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Background: The World Health Organization (WHO) encourages countries to provide appropriate vaccinations for children, adolescents, and relevant adult populations. Childhood programme have been the focus of global investments, but recent pandemics have increasingly demonstrated the value of life course vaccination. Our objective is to compare national life course immunization programmatic maturity prior to mass COVID-19 vaccine introduction, the largest adult vaccination programme, globally. As coverage estimates (typically used to assess childhood programmes) are not available for adult vaccinations, this analysis pilots a standardized quantitative metric of programmatic maturity., Methods: Through consultation with vaccination experts, we developed a standardized approach to assess national immunization programme maturity across the life course. In accordance with expert input, five vaccines were selected to represent delivery across the life course: diphtheria tetanus toxoid and pertussis (DTP); measles (MCV) second dose; human papillomavirus (HPV) final dose; pneumococcal conjugate (PCV) final dose; and seasonal influenza annual dose. Experts recommended inclusion of the following indicators for each vaccine: a legal mandate (national policy), experience delivering the vaccine (programme duration), and vaccine use (uptake for relevant populations). We developed a metric accordingly that provides up to 5 points per vaccine ("vaccine specific maturity score") which when summed forms the "life course maturity score", with a maximum score of 25. We analysed the prevalence of national policies, experience, and use by region and World Bank income group., Results: More than 55% of the 194 WHO Member States had childhood vaccine policies for all three of the vaccines considered (DTP, MCV, and PCV) compared to 60% for HPV (proxy for adolescent vaccination programme) and 52% for seasonal influenza (proxy for adult vaccination programme). Childhood vaccination programmes (e.g., MCV and DTP) had the highest vaccine specific maturity scores, while seasonal influenza and HPV vaccination programmes had much lower scores. The national life course maturity scores ranged from 1 to 23, with a global median of 12 (IQR: 8; 16)., Discussion: The piloted metric provides an overview of the maturity of life course immunization programmes. The metric is structured to be a flexible, rapid resource that can be used to assess other combinations of vaccines across the life course. The findings from this paper provide a baseline of immunization programme maturity for childhood, adolescent, and adult vaccination programmes immediately prior to the COVID-19 vaccine introduction. This maturity score, or adaptations of this approach, could be used to monitor the trajectory of national immunization programme maturity across the life course in the years ahead., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: As part of the Immunisation Agenda 2030, the World Health Organization set a goal to reduce the number of children who did not receive any routine vaccine by 50% by 2030. We aimed to describe the patterns of vaccines received for children with zero, one, and up to full vaccination, while considering newly deployed vaccines (pneumococcal conjugate vaccine (PCV) and rotavirus (ROTA) vaccine) alongside longstanding ones such as the Bacille Calmete-Guérin (BCG), diphtheria, tetanus, and pertussis (DPT), and poliomyelitis vaccines, and measles-containing vaccines (MCVs)., Methods: We used data from national household surveys (Demographic and Health Surveys and Multiple Indicator Cluster Surveys) carried out in 43 low- and middle-income countries since 2014. We calculated the immunisation cascade as a score ranging from zero to six, considering BCG, polio, DPT, and ROTA vaccines, and the MCV and PCV. We also described the most prevalent combination of vaccines. The analyses were pooled across countries and stratified by household wealth quintiles., Results: In the pooled analyses with all countries combined, 9.0% of children failed to receive any vaccines, 58.6% received at least one dose of each of the six vaccines, and 47.2% were fully vaccinated with all doses. Among the few children receiving 1-5 vaccines, the most frequent were BCG vaccines, polio vaccines, DPT vaccines, PCV, ROTA vaccines, and MCV., Conclusions: Targeting children with their initial vaccine is crucial, as those who receive a first vaccine are more likely to undergo subsequent vaccinations. Finding zero-dose children and starting their immunisation is essential to leaving no one behind during the era of Sustainable Development Goals., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: TM and DHR are employed by Gavi, the Vaccine Alliance, the sponsor of this research. The remaining (BCP, TMS, LA, FC, CGV, and AJDB) declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views or policies of the institutions with which they are affiliated., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

Streptococcus pneumoniae carriage studies are crucial to monitor changes induced by use of pneumococcal conjugate vaccines and inform vaccination policies. In this cross-sectional study, we examined changes within the pneumococcal population following introduction of PCV13 in 2015 in the National Immunization Program (NIP), in Portugal. In 2018-2020 (NIP-PCV13), we obtained 1450 nasopharyngeal samples from children ≤6 years attending day-care. We assessed serotypes, antimicrobial resistance, and genotypes (MLST and GPSC) and compared findings with earlier periods: 2009-2010 (pre-PCV13), 2011-2012 (early-PCV13), and 2015-2016 (late-PCV13). Pneumococcal carriage prevalence remained stable at 60.2 %. Carriage of PCV13 serotypes was 10.7 %, markedly reduced compared to pre-PCV13 period (47.6 %). The most prevalent PCV13 serotypes were 19F, 3, and 19A all showing a significant decreasing trend compared to the pre-PCV13 period (from 7.1 % to 4.7 %, 10.1 % to 1.8 %, and 14.1 % to 1.8 %, respectively), a notable observation given the described limited effectiveness of PCV13 against serotype 3. Non-vaccinated children and children aged 4-6 years were more likely to carry PCV13 serotypes (2.5-fold, 95 %CI [1.1-5.6], and 2.9-fold, 95 %CI [1.3-6.8], respectively). The most prevalent non-PCV13 serotypes were 15B/C, 11A, 23B, 23A, and NT, collectively accounting for 51.9 % of all isolates. In total, 30.5 % of all pneumococci were potentially covered by PCV20. Resistance to penicillin (low-level) and macrolides increased significantly, from 9.3 % and 13.4 %, respectively, in the late-PCV13 period, to approximately 20 % each, mostly due to lineages expressing non-PCV13 serotypes, nearing pre-PCV13 levels. An expansion of lineages traditionally associated with PCV13 serotypes, like CC156-GPSC6 (serotype 14) and CC193-GPSC11 (serotype 19F), but now predominantly expressing non-PCV13 serotypes (11A, 15B/C, and 24F for GPSC6; and 15A and 21 for GPSC11) was noted. These findings indicate that the pneumococcal population is adapting to the pressures conferred by PCV13 and antimicrobial use and indicate the need to maintain close surveillance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RSL has received consulting and speaking fees from Pfizer and Merck Sharp & Dome. RSL has received funds for unrestricted research grants from Pfizer and Merck Sharp & Dome, paid directly to her institution. ABA has received consulting and speaking fees from Pfizer and Merck Sharp & Dome. All other authors declare they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Streptococcus pneumonia is responsible for 18% of infant deaths in Ghana. With co-financing from Gavi in 2012, Ghana introduced the PCV13 into the childhood immunization programme to reduce the burden of Streptococcus pneumonia. However, Ghana will graduate to the Gavi fully self-financing phase in 2026, when the nation assumes full responsibility of paying for the PCV13. This research aims to evaluate the health impact and cost-effectiveness of PCV13 immunization in Ghana since its implementation and after the cessation of support from Gavi., Methods: We used the UNIVAC tool to evaluate two main scenarios of cost-effectiveness, from vaccine introduction (2012-2025) and after Gavi transition (2026-2031) in comparison with no vaccination. The sources of data include national data, international estimates and expert opinion. Cost was considered from both the government and societal perspectives. We discounted health outcomes at 3%. Currency values were stated in US Dollars. We tested the robustness of the base case results by performing scenario and sensitivity analyses., Results: PCV13 will reduce the pneumococcal disease burden by 48% from 2012 to 2031. The vaccination programme costs are USD 130 million and USD 275 million in 2012-2025 and 2026-2031 respectively. It also has a budget impact of USD 280 million for the 2026-2031 period from the perspective of government. The incremental cost-effectiveness ratios are USD 89 and USD 73 respectively from the perspectives of government and society in 2012-2025. The incremental cost-effectiveness ratios are USD 530 and USD 510 respectively from the perspectives of government and society in 2026-2031., Conclusion: The PCV13 vaccination programme in Ghana is cost-effective at 50% GDP per capita threshold even when Gavi withdraws co-financing support from 2026 onwards., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ibrahim, Owusu and Nonvignon.)

Background: Vaccination against pneumococci is currently the most effective method of protection against pneumococcal infections. The aim of the study was to analyse changes in hospitalisations and in-hospital deaths due to pneumonia before (2009-2016) and after (2017-2020) the introduction of PCV 10 vaccinations in the National Immunisation Programme in Poland., Methods: Data on hospitalisations related to community acquired pneumonia (CAP) in the years 2009-2020 were obtained from the Nationwide General Hospital Morbidity Study. Analyses were made in the age groups: <2, 2-3, 4-5, 6-19, 20-59, 60+ years in 2009-2016 and 2017-2020., Results: Overall, there were 1,503,105 CAP-related hospitalisations in 2009-2020, 0.7% of which were caused by Streptococcus pneumoniae infections. Children <2 years of age were the most frequently hospitalised for CAP per 100,000 population, followed by patients aged 2-3, 4-5 and 60+ years. In the years 2009-2016, the percentage of CAP hospital admissions increased significantly, and after the year 2017, it decreased significantly in each of the age groups (p<0.001). In the years 2009-2016, a significant increase in hospitalisations for Streptococcus pneumoniae infections was observed in the age groups <2, 2-3 and 4-5 years (p<0.05). A significant reduction in hospitalisations was observed in the age groups <2, 20-59 and 60+ in 2017-2020 (p<0.05). In the years 2009-2020, there were 84,367 in-hospital deaths due to CAP, 423 (0.5%) of which due to Streptococcus pneumoniae, with patients mainly aged 60+., Conclusions: Implementation of the PCV vaccination programme has effectively decreased the incidence of CAP hospitalisations, including children <2 years of age. The group that is most at risk of death are persons aged 60+. The results of our study can be useful in evaluating the vaccine efficacy and benefits, and they can be an essential part of public health policy. Effective prevention strategies for CAP should be implemented in different age groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier India Pvt Ltd. All rights reserved.)

