. We aimed to describe changes in acute gastroenteritis (AGE) hospitalization during RV seasons before (2007–2013) and after (2015–2018) RV UMV and compare patient profile of hospitalized AGE patients aged 0–18 years during first two consecutive RV seasons 2015 vs 2016.MethodsWe described AGE hospitalization patterns pre-and post-vaccine era using Estonian Health Insurance Fund (HIF) database. During a two-year observational multicenter study in seven Estonian hospitals from 01st of February 2015 to 30th August 2016 we assessed patient profile of all patients who met pre-determined AGE criteria.ResultsIn post-vaccine era AGE hospitalization rate decreased from 10 to 8 per 1000 population (RR 0.81, 95% CI 0.79–0.83) compared to pre-vaccine era. Decreased RV seasonal activity, 81% (95% CI 77–84) and 55% (95% CI 52–58) reduction of rotavirus gastroenteritis (RVGE) hospitalization among age groups <1 and 1–4, respectively and upsurge of norovirus gastroenteritis (NoVGE) hospitalizations (RR = 1.8; 95% CI 1.6–1.9) was seen.In the multicenter observational study, among 2249 AGE patients hospitalized median age of RVGE patients increased from 2 to 3 years (p < 0.01) and duration of hospital stay decreased among RVGE, NoVGE and other GE patients during two consecutive RV seasons. According to Vesikari Clinical Severity Scoring System statistically significant change of severity score distribution in two RV seasons was seen (p < 0.001) with trend towards less severe AGE hospitalizations; 82.5% vs 70.5% severe cases in 2015 vs 2016, respectively.ConclusionRV UMV lead to immediate and sustainable reduction of hospitalizations due to RVGE in children aged <4 years and reduction of overall AGE accompanied with the decrease in the severity of hospitalized children.     

Effectiveness and cost-effectiveness of pediatric rotavirus vaccination in British Columbia: A model-based evaluation

Background

Rotavirus gastroenteritis (RVGE) is associated with widespread morbidity and mortality in children worldwide. In high-income countries, including Canada, the burden of RVGE relates largely to morbidity and healthcare utilization. Two live rotavirus vaccines (RotaTeq^® (Merck Frosst Canada Ltd.) and Rotarix™ (GlaxoSmithKline Inc.)), are now approved for use in Canada, but their economic attractiveness has not been evaluated in the Canadian context.

Methods

We performed a model-based economic analysis using a Markov chain Monte Carlo simulation of RVGE in populations of British Columbia children. Models were parameterized based on best available data on disease natural history and epidemiology, vaccine effectiveness and cost, and healthcare costs, and calibrated such that projections of healthcare utilization and vaccine coverage closely matched empirical estimates. Robustness of projections was evaluated in deterministic and probabilistic sensitivity analyses.

Results

Based on the best available data, childhood immunization against RVGE was projected to prevent 63–81 infections per 100 children vaccinated, and to prevent substantial numbers of outpatient medical visits. It was projected that either vaccine would prevent 1–2 hospitalizations per 100 children immunized. Vaccination was projected to increase healthcare costs: immunization with Rotarix™ would prevent incident infections at a cost of approximately $10 per infection prevented or $2400 per quality-adjusted life-year gained. Vaccination with RotaTeq™ would be more costly and less effective and would not be preferred. Projections were robust in the face of wide-ranging sensitivity analyses.

Interpretation

The use of currently available vaccines against RVGE in British Columbia children is projected to result in a substantial reduction in the burden of illness and healthcare utilization associated with RVGE, with a modest increase in healthcare costs. RVGE vaccination should be considered “highly cost-effective” relative to other commonly available health interventions.     

Burden of rotavirus gastroenteritis and distribution of rotavirus strains in Asia: a systematic review

Background

Rotavirus is the leading cause of severe diarrhea in children worldwide. We systematically reviewed the burden of rotavirus gastroenteritis (RVGE) and distribution of rotavirus strains in Asia.

