Pneumococcal Vaccine Research Articles

Inequitable Distribution of Global Economic Benefits from Pneumococcal Conjugate Vaccination.

Many low- and middle-income countries have been slow to introduce the pneumococcal conjugate vaccine (PCV) into their routine childhood immunization schedules despite a high burden of disease. We estimated the global economic surplus of PCV, defined as the sum of the net value to 194 countries (i.e., monetized health benefits minus net costs) and to vaccine manufacturers (i.e., profits). We further explored the distribution of global economic surplus across country income groups and manufacturers and the effect of different pricing strategies based on cross-subsidization, pooled procurement, and various tiered pricing mechanisms. We found that current PCV pricing policies disproportionately benefit high-income countries and manufacturers. Based on the 2021 birth cohort, high-income countries and manufacturers combined received 76.5% of the net economic benefits generated by the vaccine. Over the two decades of PCV availability, low- and middle-income countries have not received the full economic benefits of PCV. Cross-subsidization of the vaccine price for low- and middle-income countries and pooled procurement policies that would relate the vaccine price to the value of economic benefits generated for each country could reduce these inequalities. This analysis offers important considerations that may improve the equitable introduction and use of new and under-utilized vaccines.

Natural carriage of Streptococcus pneumoniae is associated with increased experimental pneumococcal carriage but reduced conjugate vaccine efficacy in a human challenge model.

In Malawi, the national pneumococcal conjugate vaccine (PCV13) demonstrated less herd immunity than the USA, likely due to higher natural pneumococcal carriage rates. We assessed PCV13 efficacy against experimental pneumococcal carriage in healthy Malawian adults. We explored how natural carriage (pneumococcal carriage of any other serotype apart from 6B) influenced experimental carriage rates and vaccine efficacy. Healthy adults aged 18-40 were randomly assigned PCV13 (n=98) or saline (n=106), followed by intranasal SPN 6B inoculation at 20,000 (n=40), 80,000 (n=74), or 160,000 (n=90) CFU/100µl, 28 days post-vaccination. We evaluated natural and experimental pneumococcal carriage before and after vaccination on days 2, 7, and 14 post-inoculation using culture and multiplex qPCR targeting lytA/cpsA genes and compared carriage rates by vaccination status. Of 204 participants, 19.6% (40) exhibited experimental carriage, detected by culture and 25.5% (52) by qPCR. Vaccinated individuals had lower experimental carriage rates (10.2%, n=10/98) compared to the placebo group (28.3%, n=30/106). This difference in vaccine efficacy was more pronounced in participants without natural carriage (PCV13=8% n=6/75 vs. placebo=25.9%, n=21/81) compared to those with natural carriage (PCV13=14.8%, n=4/27 vs. placebo=26.5%, n=9/34). Using a log-binomial model, vaccine effectiveness (VE) was 62%, whether assessed by culture or qPCR. Natural carriers had a lower VE of 52% compared to participants with no natural carriage (VE=69%). We have shown that PCV13 VE estimate (62%) is robust whether carriage is assessed by culture or qPCR. PCV13 had lower VE in natural carriers compared to those without natural carriage at the inoculation visit.

Serotype distribution of invasive pneumococcal disease from countries of the WHO Africa, Americas, Eastern Mediterranean, South-East Asia, and Western Pacific regions: a systematic literature review from 2010 to 2021.

