Conjugate Vaccine Program Research Articles

Implementation and impact of a meningococcal C conjugate vaccination program in 13- to 25-year-old individuals in Galicia, Spain

BackgroundIn response to increased case numbers of meningococcal group C disease, catch-up vaccination strategies have been shown to be successful. This paper describes the results of a repeat vaccination program in Galicia, Spain, and the strategy used for it.Methods and resultsThree vaccination waves were performed: first, in 1996/1997 with a meningococcal group A and C polysaccharide vaccine in individuals aged 18 months to 19 years; second, in 2000 with a conjugate serogroup C polysaccharide vaccine in children born since 1993 and all children and adolescents up to 19 years not previously vaccinated; third, a campaign in 2006 that became necessary because of the development of a new Neisseria strain and an increase in both the incidence and lethality of meningococcal C disease. The conjugate vaccine de-O-acetylated group C meningococcal polysaccharide coupled to tetanus toxoid was used (GCMP-TT; brand name, NeisVac-C). Results: Applying a strategy based on model calculations derived from the UK setting and focusing on a population aged 13–25 years, including students, employees of companies, and underage individuals, a total of 286,000 subjects were vaccinated, resulting in global vaccination coverage of 82.2% (all age groups over 74%). Only 17 adverse events in 17 individuals were reported, which all were mild. Incidence of meningococcal disease serogroup C by season was reduced from 0.84 cases per 100,000 in 2004/05 to 0.76 cases per 100,000 in 2005/2006 to 0.18/100,000 in 2007/08. In parallel, mortality was also decreased from 8 cases during 2005/06 (0.29 per 100,000) to 1 case in 2007/2008 (0.03 per 100,000). No cases of breakthrough disease occurred in the vaccinated population.ConclusionIn Galicia, a series of vaccination campaigns, particularly focusing on high-risk groups, has shown high effectiveness, with a marked reduction in the disease incidence in the vaccination cohort accompanied by a relevant reduction in the overall population.

Streptococcus pneumoniae meningitis in Alberta pre- and postintroduction of the 7-valent pneumococcal conjugate vaccine.

To describe the epidemiology, clinical characteristics, microbiology and outcomes of patients of all ages with Streptococcus pneumoniae meningitis two years pre- and postintroduction of a S pneumoniae 7-valent conjugate vaccine program in Alberta in children <2 years of age. Between 2000 and 2004, all cases of invasive pneumococcal disease in Alberta were identified. From this cohort, patients with S pneumoniae meningitis were identified by chart review. Clinical data, laboratory data and in-hospital outcomes were collected. Of the 1768 cases of invasive pneumococcal disease identified between 2000 and 2004, 110 (6.2%) had S pneumoniae meningitis. The overall incidence was 0.7 per 100,000 persons and remained unchanged over the study period. The rate in children <2 years of age appeared to fall over time, from 10.5 per 100,000 persons in 2000 to five per 100,000 persons in 2004, although there was insufficient evidence of a statistically significant time trend within any age group. Overall, the mean age was 30 years and 47% were male. In-hospital mortality was 20%, ranging from 6% in those ≤2 years of age to 31% for those ≥18 years of age, despite appropriate antimicrobial therapy. The high mortality rate associated with S pneumoniae meningitis suggests that prevention by vaccination is critical. In children <2 years of age, there was a downward trend in the rate of S pneumoniae meningitis after implementation of the S pneumoniae 7-valent conjugate vaccine program, but rates were still high.

Impact of the seven-valent pneumococcal conjugate vaccination (PCV7) programme on childhood hospital admissions for bacterial pneumonia and empyema in England: national time-trends study, 1997–2008

BackgroundChildhood bacterial pneumonia and empyema rates have reportedly increased in recent years in Europe. In September 2006 the seven-valent pneumococcal conjugate vaccination (PCV7) was introduced to the childhood national immunisation...

