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.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.

Skin exposure to soil microbiota elicits changes in cell-mediated immunity to pneumococcal vaccine.

A resilient immune system is characterized by its capacity to respond appropriately to challenges, such as infections, and it is crucial in vaccine response. Here we report a paired randomized intervention-control trial in which we evaluated the effect of microbially rich soil on immune resilience and pneumococcal vaccine response. Twenty-five age and sex matched pairs of volunteers were randomized to intervention and control groups. The intervention group rubbed hands three times a day in microbially rich soil until participants received a pneumococcal vaccine on day 14. Vaccine response, skin and gut bacteriome and blood cytokine levels were analyzed on days 0, 14 and 35. Peripheral blood mononuclear cells (PBMCs) were stimulated with vaccine components and autoclaved soil for cytokine production. Commensal bacterial community shifted only in the intervention group during the 14-day intervention period. When PBMCs collected on day 14 before the vaccination were stimulated with the vaccine components, IFN-y production increased in the intervention but not in the control group. On day 35, vaccination induced a robust antibody response in both groups. In parallel, gut bacterial community was associated with TGF-ß plasma levels and TGF-ß decrease in plasma was lower in the intervention group. The results indicate that exposure to microbially rich soil can modulate the cell-mediated immunity to components in pneumococcal vaccine.

Effect of pneumococcal conjugate vaccine six years post-introduction on pneumococcal carriage in Ulaanbaatar, Mongolia.

Limited data from Asia are available on long-term effects of pneumococcal conjugate vaccine introduction on pneumococcal carriage. Here we assess the impact of 13-valent pneumococcal conjugate vaccine (PCV13) introduction on nasopharyngeal pneumococcal carriage prevalence, density and antimicrobial resistance. Cross-sectional carriage surveys were conducted pre-PCV13 (2015) and post-PCV13 introduction (2017 and 2022). Pneumococci were detected and quantified by real-time PCR from nasopharyngeal swabs. DNA microarray was used for molecular serotyping and to infer genetic lineage (Global Pneumococcal Sequence Cluster). The study included 1461 infants (5-8 weeks old) and 1489 toddlers (12-23 months old) enrolled from family health clinics. We show a reduction in PCV13 serotype carriage (with non-PCV13 serotype replacement) and a reduction in the proportion of samples containing resistance genes in toddlers six years post-PCV13 introduction. We observed an increase in pneumococcal nasopharyngeal density. Serotype 15 A, the most prevalent non-vaccine-serotype in 2022, was comprised predominantly of GPSC904;9. Reductions in PCV13 serotype carriage will likely result in pneumococcal disease reduction. It is important for ongoing surveillance to monitor serotype changes to potentially inform new vaccine development.

Regional differences in pediatric pneumococcal vaccine schedules for Indigenous children in Canada: an environmental scan.

BACKGROUND: Streptococcus pneumoniae bacteria causes substantial morbidity and mortality worldwide, especially in children under 5 years of age. Prevention of these outcomes by pneumococcal conjugate vaccines (PCV) is an important public health initiative, supported by publicly funded vaccination programs in Canada. While the National Advisory Committee on Immunization (NACI) provides national recommendations for vaccination schedules, decisions on vaccination program delivery are made regionally, creating potential for variability across the country. In addition, defining the groups that are most at risk has become a complex endeavor for provinces and territories in Canada, specifically considering Indigenous children. METHODS: In this environmental scan, we reviewed policy documents, provincial/territorial and international PCV schedules, and scientific literature, and consulted with vaccination program stakeholders and experts from across the country, in order to understand the evolution of PCV vaccination guidelines and policies in Canada and identify whether and how the needs of Indigenous children are addressed. RESULTS: As of March 2023, most regions do not specify particular vaccination requirements for Indigenous children; however, three provinces identify Indigenous children as "high risk" and use varying language to recommend a four dose, rather than the routine three dose, schedule. Our results also draw attention to evidence gaps supporting a differing practice for Indigenous populations. CONCLUSIONS: Future PCV program innovation requires inclusive and clear policies as well as definitive evidence-based policies and practices in order to improve equitable population health.