Most publications on invasive pneumococcal disease (IPD) serotype distribution are from about 20 countries (Australia, Canada, China, European Union members, Japan, New Zealand, South Korea, and USA). Here, we reviewed the literature among underrepresented countries in the Americas (AMRO), Africa (AFRO), Eastern Mediterranean (EMRO), South-East Asia (SEARO), and Western Pacific (WPRO) WHO regions. We performed a systematic review of the most recent IPD serotype surveillance publications (from 01/01/2010 to 31/12/2021, Medline/Embase) in those WHO regions. Selection criteria were delineated by contemporality, within-country geographical scope, and number of samples. Reported serotype distributions for each country were stratified by age group, pneumococcal conjugate vaccine (PCV) serotype category (considering undifferentiated serotypes), and PCV program period (pre-PCV, intermediate, or PCVhv [higher valency PCV formulation]). Pre-PCV period pooled data estimated PCV serotype category distribution by age group across WHO regions, while for the PCVhv period, country-level dataset tables were prepared. Of 2,793 publications screened, 107 were included (58 pediatric, 11 adult, 37 all ages, and one comprising every age group). One-third of eligible countries (51/135) published serotype distribution, ranging from 30 to 43% by WHO region. Considering number of samples per WHO region, a few countries prevailed: AMRO (Brazil), AFRO (South Africa, Malawi, and Burkina Faso), and WPRO (Taiwan). In the pre-PCV period, PCV13 formulation serotypes predominated: ranging from 74 to 85% in children and 58-86% in adults in the different WHO regions. The PCVhv period represented half of the most recent IPD surveillance by countries (26/51). Undifferentiated serotypes represented >20% of IPD from most countries (34/51). Ubiquity of undifferentiated serotypes among the publications could constrain estimates of PCV program impact and of serotype coverage for newer PCVhv formulations; consequently, we recommend that countries favor techniques that identify serotypes specifically and, rather than reporting PCV formulation serotype distributions, provide serotype results individually. The protocol has been prospectively registered at PROSPERO, identifier: CRD42021278501. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278501.

Geographical migration and fitness dynamics of Streptococcus pneumoniae

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59–1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.

Progress in research and development of preventive vaccines for children in China.

The infant and child stage is an important stage for the continuation and development of human society. The initial years of life have a lasting impact on a child's future. Children under the age of 5 have an immature immune system, especially infants and young children under 6 months of age. At this stage, the population has a low immunity to pathogen infections, making them vulnerable to bacteria and viruses. Vaccination can enhance the immunity of infants and children to specific diseases, reduce the transmission rate of infectious diseases, and promote the development of global public health. This article summarizes the current application status of Rotavirus (RV) vaccine, Hand-foot -mouth disease (HFMD) vaccine, and Pneumococcal Conjugate Vaccine (PCV) in China, as well as the research progress of clinical trial vaccine, laying a foundation for subsequent vaccine development.

Determinants of pneumococcal vaccination dropout among children aged 12-23 months in Ethiopia: a secondary analysis from the 2019 mini demographic and health survey.

Vaccination is a cost-effective public health program that helps reduce significant morbidity and mortality in children under the age of five. Worldwide, the number of vaccine-preventable causes of child death has significantly decreased since the Expanded Program of Immunization (EPI) was introduced. However, for a variety of reasons, 23 million children did not have adequate access to vaccines in 2020. Therefore, this study aimed to evaluate the determinants of pneumonia conjugate vaccine (PCV) dropout among children aged 12-23 months in Ethiopia. The study analyzed cross-sectional data obtained from the 2019 mini Ethiopian demographic and health survey. Multilevel binary logistic regression analysis was utilized, and the best fit model was chosen using the Akaike Information Criteria. The study comprised a weighted sample of 989 children aged 12 to 23 months. The study presented the Adjusted Odds Ratio (AOR) along with a 95% Confidence Interval (CI) to identify the significant factors influencing PCV dropout. The PCV dropout rate was reported at 20.2% in this study. In the multilevel analysis, possession of a health card (AOR = 0.076, 95% CI: 0.019, 0.04), vaccination for PCV 2 (AOR =0.002, 95% CI: 0.023, 0.263), and region 7 (AOR = 6.98, 95% CI: 10.1, 48.31) were significantly associated with children's PCV dropout. Having a health card, having received the PCV 2 vaccinations, and region were significant predictors of PCV dropout. Consequently, health education on immunization for all mothers and region-specific, customized public health interventions are needed to reduce the vaccination dropout rate.