Rebound in the incidence of pneumococcal meningitis in northern France: effect of serotype replacement

To determine whether the recent emergence of nonvaccine pneumococcal serotypes has affected the incidence of pneumococcal meningitis in children a few years after the introduction of the heptavalent pneumococcal conjugate vaccine. We conducted a multicentre retrospective cohort study from 2005 to 2008 in all hospitals with paediatric units in northern France. It included all patients < 18 years of age who were admitted for laboratory-confirmed pneumococcal meningitis during the study period. Data were collected from medical files and laboratory records at each hospital and compared with the regional hospital discharge codes. We assessed global and age-specific incidence rates of pneumococcal meningitis from 2005 through 2008, compared them with those from the prevaccine era (2000-2002) and evaluated pneumococcal serotypes. In all, 41 cases were found during the study period. The incidence rate of pneumococcal meningitis varied from 0.8/100,000 children < 18 years in 2005 to 1.8/100,000 children in 2008 (2.2-fold increase, p = 0.06); and from 1.8 to 11.9/100,000 children < 2 years (6.5-fold increase, p = 0.004). This increase was caused by nonvaccine pneumococcal serotypes. The incidence of pneumococcal meningitis in infants has rebounded in northern France during the pneumococcal conjugate vaccine programme, with the emergence of nonvaccine pneumococcal serotypes.

Invasive pneumococcal disease after implementation of a reduced three-dose pneumococcal conjugate vaccine program: a pediatric tertiary care center experience

Following the implementation of a government-sponsored reduced three-dose (2 + 1) heptavalent conjugate pneumococcal vaccine (PCV7) program, we report a 61.4% decrease in the number of cases of invasive pneumococcal diseases (IPD) treated at our institution. Four years after the implementation of the three-dose reduced vaccine program, only 7.4% of IPD were caused by PCV7 serotypes, and there was an increase in the proportion of IPD caused by nonPCV7 serotypes; serotype 19A represented 40.7% of the strains isolated during the last year of the study. These results, similar to those previously observed with a regular four-dose (3 + 1) PCV7 schedule, are reassuring as to the effectiveness of a reduced three-dose (2 + 1) PCV7 program. Increasing numbers of IPD caused by nonPCV7 serotypes warrant the use of a new conjugate pneumococcal vaccine that contains serotype 19A.

Impact of a Pneumococcal Conjugate Vaccination Program on Carriage among Children in Norway

In July 2006, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Norway with a reduced (2 doses + 1 boost) dose schedule. Post-PCV7 shifts in pneumococcal reservoirs were assessed by two point prevalence studies of nasopharyngeal colonization among children in day care centers, before (2006) and after (2008) widespread use of PCV7. Nasopharyngeal swabs were obtained from 1,213 children, 611 in 2006 and 602 in 2008. A total of 1,102 pneumococcal isolates were recovered. Serotyping, multilocus sequence typing, and antimicrobial drug susceptibility testing were performed on all isolates. Although carriage of PCV7 serotypes decreased among both vaccinated and unvaccinated children, the overall prevalence of pneumococcal carriage remained high (80.4%) after vaccine introduction. The pneumococcal populations were diverse, and in the shift toward non-PCV7 serotypes, expansion of a limited number of established clonal complexes was observed. While non-antimicrobial-susceptible clones persisted among PCV7 serotypes, antimicrobial resistance did not increase among non-PCV7 serotypes. Direct and indirect protection of PCV7 against nasopharyngeal colonization was inferred from an overall decrease in carriage of PCV7 serotypes. No preference was found for nonsusceptible clones among the replacing non-PCV7 serotypes.

