Economic evaluation of vaccination programme of 13-valent pneumococcal conjugate vaccine to the birth cohort in Japan

Japan is now preparing to incorporate PCV-7 into the national childhood immunisation programme. Our recently published economic evaluation of using PCV-7 to the birth cohort suggests that the cost to gain one QALY is lower than the WHO's cost-effectiveness criterion for intervention. However, many countries have started to introduce PCV-13 into their national immunisation schedule replacing PCV-7 for preventing pneumococcal diseases among young children. These raise the need to appraise the ‘value for money’ of replacing PCV-7 with PCV-13 vaccination programme in Japan.     

The cost-effectiveness of a 13-valent pneumococcal conjugate vaccination for infants in England

Background

In the immunisation schedule in England and Wales, the 7-valent pneumococcal conjugate vaccine (PCV-7) was replaced by the 13-valent vaccine (PCV-13) in April 2010 after having been used since September 2006. The introduction of PCV-7 was informed by a cost effectiveness analysis using an infectious disease model which projected herd immunity and serotype replacement effects based on the post-vaccine experience in the United States at that time.

Aim

To investigate the cost effectiveness of the introduction of PCV-13.

Method

Invasive disease incidence following vaccination was projected from a dynamic infectious disease model, and combined with serotype specific disease outcomes obtained from a large hospital dataset linked to laboratory confirmation of invasive pneumococcal disease. The economic impact of replacing PCV-7 with PCV-13 was compared to stopping the use of pneumococcal conjugate vaccination altogether.

Results

Discontinuing PCV-7 would lead to a projected increase in invasive pneumococcal disease, costs and loss of quality of life compared to the introduction of PCV-13. However under base case assumptions (assuming no impact on non-invasive disease, maximal competition between vaccine and non-vaccine types, time horizon of 30 years, vaccine price of £49.60 a dose + £7.50 administration costs and discounting of costs and benefits at 3.5%) the introduction of PCV-13 is only borderline cost effective compared to a scenario of discontinuing of PCV-7. The intervention becomes more cost-effective when projected impact of non-invasive disease is included or the discount factor for benefits is reduced to 1.5%.

Conclusion

To our knowledge this is the first evaluation of a transition from PCV-7 to PCV-13 based on a dynamic model. The cost-effectiveness of such a policy change depends on a number of crucial assumptions for which evidence is limited, particularly the impact of PCV-13 on non-invasive disease.     

Cost-effectiveness of the CRM-based 7-valent pneumococcal conjugated vaccine (PCV7) in Argentina

Due to the region's own conditions, universal vaccination with pneumococcal conjugate heptavalent vaccine (PCV-7) in Latin American countries is still controversial.     

Economic evaluation of vaccination programme of 7-valent pneumococcal conjugate vaccine to the birth cohort in Japan

Aiming to introduce 7-valent pneumococcal conjugate vaccine (PVC-7) into routine vaccination schedule, the government of Japan gives a temporary budget to encourage municipalities in launching public vaccination programme which started on November 26, 2010 and ends on March 31, 2012. This study aims to appraise the 'value for money' of PCV-7 vaccination programme from the societal perspective and the budget impact from the perspective of municipalities, which is responsible for providing routine vaccination. We conducted a cost-effectiveness analysis with Markov modelling and calculated incremental cost-effectiveness ratio (ICER) value of launching such programme with two levels of co-payment, ￥1000 (US$13) or ￥0, and two scenarios of the uptake of vaccine (vaccinated-alone or co-vaccinated with other vaccines). We found that when vaccinated-alone, ICERs in QALY were ￥7,441,000 (US$93,013) or ￥9,065,000 (US$113,313), and when co-vaccinated ￥7,441,000 (US$93,013) or ￥5,489,000 (US$68,613), without or with productivity loss, respectively, regardless of co-payment level of the programme. Co-vaccinated programmes had lower ICER than vaccinated-alone programmes due to the savings in productivity loss. By adopting WHO's classification that an intervention is 'cost-effective' if ICER (in QALY) is between 1 and 3 times of GDP as a criterion, PCV-7 vaccination programme in Japan is concluded as "cost-effective" from the perspective of society. The introduction of either no co-payment or ￥1000 (US$13) co-payment vaccination programme appears to be not budget saving for the first 6 years, whereas the level of budget impact are less than ￥11,000,000 (US$137,500) or ￥8,500,000 (US$106,250), respectively, for a municipality with 1000 birth cohort in the 1st year and 2nd to 5th year birth cohort proportional to the birth cohort population of estimated future population.     