Long-term impact of 10-valent pneumococcal conjugate vaccine in Kenya: Nasopharyngeal carriage among children in a rural and an urban site six years after introduction

BackgroundKenya introduced Synflorix™ (GlaxoSmithKline, PCV10-GSK), a 10-valent pneumococcal conjugate vaccine, in 2011, using three primary doses and, in select areas, catch-up campaigns. Surveys conducted 1–2 years post-introduction showed a stable prevalence of pneumococcal colonization, with declines in vaccine-type carriage. However, little is known about the long-term impact of PCV10-GSK in Kenya. MethodsWe conducted a cross-sectional survey of pneumococcal carriage among children aged <5 years in November–December 2017 in Kibera (Nairobi informal settlement, no catch-up) and Asembo (rural western Kenya, 2-dose catch-up for children 1–4 years), using the same methods and settings as prior annual surveys from 2009 to 2013. Participants were randomly selected from an ongoing population-based surveillance platform. Nasopharyngeal swabs were frozen in skim milk-tryptone-glucose-glycerin media within 4 h and underwent culture with broth enrichment for pneumococcus. Isolates were serotyped by polymerase chain reaction and Quellung. ResultsWe enrolled 504 children, including 252 from each site; >90 % of participants had received 3 doses of PCV10-GSK. Pneumococcal colonization was detected in 210 (83.3 %) participants in Kibera and 149 (59.1 %) in Asembo, which was significantly lower than the prevalence observed in 2013 (92.9 % and 85.7 %, respectively). PCV10-GSK serotypes were detected in 35/252 (13.9 %) participants in Kibera and 23/252 (9.1 %) in Asembo, respectively; these prevalences were lower, but not statistically different, from vaccine-type carriage prevalences in 2013 (17.3 % and 13.3 %, respectively). In 2017 in both sites, serotypes 3, 6A, 19A, 19F, and 35B were among the most common serotypes. ConclusionSix years post-PCV10-GSK introduction, the prevalence of pneumococcal carriage among children has decreased, and the impact of PCV10-GSK on vaccine-type carriage has plateaued. Kenya recently changed from PCV10-GSK to Pneumosil™ (Serum Institute of India), a 10-valent PCV that includes serotypes 6A and 19A; these data provide historical context for interpreting changes in vaccine-type carriage following the PCV formulation switch.

Pneumococcal vaccine in adults with immune-mediated inflammatory diseases

Pneumococcal vaccine in adults with immune-mediated inflammatory diseases

Safety, tolerability, and immunogenicity of an adult pneumococcal conjugate vaccine, V116 (STRIDE-3): a randomised, double-blind, active comparator controlled, international phase 3 trial

