Pneumococcal Conjugate Vaccine Coverage Research Articles

Re-evaluating the impact and cost-effectiveness of pneumococcal conjugate vaccine introduction in 112 low-income and middle-income countries in children younger than 5 years: a modelling study

Streptococcus pneumoniae has been estimated to cause 9·18 million cases of pneumococcal pneumonia, meningitis, and invasive non-pneumonia non-meningitis disease and 318 000 deaths among children younger than 5 years in 2015. We estimated the potential impact and cost-effectiveness of pneumococcal conjugate vaccine (PCV) introduction. We updated our existing pseudodynamic model to estimate the impact of 13-valent PCV (PCV13) in 112 low-income and middle-income countries by adapting our previously published pseudodynamic model with new country-specific evidence on vaccine coverage, burden, and post-introduction vaccine impact from WHO-UNICEF estimates of national immunisation coverage and a global burden study. Deaths, disability-adjusted life-years (DALYs), and cases averted were estimated for children younger than 5 years born between 2000 and 2030. We used specific PCV coverage in each country and a hypothetical scenario in which coverage increased to diphtheria-tetanus-pertussis (DTP) levels. We conducted probabilistic uncertainty analyses. Using specific vaccine coverage in countries, we estimated that PCV13 could prevent 697 000 (95% credibility interval 359 000-1 040 000) deaths, 46·0 (24·0-68·9) million DALYs, and 131 (89·0-172) million cases in 112 countries between 2000 and 2030. PCV was estimated to prevent 5·3% of pneumococcal deaths in children younger than 5 years during 2000-30. The incremental cost of vaccination would be I$851 (510-1530) per DALY averted. If PCV coverage were increased to DTP coverage in 2020, PCV13 could prevent an additional 146 000 (75 500-219 000) deaths. The inclusion of real-world evidence from lower-income settings revealed that delays in PCV roll-out globally and low PCV coverage have cost many lives. Countries with delays in vaccine introduction or low vaccine coverage have experienced many PCV-preventable deaths. These findings underscore the importance of rapidly scaling up PCV to achieve high coverage and maximise vaccine impact. Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.

Characterization of Streptococcus pneumoniae isolates obtained from the middle ear fluid of US children, 2011-2021.

Pneumococcal conjugate vaccines (PCVs), including higher valency vaccines such as PCV20, have the potential to reduce pediatric otitis media. We assessed serotype distribution, potential PCV coverage, and antimicrobial susceptibility of Streptococcus pneumoniae isolates cultured from middle ear fluid (MEF) of US children age ≤5 years. S. pneumoniae isolates identified from US hospitals participating in the SENTRY Antimicrobial Surveillance program from 2011 to 2021 were included. Serotypes were determined by in silico analysis based on Pneumococcal Capsular Typing methodology. The percentage of isolates belonging to serotypes included in PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F), PCV15 (PCV13 plus 22F, 33F), and PCV20 (PCV13 plus, 8, 10A, 11A, 12F, 15B, 22F and 33F) was calculated. Antimicrobial susceptibility testing was performed by broth microdilution and interpreted using CLSI criteria. Nonsusceptibility was defined as isolates that were intermediate or resistant to a selected antimicrobial. Among the 199 S. pneumoniae isolates that were identified, 56.8% were from children age <2 years. Six serotypes accounted for around 60% of isolates: 35B (16.6%), 15B (14.6%), 15A (7.5%), 19A (7.5%), 19F (7.5%), and 3 (7.0%). Serotypes included in PCV13, PCV15, and PCV20 accounted for 23.1%, 30.2%, and 54.8% of isolates, respectively. Overall, 45.2% of isolates were penicillin non-susceptible, and 13.6% were MDR, of which 48% were serotype 19A. Seven serotypes (19A, 15A, 15B, 15C, 23A, 33F, and 35B) accounted for the majority of non-susceptible isolates. PCVs, particularly PCV20, may prevent a substantial fraction of S. pneumoniae otitis media (OM), including OM due to non-susceptible serotypes. The addition of serotypes 15A, 23A, and 35B would improve coverage against susceptible and non-susceptible pneumococcal OM.