Objective: To assess the health and economic outcomes of a PCV13 or PCV15 age-based (65 years-and-above) vaccination program in Switzerland., Interventions: The three vaccination strategies examined were:Target population: All adults aged 65 years-and-above. Perspective(s): Switzerland health care payer., Time Horizon: 35 years. Discount rate: 3.0%. Costing year: 2023 Swiss Francs (CHF)., Study Design: A static Markov state-transition model., Data Sources: Published literature and publicly available databases or reports., Outcome Measures: Pneumococcal diseases (PD) i.e., invasive pneumococcal diseases (IPD) and non-bacteremic pneumococcal pneumonia (NBPP); total quality-adjusted life-years (QALYs), total costs and incremental cost-effectiveness ratios (CHF/QALY gained)., Results: Using an assumed coverage of 60%, the PCV15 strategy prevented a substantially higher number of cases/deaths than the PCV13 strategy when compared to the No vaccination strategy (1,078 IPD; 21,155 NBPP; 493 deaths). The overall total QALYs were 10,364,620 (PCV15), 10,364,070 (PCV13), and 10,362,490 (no vaccination). The associated overall total costs were CHF 741,949,814 (PCV15), CHF 756,051,954 (PCV13) and CHF 698,329,579 (no vaccination). Thus, the PCV13 strategy was strongly dominated by the PCV15 strategy. The ICER of the PCV15 strategy (vs. no vaccination) was CHF 20,479/QALY gained. In two scenario analyses where the vaccine effectiveness for serotype 3 were reduced (75% to 39.3% for IPD; 45% to 23.6% for NBPP) and NBPP incidence was increased (from 1,346 to 1,636/100,000), the resulting ICERs were CHF 29,432 and CHF 13,700/QALY gained, respectively. The deterministic and probabilistic sensitivity analyses demonstrated the robustness of the qualitative results-the estimated ICERs for the PCV15 strategy (vs. No vaccination) were all below CHF 30,000/QALYs gained., Conclusions: These results demonstrate that using PCV15 among adults aged 65 years-and-above can prevent a substantial number of PD cases and deaths while remaining cost-effective over a range of inputs and scenarios., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [This study was performed by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Kwame Owusu-Edusei and Nicole Cossrow are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may hold stock or stock options in Merck & Co., Inc., Rahway, NJ, USA. Andrea-Favre-Bulle and Thomas Mutschler are employees of MSD, Lucerne, Switzerland and may hold stock or stock options in Merck & Co., Inc., Rahway, NJ, USA. Eleana Tsoumani is an employee of MSD, Athens, Greece and may hold stock or stock options in Merck & Co., Inc., Rahway, NJ, USA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in—or financial conflict with—the subject matter or materials discussed in this manuscript apart from those disclosed herewith]., (Copyright © 2024. Published by Elsevier India Pvt Ltd.)

Introduction: Infant immunization programs using pneumococcal conjugate vaccines (PCVs) have reduced the rates of pneumococcal disease through direct vaccine-induced protection in vaccinated children and through indirect protection in non-vaccinated children and adults., Areas Covered: This review summarizes current evidence on the indirect protection of adults conferred by pediatric pneumococcal vaccination, including the impact on invasive pneumococcal disease (IPD) incidence and mortality, pneumonia admissions, and nasopharyngeal carriage prevalence. Factors affecting indirect protection against IPD are also discussed., Expert Opinion: Pediatric immunization with PCVs has substantially decreased vaccine-serotype IPD and pneumonia through indirect protection in both older (≥65 years of age) and younger adults, including those with underlying medical conditions. However, serotype replacement by non-vaccine serotypes, the persistence of some vaccine serotypes, and divergence of serotypes between children and adults have limited the impact of pediatric PCV programs on adult populations. Designing complementary vaccines that leverage indirect protection from pediatric immunization and target the most prevalent adult serotypes may be a preferred strategy to maximize the public health impact of pneumococcal vaccination.

Objectives: The 13-valent (PCV13) and 10-valent (PCV10) pneumococcal conjugate vaccines missed non-inferiority for certain 7-valent (PCV7) serotypes in immunogenicity trials. This study examines the population-level IPD case trends for these serotypes., Methods: We identified six countries with national IPD surveillance data that introduced PCV13 (Canada, Germany, Israel, Italy, South Africa, and the United States) and three with PCV10 (Finland, Brazil, and the Netherlands). We extracted country-specific annual IPD case counts for PCV7 serotypes that missed non-inferiority and met non-inferiority (6B + 23F and PCV7 minus [6B + 23F] serotypes for PCV10 countries; 6B +9V + 23F, and PCV7 minus [6B +9V + 23F] serotypes for PCV13 countries) in clinical trials. Case count data for each country were plotted for observed serotype trends in different age groups (<5 and ≥5 years) for 8 years following PCV13/PCV10 introduction., Results: For all ages and countries, IPD cases due to PCV7 serotypes that missed non-inferiority either decreased or remained suppressed following PCV13/PCV10 introduction. Similar trends were found for PCV7 serotypes that met non-inferiority in those <5 years. Paradoxically, cases increased in those ≥5 years in Canada, Italy, and the US, primarily driven by increases in serotypes 4 and 19F disease., Conclusions: Despite missing non-inferiority of serotypes in immunogenicity trials, higher-valent PCVs effectively suppressed these serotypes across all ages. Non-inferiority criteria from immunogenicity trials may not fully predict real-world disease impact after PCV implementation.

Objective: To assess the contribution of partners in the introduction of two new vaccines concurrently: pneumococcal 10-valent conjugate vaccine (PCV-10) and inactivated polio vaccine (IPV) into the routine Expanded Programme on Immunization (EPI) in Bangladesh., Design: We conducted a prospective process evaluation that included the theory of change development, root cause analysis and in-depth investigation. As part of process tracking, we reviewed relevant documents, observed trainers' and vaccinators' training and key stakeholder meetings. We analysed the data thematically., Setting: We purposively selected eight Upazila (subdistrict) and one city corporation covering nine districts and seven administrative divisions of Bangladesh., Participants: Nineteen national key informants were interviewed and 16 frontline health workers were invited to the group discussions considering their involvement in the vaccine introduction process., Results: The EPI experienced several challenges during the joint introduction of PCV-10 and IPV, such as frequent changes in the vaccine introduction schedule, delays in budget allocation, vaccine supply shortage and higher wastage rates of IPV. EPI addressed these challenges in collaboration with its partners, that is, the World Health Organization (WHO) and United Nations Children's Fund (UNICEF), who provided technical assistance to develop a training curriculum and communication materials and enhanced demand generation at the community level. In addition, the WHO conducted a country readiness assessment for PCV-10, and UNICEF supported vaccine shipment. Other government ministries, City Corporations and municipalities also supported the EPI., Conclusions: The partnership among the EPI stakeholders effectively addressed various operational challenges during the joint introduction of PCV-10 and IPV helped strengthen Bangladesh's immunisation systems. These accomplishments are attributed to several factors that should be supported and strengthened for future vaccine introductions in Bangladesh and other low and-middle countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The potential occurrence of disease outbreaks during the hajj season is of great concern due to extreme congestion in a confined space. This promotes the acquisition, spread and transmission of pathogenic microorganisms and pneumococcal disease are one of the most frequent infections among Hajj pilgrims. This study aimed to assess the cost-effectiveness and budget impact of introducing the PPV23 to Malaysian Hajj pilgrims. A decision tree framework with a 1-year cycle length was adapted to evaluate the cost-effectiveness of a PPV23 vaccination program with no vaccination. The cost information was retrieved from the Lembaga Tabung Haji Malaysia (LTH) database. Vaccine effectiveness was based on the locally published data and the disease incidence specifically related to Streptococcus pneumoniae was based on a literature search. Analyses were conducted from the perspective of the provider: Ministry of Health and LTH Malaysia. The incremental cost-effectiveness ratios (ICER), cases averted, and net cost savings were estimated. Findings from this study showed that PPV23 vaccination for Malaysian Hajj pilgrims was cost-effective. The PPV23 vaccination programme has an ICER of MYR -449.3 (US$-110.95) per case averted. Based on the national threshold value of US$6,200-US$8,900 per capita, the base-case result shows that introduction of the PPV23 vaccine for Malaysian Hajj pilgrims is very cost-effective. Sensitivity analysis revealed parameters related to annual incidence and hospitalised cost of septicemia and disease without vaccination as the key drivers of the model outputs. Compared with no vaccination, the inclusion of PPV23 vaccination for Malaysian Hajj pilgrims was projected to result in a net cost saving of MYR59.6 million and 109,996 cases averted over 5 years period. The PPV23 vaccination program could substantially offer additional benefits in reducing the pneumococcal disease burden and healthcare cost. This could be of help for policymakers to consider the implementation of PPV23 vaccination for Malaysian performing hajj., Competing Interests: The authors have declared that no competing interests exist.

