Pneumococcal Conjugate Vaccine In Children Research Articles

Prevalence, spatial distribution and determinants of complete childhood pneumococcal conjugate vaccination in Ethiopia: spatial and multilevel analyses

IntroductionPneumococcal disease is a serious global public health concern. The primary causative agent of severe illnesses such as pneumonia, meningitis, acute otitis media, and bacteremia is the pneumococcus bacterium. The pneumococcal conjugate vaccine is a key strategy to reduce the burden of pneumococcal disease. Understanding the spatial distribution of complete childhood pneumococcal conjugate vaccine utilization and its associated factors is crucial for designing strategies to improve vaccination implementation. Therefore, this study aimed to determine the spatial distribution of complete childhood pneumococcal conjugate vaccination coverage and identify its determinants in Ethiopia.MethodA spatial and multilevel analysis was conducted using data from the 2019 Ethiopian Mini Demographic and Health Survey. The analysis included a total of 2,055 weighted children. The association between the outcome variable and the explanatory variables was determined by calculating adjusted odds ratios at a 95% confidence interval. Explanatory variables were considered significantly associated with the outcome if the p-value was less than 0.05.ResultThe prevalence of complete childhood pneumococcal conjugate vaccination in Ethiopia was 53.94% (95% CI: 51.77, 56.08). Higher complete childhood pneumococcal vaccination coverage was observed in the Addis Ababa, Tigray, Amhara, Benishangul-Gumuz, and Oromia regions, while lower coverage was seen in the Afar, Somali, and SNNPR regions of Ethiopia. Factors significantly associated with complete childhood pneumococcal conjugate vaccination included maternal age, antenatal care visits, place of delivery, region, community women’s literacy level, community poverty level, and community antenatal care utilization.ConclusionThe distribution of complete childhood pneumococcal conjugate vaccination exhibited spatial variability across Ethiopia. Approximately half of children aged twelve to thirty-five months received the full dose of the childhood pneumococcal conjugate vaccine in the country. Several factors were identified as statistically significant determinants of complete childhood pneumococcal conjugate vaccination, including maternal age, antenatal care visits, place of delivery, region, community women’s literacy level, community poverty level, and community ANC utilization. Therefore, policies and strategies aimed at combating pneumococcal disease should consider these determinants and address areas with low vaccination coverage.

Effect of Childhood Pneumococcal Conjugate Vaccination on Invasive Disease Serotypes in Serbia.

In Serbia, PCV10 was introduced into the routine immunization for children under 2 in 2018 and replaced by PCV13 in 2022. We evaluated their impact on the distribution of invasive pneumococcal disease (IPD) serotypes across all age groups. Overall, 756 isolates were obtained from patients with IPD between 2010 and 2023 through laboratory surveillance. In the post-vaccination period, serotypes 14, 19F, 23F, and 6A significantly declined, while 3 and 19A considerably increased. This was especially evident in the ≤2 years group, making these serotypes the most prevalent among them. Serotype 3 dominated, representing 19.1% of all invasive isolates prior to 2018 and 33.1% thereafter. While serotype coverage of PCV10 has significantly decreased in the ≤2 years group (from 74.2% before 2018 to 29.5% after 2018), PCV13 coverage was 63.9% after 2018. In the post-PCV period, non-PCV13 serotypes, such as 9N, 10A, 15A, 15B, 15C, 22F, 6C, 6D, and 7C, increased across all isolates. Antibiotic non-susceptibility considerably decreased after 2018. MLST analysis showed shifts in sequence type prevalence, with pre-PCV lineages replaced and ongoing serotype 3 persistence, alongside potential capsule-switching events. These findings emphasize a noticeable shift in the distribution of serotypes and adaptability of pneumococcal populations, highlighting the importance of ongoing surveillance and the requirement for the urgent introduction of higher valent vaccines into the National Immunization Program.

Immunogenicity, Immunological Memory and Monitoring of Disease Activity Following an Anamnestic Immunization With the 13-Valent Pneumococcal Conjugate Vaccine in Children With Idiopathic Nephrotic Syndrome.