Pneumococcal population genomics changes during the early time period of conjugate vaccine uptake in southern India.

Streptococcus pneumoniae is a major cause of invasive disease of young children in low- and middle-income countries. In southern India, pneumococcal conjugate vaccines (PCVs) that can prevent invasive pneumococcal disease began to be used more frequently after 2015. To characterize pneumococcal evolution during the early time period of PCV uptake in southern India, genomes were sequenced and selected characteristics were determined for 402 invasive isolates collected from children <5 years of age during routine surveillance from 1991 to 2020. Overall, the prevalence and diversity of vaccine type (VT) and non-vaccine type (NVT) isolates did not significantly change post-uptake of PCV. Individually, serotype 1 and global pneumococcal sequence cluster (GPSC or strain lineage) 2 significantly decreased, whereas serotypes 6B, 9V and 19A and GPSCs 1, 6, 10 and 23 significantly increased in proportion post-uptake of PCV. Resistance determinants to penicillin, erythromycin, co-trimoxazole, fluoroquinolones and tetracycline, and multidrug resistance significantly increased in proportion post-uptake of PCV and especially among VT isolates. Co-trimoxazole resistance determinants were common pre- and post-uptake of PCV (85 and 93 %, respectively) and experienced the highest rates of recombination in the genome. Accessory gene frequencies were seen to be changing by small amounts across the frequency spectrum specifically among VT isolates, with the largest changes linked to antimicrobial resistance determinants. In summary, these results indicate that as of 2020 this pneumococcal population was not yet approaching a PCV-induced equilibrium and they highlight changes related to antimicrobial resistance. Augmenting PCV coverage and prudent use of antimicrobials are needed to counter invasive pneumococcal disease in this region.

Disease Burden of Meningitis Caused by Streptococcus pneumoniae Among Under-Fives in China: A Systematic Review and Meta-analysis.

Streptococcus pneumoniae is the leading cause of meningitis, with a case fatality of up to about 50%. Children younger than 5 years are at greater risk for pneumococcal meningitis compared with other populations. It is of significant importance to provide a comprehensive understanding of the burden of pneumococcal meningitis among under-fives in the low pneumococcal conjugate vaccine (PCV) coverage period in China. A systematic review was conducted. We searched both English (PubMed, Ovid-EMBASE, Biosis, Web of Science, and Cochrane) and Chinese (CNKI, Wanfang, and ViP) databases for studies on bacterial meningitis in China published between January 1980 and July 2022. Ineligible studies were excluded based on study design and data integrity. Heterogeneity was assessed with I2 and estimates of bacterial meningitis morbidity and mortality were pooled using random-effects models. Subgroup analysis was conducted to trace the source of the heterogeneity and summarize average estimates. A total of 13,082 studies were identified in the literature, and 56 studies were finally included for data analysis. The estimated incidence of pneumococcal meningitis was 2.10 cases per 100,000 children younger than 5 years each year (95% CI: 0.59-7.46), with a pooled case fatality rate of 24.59% (95%CI: 19.35-30.28%) in China. It was estimated that 1617.16 (95% CI: 454.35-5744.78) pneumococcal meningitis cases and 548.86 (95% CI: 474.80-627.62) deaths occurred among under-fives in China in 2020. Streptococcus pneumoniae played an important role in the etiology of confirmed bacterial meningitis cases, with a pooled proportion of 22.05% (95% CI: 17.83-26.27%). The most prevalent serotypes were 6B, 14, 19F, 19A, and 23F, which were preventable with a vaccine. Pneumococcal meningitis remains one of the most important health problems among children younger than 5 years in China. Immunization programs should be promoted to avoid preventable cases and deaths.