Analysis of Immunobiological Properties of Recombinant Streptococcus pneumoniae Pneumolysin.

We compared the immunogenicity of recombinant S. pneumoniae pneumolysin (rPly) when administered with and without Al(OH)3 adjuvant, and evaluated the protective properties of recombinant protein in the active defense experiment. It was shown that double immunization with rPly+Al(OH)3 increases the levels of IgG antibodies in comparison with the control (p<0.01), while triple immunization results in a more significant increase in IgG antibody levels (p<0.001). Double immunization with rPly without Al(OH)3 does not induce a significant increase in antibody levels in comparison with the control, while triple immunization results in a slight but significant increase in antibody levels (p<0.05). The active defense test proved the protective activity of rPly against S. pneumoniae serotype 3 at intranasal infection.

Multiple vaccine comparison in the same adults reveals vaccine-specific and age-related humoral response patterns: an open phase IV trial.

Vaccine responsiveness is often reduced in older adults. Yet, our lack of understanding of low vaccine responsiveness hampers the development of effective vaccination strategies to reduce the impact of infectious diseases in the ageing population. Young-adult (25-49 y), middle-aged (50-64 y) and older-adult ( ≥ 65 y) participants of the VITAL clinical trials (n = 315, age-range: 28-98 y), were vaccinated with an annual (2019-2020) quadrivalent influenza (QIV) booster vaccine, followed by a primary 13-valent pneumococcal-conjugate (PCV13) vaccine (summer/autumn 2020) and a primary series of two SARS-CoV-2 mRNA-1273 vaccines (spring 2021). This unique setup allowed investigation of humoral responsiveness towards multiple vaccines within the same individuals over the adult age-range. Booster QIV vaccination induced comparable H3N2 hemagglutination inhibition (HI) titers in all age groups, whereas primary PCV13 and mRNA-1273 vaccination induced lower antibody concentrations in older as compared to younger adults (primary endpoint). The persistence of humoral responses, towards the 6 months timepoint, was shorter in older adults for all vaccines (secondary endpoint). Interestingly, highly variable vaccine responder profiles overarching multiple vaccines were observed. Yet, approximately 10% of participants, mainly comprising of older male adults, were classified as low responders to multiple vaccines. This study aids the identification of risk groups for low vaccine responsiveness and hence supports targeted vaccination strategies. Trial number: NL69701.041.19, EudraCT: 2019-000836-24.

Impact of COVID-19 on vaccine confidence and uptake: A systematic literature review.

During the coronavirus disease 2019 (COVID-19) pandemic, scheduled vaccinations were postponed, mass vaccination programmes were suspended and opportunities for healthcare workers to administer vaccines ad hoc decreased. The aims of this systematic literature review were to determine the impact of the COVID-19 pandemic on vaccine confidence, intent and uptake in preexisting routine childhood or adult vaccination programmes, and to identify factors associated with changes in acceptance, intent and uptake of preexisting vaccines. Medline and Embase were searched for studies in Australia, Brazil, Canada, China, Japan, the USA, and European countries, published between 1 January 2021 and 4 August 2022. A complementary gray literature search was conducted between 11 and 13 October 2022, and supplemented with additional gray research in October 2023. In total, 54 citations were included in the review. Study design and geography were heterogeneous. The number of adults who received or intended to receive an influenza or pneumococcal vaccine was higher during the pandemic than in previous seasons (n = 28 studies). In addition, increased acceptance of adult vaccinations was observed during 2020-21 compared with 2019-20 (n = 12 studies). The rates of childhood vaccinations decreased during the COVID-19 pandemic across several countries (n = 11 studies). Factors associated with changes in intention to receive a vaccination, or uptake of influenza vaccine, included previous vaccination, older age, higher perceived risk of contracting COVID-19, anxiety regarding the pandemic and fear of contracting COVID-19. Acceptance and uptake of influenza and pneumococcal vaccines generally increased after onset of the COVID-19 pandemic.