Administration of many childhood vaccines requires that multiple doses be delivered within a narrow time window to provide adequate protection and reduce disease transmission. Accurately quantifying vaccination coverage is complicated by limited individual-level data and multiple vaccination mechanisms (routine and supplementary vaccination programs). We analyzed 12,541 vaccination cards from 6 districts across Madagascar for children born in 2015 and 2016. For 3 vaccines-pentavalent diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine (DTP-HB-Hib; 3 doses), 10-valent pneumococcal conjugate vaccine (PCV10; 3 doses), and rotavirus vaccine (2 doses)-we used dates of vaccination and birth to estimate coverage at 1 year of age and timeliness of delivery. Vaccination coverage at age 1 year for the first dose was consistently high, with decreases for subsequent doses (DTP-HB-Hib: 91%, 81%, and 72%; PCV10: 82%, 74%, and 64%; rotavirus: 73% and 63%). Coverage levels between urban districts and their rural counterparts did not differ consistently. For each dose of DTP-HB-Hib, the overall percentage of individuals receiving late doses was 29%, 7%, and 6%, respectively; estimates were similar for other vaccines. Supplementary vaccination weeks, held to help children who had missed routine care to catch up, did not appear to increase the likelihood of being vaccinated. Maintaining population-level immunity with multiple-dose vaccines requires a robust stand-alone routine immunization program., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

New vaccine introduction accompanied by social mobilization activities could contribute to improved routine immunization timeliness. This study assesses the impact of Kenya's introduction of pneumococcal conjugate vaccine (PCV) on the timeliness of routine childhood vaccination in two informal, urban settlements in Nairobi. Data collected from 2007 to 2015 as part of a demographic surveillance system were used to estimate annual vaccination delays of ≥ 4 weeks among children aged 12-23 months in the period before and after the introduction of PCV in Kenya. Binomial segmented regression models using generalized estimating equations examined the association between vaccine introduction and timeliness of routine immunization. Over half of all children vaccinated in the two urban areas received one or more doses ≥ 4 weeks after the recommended age. The timeliness of routine immunization showed slight improvements or nonsignificant changes during the years following PCV introduction compared with the preceding years (adjusted prevalence ratio [aPR]: 0.67, 95% CI: 0.45-0.99 for Bacille Calmette-Guerin receipt; aPR: 0.59, 95% CI: 0.41-0.83 for third dose Pentavalent receipt; aPR: 1.19, 95% CI: 0.99-1.42 for measles). However, as of 2015, delayed vaccination remained prevalent in children, particularly among the poorest residing in the settlements. Many sub-Saharan African countries have introduced new life-saving vaccines into their routine childhood immunization schedule. Additional evidence regarding the positive or neutral influence of new vaccine introduction on the performance of delivery systems provides further justification to sustain the inclusion of these more costly vaccines in the immunization schedule.

Introduction: Streptococcus pneumoniae is a cause of infections that range in severity from acute otitis media (AOM) to pneumonia and invasive pneumococcal disease (IPD). The 10-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced into the Icelandic paediatric immunisation programme in 2011. The aim was to estimate the population impact and cost-effectiveness of PHiD-CV10 introduction., Methods: Data on primary care visits from 2005-2015 and hospitalisations from 2005-2017 were obtained from population-based registries. A Bayesian time series analysis with synthetic controls was employed to estimate the number of cases of AOM, pneumonia and IPD that would have occurred between 2013-2017, had PHiD-CV10 not been introduced. Prevented cases were calculated by subtracting the observed number of cases from this estimate. The cost of the programme was calculated accounting for cost-savings due to prevented cases., Results: The introduction of PHiD-CV10 prevented 13,767 (95% credible interval [CI] 2,511-29,410) visits for AOM from 2013-2015, and prevented 1,814 (95%CI -523-4,512) hospitalisations for pneumonia and 53 (95%CI -17-177) admissions for IPD from 2013-2017. Visits for AOM decreased both among young children and among children 4-19 years of age, with rate ratios between 0.72-0.89. Decreases were observed in both pneumonia hospitalisations (rate ratios between 0.67-0.92) and IPD (rate ratios between 0.27-0.94). The total cost of implementing PHiD-CV10 in Iceland was -7,463,176 United States Dollars (USD) (95%CI -16,159,551-582,135) with 2.1 USD (95%CI 0.2-4.7) saved for every 1 USD spent., Conclusions: The introduction of PHiD-CV10 was associated with large decreases in visits and hospitalisations for infections commonly caused by pneumococcus and was cost-saving during the first five years of the immunisation programme., Competing Interests: An investigator-initiated study funded by GlaxoSmithKline Biologicals SA. Additionally, a grant was received from the Landspitali University Hospital Research Fund. GlaxoSmithKline Biologicals SA was provided the opportunity to review a draft version of this manuscript, but the authors are solely responsible for final content and interpretation. The authors received no financial support or other form of compensation related to the development of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: Pneumococcal diseases including invasive pneumococcal disease (IPD), pneumonia, and acute otitis media (AOM) impose a substantial public health burden. This study performed a budget impact analysis of the use of pneumococcal conjugate vaccines (PCVs) in the National Immunization Program (NIP) in Colombia. Methods: We compared the direct medical cost of the scenario without and with PCV vaccination using either pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) or 13-valent pneumococcal conjugate vaccine (PCV-13) over 5 years (2020-2024) from the health-care system perspective. Vaccine efficacy estimates were obtained from published sources and vaccine prices were taken from the Pan-American Health Organization Revolving Fund. Vaccine coverage was assumed to be 90% based on Colombia data. Results: Using PHiD-CV in the NIP in Colombia would reduce the estimated cost for treating pneumococcal disease by US$46.1 m over the 2020-2024 period (US$40.2 m using PCV-13), with a budget impact of US$100.1 m for PHiD-CV (US$121.4 m for PCV-13), and would cost US$3.1 m less per year on vaccine doses than using PCV-13. Conclusion: These findings are potentially valuable for the selection of vaccines for their national immunization programs under conditions of budgetary constraint.

Background: Ten-valent and 13-valent pneumococcal conjugate vaccines (PCVs) have shown important benefits by decreasing invasive pneumococcal disease caused by vaccine serotypes. Belgium had an uncommon situation with sequential use of PCV7, PCV13, and PCV10 in the childhood vaccination programmes between 2007 and 2018. We aimed to analyse the changes in incidence of invasive pneumococcal disease and serotype distribution in children throughout this period., Methods: Streptococcus pneumoniae isolates were obtained from patients with invasive pneumococcal disease in Belgium between 2007 and 2018 by the national laboratory-based surveillance. Paediatric invasive pneumococcal disease incidence, serotype distribution, and antimicrobial susceptibility were analysed in periods during which PCV7 (2009-10), PCV13 (2013-14), both PCV13 and PCV10 (2015-16), and PCV10 (2017-18) were used. Incidence rates and trends were compared. Vaccination status was collected. For a subset of serotype 19A isolates, multilocus sequence type was identified., Findings: After a decrease in PCV7 serotype invasive pneumococcal disease was observed during the PCV7 period, total paediatric invasive pneumococcal disease incidence significantly declined during the PCV13 period (-2·6% monthly, p<0·0001). During the PCV13-PCV10 period (2015-16), the lowest mean in paediatric invasive pneumococcal disease incidence was achieved, but the incidence increased again during the PCV10 period (2017-18), especially in children younger than 2 years (+1·7% monthly; p=0·028). This increase was mainly due to a significant rise in serotype 19A invasive pneumococcal disease incidence in the PCV10 period compared with the PCV13 period (p<0·0001), making serotype 19A the predominant serotype in paediatric invasive pneumococcal disease in the PCV10 period. Genetic diversity within the 2017-18 serotype 19A collection was seen, with two predominant clones, ST416 and ST994, that were infrequently observed before PCV10 introduction. In 2018, among children younger than 5 years with invasive pneumococcal disease who were correctly vaccinated, 37% (37 of 100) had PCV13 serotype invasive pneumococcal disease, all caused by serotype 19A and serotype 3., Interpretation: After a significant decrease during the PCV13 period, paediatric invasive pneumococcal disease incidence increased again during the PCV10 period. This observation mainly resulted from a significant increase of serotype 19A cases. During the PCV10 period, dominant serotype 19A clones differed from those detected during previous vaccine periods. Whether changes in epidemiology resulted from the vaccine switch or also from natural evolution remains to be further elucidated., Funding: The Belgian National Reference is funded by the Belgian National Institute for Health and Disability Insurance and the whole genome sequencing by an investigator-initiated research grant from Pfizer., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The long-term benefits of pneumococcal conjugate vaccines (PCVs) remain unknown because of serotype replacement. We aimed to estimate the effect of PCV implementation on invasive pneumococcal disease incidence in France., Methods: We did a quasi-experimental interrupted time-series analysis using data from a French national prospective surveillance system. We included all invasive pneumococcal disease cases in children and adults from more than 250 participating hospitals between Jan 1, 2001, and Dec 31, 2017. The primary outcome was incidence of invasive pneumococcal disease (meningitis and non-meningitis) over time, analysed by segmented regression with autoregressive error. Isolates were serotyped by latex agglutination with antiserum samples., Findings: We included 75 903 patients with invasive pneumococcal disease, including 4302 (5·7%) children younger than 2 years and 37 534 (49·4%) adults aged 65 years or older. Before PCV7 implementation, the estimated monthly incidence of invasive pneumococcal disease was 0·78 cases per 100 000 inhabitants, which did not change significantly up to May, 2010. PCV13 implementation in 2010 was followed by a significant decrease in the incidence of invasive pneumococcal disease (-1·5% per month, 95% CI -2·2 to -0·8), reaching an estimated monthly incidence of 0·52 cases per 100 000 inhabitants in December, 2014. From January, 2015, the incidence rebounded (1·8% per month, 95% CI 1·0 to 2·6), reaching an estimated monthly incidence of 0·73 cases per 100 000 inhabitants in December, 2017. The estimated monthly incidence increased from 0·93 cases per 100 000 in December, 2014, to 1·73 cases per 100 000 in December, 2017, for children younger than 2 years, and from 1·54 cases per 100 000 in December, 2014, to 2·08 cases per 100 000 in December, 2017, for adults aged 65 years or older. The main non-PCV13 serotypes involved in the increase were 24F in young children and 12F, 22F, 9N, and 8 in adults aged 65 years or older., Interpretation: PCV13 implementation led to a major reduction in the incidence of invasive pneumococcal disease. However, a rebound in cases among children and adults since 2015, driven by several emerging non-PCV13 serotypes, jeopardises the long-term PCV benefits. These findings, if confirmed in the coming years, should be considered in the development of next-generation PCVs and might guide policy makers in the selection of future pneumococcal vaccines., Funding: Foundation for Medical Research; Pfizer, BioMérieux, Sanofi for the Regional Observatory of Pneumococci., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Acute otitis media (AOM) is the most common reason for antimicrobial use, and tympanostomy tube placement (TTP) is the most common reason for surgery requiring general anesthesia in children. Ten-valent pneumococcal conjugate vaccine (PCV10) was introduced in Finland in 2010 for infants. We evaluated the indirect impact of PCV10 on these surrogate otitis outcomes in unvaccinated children., Methods: Using before-after design, unvaccinated children ineligible for National Vaccination Program (born January 2006 to May 2010) were followed-up during 2012-2016 (target cohort, age 1.5-7 years). The target cohort was compared with an age- and season-matched unvaccinated reference cohort (born January 2000 to May 2004) during 2006-2010. Antimicrobial purchase data were obtained from the Social Insurance Institution of Finland benefits register. We assessed the relative reduction by generalized Cox regression for outpatient purchases of antibiotics recommended for treatment of AOM in the Finnish guidelines. Data on all TTP procedures were obtained from national hospital discharge register and Social Insurance Institution benefits register., Results: The rate of outpatient purchases of antimicrobials recommended for AOM was 51 in the unvaccinated reference cohort and 44/100 person-years in the unvaccinated target cohort; relative rate reduction was 14.7% [95% confidence interval: 14.0-15.3] and absolute rate reduction 7/100 person-years. The rates of TTP in the reference and target cohorts were 1.66/100 and 1.61/100 person-years, respectively. The relative rate reduction was 3.6% (0.7-6.5)., Conclusions: Antimicrobial use and TTP procedures reduced in unvaccinated children after PCV10 introduction in infants. These indirect effects contribute to the savings in health care resource use for otitis and may also help in combating antimicrobial resistance.