Methods

We searched MEDLINE, EMBASE and the World Health Organization (WHO) website for the term “rotavirus” and the name of each country. We included studies that were conducted in children between 2000 and 2011 and that examined the epidemiology, health and/or economic burden of RVGE, and G and P-type distribution in Eastern, South East, Southern and Central Asia. Random effects models were used to pool the proportions of RVGE. We also estimated child mortality due to RVGE using the updated WHO and United Nations Children's Fund's mortality estimates in 2008.

Results

The search identified 113 eligible articles. The incidence rates of rotavirus-related hospitalizations in children under 5 years of age ranged from 2.1 to 20.0 cases per 1000 children per year with the highest rates reported in Bangladesh, South Korea, Taiwan, Thailand, and Vietnam. Rotavirus accounted for 37.5% of year-round hospitalized gastroenteritis cases, with higher proportions reported in South East Asia. Rotavirus was associated with approximately 145,000 deaths every year in Asia, with the greatest numbers occurring in India, Pakistan, and Indonesia. The highest annual societal costs of treating RVGE were reported in China (US$365 million), followed by Japan (US$254 million) and India (US$41–72 million). A diversity of rotavirus G and P-types was observed across Asia and the distribution of strains differed by country and year. The most common strains were G1P[8] (23.6%), G2P[4] (11.8%), G3P[8] (18.9%), and G9P[8] (7.4%).

Conclusions

Rotavirus is associated with substantial hospitalizations and deaths among children and causes large healthcare expenditures throughout Asia. Safe and effective rotavirus vaccines could substantially reduce the burden of disease.     

Changes in meningococcal C epidemiology and vaccine effectiveness after vaccine introduction and schedule modification

Purpose

Meningococcal C conjugate vaccine was included in December 2000 in the Spanish childhood vaccination at 2, 4 and 6 months of age. In 2006, routine vaccination was modified to two doses at 2 and 4–6 months and a booster dose during the second year of age. Additionally, successive catch-up campaigns were launched to extend protection to older groups. This study provides long-term information about the vaccine effectiveness (VE) and the impact of vaccination in meningococcal C disease epidemiology in Spain.

Methods

We assessed surveillance data from season 1996/97 to season 2012/13 to describe changes in incidence and lethality of the disease. The vaccine-effectiveness study covered all cases notified from January 1st of 2001 onwards and evaluated vaccine effectiveness in both routines and in catch-up campaigns. To investigate the decline in protection over time, we compared the vaccine effectiveness within 1 year and more than one year since vaccination.

Results

The incidence of meningococcal serogroup C disease decreased first in those age-groups targeted for vaccination. But after 2006/07 season the decrease in incidence was generalised. Vaccine effectiveness was high in all vaccination programmes, although 2, 4–6 months (+ booster dose) routine showed higher overall vaccine effectiveness than 2, 4 and 6 months routine (99.3% vs. 90.2%). VE >1 year since vaccination was lower in 2, 4 and 6 months compared to 2 and 4–6 months (+ booster) routine (81.4% vs. 89.1%). For catch-up campaigns, VE increased and loss of VE decreased with the age of administration. Overall VE was 94.83 (CI95%: 93.37, 95.97), 98.82 (CI95%: 97.96, 99.31) and 90.89 (CI95%: 87.79, 93.21) for ≤1 and >1 year since vaccination, respectively.

Conclusions

The meningococcal C conjugate vaccination programme has been extremely successful in controlling the disease and continues to be evaluated and adapted to the changes in the epidemiology of the disease to ensure long-term vaccine protection.     

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

BackgroundRotavirus (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.MethodsWe 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%.ResultsRVGE 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.ConclusionIncidence 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.     

