Burden of paediatric rotavirus gastroenteritis and potential benefits of a universal rotavirus vaccination programme with RotaTeq in France

This study aimed at estimating the paediatric RotaVirus GastroEnteritis (RVGE) burden in children aged up to 5 years, and at evaluating health and economic benefits of a universal infant vaccination with a pentavalent rotavirus vaccine, in France. A decision analytic model was constructed considering a cohort of French children from birth to 5 years old. In the absence of a universal rotavirus immunisation programme, the model predicts that of every new French birth cohort, 336,738 children would present a RVGE case, which would result in 33,386 hospitalisations, 14 deaths and more than 279,000 work days lost for the parents. The management of these RVGE cases would cost 63 million euro to the National Healthcare Payer and would reach up to 117 million euro when all indirect costs were included. The introduction of a universal rotavirus vaccination would avoid 249,400 RVGE cases and consequently about 25,700 hospitalisations, 6000 nosocomial infections, 81,200 emergency visits, 39,900 general practitioner or paediatrician consultations, 11 deaths and 206,700 parental work days lost. RVGE total costs would be reduced by 47 million euro for the National Healthcare Payer and by 88 million euro from the Societal perspective. Therefore, a routine universal rotavirus vaccination programme represents an opportunity to significantly reduce the high paediatric RVGE burden in France.     

Pharmacoeconomic assessment of implementing a universal PCV-13 vaccination programme in the Valencian public health system (Spain)

Background

Heptavalent pneumococcal conjugate vaccine (PCV-7) was licensed to provide immunity against pneumococcal disease caused by seven serotypes of S. pneumoniae. Thirteen-valent pneumococcal conjugate vaccine (PCV-13) includes 6 additional serotypes for preventing invasive pneumococcal disease.

Objective

The objective of this study was to estimate the potential health benefits, costs, and cost-effectiveness of vaccination with PCV-13 in the Community of Valencia and to generate valuable information for policy makers at regional and country levels.

Methods

A decision tree was designed to determine the health and economic outcomes in hypothetical cohorts of vaccinated and unvaccinated children followed over their lifetime. Information about disease incidence and serotype distribution were gathered from local databases and from published and unpublished local records. PCV-13 effectiveness was extrapolated from PCV-7 efficacy data. A 5% of herd effect and a serotype replacement of 25% were considered for the base case scenario. Only direct costs were taken into account and results were expressed in terms of life-years gained (LYG) and quality adjusted life years (QALY).

Results

Implementing a universal PCV-13 vaccination program in the Community of Valencia would decrease the number of hospital admitted pneumonia to less than 4571 cases while avoiding 310 cases of IPD and 82,596 cases of AOM throughout the cohort lifetime. A total of 190 S. pneumoniae related deaths would be averted over the same period. Total medical costs of non-vaccinating the cohort of newborns would reach up to 403,850.859 € compared to 438,762.712 € that would represent vaccinating the cohort. The incremental cost of vaccinating the children was estimated in 12,794 €/LYG and 10,407 €/QALY, respectively.

Conclusions

A universal PCV-13 vaccination program in the Community of Valencia would be a cost-effective intervention from the payer perspective after preventing for pneumococcal infections and for decreasing its associated mortality and morbidity.     

Measles epidemiology in Catalonia (Spain): implications for a regional vaccination programme.

BACKGROUND: To analyse progress in measles control it is recommended that immunization programmes be evaluated by means of specific epidemiological disease surveillance. The aim of the study was to analyse a series of measles cases in Catalonia in the light of vaccination records. METHODS: Cases were detected by means of the epidemiological surveillance system and then surveyed for information on: age, sex, clinical symptoms, laboratory confirmation, record of vaccination, place of infection and possible outbreak-related links. The relationship between 'record of vaccination' and the remaining variables was determined using the adjusted odds ratio (OR) and its 95% confidence interval (CI). RESULTS: The epidemiological survey confirmed that 82.2% of patients (171/208) fulfilled the case criteria. In the multivariate analysis, lack of record of vaccination was associated with age groups < 5 years (OR = 4.0; 95% CI: 1.4-11.8) and > 14 years (OR = 19.2; 95% CI: 5.1-220.5). CONCLUSIONS: Improvement in vaccination coverage at 15 months and the introduction of vaccination-status monitoring at school-entry age and among those aged > 14 years on entry into the job market, university or military service could contribute to the elimination of measles.     