Background: In 2011, Benin introduced the 13-valent pneumococcal conjugated vaccine (PCV13), in a single-dose vial, into its Expanded Programme for Immunisation (EPI) with support from Gavi. In April 2018, with the support of the Agence de Médecine Préventive Afrique (AMP) and other technical and financial partners, the single-dose vial was transitioned to a four-dose vial. Here we describe the decision-making process and the experience of the vaccinators during the change., Methods: We carried out semi-structured, individual interviews with 61 participants individuals involved in the EPI: 7 from central level, 5 from regional level, 7 from township level and 42 from district level. The interviews were recorded and transcribed, and the information categorised, using Nvivo software, and then analysed., Results: The Inter-agency Coordination Committee (ICC), the Benin National Advisory Committee for Vaccines and Vaccination, (BNACVV) and the World Health Organisation (WHO) (i.e., the traditional governance structures involved in vaccination decisions) were not involved in the decision to change to the four-dose vial for PCV13. The decision was taken by the EPI, supported by Gavi. The vaccination errors observed in the first months following the change in presentation were due to the absence of guidelines for changes in vaccine presentation and the central-level actors' perception that it was 'only a change in the vial', and therefore that the communication and training for a new vaccine were not required since the vaccine itself and its administration mode were unchanged., Conclusions: It is important that the other countries eligible for Gavi support that are about to change to the multi-dose vial PCV13 presentation learn from Benin's experience. The main lessons learned are that changes in the presentation of an established vaccine should follow the same process as the introduction of a new vaccine, and that all stakeholders involved in vaccines and vaccination should participate in the decision-making process and implementation.

Objectives: To evaluate the cost-effectiveness of introducing a domestic pneumococcal conjugate vaccine (PCV7-TT) into the Cuban National Immunization Program (NIP)., Methods: We compared PCV7-TT given at two, four and six months of age to a scenario without PCV7-TT, over a ten-year period (2020-2029). We calculated the cost (Cuban pesos - CUP) per Disability Adjusted Life Year (DALY) averted from a Government perspective. We compared results from a static cohort model and a parsimonious prediction model informed by the serotype distribution among pneumococcal carriers and cases. We ran probabilistic and deterministic uncertainty analyses., Results: PCV7-TT could prevent 6897 (95% uncertainty interval, 4344-8750) hospitalizations and 189 (115-253) deaths in children <5 years of age, over the period 2020-2029. This could cost around 25 million (20-31) discounted CUP but would be offset by treatment cost savings of around 23 million (14-31). A parsimonious model predicted less favourable impact and cost-effectiveness but the cost per DALY averted was still less than 0.4 times the current GDP per capita., Conclusions: PCV7-TT is likely to be cost-effective in Cuba. The impact of the vaccine would need to be carefully monitored following its introduction into the NIP., (Copyright © 2020. Published by Elsevier Ltd.)

Pneumococcal vaccination has been shown to reduce occurrence of invasive pneumococcal diseases in elderly patients. In this study, we investigated the real-world efficacy of pneumococcal vaccination implemented in elderly individuals in Japan. We reviewed the in-patient database of Juntendo University Hospital and selected elderly patients (≥65 years-old) who had received in-patient care in the general medicine department during 2014-2018. A total of 1355 patients were retrospectively enrolled and comprised of 1045 unvaccinated and 315 vaccinated elderly individuals. Prior vaccination was found associated with all-cause shorter hospital stays (adjusted RR = 0.66, 95% CI = 0.57 to 0.76) and less medical expenditure (adjusted RR = 0.76, 95% CI = 0.66 to 0.87) compared with no vaccination, as well as protection for all-cause in-hospital mortality (adjusted OR = 0.42, 95% CI = 0.22 to 0.83). The association of shorter hospital stays and less medical expenditure with vaccination was also observed in the context of pneumonia, although no altered risk in mortality was observed. In conclusion, this study is one of the first reporting real-world data after the initiation of pneumococcal vaccination program in 2014 in Japan. The national PPV23 vaccination program contributed to the reduction of all-cause in-patient days, mortality, and medical expenses in the elderly aged ≥65 years. Further data is warranted to evaluate the contribution from influenza vaccination and protein-conjugate based pneumococcal vaccine., Competing Interests: Declaration of Competing Interest T.N. has received honoraria for lectures from MSD K.K. A.W. has received honoraria for lectures from MSD K.K and Pfizer K.K. The authors declare that they have no known competing financial interests., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Studies have shown that pneumococcal vaccination reduces the incidence of Streptococcus pneumoniae infections but does not change the prevalence of S. pneumoniae nasopharyngeal colonization. To comprehensively and longitudinally assess the epidemiology of S. pneumoniae after the introduction of pneumococcal vaccination, we monitored the prevalence and antimicrobial susceptibility of S. pneumoniae, irrespective of its serotypes or pathogenicity, by analyzing specimens collected from a large number of patients at Jikei University Hospitals from 2009 to 2017. A total of 5763 S. pneumoniae isolates were identified out of 375,435 specimens from various sources of patients in different age groups. The prevalence of S. pneumoniae isolated only from patients <5 years old was significantly reduced with the widespread use of pneumococcal vaccines, although this reduction differed by areas where patients resided. The incidence of pneumococcal infections, including bacteremia and otitis media, clearly decreased among patients <5 years old after the introduction of pneumococcal vaccination, while the prevalence of S. pneumoniae isolated from blood specimens of patients 15-64 years old increased, suggesting the involvement of non-vaccine serotypes in the incidence of invasive pneumococcal infections. The antimicrobial susceptibility of S. pneumoniae improved after the introduction of pneumococcal vaccination. Our results show that pneumococcal vaccination has a suppressive effect on the prevalence of S. pneumoniae and the incidence of pneumococcal infections, at least for children <5 years old, in association with an improvement in the antimicrobial susceptibility of S. pneumoniae. However, further measures will be needed to control invasive pneumococcal infections caused by non-vaccine serotypes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background/objectives: Recently revised vaccination recommendations for US adults, aged 65 years and older, include both 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13), with PCV13 now recommended for immunocompetent older people based on shared decision making. The public health impact and cost-effectiveness of this recommendation or of pneumococcal vaccine uptake improvement interventions are unclear., Design: Markov decision analysis., Setting and Participants: Hypothetical 65-year-old general and black population cohorts., Intervention: Current pneumococcal vaccination recommendations for US older people, an alternative policy omitting PCV13 in immunocompetent older people, and vaccine uptake improvement programs., Results: The current pneumococcal vaccination recommendation was the most effective strategy, but afforded slight public health benefits compared to an alternative (PPSV23 for all older people plus PCV13 for the immunocompromised) and cost greater than $750 000 per quality-adjusted life-year (QALY) gained in either population group with a vaccine uptake improvement program (absolute uptake increase = 12.3%; cost = $1.78/eligible patient) in place. The alternative strategy was more economically favorable, but cost greater than $100 000/QALY in either population, with or without an uptake intervention. Results were robust in sensitivity analyses; however, in black older people, the alternative strategy with an uptake program was most likely to be favored in probabilistic sensitivity analyses at a $150 000/QALY gained threshold., Conclusion: Current pneumococcal vaccination recommendations for US older people are economically unfavorable compared to an alternative strategy omitting PCV13 in the immunocompetent. The alternative recommendation with an uptake improvement program may be economically reasonable in black population analyses and could be worth considering as a population-wide recommendation if mitigating racial disparities is a priority. J Am Geriatr Soc 68:1271-1278, 2020., (© 2020 The American Geriatrics Society.)