Antigen-driven Convergent Evolution of Polysaccharide-specific "DH-less" B Cells in Glycoconjugate Immunized Mice.

Glycoconjugate vaccines elicit robust anti-polysaccharide Ab response by recruiting T-cell help. Multiple doses of glycoconjugate vaccine are required to induce long-lasting immunity. The characteristics of anti-polysaccharide Ab response have been reported previously. However, the effect of glycoconjugate booster immunization on anti-polysaccharide and anti-carrier protein Ab repertoire remains poorly understood. In this study, we used clinically relevant pneumococcal capsular polysaccharide type 14 (PCP14) conjugated with cross-reactive material 197 (CRM197) as a model glycoconjugate Ag (PCP14-CRM197). We performed a comprehensive sequence analysis of mouse mAbs generated against PCP14 and CRM197 following immunization with one or three doses of PCP14-CRM197. Analysis of the paired Ig H and L chain transcripts revealed that anti-PCP14 Ab repertoire is extremely restricted. The reoccurrence of five replacement mutations at identical positions in anti-polysaccharide mAbs generated from different mice provided evidence for Ag-driven selection in PCP14-specific B cells. Convergent evolution was observed wherein distinct V(D)J rearrangements resulted in identical or nearly identical CDR3 in anti-PCP14 mAbs. Abs that lacked DH encoded amino acids dominated the anti-PCP14 Ab response. In contrast, anti-CRM197 Ab response was quite diverse, with fewer mutations compared with the anti-PCP14 mAbs, suggesting that conjugation of the polysaccharide to a carrier protein interferes with the development of carrier protein-specific Ab responses. Our findings provide molecular insights into the maturation of Ab responses driven by booster doses of glycoconjugate. This has fundamental implications for the design of glycoconjugate vaccines, especially where the development of Ab response against the carrier protein is also crucial.

Otitis media sequelae and hearing in adolescence after administration of an 11-valent conjugate pneumococcal vaccine in infancy: a prospective cohort study with long-term follow-up of the ARIVAC trial.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) have been shown in randomised controlled trials and epidemiological studies to prevent acute otitis media caused by vaccine serotype pneumococci, although their role in preventing complications of acute otitis media is less clear. We hypothesised that the 11-valent PCV would reduce the long-term sequelae of acute otitis media, including moderate-to-severe ear disease and hearing loss. METHODS: This prospective cohort study, referred to as 11PCV study, included follow-up after 16-20 years of children previously enrolled in 2000-04, at age 6 weeks to 6 months, in the randomised, placebo-controlled, ARIVAC trial of 11-valent PCV for the prevention of radiographical pneumonia. The ARIVAC trial and this 11PCV study were conducted at six study centres in Bohol, Philippines. Ear disease was classified using video-otoscopy review and observations derived from the ear exam. The final classification of the worst ear disease was mild (ie, acute otitis media, otitis media with effusion, healed perforation, or tympanosclerosis), moderate (ie, dry perforation or adhesive otitis media), or severe (chronic suppurative otitis media). Hearing loss was assessed following a standard schema and classified according to the worst ear as mild (>15 to 30 dB puretone average) or moderate-to-profound (>30 dB pure tone average). We calculated the relative and absolute risk reduction in the primary outcome of moderate-to-severe ear disease and the secondary outcomes of mild or moderate-to-profound hearing loss in adolescents who previously received the 11-valent PCV compared with those who received placebo during infancy in ARIVAC. FINDINGS: Of the 15 593 children assessed for eligibility in ARIVAC, 12 194 were randomly assigned and 8926 were alive and could be located for enrolment in this 11PCV study between Sept 19, 2016, and Dec 13, 2019. 8321 (4188 in the vaccine group and 4133 in the placebo group) completed follow-up of the 11PCV study by March 30, 2020, and had sufficient data to classify ear disease and be included in the primary outcome analysis. The primary outcome of the absolute risk reduction in moderate-to-severe ear disease in the vaccine group (310 [7·4%] of 4188) versus those in the placebo group (356 [8·6%] of 4133) was 1·2% (95% CI 0·0-2·4; p=0·046) and the relative risk reduction was 14·1% (0·0 to 26·0). There were no differences in secondary outcomes of mild hearing loss or moderate-to-profound hearing loss between the vaccine and placebo groups. INTERPRETATION: The absolute risk reduction for moderate-to-severe ear disease in adolescence of 1·2% (12 per 1000 children) was almost three times higher than the 0·45% reduction (4·5 per 1000 children) in radiographical pneumonia in the first 2 years of life shown in ARIVAC. Administration of 11-valent PCV in infancy was associated with absolute and relative risk reductions in the sequelae of acute otitis media 16-20 years after the original ARIVAC trial. FUNDING: Bill & Melinda Gates Foundation.