Sudden rise in uptake of hepatitis B vaccination among injecting drug users associated with a universal vaccine programme in prisons

Hitherto, services have failed to deliver the UK Government's 1988 recommendation to vaccinate injecting drug users (IDUs) against hepatitis B virus (HBV). In April 1999, the Scottish Prison Service implemented an initiative to offer HBV vaccination to all inmates; we sought to determine the impact of this initiative on the IDU population. Among community-recruited IDUs (who had injected for < or =5 years) in Glasgow, vaccine uptake was significantly higher among those surveyed in 2001-2002 (52% of 387) than in 1993 (16% of 166), 1994 (19% of 138) or January-March 1999 (15% of 128); of the 2001-2002 vaccinees, 56% had been vaccinated in prison. Our results indicate that the universal offer of vaccination to all prisoners, within two years of the initiative's implementation, has had a dramatic impact on uptake among IDUs.     

Sudden rise in uptake of hepatitis B vaccination among injecting drug users associated with a universal vaccine programme in prisons

Hitherto, services have failed to deliver the UK Government’s 1988 recommendation to vaccinate injecting drug users (IDUs) against hepatitis B virus (HBV). In April 1999, the Scottish Prison Service implemented an initiative to offer HBV vaccination to all inmates; we sought to determine the impact of this initiative on the IDU population. Among community-recruited IDUs (who had injected for ≤5 years) in Glasgow, vaccine uptake was significantly higher among those surveyed in 2001–2002 (52% of 387) than in 1993 (16% of 166), 1994 (19% of 138) or January–March 1999 (15% of 128); of the 2001–2002 vaccinees, 56% had been vaccinated in prison. Our results indicate that the universal offer of vaccination to all prisoners, within two years of the initiative’s implementation, has had a dramatic impact on uptake among IDUs.     

Costs of running a universal adolescent hepatitis B vaccination programme

In the first UK study to examine feasibility and acceptability of universal adolescent hepatitis B vaccination, the costs associated with the administration and uptake (80.2 and 89.3% for three doses and at least two doses, respectively), of a three-dose regimen in pupils in Glasgow schools (2001/2002) were measured. These data were used to estimate the economic outlay for the delivery of a routine, ongoing three-dose and two-dose hepatitis B vaccine programme in schools. Vaccine, accounting for almost 70% of the overall costs, was the largest cost item for both the pilot and routine programmes, using either regimen. However, the ongoing, two-dose regimen was the cheapest option in this analysis, irrespective of vaccine price. Cost data from this study may be useful for other countries wishing to implement a similar programme.     

Measles: effect of a two-dose vaccination programme in Catalonia, Spain

The study reports incidences of measles in Catalonia, Spain, as detected by surveillance, and analyses the specific characteristics of the outbreaks reported for the period 1986-95. Incidences per 100,000 inhabitants were calculated for the period 1971-95. The following variables were studied: year of presentation, number of cases, median age, transmission setting, cases with a record of vaccination and preventable cases. Associations between variables were determined using odds ratios (OR). The incidence of measles declined from 306.3 cases in 1971 to 30.9 in 1995. A total of 50 outbreaks were investigated. The outbreaks that occurred in the last two years of the study had a higher likelihood of having a transmission setting other than primary school (OR = 3.9); a median case age > 10 years (OR = 7.2); and fewer than 6 cases (OR = 2.3). The characteristics of recent outbreaks, marked by a rise both in transmission outside the primary-school setting and in median age, indicate the need for the introduction of a specific vaccination programme at the end of adolescence in addition to control of school-related outbreaks.     

Safety and tolerability of a liquid bovine rotavirus pentavalent vaccine (LBRV-PV) in adults

BackgroundRotavirus Gastroenteritis (RVGE) is an important global public health problem. Recently a Lyophilized Pentavalent Human Bovine Reassortant Rotavirus vaccine (BRV-PV, Rotasiil) was licensed in India. A Liquid formulation of the same vaccine (LBRV-PV) was tested in a Phase I clinical trial.MethodsTotal 20 healthy adults were given a single oral dose of LBRV-PV and were followed for one month for safety outcomes: immediate reactions, solicited reactions, unsolicited adverse events and serious adverse events.ResultsAll 20 adults completed the study without any major protocol deviations. No immediate reaction, solicited reactions and unsolicited adverse events were reported during the study. No clinically significant changes were seen in the vital parameters and safety laboratory test results.ConclusionsLBRV-PV developed in India was safe and well tolerated in adults. Further clinical development of this vaccine in infants should be undertaken.Trial Registration – CTRI/2015/11/006,384.     