Pneumonia is the third most common cause of death in Japan. Low vaccination rates are thought to be related to low levels of public subsidy. Since 2014, the Japanese government has offered subsidies through a 5-year national routine vaccination program of the 23-valent pneumococcal polysaccharide vaccine (PPV23) for older adults at age ≥65 years with 5-year age intervals. We previously reported that, 2 years into the 5-year program, the estimated vaccination rate was 40.6% at the end of 2015, a significant increase compared with periods before the program introduced. Here, we present an update on the estimated vaccination coverage of the 5-year national routine vaccination program at the end of 2018. The PPV23 vaccination rates were calculated by dividing the cumulative amount shipped to each municipality by the population aged ≥65 years. At the end of 2018, the completion of the 5-year national immunization program, the estimated cumulative vaccination rate was 74%. Stepwise regression analysis revealed that the annual PPV23 vaccination rate significantly increased after 2014 (from 2 to 5% prior to 2014, to 10-11% after 2014), and remained steady for 2014-2018. Our findings suggest that the 5-year national routine vaccination subsidy program was successful in achieving a steady and higher vaccination rate of PPV23 in Japan., Competing Interests: Declaration of Competing Interest T.N. has received a grant from Pfizer Inc. and honoraria for lectures from MSD K.K. A.W. have received honoraria for lectures from MSD K.K., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: When assessing the economic value of vaccines, decision makers should adopt a full societal perspective. One approach for estimation of the fiscal impact of a disease is to use the human capital method to determine productivity losses. The aim of this study was to test an analytical framework developed for the estimation of the fiscal impacts of vaccination programs for influenza (FLU), pneumococcus (PC), and herpes zoster (HZ), in Italy., Methods: We tested the framework in a two-stage analysis. First, we estimated the fiscal impact of the disease, second we performed a cost-benefit analysis of the individual benefits of vaccination against the cost of the vaccine. To estimate the fiscal impact of the diseases, the human capital approach was used. Epidemiological data were extrapolated from the literature. A Monte Carlo simulation enabled exploration of the uncertainty in the model variables., Results: For FLU, assuming 2.1 million people infected, the total expected impact was EUR 999,371,520; the estimated fiscal impact was EUR 159,563,520. For PC, assuming 90,000 people infected, the total impact was EUR 148,055,040 and the estimated fiscal impact was EUR 23,639,040. For HZ, assuming 6,400 people infected, the total impact was EUR 4,777,200, with EUR 630,000 resulting from a decrease in fiscal taxation., Conclusions: In conclusion, our work shows how traditional methods aimed at estimating the cost of illness from a social perspective can be improved by additionally considering the fiscal impact, which accounts for the decrease in fiscal revenues due to illness.

Background: Adults who suffer with severe and persistent mental illness (SPMI) rarely access medical care to receive preventive vaccines. Aims: To increase the rate of vaccines among the SPMI population in an outpatient community mental health center (CMHC). Methods: A review of the literature identified a gap between the general population and SPMI clients in receiving preventive vaccinations. An initial mixed-method convenience survey of SPMI clients ( n = 392) provided information on current vaccination status, demographics, beliefs, and interest in receiving vaccines. A vaccination program was developed to address identified barriers and increase vaccination rates. Postintervention data were collected through a mixed-method convenience survey of SPMI clients ( n = 60) who participated in immunizations clinics to evaluate client satisfaction. A partnership between the health department and CMHC was developed to deliver vaccines in a nontraditional site. Vaccines administered included annual influenza; hepatitis A; hepatitis B; herpes zoster; measles, mumps, and rubella; pneumococcal; and tetanus, diphtheria, and pertussis (Tdap). Results: More than 1,000 vaccines were administered in the first 8 months, with a significant increase in vaccination rates over baseline for individual vaccines ranging from 18.75% to 83%. Postintervention survey results found a 95% satisfaction rate. Conclusions: Implementation of a vaccination program in a nontraditional site that facilitates access for SPMI clients can promote an overwhelming increase in the vaccination rates for this underserved population. Results suggest that the integration of mental health and CMHC services can have a profound positive effect on SPMI population health.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official positon of the Centers for Disease Control and Prevention., Background: Continued indirect effects provided by the childhood pneumococcal conjugate vaccine (13-valent pneumococcal conjugate vaccine [PCV13]) program in the United States have decreased disease in the adult population, reducing the potential direct effects of vaccinating older adults., Objective: We examined the incremental cost-effectiveness of continuing to recommend PCV13 in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) at age 65 compared to a strategy that only included a recommendation for PPSV23 at age 65., Methods: We used a probabilistic model following a cohort of 65 year olds in 2019. We used vaccination coverage and disease incidence estimates for healthy adults and adults with chronic medical conditions. We incorporated continued indirect effects from the childhood PCV13 program on adult disease incidence., Results: In the base case scenario, continuing to recommend PCV13 at age 65 cost $561,682 per quality-adjusted life year (QALY) gained. In a scenario where PPSV23 provided modest protection against non-invasive pneumococcal pneumonia, costs increased to $2.3 million per QALY. These estimates are larger than our prior estimates for cost-effectiveness of this recommendation in the context of predicted indirect effects due to new data indicating PCV13 provided limited impact on serotype 3, the major cause of the remaining PCV13-type disease. Under our prior assumptions about PCV13 effectiveness against serotype 3 disease, the cost of continuing the recommendation is $207,607 per QALY., Conclusion: Indirect effects from the childhood PCV13 program have dramatically increased the cost per QALY of continuing to recommend PCV13 at age 65 after only a few years., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

Russia introduced PCV13 in 2014. We studied the serotype composition of S. pneumoniae isolated from the nasopharynx of healthy children younger than 6 years in St. Petersburg, Smolensk, Perm, Krasnoyarsk, Khanty-Mansiysk and Khabarovsk, between 2016 and 2018. 2.4% of children had completed a 3-dose course of PCV13, while 25.6% had received 1 or 2 doses. Pneumococcal DNA detection by PCR demonstrated S. pneumoniae in 37.2% of samples with regional variation between sites (27.3 to 56.9%). There was little difference between vaccinated, partially vaccinated and un-vaccinated children. Children who had received at least 1 dose of PCV13 had lower carriage rates of vaccine serotypes than their unvaccinated peers (49.9 vs. 61.4%; p < 0.001). Children who had received at least 1 dose of PCV13 showed increased carriage rates of non-vaccine serotypes (50 vs 38.6%; P < 0.001). Especially serogroup 15AF was more prevalent among fully immunized children than among their peers (12.5 vs 2.7%; P < 0.05)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Ontario, Canada introduced a publicly-funded 13-valent pneumococcal conjugate vaccine (PCV13) for infants in 2010, replacing the 10-valent (PCV10, 2009-2010) and the 7-valent (PCV7, 2005-2009) conjugate vaccine programs; a 23-valent pneumococcal polysaccharide vaccine (PPV23) has been available for older adults since 1996. We examined the epidemiology and serotype distribution of invasive pneumococcal disease (IPD) in Ontario in the context of provincial immunization programs., Methods: We included confirmed IPD cases reported in Ontario between 2007 and 2017. We grouped serotypes according to Ontario's current immunization program (PCV13, PPV23, and non-vaccine-preventable) and calculated incidence rates (per 100,000 population) using population data., Results: Between 2007 and 2017, annual incidence of IPD in Ontario ranged between 7.3 and 9.7/100,000 per year. Measures of illness severity were high throughout the period of surveillance. After PCV13 program implementation in 2010, incidence due to PCV13 serotypes decreased significantly across all age groups, with the greatest reductions in children <5 years and adults ≥65 years. Conversely, incidence due to PPV23 unique serotypes increased significantly between 2007 and 2017, with the greatest increases observed in adults 50-64 years (1.4 to 3.5/100,000) and ≥65 years (2.3 to 7.2/100,000). Similar increases were observed in incidence due to non-vaccine-preventable serotypes among all age groups, except infants <1 year. Within specific serotypes, incidence due to serotypes 3 (0.42 to 0.98/100,000) and 22F (0.31 to 0.72/100,000) increased significantly between 2007 and 2017, while incidence due to serotypes 19A and 7F decreased significantly during the PCV13 period (2010-2017)., Conclusions: Eight years after PCV13 implementation in Ontario, our data suggest both direct and indirect effects on serotype-specific incidence in young children and older adults. However, overall provincial rates have remained unchanged, and IPD continues to be a severe burden on the population. The rising incidence of IPD due to PPV23 unique and non-vaccine-preventable serotypes, and the growing burden of serotypes 3 and 22F, require further study., Competing Interests: The authors have declared that no competing interests exist.

Background: Streptococcus pneumoniae causes invasive pneumococcal disease (IPD), community-acquired pneumonia (CAP) and acute otitis media (AOM). Two higher-valent pneumococcal conjugate vaccines (PCV) are available, pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and 13-valent PCV (PCV-13). This study estimated the economic and health impact of PHiD-CV vaccination on pneumococcal disease burden in children <5 years of age in Brazil., Methods: The disease burden prior to the PHiD-CV vaccination program was estimated from literature and databases. The effect of PHiD-CV was estimated as a reduction of 70% for IPD, 26% for CAP and 40% for AOM, based on published studies. Residual IPD cases attributable to serotype 19A were estimated using surveillance data. PCV-13 effectiveness against 19A-IPD was set at 30%-70% higher than PHiD-CV. Vaccine prices were US$12.85/dose for PHiD-CV and US$14.50/dose for PCV-13., Results: PHiD-CV vaccination reduced IPD by 6359, CAP by 315,016 and AOM by 669,943 cases, with estimated cost savings of >US$84 million annually and US$211-22,232 per case averted depending on the outcome. Switching from PHiD-CV to PCV-13 would avoid only a few additional IPD cases at additional costs exceeding US$18 million per year (US$125,192-386,230 per IPD case averted)., Conclusions: The PHiD-CV vaccination program in Brazil has resulted in important reductions of pneumococcal disease and substantial cost savings. Instead of switching PCVs, expanding vaccine coverage or investing in other health care interventions would be a more efficient use of resources to improve the health of the population in Brazil.