Analysis on the vaccination coverage of 13-valent pneumococcal conjugate vaccine in China from 2017 to 2021

Objective: To explore the vaccination coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) in China from 2017 to 2021. Methods: Using the reported number of PCV13 administrated doses from 2017 to 2021 and the population data from 31 provinces in China, which were collected by the Immunization Program Information System and summarized data at different levels (prefecture, provincial, and national). Collecting batch release data of PCV13 during the same period through the official website of the National Institutes for Food and Drug Control. The average coverage level of PCV13 was calculated by comparing the number of PCV13 vaccinations reported annually to the number of births in that year, and the spatial auto-correlation analysis was conducted in 2021 at the prefecture level. The coverage of PCV13 vaccination was estimated by the total vaccine doses administered each year divided by the number of newborn in the year, as of the administrated dose number per 100 people. Results: From March 2017 to December 2020, the total batch release of PCV13 was 20.06 million, with a total of 71.54, 384.75, 475.45, and 10.8886 million doses each year. During the same period, PCV13 reported doses were 20.2369 million and the vaccination doses from 2017 to 2021 were 4.08, 170.46, 407.52, 599.77, and 8.4185 million doses, respectively. From 2017 to 2021, the ratio of PCV13 doses administrated per 100 infants in each year was 0.25, 10.26, 23.81, 38.16, and 69.90 doses per 100 people, respectively. The range of the ratio in each province increased from 3.85 doses in 2017 to 264.41 doses per 100 people in 2021. The spatial auto-correlation analysis results showed that based on prefecture-level cities, there was spatial clustering in a certain area of PCV13 coverage from 2017 to 2021, and the spatial correlation in 2021 was the highest. The hotspot analysis showed that the hotspot areas with high coverage levels of PCV13 were concentrated in Jiangsu, Zhejiang, Shanghai, Fujian and their surrounding areas. The cold spots with low vaccine coverage were concentrated in Yunnan, Qinghai, Tibet, and their surrounding areas. Conclusion: The average coverage level of PCV13 is low in China with significant regional differences.

Pneumococcal Disease: Global Disease Prevention Strategies with a Focus on the Challenges in Iraq.

Pneumococcal disease is a global public health concern that significantly contributes to clinical disease burden and economic burden. Patients frequently afflicted are young children and older adults, as well as the immunocompromised population. Immunization is the most effective public health strategy to combat pneumococcal disease and several vaccine formulations have been developed in this regard. Although vaccines have had a significant global impact in reducing pneumococcal disease, there are several barriers to its success in Iraq. The war and conflict situation, increasing economic crises and poverty, poor vaccine accessibility in the public sector, and high vaccine costs are a few of the major obstacles that impede a successful immunization program. The last reported third dose pneumococcal conjugate vaccine coverage for Iraq was 37% in 2019, which is expected to reduce even further owing to the COVID-19 pandemic. Thus, strategies and policies to improve pneumococcal vaccine availability and coverage need to be strengthened to achieve maximum benefits of immunization. In the current review, we provide an overview of the existing knowledge on pneumococcal disease-prevention strategies across the globe. The main aim of this manuscript is to discuss the current status and challenges of pneumococcal vaccination in Iraq as well as the strategies to prevent pneumococcal infections.

What is associated with reported acute respiratory infection in children under 5 and PCV vaccination in children aged 1-36 months in Malawi? A secondary data analysis using the Malawi 2014 MICS survey.