Effectiveness of a universal vaccination program with an HPV quadrivalent vaccine in young Brazilian women

We examined human papillomavirus (HPV) vaccine effectiveness in a nationwide sample of women aged 16 to 25 years who utilized the public health system in Brazil. This was a cross-sectional, multicentric survey conducted between September 2016 and November 2017 (POP-Brazil Study). A total of 5,945 young adult women were recruited from 119 public primary care units from all 27 federative units of Brazil by trained health professionals. The participants participated in a face-to-face interview and provided biological samples for genital HPV analysis. HPV genotyping was performed using a Linear Array HPV genotyping test in a central laboratory. Sampling weights were applied to the data. Overall, 11.92% (95% CI 10.65, 13.20) of the participants reported having been vaccinated. The frequency of vaccination was highest in 16- to 17-year-old women, with a decreasing vaccination rate with increasing age, and vaccinated women were more likely to belong to the high socioeconomic status group. The use of a quadrivalent vaccine decreased the HPV types 6, 11, 16, and 18 by 56.78%, from 15.64% in unvaccinated women to 6.76% in vaccinated women (P < 0.01), even after adjustment for age. Those who received the vaccine had lower HPV 16 (2.34% in vaccinated vs 8.91% in unvaccinated, P < 0.01) and 6 rates (2.06% vs 5.77%, P < 0.01). Additionally, a higher rate of high-risk HPV types other than HPV 16 and 18 (40.47% in vaccinated vs 32.63% in unvaccinated, P < 0.01) was observed. In conclusion, the results of this study support the effectiveness of HPV vaccination in Brazil. Continuous surveillance must be assured to monitor the HPV infection rate in the vaccination era.     

Dramatic decline of serogroup C meningococcal disease in Catalonia (Spain) after a mass vaccination campaign with meningococcal C conjugated vaccine

In the last quarter of the year 2000, the meningococcal C conjugated vaccine was incorporated into the routine vaccination schedule in Catalonia (at 2, 4 and 6 months). In addition a vaccination campaign was carried out in children <6 years of age, with a coverage of 96.2%. The effectiveness of the vaccination in this age group during 2001 and the first 28 weeks of 2002 was 100% (94.27-100%). A vaccination campaign has been carried out in 6-19-year olds during 2001 and 2002, with a coverage rate of 23.5% in the year 2001. In this age group a reduction in disease incidence was seen in the 2000-2001 season, but not in the following one.     

Seroepidemiology of varicella-zoster virus infection in Catalonia (Spain). Rationale for universal vaccination programmes

With the aim of designing a strategy for vaccination against varicella-zoster virus (VZV), the results of a seroepidemiological survey on VZV infection carried out in a sample of the population of Catalonia are presented. Representative samples from schoolchildren (30 schools) and adults (97 municipal areas) were obtained by random cluster sampling. In the study, 883 children and 1253 adults were included. Age, gender, place of birth, place of residence, educational level and occupation were investigated in the study subjects. An ELISA test was used to measure varicella antibodies. The prevalence of varicella antibodies increased with age, being 85% in the 5-9 years age group, 92% in the 10-14 years age group, 94% in the 15-34 years age group and almost 100% in people over 35. No association was found between sociodemographic variables studied and prevalence levels of antibodies. These results suggest that the best vaccination strategy in Catalonia would be to add a temporary vaccination programme of pre-adolescents at 12 years to routine vaccination at 15 months.     

Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine.