Anamnestic 13-valent pneumococcal conjugate vaccine immunization did not affect the relapse risk in pediatric idiopathic nephrotic syndrome. Pneumococcal serotype (PS)-specific antibody titers increased significantly in all groups. Children receiving immunomodulatory treatments (IMTs) displayed significantly lower levels of PS-specific antibodies for 3/8 serotypes tested. PS-specific B-cell counts significantly increased only in healthy controls and patients receiving corticosteroids.

Immunogenicity of Current and Next-Generation Pneumococcal Conjugate Vaccines in Children: Current Challenges and Upcoming Opportunities.

Global use of pneumococcal conjugate vaccines (PCVs) with increasingly broader serotype coverage has helped to reduce the burden of pneumococcal disease in children and adults. In clinical studies comparing PCVs, higher-valency PCVs have met noninferiority criteria (based on immunoglobulin G geometric mean concentrations and response rates) for most shared serotypes. A numeric trend of declining immunogenicity against shared serotypes with higher-valency PCVs has also been observed; however, the clinical relevance is uncertain, warranting additional research to evaluate the effectiveness of new vaccines. Novel conjugation processes, carriers, adjuvants, and vaccine platforms are approaches that could help maintain or improve immunogenicity and subsequent vaccine effectiveness while achieving broader protection with increasing valency in pneumococcal vaccines.

Cost-effectiveness of an in-development adult-formulated 21-valent pneumococcal conjugate vaccine in US adults aged 50 years or older

Indirect effects of childhood pneumococcal conjugate vaccines (PCV) have diminished the cost-effectiveness of current adult vaccine recommendations. An in-development adult-formulated 21-valent pneumococcal conjugate vaccine (PCV21) may play a critical role in reducing pneumococcal illness by targeting a larger number of serotypes responsible for adult pneumococcal infections. This study assesses the cost-effectiveness of PCV21 in US adults aged 50 years or older compared with currently recommended pneumococcal vaccines, from both the societal and healthcare perspectives. A Markov model evaluated the lifetime cost-effectiveness of PCV21 (given at age 50 years only, at ages 50/65 years, and risk-based at ages < 65 years plus age-based at age 65 years) compared to no vaccination and to currently recommended pneumococcal vaccines given either as currently recommended or routinely at ages 50/65 years. The analysis was conducted in hypothetical Black and non-Black cohorts aged 50 years or older, with and without considering childhood pneumococcal vaccination indirect effects. Model parameters were based on US data. Parameter uncertainty was assessed using 1-way and probabilistic sensitivity analyses.From the societal perspective, PCV21 at ages 50/65 years compared to PCV21 at age 50 years cost $7,410 per quality adjusted life year (QALY) gained in Black cohort analyses and $85,696/QALY gained in the non-Black cohort; PCV21 at ages 50/65 years had the most favorable public health outcomes. From the healthcare perspective, compared to no vaccination, PCV21 at age 50 years cost $46,213/QALY gained in the Black cohort and $86,629/QALY in non-Blacks. All other strategies were dominated in both cohorts and from both perspectives. When considering childhood pneumococcal vaccination indirect effects, costs of PCV21 at ages 50/65 years remained less than $140,000/QALY gained from the societal perspective in both populations. PCV21 is potentially cost-effective compared to currently approved pneumococcal vaccines in adults aged 50 years or older from both the societal and healthcare perspectives.

Neurological and immunological adverse events after pneumococcal conjugate vaccine in children using national immunization programme registry data.

Despite the general consensus on the safety of pneumococcal conjugate vaccine (PCV), safety concerns unveiled during post-licensure surveillance need to be addressed. We investigated whether there is a transient increased risk following a three-dose series of pneumococcal conjugate vaccine (PCV) administered at 2, 4 and 6 months of age. This was a population-based cohort study using the Korea immunization registry data linked to nationwide administrative claims data. Self-controlled risk interval analysis was conducted for PCV recipients who had an outcome of interest within pre-defined risk and control intervals between 2018 and 2022. The outcomes were anaphylaxis, asthma, encephalopathy, febrile seizure, Kawasaki disease and thrombocytopenia. We used conditional Poisson regression model to estimate the incidence rate ratios (IRRs) and 95% confidence intervals (CIs) comparing the outcomes in the risk and control intervals. Of 1 114 096 PCV recipients, 8661 had outcomes either in the risk or control intervals. Their mean age at Dose 1 was 10.0 weeks, 58.3% were boys, and 85.3% received 13-valent PCV. PCV was not associated with an increased risk of any outcomes except for febrile seizure. There were 408 (56.0%) cases of febrile seizure in the risk interval, corresponding to an IRR of 1.27 (95% CI 1.10-1.47). It is reassuring to note that there was no increased risk of the potential safety concerns following PCV administration. Despite the transient increased risk of febrile seizure, absolute numbers of cases were small. Febrile seizure is generally self-limiting with a good prognosis, and should not discourage parents or caregivers from vaccinating their children.