Intussusception incidence among infants in the UK and Republic of Ireland: A pre-rotavirus vaccine prospective surveillance study

Introduction

Intussusception, an abdominal emergency in young children, has been linked to a previous vaccine used to prevent rotavirus gastroenteritis. Although this vaccine was withdrawn, recent studies have suggested a potential, very small increased risk of intussusception following the administration of newly developed rotavirus vaccines. We aimed to determine the baseline incidence of intussusception among infants in the UK and Republic of Ireland – prior to the imminent introduction of the rotavirus vaccine into the UK schedule this year.

Methods

Prospective, active surveillance via the established British Paediatric Surveillance Unit (BPSU) was carried out from March 2008 to March 2009. Clinicians across 101 National Health Service (and equivalent) hospitals, including 27 paediatric surgical centres, reported cases admitted for intussusception in the UK and Republic of Ireland. The standard Brighton Collaboration case definition was used with only definite cases included for incidence estimation.

Results

The study response rate was 94.5% (379 questionnaires received out of 401 case notifications). A total of 250 definite cases of intussusception were identified. The annual incidence among infants in the UK and Republic of Ireland was 24.8 (95% CI: 21.7–28.2) and 24.2 (95% CI: 15.0–37.0) per 100,000 live births. In the UK, the highest incidence occurred in Northern Ireland (40.6, 95% CI: 21.0–70.8), followed by Scotland (28.7, 95% CI: 17.5–44.3), England (24.2, 95% CI: 20.9–27.9), then Wales (16.9, 95% CI: 6.8–34.8). In England, regional incidence was highest in London and lowest in the West Midlands. By age, the highest incidence (50.3/100,000 live births, 95% CI: 33.4–72.7) occurred in the fifth month of life (for England). A seasonal trend in the presentation of intussusception was observed with the incidence significantly (p = 0.001) increased during winter and spring.

Conclusion

The baseline rates obtained in this study will inform rotavirus vaccine-safety policy by enabling comparison with post-introduction incidence.     

Seroprevalence of IgG antibodies to pertussis toxin in children and adolescents in Estonia

Background and aims

Despite high immunisation coverage and frequent booster doses, the national notification rates of pertussis in Estonia have been increasing. The peak of 97/100,000 was reached in 2010 which is the highest incidence rate since 1962 (210/100,000).We aimed to measure the prevalence of pertussis toxin (PT) IgG type antibodies in subjects of <18 years and to estimate the pertussis infection activity in a recently non-immunised cohort.

Methods

In a cross-sectional serosurvey, all consecutive leftover sera were collected in the Tartu University Hospital during April–August 2012. Anti-PT IgG concentration was measured by commercial ELISA and analysed in yearly cohorts. The antibody concentrations ≥62.5 IU/mL was considered suggestive to pertussis in the last year among 9- to 14-year-olds.

Results

The GMC of the anti-PT-IgG was 7.4 IU/mL (95% CI 6.9–8.0). In the total of 1053 serum samples, the highest proportion of sera with high antibody titres ≥125 IU/mL and ≥62.5 IU/mL were at the ages when pertussis vaccine boosters were given: 7 years 10.9% (95% CI 4.1–22.3) and 2 years 36.9% (95% CI 25.3–49.8), respectively. Approximately half of all sera had undetectable anti-PT IgG levels. The estimated incidence of Bordetella pertussis infection among 9- to 14-year-olds in the year before serum sampling was 6.3% (95% CI 3.3–10.8), which is at least 60 times higher than the officially reported incidence of pertussis disease in respective years.

Conclusions

The serologic method is not suitable for diagnosing pertussis in instances when the last pertussis immunisation was less than one year ago. The relatively high proportion of subjects with undetectable anti-PT IgG levels and the relatively low rate of officially reported pertussis cases suggest that low antibody levels do not necessarily indicate the absence of protection. The estimated incidence rate of pertussis is much higher than officially reported figures, which suggests that asymptomatic/mild B. pertussis infection remains unrecognised and unreported.     

Effectiveness of the monovalent rotavirus vaccine in Colombia: A case-control study

Objective

To assess the effectiveness of the monovalent rotavirus vaccine (RV1) to prevent rotavirus diarrhea admissions to emergency departments (ED) in Colombia.