Memory B cell responses induced by pneumococcal conjugate vaccine schedules with fewer doses: analysis of a randomised-controlled trial in Viet Nam.

The use of pneumococcal conjugate vaccine (PCV) schedules with fewer doses are being considered to reduce costs and improve access, particularly in low- and middle-income countries. While several studies have assessed their immunogenicity, there are limited data on their potential for long-term immune protection, as assessed by pneumococcal serotype-specific memory B cell (Bmem) responses. This current study reports secondary outcome data that aims to compare Bmem responses following reduced-dose (0 + 1 and 1 + 1) schedules of PCV10 and PCV13 in Vietnamese infants from our randomised-controlled trial (trial registration number NCT03098628). Following vaccination at 12 months of age, Bmem levels for most serotypes peaked seven days post-vaccination and were higher in magnitude for the 1 + 1 than 0 + 1 schedules and for PCV13 than PCV10. Furthermore, Bmem did not wane as rapidly as IgG levels by 24 months of age. Further studies are needed to assess the use of Bmem as markers of long-term protection against pneumococcal carriage and disease, which is crucial to generate data for immunisation program decision-making.

Sustainability of pneumococcal conjugate vaccination in Ghana: a cost-effectiveness analysis in the context of donor transition.

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.

Multicentre case-control study of pneumococcal infections among children with pneumonia in Peninsular Malaysia (MY-Pneumo): a study protocol.

BACKGROUND: S. pneumoniae (SPN) is the most common cause of pneumonia. The disease can be effectively prevented through immunisation. Since December 2020, the Malaysian Government has included the 10-valent pneumococcal conjugate vaccine (PCV10) for all infants born on or after 1 January 2020 as part of the National Immunisation Programme (NIP). However, the epidemiology of pneumonia remains poorly understood. To fill the knowledge gap, we established a multicentre surveillance study to understand the burden of pneumococcal pneumonia among young children in Peninsular Malaysia. METHODS: MY-Pneumo is a multicentre prospective case-control study conducted in three sentinel sites located in three different states of Peninsular Malaysia - Kuala Lumpur, Pahang, and Kelantan. A cohort of at least 500 incident cases and 500 controls is enrolled beginning in October 2021 and matched for age. Cases are hospitalised children < 5 years with radiologically confirmed pneumonia, and the controls are children without any features suggestive of pneumonia. Clinical samples, including nasopharyngeal swabs (NPS) and urine, are collected according to the study protocol. Biological fluids such as blood, cerebrospinal fluid (CSF) and pleural fluid are obtained from invasive pneumonia disease (IPD) patients, if available. All children are tested for SPN using polymerase chain reaction (PCR) and pneumococcal urine antigen test (PUAT) using BinaxNow. DISCUSSION: Surveillance data, including carriage rate, serotype variations and the phylogeny data structure of SPN among young children in Malaysia during PCV implementation, will be generated from this study. Trends and patterns of pneumococcal serotypes by different regions are important for targeted public health strategies. Our data will provide baseline information for estimating the impact of PCV10 implementation and will influence policymakers' decisions regarding the upgrade from PCV10 to a higher-valency conjugate vaccine in Malaysia. TRIAL REGISTRATION: This project was registered at ClinicalTrials.gov (NCT04923035) on 2021, June 11. The study protocol was approved by the International Medical University Joint-Committee on Research & Ethics (4.15/JCM-216/2021) and the Institutional Review Board at sentinel sites (USM/JEPeM/21020190, IREC 2021-114, MREC ID No: 2021128-9769) and University of Southampton's Ethics and Research Governance (ERGo II 64844).