Pneumococcal conjugate vaccines in children

Pneumococcal conjugate vaccines (PCVs), which have been in population-wide use in children for over two decades now, are highly efficacious in preventing life threatening pneumococcal infections. The strong herd effect of PCVs through reduction in pneumococcal nasopharyngeal carriage in vaccinated children prevents disease in adults as well. Since 7vPCV, which was the first PCV used widely, several new PCVs with each adding more serotypes have been developed. These new PCVs have been approved using immune-bridging criteria based on an aggregate correlate of protection (Cp) derived from vaccine efficacy and antibody responses data from early PCV trials. This Cp that the World Health Organization (WHO) accepts for assessing new PCVs for which it is impracticable to undertake placebo-controlled trials with clinical outcomes is 0.35 μg mL–1 of enzyme-linked immunosorbent assay (ELISA) immunoglobulin G (IgG). Effectiveness and antibody response data more recently of 13vPCV has led to developing Cp for each individual vaccine serotype, that, for some, varies considerably to 0.35 μg mL–1. In trials of newest PCVs, such as 15vPCV and 20vPCV, the comparator used is 13vPCV that has, in turn, been licensed using immune bridging, which leads to potential ‘downward-drift’ risk of protection from the new PCVs. This and the data that have emerged on serotype replacement disease and dosing schedules makes it important to review and rethink how new PCVs are assessed, their clinical benefits are inferred and vaccination programs are designed.

Impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia hospitalisations in Mongolia: a time series analysis

IntroductionFew studies have assessed the potential indirect effects of childhood pneumococcal conjugate vaccine (PCV) programs on the adult pneumonia burden in resource-limited settings. We evaluated the impact of childhood PCV13 immunisation on adult all-cause pneumonia following a phased program introduction from 2016. MethodsWe conducted a time-series analysis to assess changes in pneumonia hospitalisation incidence at four district hospitals in Mongolia. Adults (≥18 years) that met the clinical case definition for all-cause pneumonia were enrolled. A negative binomial mixed-effects model was used to assess the impact of PCV13 introduction on monthly counts of pneumonia admissions from January 2015—February 2022. We also performed a restricted analysis excluding the COVID-19 pandemic period. All models were stratified by age and assessed separately. Additional analyses assessed the robustness of our findings. FindingsThe average annual incidence of all-cause pneumonia hospitalisation was highest in adults 65+ years (62·81 per 10,000 population) and declined with decreasing age. After adjusting for the COVID-19 pandemic period, we found that rates of pneumonia hospitalisation remained largely unchanged over time. We did not observe a reduction in pneumonia hospitalisations in any age group. Results from restricted and sensitivity analyses were comparable to the primary results, finding limited evidence of a reduced pneumonia burden. InterpretationWe did not find evidence of indirect protection against all-cause pneumonia in adults following childhood PCV13 introduction. Direct pneumococcal vaccination and other interventions should be considered to reduce burden of pneumonia among older adults. FundingPfizer clinical research collaboration agreement (contract number: WI236621).

Effect of 13-valent pneumococcal conjugate vaccine on experimental carriage of Streptococcus pneumoniae serotype 6B in Blantyre, Malawi: a randomised controlled trial and controlled human infection study