Methods

A multicenter case-control study was carried out in six Colombian cities from 2011 to January, 2013. Cases were laboratory confirmed rotavirus diarrhea patients admitted to ED of selected health centers. Controls were patients with non-rotavirus diarrhea. Vaccination status was card-confirmed. Vaccine effectiveness and 95% confidence intervals (CI) were calculated from the conditional logistic regression models using the formula 1 − adjusted odds ratio × 100.

Results

1051 fecal samples were collected from 193 cases and 858 controls. Vaccination history was confirmed on 173 cases (90%) and 801 controls (93%). Among the rotavirus-positive samples with vaccination history, 57% were G2P[4], 9.8% G9P[8], 6% G9P[6]. Median age of cases (17 months) was greater than controls (15 months) (P < 0.001), and mothers of cases had lower level of education (P = 0.025). The adjusted effectiveness was 79.19% (95% CI, 23.7 to 94.32) among children 6–11 months of age and −39.75% (95% CI, −270.67 to 47.24) among those >12 months of age. Against overnight rotavirus hospitalizations, RV1 provided protection of 84.42% (95% CI, 22.68 to 96.86) among children 6–11 months of age, and −79.49% (95% CI, −555.8 to 51.08) among those >12 months.

Conclusions

RV1 provided significant protection against rotavirus hospitalization among children under 1 year of age in the Colombian setting. The observation of lower effectiveness in children >12 months requires further assessment.     

Success of rotavirus vaccination in Finland,a register based study measuring impact beyond overall effectiveness

IntroductionEven with vaccines available since 2006, rotavirus continues to be a major cause of acute gastroenteritis globally in children under 5 years old. Finland introduced the rotavirus vaccine to its national vaccination programme in 2009. Since then hospitalizations due to gastroenteritis caused by rotavirus (RVGE) and of all causes (AGE) have been reduced significantly in young children.MethodsWe performed a retrospective analysis of data from register databases consisting of over 200 000 children aged 0.5-2 years. Children born before rotavirus vaccines were available (2002, 2003) and after the implementation of rotavirus vaccination programme (2014, 2015) were followed for episodes of acute infectious gastroenteritis. We calculated the incidences of hospital outpatient and inpatient episodes and used individual vaccination records to estimate the overall, total, direct and indirect vaccine effect (VE %).ResultsAmong children born in 2014 and 2015, there was a 96% reduction in inpatient RVGE episodes and a 78% reduction in episodes of inpatient AGE compared to the pre-vaccination era, comprising the overall VE. Direct effectiveness was 96% and 53% for RVGE and AGE respectively. Herd effect i.e. indirect protection was estimated to be 67% against inpatient RVGE and 56% against inpatient AGE. Protection acquired by the vaccinated children when compared to pre vaccination era i.e. the total VE was 99% for inpatient RVGE and 79% for inpatient AGE.ConclusionsAlthough overall incidences for every disease type studied were reduced, rotavirus is still circulating with seasonality and there is a slight shift of disease towards the older age groups. Together with changes observed in the distribution of rotavirus genotypes, our results indicate that continuous monitoring is still necessary.     

Relationship between peri-operative outcomes and hospital surgical volume of total hip arthroplasty in Japan

Background

This study aimed to evaluate the relationship between peri-operative complication of total hip arthroplasty (THA) and hospital surgical volume.

Methods

We reviewed discharge administrative data from 8321 patients who underwent primary THA between July and December 2008. Relationships between complications and surgical volume were analyzed with multivariate logistic regression models including age, sex, and Charlson comorbidity index. Hospitals were categorized into four groups according to the 6-month volume of THA procedures.