The same pneumococcal conjugate vaccines (PCVs) have been used in adults and children in many settings. Differences in the epidemiology of pneumococcal disease between populations necessitates an adult-specific PCV. We aimed to assess the safety, tolerability, and immunogenicity of V116, an investigational 21-valent PCV designed for adults. This randomised, double-blind, active comparator controlled, international phase 3 trial enrolled adults with or without stable chronic medical conditions at 112 clinical sites in 11 countries or territories. Random assignment was performed using a central electronic interactive response technology system. Cohort 1 (≥50 years) was stratified by age (50-64, 65-74, 75-84, and ≥85 years) and randomised 1:1 to receive one intramuscular dose of V116, or the active comparator, PCV20. Cohort 2 (18-49 years) was randomised 2:1 to receive one intramuscular dose of V116 or PCV20. Pneumococcal serotype-specific opsonophagocytic activity (OPA) and IgG responses were measured before (day 1) and after vaccination (day 30). Four primary immunogenicity outcomes were assessed per-protocol. First, in cohort 1, non-inferiority of V116 to PCV20 was tested using serotype-specific OPA geometric mean titres (GMT) ratios for serotypes common to both vaccines; the lower bound of the 95% CI had to be greater than 0·5 for non-inferiority. Second, superiority of V116 to PCV20 was tested for OPA GMT ratios for the serotypes unique to V116; the lower bound of the 95% CI had to be greater than 2·0 for superiority. Third, superiority of V116 to PCV20 was evaluated by the proportions of participants with a four-fold or greater rise from day 1 to day 30 for serotypes unique to V116; the lower bound of the 95% CI of the differences in proportions (V116 - PCV20) had to be greater than 10% for superiority. Finally, in cohort 2, immunobridging was assessed for all 21 serotypes in V116 for adults aged 18-49 years to 50-64 years; the lower bound of the 95% CI for the OPA GMTs had to be greater than 0·5 for non-inferiority. The safety analysis included all randomly assigned participants who received study vaccine. The primary safety outcome was the proportion of participants with solicited injection site and solicited systemic adverse events until day 5 and vaccine-related serious adverse events up to 6 months after vaccination. This trial is registered at ClinicalTrials.gov (NCT05425732). Between July 13, and Nov 22, 2022, 2754 individuals were screened and 2663 participants were randomly assigned. 2656 individuals were vaccinated (1179 in V116 cohort 1; 1177 in PCV20 cohort 1; 200 in V116 cohort 2; and 100 in PCV20 cohort 2). V116 met non-inferiority criteria compared with PCV20 for the ten serotypes common to both vaccines at day 30 in cohort 1 (p<0·0001 for each common serotype). V116 met superiority criteria compared with PCV20 in cohort 1 for ten of the 11 serotypes unique to V116 at day 30 (OPA GMT ratio: p<0·0001 for all unique serotypes except 15C, which was p=0·41; four-fold or greater rise in OPA from day 1-30: p<0·0001 for all serotypes except 15C, which was p=0·67). Immune responses in V116 participants aged 18-49 years were non-inferior compared with V116 participants aged 50-64 years for all V116 serotypes (p<0·0001 for all V116 serotypes). In cohort 1, 685 (58·2%) of participants in V116, and 778 (66·2%) of participants in PCV20 reported one or more adverse event. In cohort 2, 164 (82·0%) participants in V116 and 79 participants (79·0%) in PCV20 reported one or more adverse event. Six deaths were reported, all in cohort 1, none of which were considered vaccine-related (in V116: one due to sepsis, one due to cerebrovascular accident, one due to myocardial infarction, and one due to hepatic cirrhosis and hepatic encephalopathy; in PCV20: one due to cardiac arrest and one due to abdominal abscess). There were no vaccine-related serious adverse events. V116 was non-inferior to PCV20 for the ten serotypes common to both vaccines and superior to PCV20 for all serotypes unique to V116, except for 15C. Immune responses successfully immunobridged between younger and older adults for all serotypes in V116. V116 was generally well tolerated with safety profile similar to PCV20. Merck Sharp & Dohme, subsidiary of Merck & Co, Rahway, NJ, USA (MSD).

Economic Burden of Otitis Media Globally and an Overview of the Current Scenario to Alleviate the Disease Burden: A Systematic Review.

Introduction The prevalence of otitis media (OM) is substantial all over the world. Epidemiological data related to the economic burden of OM globally is minimal. The present systematic review was undertaken to estimate the economic burden of this disease in various parts of the world. Objectives An extensive literature search was done using PRISMA guidelines to identify relevant studies that estimated the economic burden of OM in monetary terms. The databases searched were PubMed Central, Ovid, and Embase. The cost estimation was done for one specific year and then compared considering the inflation rate. Data Synthesis The literature search led to the inclusion of 10 studies. The studies evaluated direct and indirect costs in monetary terms. Direct costs (health system and patient perspective) ranged from USD (United States Dollar) 122.64 (Netherlands) to USD 633.6 (USA) per episode of OM. Looking at only the patient perspective, the costs ranged from USD 19.32 (Oman) to USD 80.5 (Saudi Arabia). The total costs (direct and indirect) ranged from USD 232.7 to USD 977 (UK) per episode of OM. The economic burden per year was highest in the USA (USD 5 billion). The incidence of OM episodes was found more in children < 5 years old. Introduction of pneumococcal conjugate vaccines decreased the incidence in children and now the prevalence in adults is of concern. Conclusion The economic burden of OM is relatively high globally and addressing this public health burden is important. Approaches for the prevention, diagnosis, and treatment should be undertaken by the health system to alleviate this disease burden.