Acute respiratory illness (ARI) is a leading cause of mortality in children under 5 (CU5) in Malawi and can be prevented with 3-dose pneumococcal conjugate vaccine (PCV). There has been no national study in Malawi that seeks to associate social economic factors leading to PCV vaccine uptake and reported acute respiratory infections (RARI). The objectives of our study were to do this. We conducted a cross-sectional analysis of secondary data from the 2014 UNICEF Malawi Multiple Indicator Cluster Survey to construct mutlivariable logistic regression models for independent associations with PCV 1/2/3 immunisation and RARI. 56% of CU5 in Malawi RARI in the 2 week recall period of the survey. Independent associations with reduced odds of RARI were central region living (OR 0.82, 95%CI (0.71-0.93)) middle (OR 0.84, (0.73-0.97)) fourth (OR 0.79, (0.68-0.92)) and richest wealth quintiles (OR 0.73, (0.60-0.88)). Using straw/shrubs for fuel was associated with increased RARI (OR 3.13, (1.00-9.79)). Among 1-36 month olds, in 2014, 93.3% received PCV1, 86.8% PCV2 and 77.0% PCV3. Between 2011-2014, the average age in months for a child to receive PCV1/2/3 reduced by 26.6 for PCV1, 26.4 for PCV2, and 26.1 for PCV 3. Independent predicators for increased odds of all 3 PCV doses, relative to 0-5 age group, were age group 6-11 (OR 21.8, (18.2-26.1) 12-23 (OR 27.5, (23.5-32.2) 24-36 months (OR 9.09, (7.89-10.5), mothers having a secondary (OR 1.52, (1.25-1.84)) or higher education (OR 2.68, (1.43-5.04) when compared to no education, and children in the middle (OR 1.24, (1.07-1.43)) fourth (OR 1.27, (1.09-1.48)) richest (OR 1.54, (1.27-1.88)) wealth quintiles relative to the lowest. Children living with 4-6 other children was independently associated with reduced odds of receiving all 3 PCV doses (OR 0.56, (0.33-0.96). We report nationally representative social economic associations with RARI and PCV vaccine uptake and coverage estimates. We found reductions in the average age a child receives all 3 PCV vaccine doses between 2011-2014.

Coverage of 13-Valent Pneumococcal Conjugate Vaccine Among Children 0-15 Months of Age - 9 Provinces, China, 2019-2021.

Limited data exist regarding the coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) in China. A lack of official statistics, coupled with an insufficient body of published literature, hinders the accurate depiction of the current situation. This study investigated the utilization of PCV13 and estimated its coverage in nine provinces across eastern, central, and western China between 2019 and 2021. Despite an annual increase in PCV13 usage during this period, the overall coverage remained suboptimal. Consideration should be given to incorporating vaccines into the Expanded Program of Immunization, reducing vaccine prices, and addressing the vaccination coverage gap between eastern and western regions when there is an adequate supply of PCV13, particularly with domestic vaccines.

Prevalence of Pneumococcal Serotypes in Community-Acquired Pneumonia among Older Adults in Italy: A Multicenter Cohort Study.

Pneumococcal community-acquired pneumonia (CAP) is a leading cause of mortality. Following the introduction of pneumococcal conjugate vaccines (PCVs) in children, a decrease in the burden of the disease was reported. In parallel, an increase in non-vaccine serotypes was also noted. The objective of this study was to assess the current serotype-specific epidemiology of pneumococci among Italian older adults hospitalized for CAP. A prospective study was conducted between 2017 and 2020 in four Italian regions. Subjects aged ≥65 years hospitalized with confirmed CAP were tested for pneumococci using both pneumococcal urinary antigen and serotype-specific urine antigen tests able to identify all 24 serotypes included in the available vaccines. Of the 1155 CAP cases, 13.1% were positive for pneumococci. The most prevalent serotypes were 3 (2.0%), 8 (1.7%), 22F (0.8 %) and 11A (0.7%). These serotypes are all included in the newly licensed PCV20. The serotypes included in PCV13, PCV15 and PCV20 contributed to 3.3%, 4.4% and 7.5% of the CAP cases, respectively. In the context of a low PCV13 coverage among older adults and a high PCV coverage in children, a substantial proportion of CAP is caused by PCV13 serotypes. Higher valency PCV15 and PCV20 may provide additional benefits for the prevention of CAP in vaccinated older adults.