OBJECTIVE: The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B (HB) and Haemophilus influenzae type b (Hib) vaccines into routine childhood vaccination programs. The objectives of this study were to: 1) analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2) in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster. METHODS: In the first part of the study (primary-vaccination stage), conducted in 1998-1999, we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2, 4, and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth. Later, in the booster-vaccination stage of the study, in 1999-2000, in a subset of the children (69 toddlers, now 15-18 months old), antibody persistence was measured, and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed. RESULTS: In both primary-vaccination groups, at least 97.5% of the infants reached protective levels of antibodies (seropositivity) against the antigens employed in the vaccines. The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone, and, in terms of general reactions, there was no clinically significant difference between the combination or separate injections, and with the pentavalent vaccine having the benefit of needing one less injection. Nine months after the third dose of the primary-vaccination course, antibody persistence was similar in both groups, with over 93% of children still having protective/seropositive titers for Hib, HB, and tetanus and about 50% for diphtheria and Bordetella pertussis. At 15 months of age, virtually all the toddlers responded with a strong boost response to all the vaccine antigens, whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster. Both booster regimens were equally well tolerated, indicating that up to five doses of the HB vaccine can be given without impact on safety.CONCLUSIONS: Our study confirms that the DTPw-HB/Hib pentavalent vaccine is highly immunogenic as a primary vaccination in children who received an HB vaccine at birth, with the pentavalent combination inducing both persisting immunity and boostable memory. The pentavalent vaccine was safe both for primary and booster vaccinations. Thus, this study in Costa Rican infants supports the routine use of the pentavalent DTPw-HB/Hib vaccine as part of childhood vaccination programs in Latin America and the Caribbean.     

Declining prevalence of hepatitis B virus infection in Catalonia (Spain) 12 years after the introduction of universal vaccination

AIMS: To analyze the prevalence of hepatitis B virus infection markers and hepatitis B vaccination in a representative sample of the juvenile and adult population of Catalonia and to evaluate the changes with respect to seroepidemiological surveys carried out in 1989 and 1996. DESIGN: In all subjects anti-HBc and anti-HBs antibodies and HBsAg were determined using an ELISA test. The possible association between sociodemographic variables and the prevalence of markers was analysed by calculating the adjusted odd ratio (simple logistic regression). SETTING: The study was carried out in 2002 in representative samples of the juvenile (5-14 years) and adult population (>or= 15 years) of Catalonia (Spain). MAIN RESULTS: In 2002 the global prevalence of HBsAg+ was 0.7% (95% CI: 0.4-1.0) and that of anti-HBc+ 8.7% (95% CI: 7.6-9.8), values higher than those obtained in 1989 of 1.5% (95% CI: 1.0-2.1) and 15.6 (95% CI: 13.9-17.3). The prevalence of markers of infection increased with age. The only sociodemographic variable significantly associated with the prevalence of hepatitis B virus infection was the place of birth. The risk of infection was twice as high in subjects born outside Catalonia (p<0.01), adjusted OR 2.0 (95% CI: 1.34-2.98) compared with those born in Catalonia. CONCLUSIONS: The results of this study show that the prevalence of hepatitis B virus infection (anti-HBc+) in Catalonia (Spain) is currently the lowest it has ever been and suggest that there has been a change in the pattern of endemicity of hepatitis B virus infection in Catalonia, which has become a country of low endemicity.     

Within-season influenza vaccine waning suggests potential net benefits to delayed vaccination in older adults in the United States

BackgroundThere is growing evidence that there is within (intra-) season waning of influenza vaccine protection in older adults, suggesting there may be a benefit to giving influenza vaccine closer to the time of increased infection risk. We aimed to quantitatively evaluate the impact of modifying the timing of influenza vaccination in U.S. older adults.MethodsUsing historical data (2010/2011–2015/2016, inclusive) on influenza activity and vaccine uptake, we explore the optimal time to begin vaccinating older adults (≥65 years) in the U.S. to maximize prevention of influenza. We modelled the effect of changing the timing of vaccination by estimating the percentage change to the current disease burden and used this to calculate the estimated optimal week to begin vaccination in the U.S.ResultsWhen we assumed a relatively slower waning protection rate (over 52 weeks), the estimated optimal time to begin vaccinating those aged ≥65 years varied between mid-August (week 34, 2012–2013) and mid-late October (week 43, 2011–2012) depending on the season, resulting in 0.44% and 5.11% of the current disease burden prevented respectively. Under faster waning (over 26 weeks), the estimated optimal week varied between early September (week 37, 2012–2013) and mid-November (week 47, 2011–2012), resulting in 3.69% and 11.97% of the current disease burden prevented respectively.ConclusionsWhile it is difficult to determine the ideal time to start to vaccinate due to substantial variation in timing of individual seasons, we found that there are potentially substantial benefits to minimizing the time between vaccination and influenza activity in U.S. older adults. Modest delays in immunization were beneficial in the seasons we evaluated. If further evidence suggests fast waning, longer delays may be warrant as in these scenarios the timing of the current vaccination was often very suboptimal.     