Adult pneumococcal vaccination: what are the gaps?

Adult pneumococcal vaccination: what are the gaps?

Vaccine Hesitancy in HIV Patients Following the COVID-19 Pandemics

Introduction: The prevalence of vaccine hesitancy has been on the rise for several years in the United States leading up to the Covid19 pandemic. During the pandemic, there was controversy and media attention surrounding the effectiveness and safety of the Covid19 vaccine, with many individuals, including patients with HIV, refusing vaccination, despite evidence of its benefit. There are further concerns that patients with HIV are reluctant to receive additional vaccines that existed prior to the Covid19 pandemic. In this study, we evaluated the rate of refusal of non-Covid19 vaccines in the pre- and post-period after release of the Covid19 vaccine. Methods: We measured and compared the number of vaccines offered and refused at each visit over the total number of visits for 195 patients with HIV during a pre-Covid (approximately 18 months before the release of the Pfizer vaccine to the public on August 23, 2021) and post-Covid period (approximately 18 months after the previously mentioned date). The vaccines studied included the following: tetanus, pneumococcal, shingles, hepatitis A/B, and influenza. The data was collected using hospital records from Athena and Cerner, as well as Michigan State Records. Data was analyzed using descriptive statistics and the Wilcoxon signed ranks test. The Mann-Whitney U test, Kruskal-Wallis test and Pearson’s correlation were performed for the Covid19 vaccine statistics. In all statistical tests, a p-value less than 0.05 was taken to indicate statistical significance. Results: Collectively, there were more refusals in the period after release of the Covid19 vaccine for non-Covid19 vaccines. This was also the case for all individual vaccines, except Hepatitis A. There was an overall statistically significant difference (p &lt;0.001) in the distribution of vaccine refusals between the pre-Covid19 and post-Covid19 period. This was observed for the Pneumococcal (p=0.026), Hepatitis B (p=0.035), and Shingles vaccine (p &lt;0.001) respectively. The Covid19 vaccine was more likely to be refused in female patients (p=0.005), non-white patients (p=0.02), and younger patients (p=0.04, r= -0.21). Discussion/Conclusion: This study provides evidence that there is an increase in non-Covid19 vaccine hesitancy following the release of the Covid19 vaccine in patients with HIV at Ascension St. John Hospital. Given the small size of the study population and this study being an initial evaluation, more will need to be performed. This is to further test these findings in other regions of the United States.

Deploying an asthma dashboard to support quality improvement across a nationally representative sentinel network of 7.6 million people in England

Every year, there are ~100,000 hospital admissions for asthma in the UK, many of which are potentially preventable. Evidence suggests that carefully conceptualised and implemented audit and feedback (A&F) cycles have the potential to improve clinical outcomes for those with chronic conditions. We wanted to investigate the technical feasibility of developing a near-real time asthma dashboard to support A&F interventions for asthma management in primary care. We extracted cross-sectional data on asthma from 756 participating GP practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) database in England comprising 7.6 million registered people. Summary indicators for a GP practice were compared to all participating RCGP RSC practices using practice-level data, for the week 6–12th-Mar-2023. A weekly, automated asthma dashboard with features that can support electronic-A&F cycles that compared key asthma indicators for a GP practice to RCGP RSC could be created (https://tinyurl.com/3ydtrt85): 12-weeks-incidence 0.4% vs 0.4%, annual prevalence 6.1% vs 6.7%, inhaled relievers to preventer 1.2 vs 1.1, self-management plan given 83.4% vs 60.8%, annual reviews 36.8% vs 57.3%, prednisolone prescriptions 2.0% vs 3.2%, influenza vaccination 56.6% vs 55.5%, pneumococcal vaccination ever (aged ≥65 years) 90.2% vs 84.1% and current smokers 14.9% vs 14.8%. Across the RCGP RSC, the rate of hospitalisations was 0.024%; comparative data had to be suppressed for the study practice because of small numbers. We have successfully created an automated near real-time asthma dashboard that can be used to support A&F initiatives to improve asthma care and outcomes in primary care.