Results

The most frequent complication was dislocation (1.41%). Next was infection (1.24%). Fracture and pulmonary embolism occurred in less than 1% of procedures. Patients who underwent THA in hospitals with the highest surgical volume had lower risk of dislocation and infection than those treated in the hospitals with the lowest surgical volume (odds ratio [OR] 0.321, 95% confidence interval [CI] 0.167–0.572 and OR 0.123, 95% CI 0.020–0.421). Patients aged 65 years and older were associated with increased risk of dislocation (OR 2.342, CI 1.555–3.624) and fracture (OR 2.799, CI 1.372–6.301). Females demonstrated lower risk of dislocation (OR 0.558, CI 0.352–0.869) and infection (OR 0.560, CI 0.365–0.882).

Conclusion

These results indicated that the increase in the risk of peri-operative dislocation of primary THA may be associated with low hospital surgical volume as well as age and male sex.     

Predictors of Rehospitalization Among Elderly Patients Admitted to a Rehabilitation Hospital: The Role of Polypharmacy,Functional Status,and Length of Stay

Objectives

Rehospitalizations for elderly patients are an increasing health care burden. Nonetheless, we have limited information on unplanned rehospitalizations and the related risk factors in elderly patients admitted to in-hospital rehabilitation facilities after an acute hospitalization.

Setting

In-hospital rehabilitation and aged care unit.

Design

Retrospective cohort study.

Participants

Elderly patients 65 years or older admitted to an in-hospital rehabilitation hospital after an acute hospitalization between January 2004 and June 2011.

Measurements

The rate of 30-day unplanned rehospitalization to hospitals was recorded. Risk factors for unplanned rehospitalization were evaluated at rehabilitation admission: age, comorbidity, serum albumin, number of drugs, decline in functional status, delirium, Mini Mental State Examination score, and length of stay in the acute hospital. A multivariable Cox proportional regression model was used to identify the effect of these risk factors for time to event within the 30-day follow-up.

Results

Among 2735 patients, with a median age of 80 years (interquartile range 74–85), 98 (4%) were rehospitalized within 30 days. Independent predictors of 30-day unplanned rehospitalization were the use of 7 or more drugs (hazard ratio [HR], 3.94; 95% confidence interval, 1.62–9.54; P = .002) and a significant decline in functional status (56 points or more at the Barthel Index) compared with the month before hospital admission (HR 2.67, 95% CI: 1.35–5.27; P = .005). Additionally, a length of stay in the acute hospital of 13 days or more carried a twofold higher risk of rehospitalization (HR 2.67, 95% CI: 1.39–5.10); P = .003).

Conclusions

The rate of unplanned rehospitalization was low in this study. Polypharmacy, a significant worsening of functional status compared with the month before acute hospital admission, and hospital length of stay are important risk factors.     

Estimating rotavirus gastroenteritis hospitalisations by using hospital episode statistics before and after the introduction of rotavirus vaccine in Australia

Introduction

Hospital discharge records and laboratory data have shown a substantial early impact from the rotavirus vaccination program that commenced in 2007 in Australia. However, these assessments are affected by the validity and reliability of hospital discharge coding and stool testing to measure the true incidence of hospitalised disease. The aim of this study was to assess the validity of these data sources for disease estimation, both before and after, vaccine introduction.

Methods

All hospitalisations at a major paediatric centre in children aged <5 years from 2000 to 2009 containing acute gastroenteritis (AGE) ICD 10 AM diagnosis codes were linked to hospital laboratory stool testing data. The validity of the rotavirus-specific diagnosis code (A08.0) and the incidence of hospitalisations attributable to rotavirus by both direct estimation and with adjustments for non-testing and miscoding were calculated for pre- and post-vaccination periods.

Results

A laboratory record of stool testing was available for 36% of all AGE hospitalisations (n = 4948) the rotavirus code had high specificity (98.4%; 95% CI, 97.5–99.1%) and positive predictive value (96.8%; 94.8–98.3%), and modest sensitivity (61.6%; 58–65.1%). Of all rotavirus test positive hospitalisations only a third had a rotavirus code. The estimated annual average number of rotavirus hospitalisations, following adjustment for non-testing and miscoding was 5- and 6-fold higher than identified, respectively, from testing and coding alone. Direct and adjusted estimates yielded similar percentage reductions in annual average rotavirus hospitalisations of over 65%.