Background: Pneumococcus is a leading cause of pneumonia and meningitis. Zambia introduced a 10-valent pneumococcal conjugate vaccine (PCV10) in July 2013 using a 3-dose primary series at ages 6, 10, and 14 weeks with no booster. We evaluated the impact of PCV10 on meningitis and pneumonia hospitalizations., Methods: Using hospitalization data from first-level care hospitals, available at the Ministry of Health, and from the largest pediatric referral hospital in Lusaka, we identified children aged <5 years who were hospitalized with pneumonia or meningitis from January 2010-December 2016. We used time-series analyses to measure the effect of PCV10 on monthly case counts by outcome and age group (<1 year, 1-4 years), accounting for seasonality. We defined the pre- and post-PCV10 periods as January 2010-June 2013 and July 2014-December 2016, respectively., Results: At first-level care hospitals, pneumonia and meningitis hospitalizations among children aged <5 years accounted for 108 884 and 1742 admissions in the 42 months pre-PCV10, respectively, and 44 715 and 646 admissions in the 30 months post-PCV10, respectively. Pneumonia hospitalizations declined by 37.8% (95% confidence interval [CI] 21.4-50.3%) and 28.8% (95% CI 17.7-38.7%) among children aged <1 year and 1-4 years, respectively, while meningitis hospitalizations declined by 72.1% (95% CI 63.2-79.0%) and 61.6% (95% CI 50.4-70.8%), respectively, in these age groups. In contrast, at the referral hospital, pneumonia hospitalizations remained stable and a smaller but significant decline in meningitis was observed among children aged 1-4 years (39.3%, 95% CI 16.2-57.5%)., Conclusions: PCV10 introduction was associated with declines in meningitis and pneumonia hospitalizations in Zambia, especially in first-level care hospitals., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: In October 2017, the United Kingdom Joint Committee on Vaccination and Immunisation (JCVI) recommended removal of one primary dose of the 13-valent pneumococcal conjugate vaccine (PCV13) from the existing 2+1 schedule (2, 4, 12 months). We conducted a mathematical modelling study to investigate the potential impact of a 1+1 (3, 12 month) schedule on invasive pneumococcal disease (IPD) and pneumococcal community-acquired pneumonia (CAP). Our results and those from a 1+1 immunogenicity study formed the key evidence reviewed by JCVI., Methods and Findings: We developed age-structured, dynamic, deterministic models of pneumococcal transmission in England and Wales to describe the impact on IPD of 7-valent PCV (PCV7; introduced in 2006) and PCV13 (introduced in 2010). Key transmission and vaccine parameters were estimated by fitting to carriage data from 2001/2002 and post-PCV IPD data to 2015, using vaccine coverage, mixing patterns between ages, and population data. We considered various models to investigate potential reasons for the rapid increase in non-PCV13 (non-vaccine serotype [NVT]) IPD cases since 2014. After searching a large parameter space, 500 parameter sets were identified with a likelihood statistically close to the maximum and these used to predict future cases (median, prediction range from 500 parameter sets). Our findings indicated that the emergence of individual NVTs with higher virulence resulting from ongoing replacement was likely responsible; the NVT increase was predicted to plateau from 2020. Long-term simulation results suggest that changing to a 1+1 schedule would have little overall impact, as the small increase in vaccine-type IPD would be offset by a reduction in NVT IPD. Our results were robust to changes in vaccine assumptions in a sensitivity analysis. Under the base case scenario, a change to a 1+1 schedule in 2018 was predicted to produce 31 (6, 76) additional IPD cases over five years and 83 (-10, 242) additional pneumococcal-CAP cases, with together 8 (-2, 24) additional deaths, none in children under 15 years. Long-term continuation with the 2+1 schedule, or changing to a 1+1, was predicted to sustain current reductions in IPD cases in under-64-year-olds, but cases in 65+-year-olds would continue to increase because of the effects of an aging population. Limitations of our model include difficulty in fitting to past trends in NVT IPD in some age groups and inherent uncertainty about future NVT behaviour, sparse data for defining the mixing matrix in 65+-year-olds, and the methodological challenge of defining uncertainty on predictions., Conclusions: Our findings suggest that, with the current mature status of the PCV programme in England and Wales, removing one primary dose in the first year of life would have little impact on IPD or pneumococcal CAP cases or associated deaths at any age. A reduction in the number of priming doses would improve programmatic efficiency and facilitate the introduction of new vaccines by reducing the number of coadministered vaccines given at 2 and 4 months of age in the current UK schedule. Our findings should not be applied to other settings with different pneumococcal epidemiology or with immature programmes and poor herd immunity., Competing Interests: The authors have declared that no competing interests exist.

Aim: We aimed to assess the receipt of recommended care for young children with sickle cell disease (SCD) in a central SCD clinic in Kampala Uganda, focusing on standard vaccination and antibacterial and antimalarial prophylaxis., Methods: A cross-sectional assessment of immunisation status and timeliness and prescribed antibacterial and antimalarial prophylaxis was performed in a sample with SCD aged ≤71 months in Mulago Hospital SCD Clinic. Government-issued immunisation cards and clinic-issued visit records for prescribed prophylaxis were reviewed., Results: Vaccinations were documented by immunisation cards in 104 patients, mean age 31.7 months (range 3-70 months). Only 48 (46.2%) received all doses of each of the four recommended vaccine types, including pneumococcal 10-valent conjugate vaccine (pneumococcal conjugate vaccine (PCV)-10), which became available in 2014. Vaccination completion was associated with younger age and, for polio, maternal employment. PCV-10 series was completed in 54.8% of the sample and in 18.2% of those aged 48-71 months. Of children completing all vaccination types, an average 68.8% were immunised on time, defined as <60 days beyond the recommended age. Only 17 (13.5%) children were both fully and timely vaccinated. In an overlapping sample of 147 children, with a mean age of 38.4 months (4-70 months), 81.6% had ≥1 documented prescription for penicillin and/or antimalarial prophylaxis., Conclusions: Standardised vaccination and antibacterial and antimalarial protective measures for young children at this central SCD clinic were incomplete, especially PCV-10 for age ≥24 months, and often late. Child age, but not general maternal demographics, were associated with vaccination and chemoprophylaxis. Clinic-based oversight may improve timely uptake of these preventative measures., (© 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

After the 2016 Balkan route border closures, vaccination of refugee children in Greece was mainly performed by non-governmental organisations. Activities varied between camps, resulting in heterogeneity of vaccination coverage (VC). In April 2017, the European programme 'PHILOS - Emergency health response to refugee crisis' took over vaccination coordination. Interventions were planned for the first time for refugee children in the community and unaccompanied minors at safe zones. From April 2017-April 2018, 57,615 vaccinations were performed against measles-mumps-rubella (MMR) (21,031), diphtheria-tetanus-pertussis (7,341), poliomyelitis (7,652), pneumococcal disease (5,938), Haemophilus influenzae type b (7,179) and hepatitis B (8,474). In April 2018, the vaccination status of children at camps (reception and identification centres and community facilities such as hostels/hotels were excluded) was recorded and VC for each disease, stratified by dose, nationality and camp size, was calculated. More than 80% of the children received the first MMR dose, with VC dropping to 45% for the second dose. For all other vaccines, VC was < 50% for the first dose in children aged 0-4 years and < 25% for the second dose. Despite challenges, PHILOS improved planning and monitoring of vaccination activities; however, further efforts towards improving VC in refugee children are needed.