Projected health benefits and costs of pneumococcal and rotavirus vaccination in Uganda

We determined impact and cost-effectiveness of pneumococcal and rotavirus vaccination programs among children < 5 years of age in Uganda from the public health system perspective. Disease-specific models compared the disease burden and cost with and without a vaccination program. If introduced, pneumococcal and rotavirus vaccine programs will save 10,796 and 5265 lives, respectively, prevent 94,071 Streptococcus pneumoniae and 94,729 rotavirus cases in children < 5 years, and save 3886 and 996 million Ugandan shillings ($2.3 and $0.6 million US dollars), respectively, in direct medical costs annually. At the GAVI price ($0.15/dose), pneumococcal vaccine will be cost-saving and rotavirus vaccine highly cost-effective.     

Public health and economic impact of the 13-valent pneumococcal conjugate vaccine (PCV13) in the United States

The 7-valent pneumococcal conjugate vaccine (PCV7) has dramatically decreased pneumococcal disease incidence, and the 13-valent vaccine (PCV13) protects against 6 additional Streptococcus pneumoniae serotypes. A decision-analytic model was constructed to evaluate the impact of infant vaccination with PCV13 versus PCV7 on pneumococcal disease incidence and mortality as well as the incremental benefit of a serotype catch-up program. PCV13 effectiveness was extrapolated from observed PCV7 data, using assumptions regarding serotype prevalence and PCV13 protection against additional serotypes. The model predicts that PCV13 is more effective and cost saving compared with PCV7, preventing 106,000 invasive pneumococcal disease (IPD) cases and 2.9 million pneumonia cases, and saving $11.6 billion over a 10-year period. The serotype catch-up program would prevent an additional 12,600 IPD cases and 404,000 pneumonia cases, and save an additional $737 million compared with no catch-up program.     

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.     

Low vaccination coverage of pneumococcal conjugate vaccines (PCVs) in Shanghai,China: A database analysis based on birth cohorts from 2012 to 2020

BackgroundPneumococcal vaccines have been developed to protect infants and young children from pneumococcal diseases. Vaccination coverage studies are important in determining a population’s vaccination status and strategically adjusting national immunization programs (NIP). In this paper, we aim to describe the coverage of pneumococcal conjugate vaccines (PCVs) immunization for birth cohorts from 2012 to 2020 and discussed the factors influencing the coverage.MethodsVaccination data were collected via the vaccination information database in Shanghai, China, for children born from 2012 to 2020. The population data used in this study were collected from each community from 2012 to 2020. The coverage of initial immunization (1^st dose), basic immunization (three doses) and full immunization (3 + 1 doses) for PCVs was calculated according to the number of doses received. As vaccination coverage was assessed each year, Annual Growth Rate (AGR) was used to describe the variation trend of vaccination coverage. Immunization time and completeness of different PCVs were also analyzed.ResultsThe total number of births from 2012 to 2020 was 38,268 in Huangpu District, Shanghai, China. The initial immunization coverage of PCVs increased from 12.26% in 2012 to 49.65% in 2020, and the highest coverage was 50.61% in 2019. The cumulative vaccination coverage of PCVs was 19.4% for initial immunization and 16.8% for basic immunization from 2012 to 2020. And cumulative full immunization coverage of PCVs was 12.3% from 2012 to 2019. The PCVs coverage of most vaccination statuses showed an obvious upward trend from 2017 to 2020.ConclusionsDespite an upward trend in vaccination coverage of PCVs, the vaccination coverage of initial, basic and full immunization among children is still low. And given the heavy burden of Streptococcus pneumoniae (Sp) among children in China and the fact that the current vaccination coverage cannot effectively protect children, it is recommended that the government include PCVs into the NIP as soon as possible.     