Conclusion

Due to the limited use of stool testing and poor sensitivity of the rotavirus-specific diagnosis code routine hospital discharge and laboratory data substantially underestimate the true incidence of rotavirus hospitalisations and absolute vaccine impact. However, this data can still be used to monitor vaccine impact as the effects of miscoding and under-testing appear to be comparable between pre and post vaccination periods.     

Influenza associated mortality in Southern China, 2010–2012

Objective

Influenza caused substantial morbidity and mortality worldwide. The mortality burden caused by influenza has been under evaluation; however, data assessing this burden have been relatively sparse in tropical or subtropical regions. We estimated influenza-associated mortality in Guangzhou, China and assessed the excess mortality due to different influenza virus subtypes.

Methods

We estimated influenza-associated excess mortality due to all-cause, pneumonia and influenza, cardiorespiratory disease and other influenza-associated diagnoses from weekly numbers of deaths and influenza surveillance data through negative binomial regression model during 2010–2012.

Results

Estimates derived from the model indicated that influenza resulted in 14.72 (95% confidence interval (CI), 12.12–17.31) deaths per 100,000 population per year from all-cause death among all ages group. Most deaths (84.2%) occurred among people aged ≥65 years. B virus caused 5.84 (95%CI, 4.10–7.58) deaths per 100,000 population for all-cause death, which was higher than A (H3N2) (4.89, 95%CI, 3.19–6.59) or A(H1N1)pdm09 (3.99, 95%CI, 2.32–5.66).

Conclusions

Influenza is responsible for a substantial mortality especially among people aged ≥65 years and influenza B virus caused the highest influenza-associated mortality. The results highlight the need for seasonal influenza vaccination programs in subtropical areas to decrease excess mortality.     

Evaluation of Australia's varicella vaccination program for children and adolescents

Objective

This paper examines how the monovalent varicella vaccine for children, with an adolescent catch-up dose, was introduced into Australia's National Immunisation Program (NIP), focusing on programme implementation.

Methods

Semi-structured interviews were conducted with key informants involved in programme implementation. Key themes from interviews were identified through content analysis. Childhood coverage was assessed using data from the Australian Childhood Immunisation Register (ACIR) with adolescent coverage obtained from state/territory immunisation programmes. Seroprevalence data were analysed from national serosurveys conducted before and after programme commencement.

Results

Implementation challenges for both parents and providers included: (a) parental report of previous infection as an exclusion criterion; (b) introducing a vaccine on its own at 18 months of age; and (c) adding the adolescent dose into existing school-based vaccination programmes with parental reported exclusion criteria. Despite these challenges, coverage rapidly reached 83% by 24 months of age and 30–33% for the adolescent catch-up dose. When considered in conjunction with estimated pre-vaccination natural immunity in both target groups (20% and 83%, respectively) coverage can be considered high. The serosurvey under-estimated coverage in 2-year-old children but was useful to assess trends in population immunity.

Conclusion

The introduction of a single dose of monovalent varicella vaccine at 18 months of age and a school-based catch-up programme at 11–13 years of age successfully achieved high coverage, notwithstanding some challenges. Reported natural infection has been an exclusion criterion for vaccination, but as the programme matures and circulation of wild-type virus decreases, the need for this warrants consideration. There is a need for sensitive laboratory assays to measure vaccine-induced immunity at a population level.     

Prevalence of human papillomavirus (HPV) infections in sexually active adolescents and young women in England, prior to widespread HPV immunisation

Introduction

The introduction of an HPV immunisation programme in England should result in a significant reduction in the prevalence of vaccine type infections in young women. Here we describe type-specific HPV prevalence in three samples of the young female population in England, prior to the beginning of mass immunisation in 2008.