Vaccine hesitancy and receipt of mandatory and optional pediatric vaccines in Shanghai, China

ABSTRACT Given increased global concern about vaccine hesitancy, this study estimates coverage of mandatory vs non-mandatory vaccines in children, and assesses whether vaccine hesitancy among young parents relates to their childʻs eventual vaccination status in Shanghai, China. In a cohort study within Shanghai, China, we ascertained vaccine hesitancy among parents of young infants, and later abstracted their childʻs electronic immunization records. We measure full coverage of vaccines on the mandatory, and publicly funded Expanded Program on Immunization (EPI). Non-EPI vaccines included pneumococcal conjugate vaccine, Haemophilus influenzae type b vaccine, and rotavirus vaccine. Vaccine hesitancy was linked to vaccine uptake through mixed effects logistic regression models. Among 972 children, full coverage of all EPI vaccines by 15 months was 95%, compared to dose 1 coverage of pneumococcal conjugate vaccine at 13%, Haemophilus influenzae type b vaccine at 68%, and rotavirus vaccine at 52%. Vaccine hesitancy was not significantly linked with full coverage of all EPI vaccines (OR: 1.55, 95% CI: .89, 2.72), but coverage in the vaccine hesitant was lower for pneumococcal conjugate vaccine dose 1 (OR: .70, 95% CI: .53, .91), and rotavirus vaccine dose 1 (OR: .69, 95% CI: .56, .86). Disparities by education level were not significant for EPI vaccines, but were for dose 1 of pneumococcal conjugate vaccine rotavirus vaccine. Overall, vaccine hesitancy was related to lower uptake of non-EPI, but not EPI vaccines. Shanghai has a robust system for insurance equitable access to EPI vaccines, but if vaccine hesitancy grows, it could reduce coverage of non-EPI vaccines.

Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae in the Philippines, 2012-2018.

ObjectiveData are scarce on the prevailing Streptococcus pneumoniae serotypes in the Philippines, including the relative antimicrobial resistance (AMR) of these bacteria. This study is designed to fill that gap by describing the serotype distribution and AMR of S. pneumoniae in the Philippines from 2012 to 2018.MethodsS. pneumoniae isolates from clinical specimens were collected through the Philippine Department of Health Antimicrobial Resistance Surveillance Program from 1 January 2012 to 31 December 2018. Identification and antimicrobial susceptibility testing (AST) were performed using conventional and automated methods (Vitek2 Compact Automated Machine). AST for penicillin, erythromycin, co-trimoxazole, ceftriaxone and levofloxacin was done following the Clinical and Laboratory Standard Institute recommendations. Serotyping was done through slide agglutination following the Denka Seiken slide agglutination method.ResultsFrom a total of 307 isolates of S. pneumoniae, 32 serotypes were identified; the most frequently occurring were serotypes 1, 3, 5, 4, 18, 19A, 6B, 15 and 14. Many (n = 113, 36.53%) of the isolates were from those aged £5 years. Pneumococcal conjugate vaccine (PCV) coverage was as follows: PCV7 (32.69%), PCV10 (54.16%) and PCV13 (69.23%). The overall AMR of invasive S. pneumoniae isolates was low. Penicillin-resistant serotypes were 14, 19, 24, 4, 5, 1, 15, 6 and 32.DiscussionWith the inclusion of PCV13 in the National Immunization Program, continued monitoring of the prevailing serotypes of S. pneumoniae isolates in the Philippines is needed to guide disease and AMR control measures.

Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae in the Philippines, 2012–2018