Non-clinical immunological comparison of a Next-Generation 24-valent pneumococcal conjugate vaccine (VAX-24) using site-specific carrier protein conjugation to the current standard of care (PCV13 and PPV23)

Despite widespread utilization of pneumococcal conjugate vaccines (PCVs) and the resultant disease reduction, the development of PCVs containing additional serotypes remains a public health priority due to serotype replacement and the resultant shift to non-vaccine containing serotypes. However, incorporating additional serotypes to existing PCVs using conventional technologies has proven problematic. Immune responses to individual serotypes have consistently decreased as more polysaccharide-conjugates are added due to carrier suppression. Using our proprietary cell-free protein synthesis (CFPS) platform, we have successfully produced eCRM® based on the CRM₁₉₇ sequence for use as an enhanced carrier protein to develop a 24-valent PCV. The eCRM carrier protein contains multiple non-native amino acids (nnAAs) located outside of the primary T-cell epitope regions, thereby enabling site-specific covalent conjugation of the pneumococcal polysaccharides to the nnAAs to consistently expose the critical T-cell epitopes. eCRM also serves to reduce structural heterogeneity associated with classic reductive-amination conjugation while promoting formation of the conjugate matrix structures, the hallmark of PCVs. This process serves to increase the overall polysaccharide:protein ratio, enabling the inclusion of more serotypes while minimizing carrier-mediated immunological interference.The aim of this non-clinical study was to construct a 24-valent PCV and evaluate its immunogenicity. Using the XPressCF® CFPS platform, the eCRM carrier protein was separately conjugated through nnAAs to each of the 24 pneumococcal polysaccharides through click chemistry and mixed with aluminum phosphate to produce VAX-24, Vaxcyte’s proprietary PCV preclinical candidate. VAX-24, Prevnar13® and Pneumovax®23 were administered to New Zealand White rabbits to compare the resulting opsonophagocytic activity (OPA) and anti-capsular IgG antibodies. VAX-24 showed conjugate-like immune responses to all 24 serotypes based on comparable OPA and IgG responses to Prevnar13 and higher responses than Pneumovax 23. This study demonstrates the utility of site-specific conjugation technology in a preclinical setting and the potential for a PCV with improved serotype coverage.     

Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) formulated with 2-phenoxyethanol in multidose vials given with routine vaccination in healthy infants: An open-label randomized controlled trial

BackgroundThis open-label randomized controlled trial in infants compared safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated with the preservative 2-phenoxyethanol (2-PE) in a multidose vial (MDV) to the current PCV13 without 2-PE in a single-dose syringe (SDS).MethodsGambian infants were randomized 1:1 to receive PCV13 as either MDV or SDS at ages 2, 3, and 4 months. Serotype-specific antipneumococcal antibody responses and opsonophagocytic activity ([OPA]; subset) were measured at age 5 months. Noninferiority was declared if the lower bound of the 97.5% CI for the difference (MDV-SDS) in proportions of subjects achieving IgG concentrations ≥0.35 μg/mL (primary endpoint) was greater than −10%. IgG geometric mean concentrations (GMCs) were noninferior if the lower limit of the two-sided 97.5% CI of the geometric mean ratio (MDV vs SDS) was greater than 0.5. Reactogenicity and other adverse events were collected.Results500 participants were randomized and vaccinated; 489 (MDV: n = 245; SDS: n = 244) completed the trial. Noninferiority of MDV was demonstrated for all serotypes as measured by percentage of subjects achieving antibody responses above ≥0.35 μg/mL. IgG GMCs (coprimary endpoint) also demonstrated noninferiority of MDV; OPA results supported these findings. Safety and tolerability were comparable between groups.ConclusionsPCV13 in MDV was safe and immunogenic when administered according to the routine schedule to infants. MDV was noninferior to SDS for all 13 pneumococcal serotypes. Comparable immunogenicity and safety profiles of PCV13 MDV and SDS suggest PCV13 MDV can help optimize vaccination in resource-limited settings. ClinicalTrials.gov NCT01964716 https://clinicaltrials.gov/ct2/show/NCT01964716.     