Methods

Residual vulva-vaginal swab samples from females aged under 25 years undergoing chlamydia testing as part of the National Chlamydia Screening Programme (NCSP) or Prevention of Pelvic Infection (POPI) trial were collected from sites across England, together with available demographic and sexual behaviour data. Residual samples were screened for HPV infection using the Hybrid Capture 2 (hc2) HPV DNA Test, including the high-risk (HR) and low-risk (LR) probes. Hc2 positive samples were genotyped using the Roche Linear Array (LA) HPV Genotyping Test.

Results

A total of 3829 samples were included: 2369 from 16 to 24 year old NCSP participants, 275 from 13 to 15 year old NCSP participants and 1185 from 16 to 24 year old POPI participants. Variations in HPV prevalence between and within the different samples followed a pattern largely consistent with differences in sexual behaviour. The prevalence of total HR HPV infection, of HPV 16 and/or 18 (16/18) infection and of five HR HPV types closely related to HPV 16/18 (HPV 31, 33, 45, 52 or 58) amongst 16–24 year old NCSP participants was 35% (95% CI 33–37%), 18% (95% CI 16–19%), and 16% (95% CI 14–18%), respectively. Risk of HR HPV infection increased with age during the teen years and was higher in women who reported two or more sexual partners in the last year and in women with chlamydia infection. Approximately half of women with HPV 16/18 infection also had another non-vaccine HR HPV type present.

Conclusions

Prior to HPV immunisation, there was a high prevalence of HPV infections in the lower genital tract of young, sexually active females in England. The overall, type-specific, and multiple infection prevalence closely reflected age and sexual activity. These data provide a baseline against which the early impact of HPV immunisation on the prevalence of HPV 16/18 and closely related types in young women can be measured, in order to inform immunisation and cervical screening policies.     

Bivalent human papillomavirus vaccine and the risk of fatigue syndromes in girls in the UK

Introduction

Over 70% of cervical cancers are related to human papillomavirus types 16 and 18. In 2008, the vaccine Cervarix, protecting against these two strains, was introduced into the routine UK immunisation programme for girls aged 12–13 years, with a catch-up in girls aged up to 18 years. As part of the risk management planning for this new campaign, the Medicines and Healthcare products Regulatory Agency (MHRA) anticipated a range of conditions, including chronic fatigue syndrome, which might be reported as adverse events in temporal association with the vaccine.

Methods

Near-real time ‘observed vs. expected’ analyses were conducted comparing the number of reports of fatigue syndromes submitted via the MHRA's Yellow Card passive surveillance scheme to the expected number, using background rates calculated from the Clinical Practice Research Datalink (CPRD) and estimates of vaccination coverage. Subsequently, an ecological analysis and a self-controlled case series (SCCS), both using CPRD, compared the incidence rate of fatigue syndromes in girls before and after the start of the vaccination campaign and the risk in the year post-vaccination compared to other periods.

Results

The number of spontaneous reports of chronic fatigue following Cervarix vaccination was consistent with estimated background rates even assuming low reporting. Ecological analyses suggested that there had been no change in the incidence of fatigue syndromes in girls aged 12–20 years after the introduction of the vaccination despite high uptake (IRR: 0.94, 95% CI: 0.78–1.14). The SCCS, including 187 girls, also showed no evidence of an increased risk of fatigue syndromes in the year post first vaccination (IRR: 1.07, 95% CI: 0.57–2.00, p = 0.84).

Discussion

The successful implementation of an enhanced pharmacovigilance plan provided immediate reassuring evidence that there was no association between vaccination with Cervarix and an increased risk of chronic fatigue syndromes. This has now also been further demonstrated in more comprehensive epidemiological studies.     

Economic burden of neural tube defects in Germany

Objective

Failure of closure of the neural tube often leads to serious malformations, including spina bifida, anencephaly and encephalocoele. Despite improvements in medical and surgical treatment, the burden associated with spina bifida is substantial but country-specific data are lacking outside North America. This study aims to improve understanding of the economic implications and burden associated with the morbidity of children and adults with neural tube defects (NTDs) in Germany.