Expert panel opinion on adult pneumococcal vaccination in the post-COVID era (NAP- EXPO Recommendations-2024).

Pneumococcal diseases pose a significant public health concern in India, with substantial morbidity and mortality, with the elderly and those with coexisting medical conditions being most at risk. Pneumococcus was also seen to be one of the main reasons for co-infection, pneumonia and complications in COVID. Current guidelines recommend vaccination for specific adult populations, but there is a lack of uniformity and guidance on risk stratification, prioritisation and optimal timing. Nation Against Pneumococcal Infections - Expert Panel Opinion (NAP-EXPO) is a panel convened to review and update recommendations for adult pneumococcal vaccination in India. The panel of 23 experts from various medical specialties engaged in discussions and evidence-based reviews, discussed appropriate age for vaccination, risk stratification for COPD and asthma patients, vaccination strategies for post-COVID patients, smokers and diabetics, as well as methods to improve vaccine awareness and uptake. The NAP-EXPO recommends the following for adults: All healthy individuals 60 years of age and above should receive the pneumococcal vaccine; all COPD patients, regardless of severity, high-risk asthma patients, post-COVID cases with lung fibrosis or significant lung damage, should be vaccinated with the pneumococcal vaccine; all current smokers and passive smokers should be educated and offered the pneumococcal vaccine, regardless of their age or health condition; all diabetic individuals should receive the pneumococcal vaccine, irrespective of their diabetes control. Strategies to improve vaccine awareness and uptake should involve general practitioners (GPs), primary health physicians (PHPs) and physicians treating patients at high risk of pneumococcal disease. Advocacy campaigns should involve media, including social media platforms. These recommendations aim to enhance pneumococcal vaccination coverage among high-risk populations in India in order to ensure a reduction in the burden of pneumococcal diseases, in the post-COVID era. There is a need to create more evidence and data to support the recommendations that the vaccine will be useful to a wider range of populations, as suggested in our consensus.

Hospital Burden of All-Cause Pneumonia and Nonbacteremic Pneumococcal Pneumonia in Adults in France Between 2013 and 2019.

Community-acquired pneumonia (CAP) is associated with significant morbidity and mortality. The study objective was to describe the hospital burden of pneumonia in the adult population in France. This retrospective study was conducted from the National Health Insurance Database. All hospitalizations for pneumonia (all-cause) between 2013 and 2019 were included. Different risk categories for patients were established based on pneumococcal vaccine recommendations by French health authorities. A total of 2 199 240 episodes of CAP were registered over the study period (annual mean, 314 177 [standard deviation, 17 818.6]); 75% occurred in patients aged ≥65 years, among whom 47% were not classified in the moderate- or high-risk categories recommended for French pneumococcal vaccination. The incidence of CAP increased with age (117.9, 395.3, and 1916.7 per 100 000 for the age groups 18-49, 50-64, and ≥65 years, respectively, in 2019). Furthermore, being at risk of pneumococcal disease resulted in more severe outcomes, including longer episode duration (mean, 14 days in low-risk vs 17 days in high-risk patients) and higher risk of referral to critical care units (from 20% to 27%), of rehospitalization up to 180 days (from 39% to 67%), of in-hospital death (from 12% to 19%), and of 1-year mortality (from 26% to 49%). This study establishes the incidence of CAP in adults in France, describes the significant burden of disease, and highlights the need for better prevention policies.