Background: A notable reduction of the pneumococcal disease burden among adults was observed after the introduction of a 7-valent pneumococcal conjugate vaccine (PCV7) in childhood immunization programs. In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in many jurisdictions; a comparative assessment of PCV13's impact was missing. Our objective was to summarize the available data and assess the change in the incidence of invasive pneumococcal disease (IPD) in adults after the introduction of PCV13 in childhood immunization programs., Methods: We conducted a systematic literature search from January 1946 to May 2017 of randomized, controlled trials and observational studies OBS reporting the incidence of IPD, non-invasive pneumococcal disease, hospitalizations, and mortality in adults for the periods before and after the introduction of PCV13. Incidence rate ratios (IRRs) were pooled across studies using restricted, maximum-likelihood, random-effects models., Results: From 3306 records,we included 29 OBS studies and 2033961 cases. Significantly lower IPD rates were seen after PCV13 introduction in adults aged <65 years (IRR 0.78, 95% confidence interval [CI] 0.72-0.85) and those aged ≥65 years (IRR 0.86, 95% CI 0.81-0.91). Lower rates of IPD were seen with PCV7 (IRR 0.45, 95% CI 0.38-0.54) and PCV13 serotypes (IRR 0.60, 95% CI 0.54-0.68). A significantly higher IRR of 1.10 (95% CI 1.04-1.17) for non-vaccine serotypes was observed, especially among those aged 65 years and older (IRR 1.20, 95% CI 1.11-1.29)., Conclusions: PCV13 use in children had a moderate impact on reducing the overall and vaccine-type IPDs, but there was a significant increase in non-vaccine type IPDs among adults, especially in those over 65 years., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Invasive pneumococcal disease (IPD) has declined significantly since the introduction of pneumococcal conjugate vaccines (PCVs). It is not known whether certain infant populations remain at higher risk of IPD in countries with established 13-valent PCV (PCV13) programs. We aimed to describe the epidemiology, clinical characteristics, serotype distribution, and outcomes of IPD in infants, and to estimate the relative risk of PCV13-type, non-PCV13-type, and overall IPD in premature infants compared to term infants during a 4-year period after the PCV13 program was established., Methods: This was a prospective, enhanced national surveillance of laboratory-confirmed IPD in England in infants aged <1 year diagnosed during 2013-2016., Results: There were 517 cases of IPD (incidence: 19/100000 infants). Incidence was significantly higher in premature infants compared with those born at term (49/100000 vs 17/100000; incidence rate ratio [IRR], 2.87; P < .001), with infants born before 28 weeks' gestation having the highest incidence (150/100000; IRR, 8.8; P < .001). Of the 454 IPD cases with serotyped isolates, most were caused by non-PCV13 serotypes (369 cases, 71.4%), with 85 cases (16.4%) due to PCV13 serotypes. There were 31 deaths (case fatality rate [CFR], 6.2% [95% confidence interval, 4.3%-8.6%]). Premature infants did not have a higher CFR than term infants (P = .62)., Conclusions: IPD incidence in infants remains lower than rates reported prior to PCV7 introduction in England. The risk of IPD remains significantly higher in premature infants compared to infants born at term, for both PCV13 and non-PCV13 serotypes. Any changes to the infant PCV13 immunization schedule may disproportionally affect premature infants., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Pneumococcal conjugate vaccines (PCVs) have had a well-documented impact on the incidence of invasive pneumococcal disease (IPD). However, declines in IPD due to vaccine-targeted serotypes have been partially offset by increases in IPD due to nonvaccine serotypes (NVTs). The goal of this study was to quantify serotype-specific changes in the incidence of IPD that occurred in different age groups, with or without certain comorbidities, following the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) in the childhood vaccination program in Denmark., Methods: We used nationwide surveillance data for IPD and a hierarchical Bayesian regression framework to estimate changes in the incidence of IPD associated with the introduction of PCV7 (2007) and PCV13 (2010) while controlling for serotype-specific epidemic cycles and unrelated secular trends., Results: Following the introduction of PCV7 and PCV13 in children, the net impact of serotype replacement varied considerably by age group and comorbidities. Differences in the magnitude of serotype replacement were due to variations in the incidence of NVTs in the different risk groups before the introduction of PCVs. The relative increases in the incidence of IPD caused by specific NVTs did not differ appreciably between risk groups in the postvaccination period. Serotype replacement offset a greater proportion of the benefit of PCVs in strata in which the NVTs comprised a larger proportion of cases prior to the introduction of the vaccines., Conclusions: These findings could help to predict the impact of next-generation PCVs in specific risk groups., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose: To explore the impact of pneumococcal conjugate vaccines (PCVs) in preventing childhood pneumonia in the United Kingdom., Methods: We carried out a population-based study to assess the trend of all-cause pneumonia in children aged under 10 years between 2002 and 2012. Data were obtained from the IMS Disease Analyser, a primary care database in the United Kingdom. Three time periods were defined to estimate monthly incidence: pre-PCV7 (January 2002 to August 2006), post-PCV7 (September 2006 to March 2010), and post-PCV13 (April 2010 to December 2012). Interrupted time series analysis (ITS) was performed to assess any immediate change or gradual change in the monthly incidence of pneumonia between prevaccination and postvaccination introduction., Results: A total of 4228 children with at least one all-cause pneumonia episode were identified. The overall annual incidence rate of all-cause pneumonia declined by 37% from 3.8 episodes/1000 person-years in 2002 to 2.4 episodes/1000 person-years in 2012. Results of ITS analyses indicated that the incidence did not decline immediately after the introduction of PCV7 and PCV13. The incidence declined gradually in children aged under 2 years (IRR = 0.98; 95% CI, 0.97-0.99) post PCV7 and levelled off during post PCV13 (IRR = 1.00; 95% CI, 0.99-1.02). No significant changes in incidence trend was observed in children aged 2 to 4 years (IRR = 0.86; 95% CI, 0.68-1.07) and 5 to 9 years (IRR = 0.92; 95% CI, 0.73-1.15) after PCV13 introduction., Conclusions: In the United Kingdom, the incidence of all-cause pneumonia in children under 2 years declined after the introduction of PCV7 and levelled off in the first 2 years of introduction of PCV13. Continual monitoring is warranted to assess the population impact of PCV13 in preventing childhood pneumonia in the long term., (© 2019 John Wiley & Sons, Ltd.)

Vaccines are excellent investments with far-reaching rewards beyond individual and population health, but their introduction into national programs has been historically slow in Africa. We provide an overview of the introduction of new and underutilized vaccines in countries of the WHO African Region by 2017, using data from the WHO-UNICEF Joint Reporting Form. By 2017, all 47 countries had introduced vaccines containing hepatitis B (compared to 11% in 2000 and 98% in 2010) and Haemophilus influenzae type b (Hib) (compared to 4% in 2000 and 91% in 2010). The proportion of countries that had introduced other vaccines by 2017 was 83% for pneumococcal conjugate vaccine (PCV) from 7% in 2010, 72% for rotavirus vaccine from 2% in 2010, 55% for the second dose of a measles-containing vaccine (MCV2) (compared to 11% in 2000 and 17% in 2010), and 45% for rubella-containing vaccines (RCV) (compared to 4% in 2000 and 7% in 2010). From 2000 to 2010, there was no significant difference between countries eligible (N = 36) and those not eligible (N = 10) for Gavi support in the introduction of hepatitis B and PCV. However, Gavi eligible countries were more likely to introduce Hib and non-Gavi eligible countries were more likely to introduce MCV2 and RCV. From 2010 to 2017, the only significant differences that remained between the two groups of countries were with mumps, inactivated polio and seasonal influenza vaccines; which non-Gavi eligible countries were more likely to have introduced. There has been significant progress in the introduction of new childhood vaccines in Africa, mostly driven by Gavi support. As many countries are expected to transition out of Gavi support soon, there is need for countries in the region to identify predictable, reliable and sustainable immunization funding mechanisms. This requires commitments and actions that go beyond the purchase of vaccines., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Poland introduced the 10-valent conjugate pneumococcal vaccine (PCV10) into the childhood immunization program in January 2017. During previous decades, considerable changes had occurred in the surveillance system for invasive pneumococcal disease. Therefore, to provide baseline data on pneumococcal diseases before PCV10 introduction, we evaluated the epidemiology of pneumococcal meningitis (PM), the only syndrome monitored consistently since 1970., Methods: Based on laboratory-confirmed cases reported during 2005-2015, we calculated the reported rates, serotypes distribution and antimicrobial resistance of pneumococcal meningitis isolates. Data from the mandatory national surveillance system was linked with data on cerebrospinal fluid isolates submitted to the National Reference Centre for Bacterial Meningitis. We used negative binomial regression with Newey West method to test for trend in rates of pneumococcal meningitis notified during 2005-2015 and Chi-squared test to assess changes in the serotype distribution from 2008-2011 to 2012-2015., Results: From 2005 to 2015, the overall reported incidence of PM increased from 0.21 to 0.47 cases per 100,000 population, average yearly increase of 7% (rate ratio 1.07; 95% CI 1.06-1.08). The increase was primarily due to annual increase of 3% (1.02-1.05) among 15-49 years of age, 12% (95% CI: 1.10-1.13) among 50-64 years of age, 18% (95% CI: 1.16-1.19) among persons 65-74 years of age and 9% (95% CI 1.07-1.10) among persons ≥75 years of age. In children <5 years of age, serotypes included in PCV10 and PCV13 accounted for 75% and 80% of reported isolates, respectively. From 2008-2011 to 2012-2015, the proportion of PM cases caused by PCV10 serotypes decreased from 52% to 41% (p < 0.01). Overall, 28% of isolates were resistant to penicillin and 13% were non-susceptible to cefotaxime., Conclusions: The introduction of PCV10 into national immunization program may have considerable impact on disease burden, especially on number of cases caused by isolates non-susceptible to antimicrobials., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: World Health Organization has recommended the introduction of pneumococcal conjugate vaccine (PCV) in the childhood immunisation programme of all the countries in the world. In lieu of its introduction in India, there is a need to generate evidence on cost-effectiveness of this vaccine. The current study looks into the impact and cost-effectiveness of PCV vaccine in India., Methods: We evaluated the cost effectiveness of implementation of PCV 13 vaccination program at national level by comparing with no vaccination program for a period of 10 birth cohorts from 2018 to 2027. UNIVAC, a deterministic static cohort model is developed by giving the conservative estimates of vaccine program related to mortality, disease event rates, vaccine efficacy and coverage projections, system and health care costs for the first five years of life. Cost effectiveness is reported as Incremental Cost Effectiveness Ratio (ICER). Further scenario and sensitivity analysis were done. Probability of PCV intervention to be cost effective at a willingness to pay (WTP) threshold equal to per capita gross domestic product (GDP) is calculated using the government perspective., Results: We found that the introduction of PCV vaccination program can cost an additional $467 (INR 31,666) for averting per DALY which is less than one time GDP per capita of India. Even with the most unfavourable scenario for PCV vaccine, cost per DALY averted is found to be $2323 (INR 1,57,520) which is still a cost effective intervention in India. Probabilistic sensitivity analysis found the ICER for PCV to be $649 (INR 44,008) with 95% CI: $374-$1161., Conclusion: This study shows that the PCV program is a highly cost effective intervention and justifies the introduction of PCV into routine immunisation schedule in some of the states and recommends introducing it throughout the country to reduce morbidity and mortality among the under-five children., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: In February 2012 the ten-valent pneumococcal conjugate vaccine (PCV10) with a 2+1 doses schedule (3, 5, 12 or 14 months of age) without catch-up vaccination was introduced in Austria. We assessed direct and indirect vaccine effects on invasive pneumococcal disease (IPD) by a population-based intervention study., Methods: The study period was divided into pre- (2009-2011) and post-period (2013-2017, February), regarding 2012 as transition year. Outcomes were defined as PCV10 ST-IPD, the PCV10-related ST 6A and 19A IPD and non-PCV10 excluding ST 6A-/19A-IPD (NVT-IPD). We used national surveillance data and compared average monthly incidence rate (IR) between pre- and post-period among <5, 5-49 and ≥50 years old. Additionally, for the 5-49 and ≥50 years old, and the 50-59 and ≥60 years old, we analyzed monthly incidence data of the pre-, post-period, and estimated trend and level changes by using a segmented time-series regression., Results: The PCV-10 IPD was reduced by 58% (95% CI: 30%; 74%) and 67% (95% CI: 32%; 84%) among <5 and ≥50 years old; the reduction in ≥60 years was 71% (95% CI: 36%; 88%). There were no significant changes in the pre-post-rate or incidence trend of NVT-IPD in the <5 and ≥50 years old. ST-specific analyses revealed no ST 6A- and ST 19A IPD decline in any age-group, and a ST 8 IPD increase among ≥50 years old (IR ratio: 3.5; 95% CI: 1.7; 7.2). We found no vaccine effects among 5-49 years old., Conclusions: Our study adds to the evidence on direct and indirect protection of a childhood PCV10 vaccine program. Elderlies seem to benefit the most. Findings did not support PCV 10 cross-protection, but indicate replacement at least for ST 8 among the ≥50 years old. Follow-up analyses of IPD surveillance data are needed to fully characterize the magnitude of serotype replacement and further vaccine-attributable IPD reduction with time., Competing Interests: LR, DS, EK, MK, and HB did not receive any specific funding, their work was part of the national surveillance programm of the Austrian Agency for health and Food Safety. UW, JJ, EP are employed by the Medical University Vienna, which received an investigator initiated grant from Pfizer AG for cooperation with children hospitals in Austria. We thus confirm that we adhere to all Plos One policies on sharing data and material.