Study design

Retrospective data analysis.

Methods

2006–2009 German health insurance data of persons with NTDs (spina bifida and encephalocoele) were analysed to determine the economic burden of illness associated with NTDs in Germany. Cases were identified using ICD-10 codes; data included outpatient and inpatient care, rehabilitation, remedies and medical aids, pharmacotherapy use, long-term care and information on sick leave. The analysis was stratified by age group to provide a burden estimate specific to a person's age. To obtain an indicator of incremental burden to the Statutory Health Insurance (SHI), results were compared to the standardized healthcare expenditures according to the German Risk Compensation Scheme (RSA).

Results

Overall, 4141 persons with an ICD code related to NTDs were identified (out of a population of 7.28 million persons screened). The administrative prevalence ranged from 0.54 to 0.58 per 1000 enrollees. Of those, 3952 (95.4%) were diagnosed with spina bifida. The average annual mean healthcare expenditure of persons with spina bifida was €4532 (95% CI = 4375–4689, SD = 9590, Median = 1000), with inpatient care contributing €1358 (30.0%), outpatient care €644 (14.2%), rehabilitation €29 (0.6%), pharmacotherapy €562 (12.4%), and remedies and medical aids €1939 (42.8%). The incremental cost due to spina bifida was substantially higher than the standardized SHI expenditures for all age groups. The difference was highest for persons ≤10 years old (€10,971 vs €2360 for the age group ≤1, €8599 vs €833 for the age group 2–5 years and €10,601 vs €863 for the age group 6–10 years). The difference was smallest for the age group 41–50 years (€2524 vs €1101) and for 71 years and over (€5278 vs €4389).

Conclusion

Expenditures of persons with spina bifida exceeded the standardized SHI expenditures, indicating a considerable economic burden. The economic burden is continuous throughout the person's life, with high monetary impact and exposure to the healthcare system (especially in early years of life). Efforts should be devoted to improve the prevention of NTDs and provide appropriate support for persons with NTDs, parents, and caregivers—especially in early years.     

Modelling the epidemiological impact of rotavirus vaccination in Germany – A Bayesian approach

Background

Rotavirus (RV) infection is the primary cause of severe gastroenteritis in children aged <5 years in Germany and worldwide. In 2013 the German Standing Committee on Vaccination (STIKO) developed a national recommendation for routine RV-immunization of infants. To support informed decision-making we predicted the epidemiological impact of routine RV-vaccination in Germany using statistical modelling.

Methods

We developed a population-based model for the dynamic transmission of RV-infection in a vaccination setting. Using data from the communicable disease reporting system and survey records on the vaccination coverage from the eastern federal states, where the vaccine was widely used before recommended at national level, we first estimated RV vaccine effectiveness (VE) within a Bayesian framework utilizing adaptive Markov Chain Monte Carlo inference. The calibrated model was then used to compute the predictive distribution of RV-incidence after achieving high vaccination coverage with the introduction of routine vaccination.

Results

Our model estimated that RV-vaccination provides high protection against symptomatic RV-infection (VE = 96%; 95% credibility interval (CI): 91–99%) that remains at its maximum level for three years (95% CI: 1.43–5.80 years) and is fully waned after twelve years. At population level, routine vaccination at 90% coverage is predicted to reduce symptomatic RV-incidence among children aged <5 years by 84% (95% prediction interval (PI): 71–90%) including a 2.5% decrease due to herd protection. Ten years after vaccine introduction an increase in RV incidences of 12% (95% PI: −16 to 85%) among persons aged 5–59 years and 14% (95% PI: −6 to 109%) within the age-group >60 years was predicted.

Conclusion

Routine infant RV-vaccination is predicted to considerably reduce RV-incidence in Germany among children <5 years. Our work generated estimates of RV VE in the field and predicted the population-level impact, while adequately addressing the role of model and prediction uncertainty when making statements about the future.