The effect of childhood pneumococcal conjugate vaccine implementation in Malawi is threatened by absence of herd effect. There is persistent vaccine-type pneumococcal carriage in both vaccinated children and the wider community. We aimed to use a human infection study to measure 13-valent pneumococcal conjugate vaccine (PCV13) efficacy against pneumococcal carriage. We did a double-blind, parallel-arm, randomised controlled trial investigating the efficacy of PCV13 or placebo against experimental pneumococcal carriage of Streptococcus pneumoniae serotype 6B (strain BHN418) among healthy adults (aged 18-40 years) from Blantyre, Malawi. We randomly assigned participants (1:1) to receive PCV13 or placebo. PCV13 and placebo doses were prepared by an unmasked pharmacist to maintain research team and participant masking with identification only by a randomisation identification number and barcode. 4 weeks after receiving either PCV13 or placebo, participants were challenged with 20 000 colony forming units (CFUs) per naris, 80 000 CFUs per naris, or 160 000 CFUs per naris by intranasal inoculation. The primary endpoint was experimental pneumococcal carriage, established by culture of nasal wash at 2, 7, and 14 days. Vaccine efficacy was estimated per protocol by means of a log-binomial model adjusting for inoculation dose. The trial is registered with the Pan African Clinical Trials Registry, PACTR202008503507113, and is now closed. Recruitment commenced on April 27, 2021 and the final visit was completed on Sept 12, 2022. 204 participants completed the study protocol (98 PCV13, 106 placebo). There were lower carriage rates in the vaccine group at all three inoculation doses (0 of 21 vs two [11%] of 19 at 20 000 CFUs per naris; six [18%] of 33 vs 12 [29%] of 41 at 80 000 CFUs per naris, and four [9%] of 44 vs 16 [35%] of 46 at 160 000 CFUs per naris). The overall carriage rate was lower in the vaccine group compared with the placebo group (ten [10%] of 98 vs 30 [28%] of 106; Fisher's p value=0·0013) and the vaccine efficacy against carriage was estimated at 62·4% (95% CI 27·7-80·4). There were no severe adverse events related to vaccination or inoculation of pneumococci. This is, to our knowledge, the first human challenge study to test the efficacy of a pneumococcal vaccine against pneumococcal carriage in Africa, which can now be used to establish vaccine-induced correlates of protection and compare alternative strategies to prevent pneumococcal carriage. This powerful tool could lead to new means to enhance reduction in pneumococcal carriage after vaccination. Wellcome Trust.

Community-Acquired Pneumonia Incidence in Adults Aged 18 Years and Older in Goto City, Japan: A Prospective Population-Based Study

Community-Acquired Pneumonia Incidence in Adults Aged 18 Years and Older in Goto City, Japan: A Prospective Population-Based Study

Streptococcus pneumoniae and other bacterial nasopharyngeal colonization seven years post-introduction of 13-valent pneumococcal conjugate vaccine in South African children

Pneumococcal Conjugate Vaccines (PCVs) reduce pneumococcal-associated disease by reducing vaccine-serotype (VT) acquisition in vaccinated children, thereby interrupting VT transmission. The 7-valent-PCV was introduced in the South African immunisation program since 2009 (13-valent-PCV since 2011) using a 2+1 schedule (6-, 14- and 40-weeks age). We aimed to evaluate temporal changes in VT and non-vaccine-serotype (NVT) colonisation after nine years of childhood PCV immunisation in South Africa. Nasopharyngeal swabs were collected from healthy children <60-months-old (n=571) in 2018 (Period-2) and compared with samples (n=1135) collected during early PCV7-introduction (Period-1, 2010-11) in an urban low-income setting (Soweto). Pneumococci were tested for using a multiplex quantitative-PCR serotyping reaction-set. Overall pneumococcal colonisation in Period-2 (49.4%; 282/571) was 27.5% lower than Period-1 (68.1%; 773/1135; aOR:0.66; 95%CI:0.54-0.88). Colonisation by VT was reduced by 54.5% in Period-2 (18.6%; 106/571) compared with Period-1 (40.9%; 465/1135; aOR:0.41; 95%CI:0.3-0.56). Nevertheless, serotype 19F carriage prevalence was higher (8.1%; 46/571) in Period-2 compared with Period-1 (6.6%; 75/1135; aOR:2.0; 95%CI:1.09-3.56). NVT colonisation prevalence was similar in Period-2 and Period-1 (37.8%; 216/571 and 42.4%; 481/1135). There remains a high residual prevalence of VT, particularly 19F, colonisation nine years post introduction of PCV in the South African childhood immunisation program.

Reanalysis of the Clinical and Economic Burden of Pneumococcal Disease Due to Serotypes Contained in Current and Investigational Pneumococcal Conjugate Vaccines in Children < 5 Age: A Societal Perspective.