Objective: Data are scarce on the prevailing Streptococcus pneumoniae serotypes in the Philippines, including the relative antimicrobial resistance (AMR) of these bacteria. This study is designed to fill that gap by describing the serotype distribution and AMR of S. pneumoniae in the Philippines from 2012 to 2018. Methodology: S. pneumoniae isolates from clinical specimens were collected through the Philippine Department of Health Antimicrobial Resistance Surveillance Program from 1 January 2012 to 31 December 2018. Identification and antimicrobial susceptibility testing (AST) were performed using conventional and automated methods (Vitek2 Compact Automated Machine). AST for penicillin, erythromycin, co-trimoxazole, ceftriaxone and levofloxacin was done following the Clinical and Laboratory Standard Institute recommendations. Serotyping was done through slide agglutination following the Denka Seiken slide agglutination method. Results: From a total of 307 isolates of S. pneumoniae, 32 serotypes were identified; the most frequently occurring were serotypes 1, 3, 5, 4, 18, 19A, 6B, 15 and 14. Many (n=113, 36.53%) of the isolates were from those aged &lt;5 years. Pneumococcal conjugate vaccine (PCV) coverage was as follows: PCV7 (32.69%), PCV10 (54.16%) and PCV13 (69.23%). The overall AMR of invasive S. pneumoniae isolates was low. Penicillin-resistant serotypes were 14, 19, 24, 4, 5, 1, 15, 6 and 32. Discussion: With the inclusion of PCV13 in the National Immunization Program, continued monitoring of the prevailing serotypes of S. pneumoniae isolates in the Philippines is needed to guide disease and AMR control measures.

Value of pneumococcal vaccination in controlling the development of antimicrobial resistance (AMR): Case study using DREAMR in Ethiopia

BackgroundAntimicrobial resistance (AMR) poses an imminent threat to global health security. Pneumococcal vaccination reduces disease incidence, prevents antibiotic use, and decreases antibiotic-resistant infections. However, the benefit of vaccination in reducing AMR has been poorly quantified to date. MethodsWe developed an agent-based model, DREAMR (Dynamic Representation of the Economics of AMR) to evaluate the economic value of childhood immunization with the pneumococcal conjugate vaccine (PCV) in mitigating the development of AMR. Our model incorporates vaccination coverage, disease incidence, care seeking, and antibiotic use. Accumulation of AMR is simulated based on antibiotic exposure through pharmacokinetics and resulting pharmacodynamics. The model was applied to Ethiopia. ResultsIntroduction of PCV vaccination has helped slow the development of AMR by 14.77% for amoxicillin and 0.59% for ceftriaxone in Ethiopia since 2011. In addition to the benefit of reduction in disease incidence, PCV vaccination has averted approximately 718,100 antibiotic treatment failures and 9,520 AMR-related deaths (27.8% reduction) in Ethiopia between 2011 and 2017, resulting in savings of $32.7 million. Maintaining current PCV immunization coverage will contribute an additional $7.67 million in annual AMR cost savings over five years compared to no vaccination scenario, which could increase to $11.43 million by increasing PCV coverage to 85% by 2022. ConclusionsThis study is the first to demonstrate the broader economic value of pneumococcal vaccination in controlling the development of AMR in Africa. Vaccination not only saves lives by preventing illnesses, but also benefits society by reducing antibiotic utilization and treatment failures due to AMR.

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

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

Levels of pneumococcal conjugate vaccine coverage and indirect protection against invasive pneumococcal disease and pneumonia hospitalisations in Australia: An observational study.