Association of pneumococcal vaccination with cardiovascular diseases in older adults: The vaccine effectiveness,networking, and universal safety (VENUS) study

The protective effect of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against cardiovascular disease has been investigated in the United States and Europe; however, its effect has not been fully established. This study aimed to investigate the protective effect of PPSV23 on cardiovascular events in adults aged ≥ 65 years. This population-based nested case-control study was conducted using the claims data and vaccine records between April 2015 and March 2020 from the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) Study. PPSV23 vaccination was identified using vaccination records in each municipality. The primary outcome was acute myocardial infarction (AMI) or stroke. The adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for PPSV23 vaccination were calculated using conditional logistic regression. Among 383,781 individuals aged ≥ 65 years, 5,356 and 25,730 individuals with AMI or stroke were matched with 26,753 and 128,397 event-free controls, respectively. Individuals who were PPSV23 vaccinated, compared with the unvaccinated individuals, had significantly lower odds of AMI or stroke events (aOR, 0.70 [95% CI, 0.62–0.80] and aOR, 0.81 [95% CI, 0.77–0.86], respectively). More recent PPSV23 vaccination was associated with lower odds ratios (AMI, aOR 0.55 [95% CI, 0.42–0.72] for 1–180 days and aOR 1.11 [95% CI, 0.84–1.47] for 720 days or longer; stroke, aOR 0.83 [95% CI, 0.74–0.93] for 1–180 days and aOR 0.90 [95% CI, 0.78–1.03] for 720 days or longer). Among Japanese older adults, individuals who were PPSV23 vaccinated, compared with unvaccinated individuals, had significantly lower odds of AMI or stroke events.     

Dramatic decline of serogroup C meningococcal disease incidence in Catalonia (Spain) 24 months after a mass vaccination programme of children and young people

STUDY OBJECTIVES: The objective of this study was to evaluate the effectiveness of a mass vaccination programme carried out in Catalonia (Spain) in the last quarter of 1997 in response to an upsurge of serogroup C meningococcal disease (SCMD). DESIGN: Vaccination coverage in the 18 month to 19 years age group was investigated by means of a specific vaccination register. Vaccination effectiveness was calculated using the prospective cohort method. Cases of SCMD were identified on the basis of compulsory reporting and microbiological notification by hospital laboratories. Vaccination histories were investigated in all cases. Unadjusted and age adjusted vaccination effectiveness referred to the time of vaccination and the corresponding 95% confidence intervals (CI) were estimated at 6, 12, 18 and 24 months of follow up. SETTING: All population aged 18 months to 19 years of Catalonia. MAIN RESULTS: A total of seven cases of SCMD were detected at six months of follow up (one in the vaccinated cohort), 12 cases at 12 months (one in the vaccinated cohort), 19 cases at 18 months (two in the vaccinated cohort) and 24 at 24 months (two in the vaccinated cohort). The age adjusted effectiveness was 84% (95%CI 30, 97) at six months, 92% (95%CI 63, 98) at 12 months, 92% (95% CI 71, 98) at 18 months and 94% (95%CI 78, 98) at 24 months. In the target population, cases have been reduced by more than two thirds (68%) two years after the vaccination programme. In the total population the reduction was 43%. CONCLUSION: Vaccination effectiveness has been high in Catalonia, with a dramatic reduction in disease incidence in the vaccinated cohort accompanied by a relevant reduction in the overall population. Given that vaccination coverage was only 54.6%, it may be supposed that this vaccination effectiveness is attributable, in part, to the herd immunity conferred by the vaccine.     

Drivers for human papillomavirus vaccination in Valencia (Spain)

Objective

To describe the drivers associated with HPV vaccination in adolescent girls and their parent's opinion on the vaccine.

Impact of mass vaccination with polysaccharide conjugate vaccine against serogroup C meningococcal disease in Spain

During the fourth quarter of 1997, a vaccination campaign using the meningococcal C polysaccharide vaccine was carried out in 14 autonomous regions of Spain. The remaining three regions did not participate. In the last quarter of the year 2000, a mass vaccination campaign using the meningococcal C conjugated vaccine was carried out in all regions. In the year 2001 the incidence decreased in all regions, although the decrease was greater in regions that did not vaccinate in 1997. In contrast, case fatality rates did not decrease. During 2001, the incidence rate of meningococcal C disease was still lower (0.32 per 100000 persons-year) in the regions that vaccinated in 1997 with the polysaccharide vaccine than in those that did not (0.64 per 100000 persons-year).