Estimating the cost-effectiveness of pneumococcal conjugate vaccination in Brazil

To compare the costs and benefits of pneumococcal conjugate vaccination compared with no vaccination from the perspectives of the health care system and society. Using data from established sources, we estimated the incidence and mortality due to invasive pneumococcal disease, pneumonia, and acute otitis media (AOM) for a hypothetical birth cohort of children from birth to 5 years. A universal pneumococcal conjugate vaccination program was estimated capable of annually avoiding 1 047 cases of invasive disease, 58 226 cases of pneumonia, and 209 862 cases of AOM. When herd immunity effects were considered, the program prevented 1.3 million cases of pneumococcal disease and over 7 000 pneumococcal deaths. At a vaccination cost of R$ 51.12 (US$ 26.35) per dose, vaccination would cost annually R$ 4 289 (US$ 2,211) per disability-adjusted life years averted. This does not take into account herd immunity effects. At the current vaccine price, conjugate vaccination could be a cost-effective investment compared to other options to control childhood diseases. Further analysis is required to determine whether vaccination at the current price is affordable to Brazil.

Cost-effectiveness of a 3-dose pneumococcal conjugate vaccine program in the province of Quebec, Canada

In the province of Quebec, Canada, the pneumococcal 7-valent conjugate vaccine (PCV-7) was licensed in 2001 and a publicly funded program was implemented in 2004, recommending 3 doses for healthy children. An economic analysis was performed both from a health care and societal perspective. Outcomes possibly prevented by PCV-7 and observed in 2006–2007 were compared to expected frequencies based on rates measured before PCV-7 use. Annual program costs were close to $21 M for the health system and $23 M for society. Approximately 20 000 infections were prevented annually and estimated economic benefits were $5 M for the health system and $23 M for society, using a 3% per annum discounting rate. The incremental cost-effectiveness ratio was $18 000 per QALY gained for the health system and the program was close to the break-even threshold in a societal perspective.

Reduced Physician Claims for Otitis Media After Implementation of Pneumococcal Conjugate Vaccine Program in the Province of Quebec, Canada

In Canada, a 7-valent pneumococcal conjugate vaccine (PCV-7) was licensed in 2001, and free vaccination of children <5 years of age was offered in December 2004 in the province of Quebec. To describe the frequency of physician claims for otitis media (OM) in relation to PCV-7 coverage during the period from 1996 to 2007. The monthly frequency of OM claims in the population aged <10 years was obtained from the provincial health insurance board. Time series in different age categories were analyzed using structural models with unobserved components, including seasonality, linear trends, level changes, and outliers. The candidate explanatory variable was PCV-7 uptake rate as measured in the population <5 years of age in the Quebec City area. Free PCV-7 program implementation was followed by a marked increase in uptake and by the end of 2007, >90% of children had received >or=1 dose. In all models, seasonality was a major determinant of OM frequency rates and there were statistically significant downward trends, as well as downward level breaks and outliers. PCV-7 coverage (>or=1 dose) was a significant predictor in children 6 months to 2 years of age. The effect was of lesser magnitude and not significant in the group of children aged 2 to 4 years, and absent in the group 5 to 9 years. Since PCV-7 licensure, an estimated 100,000 visits were averted in children <5 years of age, and OM claim frequency reduction attributable to PCV-7 was 13.2% by the end of the study period. PCV-7 implementation was associated with a significant reduction in the frequency of OM in the target population, and there was no indication of herd protection in older children.

Meningococcal vaccines and herd immunity: lessons learned from serogroup C conjugate vaccination programs

Effective vaccines provide direct protection to immunized individuals, but may also provide benefits to unvaccinated individuals by reducing transmission and thereby lowering the risk of infection. Such herd immunity effects have been demonstrated following the introduction of meningococcal serogroup C conjugate (MCC) vaccines, with reductions in disease attack rates in unimmunized individuals and significantly lower serogroup C carriage attributable to the vaccine introduction. In the UK, targeting teenagers for immunization was crucial in maximizing indirect effects, as most meningococcal transmission occurs in this age group. Questions remain regarding the duration of herd protection and the most appropriate long-term immunization strategies. The magnitude of the herd effects following MCC vaccination was largely unanticipated, and has important consequences for the design and evaluation of new meningococcal vaccines.