Long-term effect of pneumococcal conjugate vaccines on invasive pneumococcal disease incidence among people of all ages from national, active, laboratory-based surveillance in South Africa, 2005-19: a cohort observational study.

BACKGROUND: In South Africa, 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2009 and 13-valent PCV (PCV13) was introduced in 2011, both in a two plus one schedule. We evaluated the ongoing effects of PCV on the prevention of invasive pneumococcal disease (IPD) over 15 years of sustained surveillance in South Africa before the COVID-19 pandemic. METHODS: We conducted national, active, laboratory-based surveillance for IPD among all ages in South Africa, including isolate serotyping and susceptibility testing. We fitted linear regression models with vaccine covariates to imputed IPD case counts each year by serotype and age to compare expected and actual IPD cases in 2019, which was the main outcome. Vaccine effects were set to zero to identify expected incidence after the introduction of PCV7 and PCV13. FINDINGS: From Jan 1, 2005, to Dec 31, 2019, surveillance identified 52 957 IPD cases. Among the 50 705 individuals with age data available, 9398 (18·5%) were infants aged younger than 2 years. Compared with expected case numbers (no vaccination) predicted using all available data, overall IPD rates among children younger than 2 years declined by 76·0% (percentage risk difference; 95% CI -79·0 to -72·8%) in 2019; notably, PCV7 and additional PCV13 serotype IPD rates declined by 95·5% (-97·0 to -93·4%) and 93·8% (-96·2 to-90·5%), respectively, whereas non-vaccine serotypes (NVTs) did not change significantly. Among adults aged 25-44 years, overall IPD declined by 50·4% (-54·2 to -46·3%), and PCV7 and additional PCV13 serotype IPD rates declined by 86·1% (-88·7 to -83·1%) and 77·2% (-80·9 to -73·0%), respectively, whereas NVTs increased by 78·5% (56·8 to 103·4%). Individuals aged older than 64 years also benefited from declines in IPD (-30·2%; -41·9 to -16·2%), but NVTs increased (234·9%; 138·1 to 379·4%). INTERPRETATION: We documented sustained direct and indirect benefits of PCV across age groups, and NVT increases in adults older than 24 years. Higher valency PCVs would have the added benefit of preventing this residual disease. FUNDING: National Institute for Communicable Diseases of the National Health Laboratory Service (South Africa) and US Agency for International Development Antimicrobial Resistance Initiative, US Centers for Disease Control and Prevention.

Clonal Expansion of a Streptococcus pneumoniae Serotype 3 Capsule Variant Sequence Type 700 With Enhanced Vaccine Escape Potential After 13-Valent Pneumococcal Conjugate Vaccine Introduction.

BACKGROUND: Streptococcus pneumoniae serotype 3 remains a problem globally. Malawi introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2011, but there has been no direct protection against serotype 3 carriage. We explored whether vaccine escape by serotype 3 is due to clonal expansion of a lineage with a competitive advantage. METHODS: The distribution of serotype 3 Global Pneumococcal Sequence Clusters (GPSCs) and sequence types (STs) globally was assessed using sequences from the Global Pneumococcal Sequencing Project. Whole-genome sequences of 135 serotype 3 carriage isolates from Blantyre, Malawi (2015-2019) were analyzed. Comparative analysis of the capsule locus, entire genomes, antimicrobial resistance, and phylogenetic reconstructions were undertaken. Opsonophagocytosis was evaluated using serum samples from vaccinated adults and children. RESULTS: Serotype 3 GPSC10-ST700 isolates were most prominent in Malawi. Compared with the prototypical serotype 3 capsular polysaccharide locus sequence, 6 genes are absent, with retention of capsule polysaccharide biosynthesis. This lineage is characterized by increased antimicrobial resistance and lower susceptibility to opsonophagocytic killing. CONCLUSIONS: A serotype 3 variant in Malawi has genotypic and phenotypic characteristics that could enhance vaccine escape and clonal expansion after post-PCV13 introduction. Genomic surveillance among high-burden populations is essential to improve the effectiveness of next-generation pneumococcal vaccines.