The status of pneumococcal diseases and pneumococcal vaccination in Singaporean adults

The status of pneumococcal diseases and pneumococcal vaccination in Singaporean adults

Characterization of bacterial and viral pathogens in the respiratory tract of children with HIV-associated chronic lung disease: a case–control study

IntroductionChronic lung disease is a major cause of morbidity in African children with HIV infection; however, the microbial determinants of HIV-associated chronic lung disease (HCLD) remain poorly understood. We conducted a case–control study to investigate the prevalence and densities of respiratory microbes among pneumococcal conjugate vaccine (PCV)-naive children with (HCLD +) and without HCLD (HCLD-) established on antiretroviral treatment (ART).MethodsNasopharyngeal swabs collected from HCLD + (defined as forced-expiratory-volume/second < -1.0 without reversibility postbronchodilation) and age-, site-, and duration-of-ART-matched HCLD- participants aged between 6–19 years enrolled in Zimbabwe and Malawi (BREATHE trial-NCT02426112) were tested for 94 pneumococcal serotypes together with twelve bacteria, including Streptococcus pneumoniae (SP), Staphylococcus aureus (SA), Haemophilus influenzae (HI), Moraxella catarrhalis (MC), and eight viruses, including human rhinovirus (HRV), respiratory syncytial virus A or B, and human metapneumovirus, using nanofluidic qPCR (Standard BioTools formerly known as Fluidigm). Fisher's exact test and logistic regression analysis were used for between-group comparisons and risk factors associated with common respiratory microbes, respectively.ResultsA total of 345 participants (287 HCLD + , 58 HCLD-; median age, 15.5 years [IQR = 12.8–18], females, 52%) were included in the final analysis. The prevalence of SP (40%[116/287] vs. 21%[12/58], p = 0.005) and HRV (7%[21/287] vs. 0%[0/58], p = 0.032) were higher in HCLD + participants compared to HCLD- participants. Of the participants positive for SP (116 HCLD + & 12 HCLD-), 66% [85/128] had non-PCV-13 serotypes detected. Overall, PCV-13 serotypes (4, 19A, 19F: 16% [7/43] each) and NVT 13 and 21 (9% [8/85] each) predominated. The densities of HI (2 × 104 genomic equivalents [GE/ml] vs. 3 × 102 GE/ml, p = 0.006) and MC (1 × 104 GE/ml vs. 1 × 103 GE/ml, p = 0.031) were higher in HCLD + compared to HCLD-. Bacterial codetection (≥ any 2 bacteria) was higher in the HCLD + group (36% [114/287] vs. (19% [11/58]), (p = 0.014), with SP and HI codetection (HCLD + : 30% [86/287] vs. HCLD-: 12% [7/58], p = 0.005) predominating. Viruses (predominantly HRV) were detected only in HCLD + participants. Lastly, participants with a history of previous tuberculosis treatment were more likely to carry SP (adjusted odds ratio (aOR): 1.9 [1.1 -3.2], p = 0.021) or HI (aOR: 2.0 [1.2 – 3.3], p = 0.011), while those who used ART for ≥ 2 years were less likely to carry HI (aOR: 0.3 [0.1 – 0.8], p = 0.005) and MC (aOR: 0.4 [0.1 – 0.9], p = 0.039).ConclusionChildren with HCLD + were more likely to be colonized by SP and HRV and had higher HI and MC bacterial loads in their nasopharynx. The role of SP, HI, and HRV in the pathogenesis of CLD, including how they influence the risk of acute exacerbations, should be studied further.Trial registrationThe BREATHE trial (ClinicalTrials.gov Identifier: NCT02426112, registered date: 24 April 2015).

Pneumococcal vaccination, but not influenza vaccination, is negatively associated with incident dementia among Japanese older adults: The JAGES 2013–2022 prospective cohort study