There is limited empiric evidence on the coverage of pneumococcal conjugate vaccines (PCVs) required to generate substantial indirect protection. We investigate the association between population PCV coverage and indirect protection against invasive pneumococcal disease (IPD) and pneumonia hospitalisations among undervaccinated Australian children. Birth and vaccination records, IPD notifications, and hospitalisations were individually linked for children aged <5 years, born between 2001 and 2012 in 2 Australian states (New South Wales and Western Australia; 1.37 million children). Using Poisson regression models, we examined the association between PCV coverage, in small geographical units, and the incidence of (1) 7-valent PCV (PCV7)-type IPD; (2) all-cause pneumonia; and (3) pneumococcal and lobar pneumonia hospitalisation in undervaccinated children. Undervaccinated children received <2 doses of PCV at <12 months of age and no doses at ≥12 months of age. Potential confounding variables were selected for adjustment a priori with the assistance of a directed acyclic graph. There were strong inverse associations between PCV coverage and the incidence of PCV7-type IPD (adjusted incidence rate ratio [aIRR] 0.967, 95% confidence interval [CI] 0.958 to 0.975, p-value < 0.001), and pneumonia hospitalisations (all-cause pneumonia: aIRR 0.991 95% CI 0.990 to 0.994, p-value < 0.001) among undervaccinated children. Subgroup analyses for children <4 months old, urban, rural, and Indigenous populations showed similar trends, although effects were smaller for rural and Indigenous populations. Approximately 50% coverage of PCV7 among children <5 years of age was estimated to prevent up to 72.5% (95% CI 51.6 to 84.4) of PCV7-type IPD among undervaccinated children, while 90% coverage was estimated to prevent 95.2% (95% CI 89.4 to 97.8). The main limitations of this study include the potential for differential loss to follow-up, geographical misclassification of children (based on residential address at birth only), and unmeasured confounders. In this study, we observed substantial indirect protection at lower levels of PCV coverage than previously described-challenging assumptions that high levels of PCV coverage (i.e., greater than 90%) are required. Understanding the association between PCV coverage and indirect protection is a priority since the control of vaccine-type pneumococcal disease is a prerequisite for reducing the number of PCV doses (from 3 to 2). Reduced dose schedules have the potential to substantially reduce program costs while maintaining vaccine impact.

Invasive Pneumococcal Disease burden and PCV coverage in children under five in Southeast Asia: implications for India.

Pneumococcal diseases, though preventable, are a major public health problem in Southeast Asia and particularly in India. Pneumococcal conjugate vaccines (PCVs) are used in the region for over a decade, but to understand their impact, invasive pneumococcal diseases (IPD) burden and PCV coverage data in the region are needed. A literature search was conducted to identify i) key evidence published between February 2008 and February 2018 on IPD burden, serotype prevalence and antibiotic resistance in Southeast Asia, and ii) PCV serotype and vaccination coverage in Southeast Asia. 49 relevant articles were included in the final analysis. Mortality in children under 5 years remains high in Southeast Asian countries, with around 25% of deaths due to IPD in India and Pakistan. There was a lack of recent data on IPD incidence. Antibiotic resistance to IPD isolates is increasing, with high resistance rates especially for meningeal isolates. Based on serotype distribution data, primarily for India, available PCVs would cover around 70-80% of IPD-causing serotypes. Vaccine coverage was around 15-20% in India to 98% in South Korea. Widespread PCV use could successfully reduce IPD burden in the region due to high serotype coverage by available PCVs; emphasis should be placed on increasing vaccination uptake, for every child, particularly in India. Reducing health system barriers and improving surveillance and awareness is essential to improve coverage and effectively prevent IPD morbidity and mortality particularly in at risk regions.

Indirect effects of 13-valent pneumococcal conjugate vaccine on pneumococcal carriage in children hospitalised with acute respiratory infection despite heterogeneous vaccine coverage: an observational study in Lao People’s Democratic Republic

IntroductionEmpiric data on indirect (herd) effects of pneumococcal conjugate vaccines (PCVs) in settings with low or heterogeneous PCV coverage are limited. The indirect effects of PCV, which benefits both vaccinated...

The Impact of Pneumococcal Conjugate Vaccine (PCV) Coverage Heterogeneities on the Changing Epidemiology of Invasive Pneumococcal Disease in Switzerland, 2005-2019.