Estimating the Global and Regional Burden of Streptococcus pneumoniae Meningitis in Children: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Streptococcus pneumoniae (Spn) has been a leading cause of bacterial meningitis in children. The most recent estimation of the global burden of Spn meningitis indicates a positive trajectory in eliminating Spn through the implementation of pneumococcal conjugate vaccines. However, continuous monitoring and assessment of the disease burden are necessary due to the evidence of serotype replacement, antibiotic resistance, and the impact of the recent COVID-19 pandemic. OBJECTIVE: The aim of this systematic review is to provide an updated and focused assessment of the global and regional burden of Spn meningitis in children, which can guide policies and strategies to reduce the disease burden. METHODS: Population-based studies published from January 1, 2000, to January 1, 2022, were preliminarily searched from the electronic databases PubMed, Embase, Global Health (CABI), and CINAHL Plus without any language restrictions. Studies were included if they reported the incidence, prevalence, mortality, or case-fatality ratio (CFR) for Spn meningitis in children aged 0-4 years; meningitis was confirmed by cerebrospinal fluid culture; the study period was a minimum of 1 year; the number of reported cases was at least 10; and the study had no methodological ambiguities. The article screening process follows the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Characteristics including study period, setting, World Health Organization region, income level, vaccination information, and participant data (age, number of cases, deaths, sequelae, and risk factors) will be extracted from the included studies. Search results will be updated and incorporated into our review prior to finalizing the extraction of data. Generalized linear mixed models meta-analysis will be performed to estimate the pooled incidence and CFR. We will further assess the risk of bias and heterogeneity, and will perform subgroup and sensitivity analyses to provide a meaningful interpretation of the current burden and literature for pneumococcal meningitis. RESULTS: Our preliminary search in December 2021 yielded 9295 articles. Out of 275 studies that were assessed with our eligibility criteria, 117 articles were included. Data extraction and analysis are expected to be complete by January 2025. We plan to publish the results from the full study, including an updated search in 2024, by March 2025. CONCLUSIONS: Given that the major burden of Spn meningitis affects children under the age of 5 years, this systematic review will provide a thorough understanding of the global burden of Spn meningitis in this vulnerable population over a span of 2 decades. Insights into incidence trends, geospatial distribution, risk factors, and sequelae will be valuable for stakeholders, policy makers, and the academic community. This information will aid in the ongoing monitoring of the disease and in enhancing targeted vaccine programs to further mitigate the impact of the disease on children worldwide. TRIAL REGISTRATION: PROSPERO CRD42021293110; https://tinyurl.com/kc3j5k4m. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50678.

Effectiveness of pneumococcal vaccination in adults with common immune-mediated inflammatory diseases in the UK: a case-control study.