Studies that estimate the economic burden of pediatric pneumococcal disease often only report direct medical costs and omit indirect non-medical costs. Given these indirect costs are not included in most calculations, the full economic burden attributable to pneumococcal conjugate vaccine (PCV) serotypes is often underestimated. This study seeks to quantify the full broader economic burden of pediatric pneumococcal disease associated with PCV serotypes. We conducted a reanalysis of a previous study where non-medical costs associated with caregiving for a child with pneumococcal disease are considered. The annual indirect non-medical economic burden attributed to PCV serotypes was subsequently calculated for 13 countries. We included five countries with 10-valent (PCV10) national immunization programs (NIPs) (Austria, Finland, The Netherlands, New Zealand, and Sweden) and eight countries with 13-valent (PCV13) NIPs (Australia, Canada, France, Germany, Italy, South Korea, Spain, and the UK). Input parameters were derived from published literature. Indirect costs were inflated to 2021 values in US dollars (USD). The total annual indirect economic burden associated with pediatric pneumococcal diseases attributable to PCV10, PCV13, the 15-valent (PCV15), and the 20-valent (PCV20) serotypes were $46.51million, $158.95million, $223.00million, and $413.97 million, respectively. The five countries with PCV10 NIPs bear a greater societal burden associated with PCV13 serotypes, whereas the residual societal burden in the eight countries with PCV13 NIPs was primarily attributable to non-PCV13 serotypes. The inclusion of non-medical costs nearly tripled the total economic burden compared with only including direct medical costs estimated from a previous study. The results from this reanalysis can help inform decision-makers on the broader economic societal burden associated with PCV serotypes and the need for higher-valent PCVs.

583. Preferences and Attitudes of Healthcare Providers towards Pneumococcal Conjugate Vaccines (PCVs) for Children Ages Two and Under in the United States (US)

Abstract Background As higher-valent PCVs are currently in late-stage clinical development for pediatric use, it is important to understand how healthcare providers (HCPs) evaluate vaccine attributes when making recommendations for newer PCVs. The Advisory Committee on Immunization Practices considers feasibility and stakeholder acceptability in making vaccine recommendations; this study examined HCP preferences and attitudes towards new, higher-valent PCVs in children in the US. Methods Semi-structured qualitative interviews were conducted with 13 HCPs (6 pediatricians, 3 family practitioners, 3 nurse practitioners, and 1 physician assistant). US HCPs were recruited from an online panel and were eligible if they recommended or prescribed vaccines to children ≤ 2 years and spent ≥ 2 days a week providing care to pediatric patients. Providers were asked to rate a list of PCV attributes (generated by literature search) by their importance in influencing their PCV choices (1, not important; 10, most important). Interviews were recorded, transcribed, and analyzed. Results Among HCPs (mean age=49 years; 62% women; 38% urban, 38% suburban; mean years in practice=18 years), three main themes emerged: 1) Preferred attributes: The three most important PCV characteristics that affect HCPs’ recommendations are effectiveness against serotype 3 (rated 9.1), percent serotype coverage for invasive pneumococcal disease (IPD) (rated 8.9), and immune response for the shared PCV13 serotypes (rated 8.2). 2) PCV choice: Most respondents are interested in having more PCV options, particularly options with higher efficacy or broader serotype coverage. 3) Immunogenicity vs serotype coverage: Between a higher immune response to certain serotypes and broader serotype coverage, 46% of HCPs prefer PCVs that elicit a higher immune response but narrower coverage, 31% prefer a PCV with broader serotype coverage, and 23% require more data before making a determination. Conclusion Both immune response and breadth of serotype coverage may influence HCPs decisions when recommending new PCVs. Additional analyses and interviews are underway to validate these findings and further explore other factors that may influence their preferences for recommending PCVs. Disclosures Salini Mohanty, DrPH, MPH, Merck &amp; Co., Inc.: Employee Jui-Hua Tsai, MD, MHS, OPEN Health: Employee of OPEN Health, which received funding from Merck &amp; Co., Inc. to conduct this research Ning Ning, PhD, MS, Open Health: I am an employee of OPEN Health, which received funding from Merck Ana Pena-Molina, MPH, OPEN Health: I am an employee of OPEN Health, which received funding from Merck Rishi P. Verma, MPH, OPEN Health: I am an employee of OPEN Health, which received funding from Merck Marieke Heisen, PhD, MSc, OPEN Health: I am an employee of OPEN Health, which received funding from Merck Jessica Weaver, PhD, MPH, Merck &amp; Co., Inc.: Employee Kristen A. Feemster, MD, MPH, MSHPR, FAAP, Merck &amp; Co., Inc.: Employee Thomas Weiss, DrPH, MPH, Merck &amp; Co., Inc.: Employee Jordana Schmier, MA, OPEN Health: I am an employee of OPEN Health, which received funding from Merck.