BackgroundIt is unclear whether inactivated influenza vaccination (IIV) or pneumococcal vaccination are associated with the risk of dementia; however, both types of vaccination are recommended for older adults. Studies have shown that the IIV is negatively associated with incident dementia; however, the uptake of pneumococcal vaccinations has not been considered. We investigated the independent associations of IIV and 23-valent pneumococcal polysaccharide vaccine (PPSV23) with incident dementia in older adults. MethodsHealth-related information on older Japanese adults was obtained through a baseline survey conducted in 2013 (baseline survey). The uptake of IIV and PPSV23 was determined in a second survey conducted in 2016 (second wave). Both surveys were conducted among independent Japanese older adults aged ≥ 65 years at the two surveys and who had not been certified as needing long-term care (LTC). In the second wave, 9,865 participants were followed up for 3.5 years (short-term follow-up), and 6,995 participants were followed up for six years and five months (long-term follow-up) until they required LTC due to dementia onset (incident dementia). A competing risk model with stabilized inverse probability weighting (SIPW) was constructed to calculate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of incident dementia. ResultsPPSV23 uptake was negatively associated with incident dementia among participants in both the short- and long-term follow-up periods after SIPW (short-term follow-up: HR: 0.77, 95 % CI: 0.63 – 0.95; long-term follow-up: HR: 0.83, 95 % CI: 0.70 – 0.97). Conversely, IIV uptake was not associated with incident dementia among participants in either follow-up group (short-term follow-up: HR: 0.86, 95 % CI: 0.63–1.16; long-term follow-up: HR: 0.99, 95 % CI: 0.76–1.29). The PPSV23 uptake was negatively associated with incident dementia in participants without the IIV uptake (short-term follow-up: HR: 0.44, 95 % CI: 0.24 – 0.81; long-term follow-up: HR: 0.47, 95 % CI: 0.29 – 0.76). Conversely, the IIV uptake was not associated with incident dementia regardless of the PPSV23 status (short-term follow-up: HR: 0.87, 95 % CI: 0.62 – 1.23; long-term follow-up: HR: 1.00, 95 % CI: 0.74 – 1.35). ConclusionOur results suggest that the PPSV23 uptake was independently associated with the incidence of dementia. However, the IIV uptake was not associated with the incidence of dementia.

Serotype spectrum of &lt;i&gt;S. pneumoniae&lt;/i&gt; in children after the introduction of pneumococcal vaccine in Uzbekistan

Assessment of the effect of vaccination against Streptococcus pneumoniae on the serotype spectrum of pneumococcus.Materials and methods. Bacteriological study of nasopharyngeal mucus of 247 healthy children attending kindergarten, as well as serotyping of the obtained samples. The specific immune response to various serotypes of S. pneumoniae was determined by ELISA.Results. A bacteriological study of nasopharyngeal mucus from 247 healthy children attending kindergarten showed that S. pneumoniae was isolated from 35.6% (20) of practically healthy children. When serotyping the isolated samples, the most common pneumococcal serotypes were 15A/F, 6 A/B, 9 A /V and 9 F, then in frequency 5 and 7 A/F, 23F serotypes. A study of specific antibodies to pneumococcus in vaccinated children showed a high level of immune response. Thus, it was found that vaccination with commercial pneumococcal vaccines protects the majority of vaccinated children. To assess the effectiveness of vaccination, it is necessary to study the circulation of serotypes in children after vaccination.

Protective Effects from Prior Pneumococcal Vaccination in Patients with Chronic Airway Diseases during Hospitalization for Influenza-A Territory-Wide Study.

Influenza is an important respiratory viral pathogen in adults, with secondary bacterial pneumonia being a common complication. While pneumococcal vaccines can prevent pneumococcal pneumonia and invasive pneumococcal disease, whether they can also prevent the severe in-hospital outcomes among patients hospitalized for influenza has not been examined. A territory-wide retrospective study was conducted in Hong Kong, which included all adult patients having chronic airway diseases (asthma, bronchiectasis, and chronic obstructive pulmonary disease) hospitalized for influenza and who had received seasonal influenza vaccine. The occurrence of secondary bacterial pneumonia, mortality, and other severe in-hospital outcomes were compared among subjects with or without pneumococcal vaccination. There was a total of 3066 eligible patients who were hospitalized for influenza in public hospitals in Hong Kong from 1 January 2016 to 30 June 2023. Completed pneumococcal vaccination with PSV23/PCV13 conferred protection against secondary bacterial pneumonia, all-cause mortality, and respiratory cause of mortality with adjusted odds ratios of 0.74 (95% CI = 0.57-0.95, p = 0.019), 0.12 (95% CI = 0.03-0.53, p = 0.005), and 0.04 (95% CI = 0.00-0.527, p = 0.0038), respectively.