BACKGROUND: People with immune-mediated inflammatory disease are at increased risk of pneumococcal pneumonia. The effectiveness of pneumococcal vaccination in people with immune-mediated inflammatory diseases has not been evaluated. We investigated the effectiveness of pneumococcal vaccination in preventing morbidity and mortality associated with pneumonia in patients with immune-mediated inflammatory diseases. METHODS: In this matched case-control study, we used primary-care electronic health record data from the Clinical Practice Research Datalink Gold database in the UK, with linked hospitalisation and mortality data. Adults with incident common immune-mediated inflammatory diseases diagnosed between April 1, 1997, and Dec 31, 2019, were followed up from the first diagnosis date to the occurrence of an outcome or date of last follow-up. Cases (ie, those with an outcome of interest) were age-matched and sex-matched to up to ten contemporaneous controls by use of incidence density sampling. Outcomes were hospitalisation due to pneumonia, death due to pneumonia, or primary-care consultation for lower respiratory tract infection requiring antibiotics. We defined hospital admission for pneumonia using hospital discharge diagnoses, death due to pneumonia using death certification data, and lower respiratory tract infection as present when primary-care consultation and antibiotic prescription occurred on the same date. We used multivariable, unconditional, logistical regression and constructed three models to examine the association between pneumococcal vaccination as an exposure and each of the three outcomes. FINDINGS: The first nested case-control analysis included 12 360 patients (7326 [59·3%] women and 5034 [40·7%] men): 1884 (15·2%) who were hospitalised due to pneumonia and 10 476 (84·8%) who were not admitted to hospital due to pneumonia. The second analysis included 5321 patients (3112 [58·5%] women and 2209 [41·5%] men): 781 (14·7%) who died due to pneumonia and 4540 (85·3%) who were alive on the index date. The third analysis included 54 530 patients (33 605 [61·6%] women and 20 925 [38·4%] men): 10 549 (19·3%) with lower respiratory tract infection treated with antibiotics and 43 981 (80·7%) without infection. In the multivariable analysis, pneumococcal vaccination was negatively associated with hospitalisation due to pneumonia (adjusted odds ratio 0·70 [95% CI 0·60-0·81]), death due to pneumonia (0·60 [0·48-0·76]), and lower respiratory tract infection treated with antibiotics (0·76 [0·72-0·80]). INTERPRETATION: Pneumococcal vaccination is associated with protection against hospitalisation and death due to pneumonia in patients with immune-mediated inflammatory diseases, without apparent residual confounding. However, residual unmeasured confounding cannot be fully excluded in observational research, which includes nested case-control studies. These findings should also be corroborated with data from other countries, given that this study used UK-based data. FUNDING: National Institute for Health and Care Research.

Association between Socioeconomic Status and Vaccination Hesitancy, Reluctancy and Confidence among Asian-Americans Living in the State of New Jersey.

BACKGROUD: Socioeconomic status (SES) plays a vital role in determining vaccination uptake and attitudes. Vaccine hesitancy varies among different communities, yet knowledge of vaccine attitudes among Asian-Americans is limited. OBJECTIVE: This study aims to investigate the relationship between SES and vaccine attitudes among Asian-Americans in the State of New Jersey (NJ). METHODS: Asian-Americans aged ≥ 18 years living in NJ were included (N = 157). SES was measured by education level, employment type, employment status, and household income. The primary outcomes were vaccine hesitancy, reluctance, and confidence for COVID-19, influenza, and pneumococcal vaccines. Descriptive and inferential statistics were performed. Multivariable logistic regression was used to identify associations between SES and vaccine hesitancy while controlling for confounders such as age, gender, birthplace, and religion. RESULTS: Among 157 participants, 12.1% reported vaccine hesitancy. There was no statistically significant association between vaccine hesitancy and education level (p = 0.68), employment status (p = 1), employment type (p = 0.48), and household income (p = 0.15). Multivariable logistic regression modeling confirmed that none of the SES predictor variables were associated with vaccine hesitancy. However, as exploratory finding, gender was found to be a significant predictor, with males having lower odds of vaccine hesitancy than females (Adjusted OR = 0.14; p < 0.05). Confidence in influenza and pneumococcal vaccines increased during the pandemic, from 62.34% to 70.13% and from 59.2% to 70.51%, respectively. For the COVID-19 vaccine, 73.1% of participants reported having "a lot of confidence" in taking vaccine. CONCLUSION: Most sampled Asian-Americans in NJ have high confidence in taking COVID-19 vaccines, and there is no significant association between vaccine hesitancy and SES.