Serotypes and antimicrobial susceptibilities of invasive Streptococcus pneumoniae pre- and post-seven valent pneumococcal conjugate vaccine introduction in Alberta, Canada, 2000–2006

Alberta, Canada introduced the Streptococcus pneumoniae seven valent conjugate vaccine (PCV7) program for children less than 2 years of age in September 2002. We determined the rates of invasive pneumococcal disease in Alberta, Canada 2 years pre- and 4 years post-PCV7 introduction (2000–2006) as well as the rates of antibiotic resistance and serotype distribution in this same time period. Overall, PCV7 serotypes decreased 61% from 2000 to 2006. The greatest decrease in incidence of invasive pneumococcal disease occurred in children less than 2 years of age declining from a high of 96.7/100,000 (2000) to 25.8/100,000 (2006) ( P < 0.0001). Non-susceptibility of S. pneumoniae isolates to penicillin dropped significantly from 14% in 2000 to 4.6% in 2006 ( P < 0.0001). Non-susceptible erythromycin isolates also decreased from 8.8% (2000) to 5.8% (2006) ( P = 0.13). The introduction of PCV7 in Alberta, Canada has decreased the incidence of invasive pneumococcal disease in Alberta as well as resulting in a decrease in antibiotic resistance over this same time frame, principally for penicillin resistance.

The Impact of Childhood Meningococcal Serogroup C Conjugate Vaccine Programs in Canada

Conjugate meningococcal vaccines may decrease the incidence of disease. The staggered implementation of universal childhood meningococcal C conjugate (MenC) immunization programs across Canada offers an opportunity to evaluate the influence of these programs. From 2002 to 2006, we conducted active, population-based surveillance for adult and pediatric hospital admissions related to meningococcal infections at the 12 centers of the Canadian Immunization Monitoring Program, Active (IMPACT), in collaboration with local public health officials. A total of 376 cases were reported during the 5 years of surveillance. Yearly totals were as follows: 96 in 2002, 73 in 2003, 81 in 2004, 58 in 2005, and 68 in 2006. Case fatality was 9.3% and adults had a significantly higher case fatality rate than children.Average incidence per 100,000 was 0.62 (95% confidence interval [CI]: 0.50-0.76) in 2002 and 0.42 (95% CI: 0.32-0.53) in 2006. The highest rates were in children age 0 to 4 years, followed by adolescents age 15 to 19 years. Incidence of group C disease decreased significantly during the 5 years from 0.23 (95% CI: 0.16-0.32) in 2002 to 0.08 (95% CI: 0.04-0.14) in 2006, whereas incidence remained stable for groups B, Y, and W135. The decrease in group C disease was seen in provinces that first implemented MenC immunization programs. A substantial decrease in group C incidence occurred in provinces with early MenC immunization programs. Serogroup C incidence remained stable in provinces without MenC programs. We found no evidence of serogroup replacement.

General practitioners’ perceptions on pneumococcal vaccination for children in United Kingdom

Following the introduction of the pneumococcal conjugate vaccination programme for children in the UK, a study of General Practitioners in Walsall and Liverpool was undertaken to identify the possible reasons for the delay in implementation of the programme. A total of 143 GPs were contacted, of whom 39 responded (response rate =27%). One-third of the GPs felt that there was ‘delay’ in the introduction of the programme. The main reasons for possible delay in the implementation of the programme were ‘problems with databases’, ‘inadequate/unclear information from Primary Care Trust’, ‘lack of public awareness’, and ‘parental delay’. 12% of the respondents said that issue of ‘payment’ to them was the reason for not implementing the programme. Most of the reasons given were ‘external’ to the practitioners. This being an initial exploratory study of its kind, the authors recommend that the results of this study be used in conjunction with other quantitative data by commissioners of health services in designing the implementation of a new vaccination programme.