Building on a Strong Foundation to Address a New Era to Help Protect Against Pneumococcal Disease

Antoni Torres, Respiratory Intensive Care Unit, Department of Pneumology and Respiratory Allergy, Hospital Clinic of Barcelona, University of Barcelona, Spain, opened the symposium, noting that pneumococcal conjugate vaccines (PCV) have reduced pneumococcal disease through direct and indirect effects. However, the burden of pneumococcal disease remains substantial in adults, supporting the importance of further reducing vaccine-preventable disease and its impact on healthcare resource utilisation and public health. Mário Ramirez, Faculty of Medicine, University of Lisbon, Portugal, and Molecular Microbiology and Infection Laboratory, Institute of Molecular Medicine, University of Lisbon, Portugal, reviewed the changing serotype epidemiology of pneumococcal disease in Europe, and described important differences between pneumococcal polysaccharide vaccines and PCVs. He detailed the dramatic direct impact of PCVs in children in decreasing the burden of vaccine-type (VT) pneumococcal disease, as well as indirect effects in unvaccinated populations, particularly adults. Residual VT-disease and increases in non-PCV13 disease underscore the need for additional disease coverage that may be afforded by higher-valent PCVs. Charles Feldman, Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa, reviewed the considerable worldwide burden of lower respiratory tract infections (LRTI), including pneumococcal pneumonia. He noted that indirect effects in adults may be suboptimal, and herd effects may have reached their limit. Feldman described adult populations that should be prioritised for pneumococcal vaccination based on risk factors, and stressed the importance of a comprehensive approach to increase adult vaccination. Finally, Wendy Watson, Vaccines Clinical Research, Pfizer, Collegeville, USA, described the adult PCV20 clinical development programme, emphasising that it was built on the well-established PCV13 platform. In the Phase III clinical trial programme, PCV20 was well tolerated, with a safety profile similar to PCV13, regardless of prior pneumococcal vaccination history. Importantly, it was immunogenic across all ages studied and in those with chronic medical conditions. Wendy Watson concluded that PCV20 has the potential to simplify adult vaccination and help reduce the burden of adult pneumococcal disease.

Cost-effectiveness analyses of 15- and 20-valent pneumococcal conjugate vaccines for Japanese elderly

BackgroundDespite the 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccination programme implementation, pneumococcal disease (PD) remains an important cause of morbidity and mortality among the elderly in Japan, particularly since childhood pneumococcal conjugate vaccine (PCV) vaccination programme continues to alter the serotype PD distribution among the elderly. Recently, in the United States, PCV15/PCV20 were recommended for adults aged ≥ 65 years and those aged 19–64 years with certain underlying conditions. In Japan, PCV15 is under the approval application process and PCV20 undergoing clinical trials, which has warranted the need in evaluating their value for money. MethodsWe conducted cost-effectiveness analyses with Markov model and calculated incremental cost-effectiveness ratios of PCV15/PCV20 vaccination programme compared to status quo from payers’ perspective. Transition probabilities and utility weights in estimating quality-adjusted life-year (QALY), and disease treatment costs were either estimated or obtained from literature. To reflect the situation of COVID-19 pandemic, epidemiological data from 2020 and beyond were used. ResultsCompared to the current vaccination programme, PCV20 vaccination programme gained more QALYs with less cost, while PCV15 vaccination programme cost ¥35,020 (US$318, US$1 = ¥110) to gain an additional QALY. Replacing PPSV23 vaccination programme with PCV20 vaccination programme is cost-saving. One-way sensitivity analyses revealed that lower VE limits of PCVs against non-bacteremic pneumonia (NBP) have large impact to change the result from PCV20 vaccination programme dominated PPSV23 vaccination programme to PPSV23 vaccination programme dominated PCV20 vaccination programme. ConclusionIn the COVID-19 era, replacing current PPSV23 with a single-dose PCV15- or PCV20 immunisation programme for 65-year-old adults in Japan is highly cost-effective, while the PCV 20 vaccination programme was observed to be more favourable.