Stable dynamics of pneumococcal carriage over a decade in the pre-PCV era

Streptococcus pneumoniae (SP) nasopharyngeal carriage studies are important to understand SP circulation prior to implementation of vaccination programs. It is generally not known how stable these carriage rates are over time.Carriage studies were conducted in Southern Israel during a decade preceding Pneumococcal Conjugate Vaccine (PCV) introduction. We estimated total and vaccine-type SP carriage at 6 months of age to be stable at 35% (95% CI: 26, 44) and 19% (95% CI: 15, 24), respectively in Jewish and 70% (95% CI, 62, 77) and 41% (95% CI: 38, 45) in Bedouin populations.The stability of carriage rates in two disparate populations over 10 years suggests a single survey may be sufficient to characterize pneumococcal carriage pre-PCV.     

Cost-utility analysis of the use of the 20-valent anti-pneumococcal vaccine (PCV20) in adults older than 60 years in Spain

Background and objectivesA cost-utility analysis was conducted to assess the efficiency of implementing a PCV20 vaccination strategy in the Spanish adult population older than 60 years, for the prevention of non-bacteremic pneumococcal pneumonia (NBP) and invasive pneumococcal disease (IPD).MethodsA Markov model, with annual cycles and a time horizon of 10 years was used. The analysis population was stratified by age and risk groups. The comparator was the sequential vaccination with the 15-valent pneumococcal conjugate vaccine (PCV15) followed by one dose of the pneumococcal polysaccharide vaccine (PPV23). The base case analysis was performed from the National Healthcare System (NHS) perspective including direct costs (€2018) and applying a discount of 3% to future costs and outcomes. Alternative scenarios explored a shorter time horizon (5 years), the societal perspective and other available vaccination strategies. All the parameters and assumptions were validated by a panel of experts. To evaluate the robustness of the model, deterministic and probabilistic sensitivity analyses (PSA) were carried out.ResultsThe results of the study showed that the vaccination strategy with PCV20 is a dominant option compared to the sequential regimen (PCV15 + PPSV23), resulting in direct cost savings of €85.7 M over 10 years, with a small increase in quality-adjusted life years (QALYs). PCV20 vaccination avoided 2,161 cases of IPD, 19,470 of NBP and 3,396 deaths and according to the PSA, the probability of PCV20 being cost-effective compared to a sequential regimen (PCV15 + PPSV23) was 100%.Conclusions/RecommendationsIn the Spanish adult population older than 60 years, the vaccination strategy with one dose of PCV20 is more effective and less expensive (dominant) than vaccination with a sequential schedule with PCV15 and PPSV23.     

Effect of Tdap when administered before,with or after the 13-valent pneumococcal conjugate vaccine (coadministered with the quadrivalent meningococcal conjugate vaccine) in adults: A randomised controlled trial

Sequential or co-administration of vaccines has potential to alter the immune response to any of the antigens. Existing literature suggests that prior immunisation of tetanus/diphtheria-containing vaccines can either enhance or suppress immune response to conjugate pneumococcal or meningococcal vaccines. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage 2014. We also investigated tolerability of these vaccines separately and concomitantly. We randomly assigned each participant to one of three vaccination schedules. Group A received adult tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3–4 weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) and CRM197-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines on one day. Group C received PCV13 and MCV4 3–4 weeks before Tdap. Blood samples collected at baseline, each vaccination visit and 3–4 weeks after vaccination were tested using the pneumococcal opsonophagocytic assay (OPA) and by ELISA for diphtheria and tetanus antibodies. Funding for meningococcal serology was not available. Participants completed symptom diaries after each vaccination. A total of 111 participants aged 18–64 (median 40) years were recruited. No statistically significant difference was detected across the three groups in achieving OPA titre ⩾1:8 post vaccination. However, compared to other groups, Group A had a statistically significant lower number of subjects achieving ⩾4-fold rise in serotype 3, and also significantly lower geometric mean titres (GMTs) to six (of 13) pneumococcal serotypes (3, 5, 18C, 4, 19A and 9V). Group C (given prior PCV13 and MVC4) had statistically significant higher pre-Tdap geometric mean concentration (GMC) of anti-diphtheria IgG; however, there was no difference across the three groups following Tdap. Anti-tetanus IgG GMCs were similar across the groups before and after Tdap. No serious adverse events were reported. In conclusion, Tdap vaccination 3–4 weeks before concomitant administration of PCV13 and MCV4 significantly reduced the antibody response to six of the 13 pneumococcal serotypes in adults.The trial is registered at the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000536763.     