Over the course of this project, we utilized pharmacists at 159 community pharmacies in Nebraska and Iowa to administer vaccinations to adults 19 years of age or older with the objective of improving immunization rates in both states. We implemented a pharmacy-based technology platform and partnered with public health via the state immunization registries of both states to ensure that immunizations provided at the pharmacy were transmitted to the statewide registry, for which reporting is currently voluntary for health care providers. After using the technology platform for one year, an increase of immunization rates for influenza, herpes zoster, and pertussis vaccination rates by 37%, 12%, and 74%, respectively, was recorded in comparison to the prior year numbers. However, there was about 16% decrease in vaccination rates for pneumococcal vaccine. For the first time, the project's participating pharmacies in Nebraska reported immunization counts to their state's immunization registries. This project leveraged community pharmacies as healthcare destinations to achieve further gains in increasing immunization rates, improving the health of adults, and creating a community-wide network for prevention., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: National pediatric vaccination programs have been introduced in Latin America (LatAm) to reduce the burden of diseases due to pathogens such as rotavirus, Haemophilus influenzae type b (Hib) and pneumococcus. Vaccination health benefits may extend to unvaccinated populations by reducing pathogen transmission. Understanding herd effect is important for implementation and assessment of vaccination programs. The objective was to conduct a systematic review of published epidemiological evidence of herd effect with Hib, rotavirus and pneumococcal conjugate vaccines (PCV) in LatAm., Methods: Searches were conducted in PubMed, Virtual Health Library (VHL), SciELO and SCOPUS databases, for studies reporting data on herd effect from Hib, rotavirus and PCV vaccination in LatAm, without age restriction. Searches were limited to articles published in English, Spanish or Portuguese (1990-2016). After screening and full-text review, articles meeting the selection criteria were included to be critically appraised following criteria for observational and interventional studies. The presence of a herd effect was defined as a significant decrease in incidence of disease, hospitalization, or mortality., Results: 3,465 unique articles were identified, and 23 were included (Hib vaccine n = 5, PCV n = 8, rotavirus vaccine n = 10). Most studies included children and/or adolescents (age range varied between studies). Studies in adults, including older adults (aged > 65 years), were limited. Few studies reported statistically significant reductions in disease incidence in age groups not targeted for vaccination. Hib-confirmed meningitis hospitalization decreased in children but herd effect could not be quantified. Some evidence of herd effect was identified for PCV and rotavirus vaccine in unvaccinated children. Evidence for herd effects due to PCV in adults was limited., Conclusion: After introduction of Hib, PCV and rotavirus vaccination in LatAm, reductions in morbidity/mortality have been reported in children not targeted for vaccination. However, due to methodological limitations (e.g. short post-vaccination periods and age range studied), there is currently insufficient evidence to quantify the herd effect in adult populations. More research and higher quality surveillance is needed to characterize herd effect of these vaccines in LatAm.

Introduction: Pneumococcal diseases caused by Streptococcus pneumoniae represent a significant health and economic burden. Mexico has benefited from the inclusion of the 7-valent (PCV7) and 13-valent pneumococcal conjugate vaccines (PCV13) since their inclusion in the National Immunization Program (NIP) in 2006 and 2010, respectively. The objective of this study is to estimate the impact of the existing program and predict future implications of a change in the current program., Methods: A previously published model was updated to estimate the historic impact of the PCV programs relative to pre-PCV implementation. Future disease trends were forecasted based on historical serotype behaviors for each PCV13 serotype and non-vaccine serotypes across different age groups. Costs and outcomes were estimated over a 10-year period based on continued use of PCV13 compared to a switch to PCV10., Results: The PCV7 and subsequent PCV13 NIP were estimated to prevent over 1.5 million cases of pneumococcal disease and 1,854 deaths, corresponding to a net savings of $34.50 Billion MXN. Continued use of PCV13 was estimated to save over 300 thousand cases of pneumococcal disease and 373 deaths compared to switching to PCV10 over a 10-year period. Despite a higher vaccine cost, maintaining PCV13 was cost-saving compared to PCV10, saving $6.71 billion MXN over 10 years., Conclusion: The PCV program in Mexico has provided a significant return on investment. Sustained PCV13 use was estimated to provide the greatest healthcare and economic impact in Mexico. Changes to the pneumococcal vaccination program could result in serotype replacement and reduction in herd effects.

Background: The benefits of childhood vaccines are critically dependent on vaccination coverage. We used a vaccine registry (as gold standard) in Kenya to quantify errors in routine coverage methods (surveys and administrative reports), to estimate the magnitude of survivor bias, contrast coverage with timeliness and use both measures to estimate population immunity., Methods: Vaccination records of children in the Kilifi Health and Demographic Surveillance System (KHDSS), Kenya were combined with births, deaths, migration and residence data from 2010 to 17. Using inverse survival curves, we estimated up-to-date and age-appropriate vaccination coverage, calculated mean vaccination coverage in infancy as the area under the inverse survival curves, and estimated the proportion of fully immunised children (FIC). Results were compared with published coverage estimates. Risk factors for vaccination were assessed using Cox regression models., Results: We analysed data for 49,090 infants and 48,025 children aged 12-23 months in 6 birth cohorts and 6 cross-sectional surveys respectively, and found 2nd year of life surveys overestimated coverage by 2% compared to birth cohorts. Compared to mean coverage in infants, static coverage at 12 months was exaggerated by 7-8% for third doses of oral polio, pentavalent (Penta3) and pneumococcal conjugate vaccines, and by 24% for the measles vaccine. Surveys and administrative coverage also underestimated the proportion of the fully immunised child by 10-14%. For BCG, Penta3 and measles, timeliness was 23-44% higher in children born in a health facility but 20-37% lower in those who first attended during vaccine stock outs., Conclusions: Standard coverage surveys in 12-23 month old children overestimate protection by ignoring timeliness, and survivor and recall biases. Where delayed vaccination is common, up-to-date coverage will give biased estimates of population immunity. Surveys and administrative methods also underestimate FIC prevalence. Better measurement of coverage and more sophisticated analyses are required to control vaccine preventable diseases., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate cost-effectiveness of 10-valent pneumococcal conjugate vaccine in the routine immunization program for children younger than 5 years in Brazil by a postintroduction study., Methods: Ecological study of prevaccine (2006-2009) versus postvaccine (2011-2014) period related the changes in mortality rate and hospitalization rate to direct cost of pneumonia treatment from the payer's perspective to estimate the cost-effectiveness regarding lives saved, life-years gained, and disability-adjusted life-year for children younger than 5 years in the southern Brazilian state of Santa Catarina. All-cause pneumonia (ICD-10 J12-J18) deaths, hospital admissions, and associated costs were retrieved from the Brazilian Ministry of Health official Web site. Life expectancy at birth, population, ambulatory costs, cost savings, and plausible range of these parameters were used from published sources. Computer simulations with sensitivity analysis were performed to obtain the cost-effectiveness estimates., Results: About 27 lives were saved and 2573 hospitalizations averted by the 10-valent pneumococcal conjugate vaccine vaccination in the 2011 to 2014 period at the cost of US $24,348 per life-year gained and US $27,748 per disability-adjusted life-year. The latter cost is 81% of Brazilian gross domestic product per capita over the same period., Conclusions: The vaccine was very cost-effective according to the World Health Organization criterion., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)