Pneumonia hospitalizations of children aged

ABSTRACT As infection with Streptococcus pneumoniae is an important cause of pneumonia in children, the World Health Organization recommends childhood pneumococcal conjugate vaccines (PCVs). In January 2017, PCV universal mass vaccination (UMV) was introduced in Poland for children aged <2 years. The objective of this study was to estimate and describe the trends in the incidences of various types of pneumonia hospitalizations in Poland before (2013–2016) and after (2017–2018) introduction of the UMV program. The study was conducted at the regional hospitals of Opole and Bialystok and included all hospitalized children aged <2 years with a primary or secondary diagnosis of pneumonia in their electronic medical records. Pneumonia diagnoses were identified based on International Classification of Diseases 10th revision (ICD-10) codes for bacterial, viral, and other/unknown-cause pneumonias. The effect of the implementation of PCV UMV was modeled via an inferential multivariate model. Among 4,168 children included in the study, 64.3% were admitted before PCV UMV. The number of radiograph-confirmed likely bacterial pneumonia cases varied between 55 and 176 cases per 100,000 person-years, and no trend was observed over time. However, inferential modeling showed statistically significant decreasing trends in the incidence rates of bacterial-coded pneumonia (28.48%), viral-coded pneumonia (35.36%), all-cause pneumonia (24.60%), and radiograph-confirmed likely non-bacterial pneumonia (24.98%) among children eligible for UMV. This might be the first indication of the impact of the PCV UMV program in Poland.

Quality of antibody responses by adults and young children to 13-valent pneumococcal conjugate vaccination and Streptococcus pneumoniae colonisation

Childhood pneumococcal conjugate vaccine (PCV) protects against invasive pneumococcal disease caused by vaccine-serotype (VT) Streptococcus pneumoniae by generating opsonophagocytic anti-capsular antibodies, but how vaccination protects against and reduces VT carriage is less well understood. Using serological samples from PCV-vaccinated Malawian individuals and a UK human challenge model, we explored whether antibody quality (IgG subclass, opsonophagocytic killing, and avidity) is associated with protection from carriage. Following experimental challenge of adults with S. pneumoniae serotype 6B, 3/21 PCV13-vaccinees were colonised with pneumococcus compared to 12/24 hepatitis A-vaccinated controls; PCV13-vaccination induced serotype-specific IgG, IgG1, and IgG2, and strong opsonophagocytic responses. However, there was no clear relationship between antibody quality and protection from carriage or carriage intensity after vaccination. Similarly, among PCV13-vaccinated Malawian infants there was no relationship between serotype-specific antibody titre or quality and carriage through exposure to circulating serotypes. Although opsonophagocytic responses were low in infants, antibody titre and avidity to circulating serotypes 19F and 6A were maintained or increased with age. These data suggest a complex relationship between antibody-mediated immunity and pneumococcal carriage, and that PCV13-driven antibody quality may mature with age and exposure.

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against community-acquired pneumonia in older individuals after the introduction of childhood 13-valent pneumococcal conjugate vaccine: A multicenter hospital-based case-control study in Japan

BackgroundIn the era of childhood pneumococcal conjugate vaccine (PCV) immunization, especially 13-valent pneumococcal conjugate vaccine (PCV13) immunization, serotype replacement of Streptococcus pneumoniae and herd immunity in adults have been reported worldwide. Therefore, continuous evaluation of the effectiveness of the pneumococcal vaccine in adults is crucial because vaccine effectiveness may change owing to these factors. The purpose of this study was to evaluate the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against all-cause pneumonia and pneumococcal pneumonia in older individuals with community-acquired pneumonia (CAP) after the introduction of childhood PCV13 in Japan, a topic that has remained largely unexplored. MethodsWe evaluated pneumococcal vaccine effectiveness in this multicenter, matched case-control study conducted in hospitals and clinics. Cases included patients (aged ≥ 65 years) newly diagnosed with CAP between October 2016 and September 2019. A maximum of five non-pneumonia control patients matched for sex, school grade, date of outpatient visit, and medical institution were selected for each case. Conditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pneumococcal vaccines for the occurrence of all-cause CAP and pneumococcal CAP. ResultsThe analysis included 740 individuals (142 patients and 598 controls). The median age of participants was 75 years (men: 54%). The adjusted OR for pneumococcal vaccination against all-cause CAP was 1.31 (95% CI: 0.84–2.06), while that for PPSV23 vaccination in the previous 5 years was 1.33 (95% CI: 0.85–2.09). The adjusted OR for PPSV23 vaccination in the previous 5 years against pneumococcal CAP was 0.93 (95% CI: 0.35–2.50). ConclusionsThis study was unable to demonstrate the effectiveness of PPSV23 against all-cause and pneumococcal pneumonia after the introduction of childhood PCV13 in Japan. Nonetheless, additional studies are needed to validate these results.