Pneumococcal carriage in households in Karonga District,Malawi, before and after introduction of 13-valent pneumococcal conjugate vaccination

BackgroundThirteen-valent pneumococcal conjugate vaccine (PCV13) was introduced in Malawi in November 2011 and is offered to infants at 6, 10 and 14 weeks of age as part of routine immunisation. PCV13 is expected to reduce vaccine type (VT) nasopharyngeal carriage, leading to reduced transmission and herd protection.MethodsWe compared pneumococcal carriage in rural Karonga District, Malawi, pre-vaccine in 2009–2011 and post-vaccine in 2014 using a combination of cross-sectional and longitudinal analyses. Nasopharyngeal swabs were collected from a cohort of mother-infant pairs and household members <16 years. Pneumococci from 2009 to 2011 were serogrouped using latex agglutination and serotyped by Quellung reaction. In 2014, latex agglutination was used for both steps. Carriage prevalence ratios using prevalence data from before and after vaccine introduction were calculated by log-binomial regression, adjusted for age, seasonality and household composition. Participating infants in 2014 received PCV13 as part of routine immunisation.ResultsVT carriage prior to PCV-13 introduction was 11.4%, 45.1%, 28.2%, 21.2% and 6.6% for 6-week old infants, 18-week old infants, children 1–4 years, children 5–15 years and mothers, respectively. After vaccine introduction, VT carriage decreased among vaccinated 18-week old infants (adjusted prevalence ratio 0.24 (95%CI 0.08–0.75)), vaccinated children 1–4 years (0.54 (0.33–0.88)), unvaccinated children 5–15 years (0.37 (0.17–0.78)) and mothers (0.34 (0.15–0.79)). No decrease in VT carriage was observed for 6-week old infants too young to be vaccinated (1.07 (0.38–3.02)) and PCV-13 ineligible children 1–4 years (0.84 (0.53–1.33)). Non-VT carriage increased only among vaccinated children 1–4 years (1.58 (1.21–2.06)).ConclusionsThere is evidence of reduced VT pneumococcal carriage three years after vaccine introduction in this rural Malawian population with good vaccine coverage using a 3 + 0 schedule. However carriage was sustained among 6-week-old infants and PCV13 ineligible 1–4 year olds, and there was some indication of serotype replacement in vaccinated 1–4 year olds.     

Compared effectiveness of the 7-valent pneumococcal conjugate vaccine in children with the 13-valent vaccine in adults

13-valent-pneumococcal conjugated vaccine was recently approved in the USA and Europe for adults 50 years of age or more. But this approval was followed by recommendations limiting its use to immunocompromised and asplenic patients. The extension of indications to adults was based on the well-demonstrated clinical effectiveness in infants less than 2 years of age, and on a better immune response either quantitatively or qualitatively with conjugated vaccines compared to the immunogenicity of plain polysaccharide vaccines. Nevertheless, the issue was to know whether results observed with the 7-valent pneumococcal conjugate vaccine in children are reproducible in adults with the 13-valent. The answer was given by comparing the epidemiological and physiopathological data, and the immunological response of the two populations. Very few clinical effectiveness studies in adults are available. We had for aim to assess these various issues in infants and adults. A lot of questions remain, such as the unknown impact of serotype replacement with the 13-valent pneumococcal conjugated vaccine on the clinical epidemiology and emergent Streptococcus pneumoniae pathogenicity, while waiting for the CAPITA study results expected in 2014.     

Cost-effectiveness analysis of the 10- and 13-valent pneumococcal conjugate vaccines in Argentina

Objective

Since the 10-valent pneumococcal conjugate vaccine (PCV-10) and 13-valent pneumococcal conjugate vaccine (PCV-13) were recently licensed for use in Argentina, both vaccines were evaluated to estimate the costs, health benefits and cost-effectiveness of adding a PCV to the routine child immunization schedule.

Methodology

The integrated TRIVAC vaccine cost-effectiveness model from Pan American Health Organization's ProVac Initiative (Version 1.0.65) was used to assess the health outcomes of 20 successive cohorts from birth to 5 years of age. PCV-10 and PCV-13 were each compared to a scenario assuming no PCV vaccination. A 3 + 1 (three doses + booster) schedule and a vaccination price of US$ 20.75 per dose was assumed in the base case for both vaccines.