Pneumococcal conjugate vaccines (PCVs) have lowered the incidence of invasive pneumococcal disease (IPD) worldwide. However, the influence of regional vaccine uptake differences on the changing epidemiology of IPD remains unclear. We aimed to examine the overall impact of both seven- and 13-valent PCVs (PCV7 and PCV13) on IPD in Switzerland. Three-year periods from 2005–2010 and 2011–2019 were considered, respectively, as (early and late) PCV7 eras and (early, mid and late) PCV13 eras. Vaccine coverage was estimated from a nationwide survey according to east (German-speaking) and west (French/Italian-speaking) regions for each period. Reported incidence rate ratios (IRRs) were compared between successive periods and regions using nationwide IPD surveillance data. Overall IPD incidence across all ages was only 16% lower in the late PCV13 era compared to the early PCV7 era (IRR 0.83, 95% CI 0.79–0.88), due to increasing incidence of non-PCV-type IPD (2.59, 2.37–2.83) in all age groups, except children <5 years. PCV uptake rates in swiss children were slightly higher in the west than the east (p < 0.001), and were accompanied by lower IPD incidences across all age groups in the former region. Post-PCV13, non-PCV serotypes 8, 22F and 9N were the major cause of IPD in adults ≥65 years. Increased PCV coverage in both areas of Switzerland resulted in a decrease in vaccine-type and overall IPD incidence across all age groups, in a regionally dependent manner. However, the rising incidence of non-vaccine-type IPD, exclusive to older adults, may undermine indirect beneficial effects.

Pneumococcal Vaccination Mandates for Child Care: Impact of State Laws on Vaccination Coverage at 19–35 Months

Vaccination mandates for elementary and middle school attendance have been shown to increase vaccination rates and decrease the burden of vaccine-preventable diseases. Fewer studies have evaluated similar requirements for child care attendance. This study provides robust, quasi-experimental estimates of the effect of state laws mandating the pneumococcal conjugate vaccine for child care attendance on vaccination coverage among children aged 19-35 months. Using provider-verified immunization histories from the 2001-2018 waves of the National Immunization Survey-Child and leveraging the staggered implementation of vaccination requirements across states, a generalized difference-in-differences approach was implemented to compare regression-adjusted changes in vaccination coverage among children in states with and without a child care mandate for the pneumococcal conjugate vaccine. The dynamics of estimated treatment effects were analyzed using an event study analysis. All data analyses were conducted in 2019‒2020. State adoption of a child care mandate for the pneumococcal conjugate vaccine increased the likelihood that resident children aged 19-35 months completed the 4-dose pneumococcal conjugate vaccine series by 3.12 percentage points (p<0.01). Statistically significant gains in pneumococcal conjugate vaccine coverage were identified in the first year following policy implementation and were found to persist over a period of ≥7 years. Results indicate that state adoption of a child care mandate for the pneumococcal conjugate vaccine leads to an increase in the proportion of resident children aged 19-35 months who are up to date with pneumococcal conjugate vaccine.

Health and economic impact of the pneumococcal conjugate vaccine in hindering antimicrobial resistance in China

Antimicrobial resistance (AMR) poses a serious threat to global public health. However, vaccinations have been largely undervalued as a method to hinder AMR progression. This study examined the AMR impact of increasing pneumococcal conjugate vaccine (PCV) coverage in China. China has one of the world's highest rates of antibiotic use and low PCV coverage. We developed an agent-based DREAMR (Dynamic Representation of the Economics of AMR) model to examine the health and economic benefits of slowing AMR against commonly used antibiotics. We simulated PCV coverage, pneumococcal infections, antibiotic use, and AMR accumulation. Four antibiotics to treat pneumococcal diseases (penicillin, amoxicillin, third-generation cephalosporins, and meropenem) were modeled with antibiotic utilization, pharmacokinetics, and pharmacodynamics factored into predicting AMR accumulation. Three PCV coverage scenarios were simulated over 5 y: 1) status quo with no change in coverage, 2) scaled coverage increase to 99% in 5 y, and 3) accelerated coverage increase to 85% over 2 y followed by 3 y to reach 99% coverage. Compared to the status quo, we found that AMR against penicillin, amoxicillin, and third-generation cephalosporins was significantly reduced by 6.6%, 10.9%, and 9.8% in the scaled scenario and by 10.5%, 17.0%, and 15.4% in the accelerated scenario. Cumulative costs due to AMR, including direct and indirect costs to patients and caretakers, were reduced by $371 million in the scaled and $586 million in the accelerated scenarios compared to the status quo. AMR-reducing benefits of vaccines are essential to quantify in order to drive appropriate investment.