Effectiveness of 7-Valent Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease in Medically At-Risk Children in Australia: A Record Linkage Study.

BackgroundChildren with chronic medical conditions are at higher risk of invasive pneumococcal disease (IPD), but little is known about the effectiveness of the primary course of pneumococcal conjugate vaccine (PCV) in these children.MethodsA cohort born in 2001–2004 from two Australian states and identified as medically at-risk (MAR) of IPD either using ICD-coded hospitalizations (with conditions of interest identified by 6 months of age) or linked perinatal data (for prematurity) were followed to age 5 years for notified IPD by serotype. We categorized fully vaccinated children as either receiving PCV dose 3 by <12 months of age or ≥1 PCV dose at ≥12 months of age. Cox proportional hazard modeling was used to estimate hazard ratios (HRs), adjusted for confounders, and vaccine effectiveness (VE) was estimated as (1-HR) × 100.ResultsA total of 9220 children with MAR conditions had 53 episodes of IPD (43 vaccine-type); 4457 (48.3%) were unvaccinated and 4246 (46.1%) were fully vaccinated, with 1371 (32.3%) receiving dose 3 by 12 months and 2875 (67.7%) having ≥1 dose at ≥12 months. Estimated VE in fully vaccinated children was 85.9% (95% CI: 33.9–97.0) against vaccine-type IPD and 71.5% (95% CI: 26.6–88.9) against all-cause IPD.ConclusionThis is the first population-based study evaluating the effectiveness of PCV in children with MAR conditions using record linkage. Our study provides evidence that the VE for vaccine-type and all-cause IPD in MAR children in Australia is high and not statistically different from previously reported estimates for the general population. This method can be replicated in other countries to evaluate VE in MAR children.

Bacterial etiology of pneumonia in children up to 2 months of age: a systematic review

Background: Following the widespread introduction of childhood pneumococcal conjugate vaccines (PCVs), a significant impact on pneumonia mortality in children under five years of age has been reported. It is still unknown whether PCVs are expected to reduce pneumonia burden in younger children, particularly ≤2 months of age, as current evidence on the role of S. pneumoniae in pneumonia etiology in this age group is scarce. We aimed to summarize the evidence of bacterial etiology of pneumonia in children ≤2 months of age. Methods: We conducted a systematic review considering studies evaluating a variety of syndromes associated with pneumonia, and reporting on laboratory confirmed etiologies, considering any diagnostic method and a variety of clinical specimens. We searched Medline/PubMed, Embase, WoS, Central and Index Medicus Global published in any language till April 30th, 2021. We included studies addressing the outcomes of interest in children ≤2 months of age and reporting on clinical trials, observational studies, and case series with at least 10 events. Screening of citations and data extraction were conducted in duplicate by independent reviewers, according to the study protocol registered on PROSPERO. Descriptive analyses of the various etiologic agents by syndrome are reported. Results: We identified 3,744 citations, of which 22 publications reporting on 13 studies were included. Study methods varied significantly. Nonetheless, gram positive organisms, in particular S. pneumoniae, were identified as important etiologic agents of pneumonia in children ≤2 months of age. Viral etiologies, in particular Respiratory Syncytial Virus, Rhinovirus, and Influenza were also identified. Conclusions: This review provides the most comprehensive analysis to date of the etiologies of pneumonia in children ≤2 months of age, suggesting that PCV impact is expected to occur in this age group. These results also have major implications for diagnosis and treatment of pneumonia in this age group.