Results

Introduction of PCV-13 rather than PCV-10 would increase the number of life years gained (LYG) by at least 10%. The number of LYG (and LYG after adjustment for DALY morbidity weights) was 56,882 (64,252) for PCV-10 compared to 65,038 (71,628) for PCV-13. From the health system perspective, the cost per DALY averted was US$ 8973 and US$ 10,948 for PCV-10 and PCV-13 respectively, and US$ 8546 and US$ 10,510 respectively, after incorporating costs saved by households. When PCV13 was compared to PCV10 directly, the additional benefits of PCV-13 was conferred at a cost of US$ 28,147 per DALY averted. Cost-effectiveness was influenced mainly by vaccine price, serotype replacement, pneumonia mortality and discount rate.

Conclusion

Routine vaccination against S. pneumoniae in Argentina would be cost-effective with either PCV-10 or PCV-13. PCV-13, with higher coverage of local serotypes, would prevent more cases of pneumonia, invasive pneumococcal disease, sequelae and deaths with a higher number of LYG and DALYs averted, but PCV-10, due its higher impact in the prevention of AOM, would save more costs to the healthcare system.     

Immunogenicity and safety of a second administration of 13-valent pneumococcal conjugate vaccine 5 years after initial vaccination in adults 50 years and older

BackgroundVaccination effectively reduces invasive disease and pneumonia caused by Streptococcus pneumoniae. However, waning antibody titers and the ability of revaccination to boost titers in older adults have been concerns. A study to describe antibody persistence after vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) and response to revaccination 5 years after the initial dose was conducted.MethodsPneumococcal vaccine–naive subjects aged 50–59 years were randomized and vaccinated with PCV13 plus trivalent inactivated influenza vaccine concomitantly or 1 month apart, then revaccinated with PCV13 five years later. Antipneumococcal polysaccharide opsonophagocytic activity (OPA) geometric mean titers (GMTs) and immunoglobulin G (IgG) geometric mean concentrations (GMCs) were determined before and approximately 1 month after each vaccination. Targeted local reactions and systemic events were collected for 14 days, adverse events (AEs) for 1 month, and serious AEs (SAEs) for 6 months after each vaccination.ResultsOf 1116 randomized subjects, 727 were revaccinated at year 5. Between the time of initial vaccination and revaccination, OPA GMTs and IgG GMCs declined but remained higher than levels before initial vaccination for 12 of the 13 vaccine serotypes. One month after revaccination, OPA GMTs and IgG GMCs were comparable with, or higher than, levels observed 1 month after initial vaccination for most vaccine serotypes. Local reactions were mostly mild. AEs were reported by <5% and SAEs by <1% of subjects at 1 and 6 months after revaccination, respectively. No SAEs were vaccine-related.ConclusionsRevaccination of adults ≥50 years with PCV13 five years after primary vaccination was safe and immunogenic. Additionally, antibody titers were maintained for at least 5 years after vaccination. The vaccine stimulated a memory response as shown by enhanced responses that were maintained or enhanced by revaccination.ClinicalTrials.gov registrationNCT00521586.     

Impact of private use of the 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal carriage among Portuguese children living in urban and rural regions