Meningococcal tetravalent conjugate vaccine

Background: Neisseria meningitidis is a leading cause of meningitis and sepsis worldwide. Since 1981, a tetravalent meningococcal polysaccharide vaccine has been available in the US but it has been limited to high-risk patients and outbreak settings. In 2005, a tetravalent polysaccharide meningococcal conjugate vaccine (MCV4) was licensed for routine use in the US. Objective: To assess the immunogenicity and safety of MCV4, and to extrapolate the anticipated clinical effectiveness of MCV4 using data from other polysaccharide conjugate vaccination programs. Methods: All published controlled studies of MCV4 immunogenicity, safety and cost-effectiveness are analyzed. Publicly-available clinical trial data and the Advisory Committee on Immunization Practices guidelines were also reviewed. Conclusion: MCV4 is as safe and immunogenic as the previously available polysaccharide vaccine, and seems to provide longer lasting protection against meningococcal disease. Long-term studies are continuing and will shed further light on the effectiveness of MCV4 at the population level.

Pneumonia After Implementation of the Pneumococcal Conjugate Vaccine Program in the Province of Quebec, Canada

In Canada, a pneumococcal conjugate vaccine was licensed in 2001, and in the province of Quebec, a publicly-funded program was implemented for high-risk children in 2002, using a 4-dose schedule, and for all children in 2004, using a 3-dose schedule. To describe the epidemiology of hospitalized pneumonia in the population aged <5 years. Hospital discharge records with a main diagnosis of pneumonia, pleurisy, or empyema were analyzed regarding monthly frequencies by diagnostic categories, duration of stay, proportion of cases admitted to the intensive care unit, and case fatality. Lobar pneumonia represented 32% of 25,319 all-cause pneumonia admissions during the period April 1997 to March 2006. Beginning in the spring of 2004, there was a marked decrease in the frequency of lobar pneumonia, whereas unspecified pneumonia tended to increase to a lesser extent. Compared with the pre-pneumococcal conjugate vaccine period, admissions for all-causes pneumonia decreased by 13% after program implementation and there was no increase in empyema cases. Results are reassuring as to the effectiveness of the pneumococcal vaccination program in Quebec.

Childhood invasive pneumococcal disease in Germany between 1997 and 2003: Variability in incidence and serotype distribution in absence of general pneumococcal conjugate vaccination

Based on active prospective surveillance, we report the incidence and serotype distribution for invasive pneumococcal disease in German children between 1997 and 2003. While incidence of meningitis cases was stable over time, there was an increase in non-meningitis cases. In absence of a general pneumococcal conjugate vaccination program, there were considerable and significant changes in serotype distribution over time. These should be considered when discussing the effect of vaccination programs and related changes in serotype distribution.

Effectiveness of a 2+1 dose schedule pneumococcal conjugate vaccination programme on invasive pneumococcal disease among children in Norway

The 7-valent pneumococcal conjugate vaccine (PCV-7) was licensed in Norway in 2001. In July 2006, PCV-7 was introduced in the Norwegian Childhood Vaccination Programme in a 2+1 dose schedule, with immunizations administered at 3, 5 and 12 months of age. PCV-7 was offered through the vaccination programme to all children born from January 2006, i.e. a catch-up for children aged 3–6 months. Prior to 2006 the use of PCV-7 was negligible. The effectiveness of the PCV-7 vaccination programme was assessed using data on invasive pneumococcal disease (IPD) incidence obtained from the Norwegian Surveillance System for Communicable Diseases, serotype distribution from the National Reference Laboratory for Pneumococci, and vaccine coverage and vaccination status from the Norwegian National Vaccination Register. Vaccine coverage quickly reached high levels; 95% of children >3 months born from January 2006 had received at least one immunization with PCV-7. The incidence rate of IPD among children <2 years rapidly declined; the rate of vaccine serotype IPD in this age group fell from an average of 47.1 cases/100,000 population in the 2 years prior to PCV-7 introduction to 13.7 cases/100,000 population in 2007. The incidence rate of nonvaccine serotype IPD remained stable. The vaccine programme effectiveness was estimated to be 74% (95% CI 57–85%). No vaccine failure was seen after complete primary immunization with two vaccine doses. Our findings indicate that PCV-7 provides highly effective protection against vaccine serotype IPD when administered in a 2+1 dose schedule.