In Portugal, the 13-valent pneumococcal conjugate vaccine (PCV13) was commercially available between 2010 and 2015, following a decade of private use of PCV7. We evaluated changes on serotype distribution and antimicrobial susceptibility of pneumococci carried by children living in two regions of Portugal (one urban and one rural). Three epidemiological periods were defined: pre-PCV13 (2009–2010), early-PCV13 (2011–2012), and late-PCV13 (2015–2016). Nasopharyngeal samples (n = 4,232) were obtained from children 0–6 years old attending day-care centers. Private use of PCVs was very high in both regions (>75%). Pneumococcal carriage remained stable and high over time (62.1%, 62.4% and 61.6% (p = 0.909) in the urban region; and 59.8%, 62.8%, 59.5% (p = 0.543) in the rural region). Carriage of PCV7 serotypes remained low (5.3%, 7.8% and 4.3% in the urban region; and 2.5%, 3.7% and 4.8% in the rural region). Carriage of PCV13 serotypes not targeted by PCV7 decreased in both the urban (16.4%, 7.3%, and 1.6%; p < 0.001) and rural regions (13.2%, 7.8%, and 1.9%; p < 0.001). This decline was mostly attributable to serotype 19A (14.1%, 4.4% and 1.3% in the urban region; and 11.1%, 3.6% and 0.8% in the rural region, both p < 0.001). Serotype 3 declined over time in the urban region (10.1%, 4.4%, 0.8%; p < 0.001) and had no obvious trend in the rural region (4.2%, 6.7%, 2.4%; p = 0.505). Serotype 6C decreased in both regions while serotypes 11D, 15A/B/C, 16F, 21, 22F, 23A/B, 24F, 35F, and NT were the most prevalent in the late-PCV13 period. Intermediate resistance to penicillin and non-susceptibility to erythromycin decreased significantly in both regions (19.5%, 13.3%, and 9.3%; and 25.4%, 25.9%, and 13.4%; both p < 0.001, respectively in the urban region; and 12.4%, 11.1%, and 2.8% (p < 0.001); and 15.3%, 14.7%, and 9.2% (p = 0.037), respectively, in the rural region). In conclusion, private use of PCV13 led to significant changes on the pneumococcal population carried by children in Portugal.     

Cost-effectiveness of conjugate pneumococcal vaccination in Singapore: comparing estimates for 7-valent, 10-valent, and 13-valent vaccines

Introduction

Although multiple studies of cost-effectiveness of pneumococcal conjugate vaccines have been conducted, no such study has examined Singapore's situation nor compared the licensed conjugate vaccines in an Asian population. This paper estimates the costs and public health impacts of pneumococcal conjugate vaccine programs, varying estimates of serotype replacement and herd immunity effects as key parameters in the analysis. Based in part on a 2008 analysis also presented here, Singapore has approved the PCV-7, PHiD-10, and PCV-13 pneumococcal conjugate vaccines as part of its National Childhood Immunisation Programme.

Methods

An economic evaluation was performed using a Markov simulation model populated with Singapore-specific population parameters, vaccine costs, treatment costs, and disease incidence data. The vaccinated infant and child cohort of 226,000 was 6% of the Singapore resident population of 3.8 million. Vaccine efficacy estimates were constructed for PCV-7, PHiD-10, and PCV-13 vaccines based on their serotype coverage in Singapore and compared to ‘no vaccination’. The model estimated impacts over a five-year time horizon with 3% per year discounting of costs and health effects. Costs were presented in 2010 U.S. dollars (USD) and Singapore dollars (SGD). Sensitivity analyses included varying herd immunity, serotype replacement rates, vaccine cost, and efficacy against acute otitis media.

Results

Under base case assumptions for the revised analysis (i.e., herd effects in the unvaccinated population equivalent to 20% of direct effects) PCV-13 prevented 834 cases and 7 deaths due to pneumonia, meningitis, and bacteremia in the vaccinated population, and 952 cases and 191 deaths in the unvaccinated population over the 5-year time horizon. Including herd effects, the cost-effectiveness ratio for PCV-13 was USD $37,644 (SGD $51,854) per QALY. Without herd effects, however, the ratio was USD $204,535 (SGD $281,743) per QALY. The PCV-7 cost per QALY including herd effects was USD $43,275 (SGD $59,610) and for PHiD-10 the ratios were USD $45,100 (SGD $62,125). The original 2008 analysis, which had higher estimates of pneumonia prevention due to herd immunity and lower estimates of cost per dose, had found a cost-effectiveness ratio of USD $5562 (SGD $7661) per QALY for PCV-7.

Conclusions

When compared to cost-effectiveness thresholds recommended by the World Health Organization (WHO), our 2008 analysis found that vaccination of infants in Singapore with PCV-7 was very cost-effective if herd immunity effects were present. However, knowledge on herd immunity and serotype replacement that emerged subsequent to this analysis changed our expectations about indirect effects. Given these changed inputs, our current estimates of infant vaccination against pneumococcal disease in Singapore find such programs to be moderately cost-effective compared to WHO thresholds. The different findings from the 2008 and 2011 analyses suggest that the dynamic issue of serotype replacement should be monitored post-licensure and, as changes occur, vaccine effectiveness and cost-effectiveness analyses should be re-evaluated.