Has the seven-valent pneumococcal conjugate vaccine had an impact on invasive pneumococcal disease in Western Australia?

Enhanced surveillance for invasive pneumococcal disease (IPD) has been ongoing in Western Australia since 1996. We describe the epidemiology of invasive pneumococcal disease in children aged <2 years between 1996 and 2005. Pneumococcal conjugate vaccine has been offered to Aboriginal children and other high-risk children since July 2001 and to all Australian children since January 2005. A total of 1655 IPD cases were reported of whom 361 (55 Aboriginal) were aged <2 years. From 1996–2001 to 2002–2005, IPD incidence declined from 192 to 124/100,000/annum in Aboriginal children and from 70 to 56/100,000/annum in non-Aboriginal children. Incidence of IPD due to vaccine serotypes (VT) declined from 118 to 43/100,000/annum ( p = 0.05) in Aboriginal children and from 59 to 45/100,000/annum in non-Aboriginal children ( p < 0.001), with no increased incidence of disease due to non-vaccine serotypes. Continued surveillance is essential to measure the impact of the childhood pneumococcal conjugate vaccination program on IPD incidence and to identify the emergence of disease due to non-vaccine serotypes.

Modeling Future Changes to the Meningococcal Serogroup C Conjugate (MCC) Vaccine Program in England and Wales

The UK meningococcal serogroup C conjugate (MCC) vaccine program has successfully controlled serogroup C disease, due to high vaccine effectiveness and substantial herd immunity. However, children immunised at 2, 3 and 4 months of age receive only short-term direct protection and may be at risk of disease 15 months after vaccination. To investigate this we applied a mathematical model to predict the future epidemiology of serogroup C disease, with and without changes to the immunisation schedule. Only a few cases of serogroup C disease were predicted to occur over the next few years because of persisting herd immunity, even without a change to the vaccine schedule, indicating that urgent schedule changes are not required. The inclusion of a booster dose is likely to improve the impact of the MCC program and reducing the number of doses in infancy will improve cost-effectiveness and create space in the schedule for the addition of other vaccines.

Reassessing the Cost-Effectiveness of Meningococcal Serogroup C Conjugate (MCC) Vaccines Using a Transmission Dynamic Model

The meningococcal serogroup C conjugate (MCC) vaccination program has successfully reduced morbidity and mortality from serogroup C disease in England and Wales, owing to high short-term vaccine effectiveness and substantial herd immunity. The latter effect was not accounted for in the previous economic analysis of the MCC program. The authors applied a transmission dynamic model, which accounts for herd immunity, to reevaluate the cost-effectiveness of MCC vaccination. The direct and indirect benefits of the MCC vaccine strategy implemented in England and Wales were compared. The cost-effectiveness of alternative MCC vaccine strategies, including future changes to the current schedule, were evaluated. The authors found that including herd immunity improved the average cost-effectiveness ratio in all cases, although the extent depended on the vaccine strategy considered. Incremental analysis showed that those strategies that offered 1 dose early in the 2nd year of life dominated strategies that offered 3 doses of vaccine in infancy and that catch-up vaccination up to the age of 18 years was also highly attractive. Furthermore, the authors analyzed the effect of future changes to the routine vaccine schedule and predicted that shifting the age at routine vaccination from 2, 3, and 4 months (3 doses) to 12 months (1 dose) resulted in a net gain in the total number of cases prevented with only a few extra cases occurring in children under 1 year of age. This program dominated the current strategy. Models that do not include the indirect effects of vaccination will underestimate the impact of MCC vaccination and may lead to distorted decision making.