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BACKGROUND: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in US children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts. METHODS: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national health care surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses. RESULTS: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval, 1.8-3.9) visits and 2.4 (95% CI, 1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (95% CI, 11.2-20.4) visits and 13.2 (95% CI, 9.9-18.0) antibiotic prescriptions annually per 1000 children. PCV15/20-additional serotypes account for 0.4% (95% CI, 0.2%-0.6%) and 2.1% (95% CI, 1.5%-3.0%) of pediatric outpatient antibiotic use. CONCLUSIONS: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for > 5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use.

Sensory neurons sense pathogenic infiltration to drive innate immune responses, but their role in humoral immunity is unclear. Here, using mouse models of Streptococcus pneumoniae infection and Alternaria alternata asthma, we show that sensory neurons are required for B cell recruitment and antibody production. In response to S. pneumoniae, sensory neuron depletion increases bacterial burden and reduces B cell numbers, IgG release, and neutrophil stimulation. Meanwhile, during A. alternata-induced airway inflammation, sensory neuron depletion decreases B cell population sizes, IgE levels, and asthmatic characteristics. Mechanistically, during bacterial infection, sensory neurons preferentially release vasoactive intestinal polypeptide (VIP). In response to asthma, sensory neurons release substance P. Administration of VIP into sensory neuron-depleted mice suppresses bacterial burden, while VIPR1 deficiency increases infection. Similarly, exogenous substance P delivery aggravates asthma in sensory neuron-depleted mice, while substance P deficiency ameliorates asthma. Our data, thus demonstrate that sensory neurons release select neuropeptides which target B cells dependent on the immunogen.

A national program to improve vaccination prevention was adopted in Bulgaria at the beginning of 2024, with main objectives: to reduce morbidity, complications and mortality from seasonal influenza and invasive pneumococcal infections in adults aged 65 and over by increasing immunization coverage in this age group and by increasing public and medical specialist awareness on the risk of influenza and pneumococcal infections. The aim of the present study was to examine the awareness about immunoprophylaxis for seasonal influenza and pneumococcal infections in persons over 65 years of age and nursing student attitudes toward specific immunoprophylaxis and the education of adult patients related to it. Material and Methods: 122 students from the Faculty of Health, MU ‒ Sofia, majoring in "Nursing", 2nd year of education, studying the course "Nursing Care for Infectious Patients" participated voluntarily in the study. The survey was conducted in March 2024. The following were used: documentary method ‒ for the analysis of regulatory documents and scientific literature regarding the specific immunoprophylaxis of seasonal flu and pneumococcal infections in EU countries and Bulgaria for persons over 65 years of age; sociological method ‒ a direct, anonymous survey, specially developed for the study purpose, and mathematical and statistical methods for data processing, analysis and interpretation and for graphical presentation of the obtained results. The processing and graphical analysis were conducted with the MS Excel 2010 program. Results and conclusion: The problems of seasonal immunoprophylaxis for influenza and pneumococcal infections for persons over 65 years of age in our country are mainly related to the low activity and insufficient awareness of the concerned people. Nursing students who have completed training in the discipline "Nursing Care of Patients with Infectious Diseases" have the necessary knowledge about immunoprophylaxis, and over 90.0% is immunized, along with their children, according to the immunization calendar of the Republic of Bulgaria. Most of the respondents have information about the availability of free vaccines for people over 65 years at their GP and their benefits, especially for risk groups. Future nurses have the attitude and desire to participate in information campaigns and health education of patients in order to increase the health culture of the population regarding immunoprophylaxis. [ABSTRACT FROM AUTHOR]

A U.S. case-control study (2010–2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes. We used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC's Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010–2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %). Among 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4–96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7–93.3 %), 50.2 % (28.4–80.5 %), and 93.8 % (69.8–98.8 %) against serotypes 19A, 3, and 19F, respectively. At least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance. [ABSTRACT FROM AUTHOR]

While hypogammaglobulinemia is associated with COPD exacerbations, it is unknown whether frequent exacerbators have specific defects in antibody production/function. We hypothesized that reduced quantity/function of serum pneumococcal antibodies correlate with exacerbation risk in the SPIROMICS cohort. We measured total pneumococcal IgG in n = 764 previously vaccinated participants with COPD. In a propensity-matched subset of n = 200 with vaccination within five years (n = 50 without exacerbations in the previous year; n = 75 with one, n = 75 with ≥2), we measured pneumococcal IgG for 23 individual serotypes, and pneumococcal antibody function for 4 serotypes. Higher total pneumococcal IgG, serotype-specific IgG (17/23 serotypes), and antibody function (3/4 serotypes) were independently associated with fewer prior exacerbations. Higher pneumococcal IgG (5/23 serotypes) predicted lower exacerbation risk in the following year. Pneumococcal antibodies are inversely associated with exacerbations, supporting the presence of immune defects in frequent exacerbators. With further study, pneumococcal antibodies may be useful biomarkers for immune dysfunction in COPD.

BackgroundInteractions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses.MethodsWe undertook a case-control study among adults at Kaiser Permanente Southern California between 2015 and 2019. Case patients had diagnoses of lower respiratory tract infection (LRTI; including pneumonia or nonpneumonia LRTI diagnoses), with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to case patients by demographic and clinical attributes. We measured vaccine effectiveness (VE) for 13-valent (PCV13) against virus-associated LRTI by determining the adjusted odds ratio for PCV13 receipt, comparing case patients and controls.ResultsPrimary analyses included 13 856 case patients with virus-associated LRTI and 227 887 matched controls. Receipt of PCV13 was associated with a VE of 24.9% (95% confidence interval, 18.4%-30.9%) against virus-associated pneumonia and 21.5% (10.9%-30.9%) against other (nonpneumonia) virus-associated LRTIs. We estimated VEs of 26.8% (95% confidence interval, 19.9%-33.1%) and 18.6% (9.3%-27.0%) against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses but not respiratory syncytial virus or adenoviruses.ConclusionsAmong adults, PCV13 conferred moderate protection against virus-associated LRTI. The impacts of pneumococcal conjugate vaccines may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.

Background Vaccination of infants with pneumococcal conjugate vaccines is recommended by the World Health Organization. Evidence is mixed regarding the differences in immunogenicity and efficacy of the different pneumococcal vaccines. Objectives The primary objective was to compare the immunogenicity of pneumococcal conjugate vaccine-10 versus pneumococcal conjugate vaccine-13. The main secondary objective was to compare the seroefficacy of pneumococcal conjugate vaccine-10 versus pneumococcal conjugate vaccine-13. Methods We searched the Cochrane Library, EMBASE, Global Health, MEDLINE, ClinicalTrials.gov and trialsearch.who.int up to July 2022. Studies were eligible if they directly compared either pneumococcal conjugate vaccine-7, pneumococcal conjugate vaccine-10 or pneumococcal conjugate vaccine-13 in randomised trials of children under 2 years of age, and provided immunogenicity data for at least one time point. Individual participant data were requested and aggregate data used otherwise. Outcomes included the geometric mean ratio of serotype-specific immunoglobulin G and the relative risk of seroinfection. Seroinfection was defined for each individual as a rise in antibody between the post-primary vaccination series time point and the booster dose, evidence of presumed subclinical infection. Each trial was analysed to obtain the log of the ratio of geometric means and its standard error. The relative risk of seroinfection (‘seroefficacy’) was estimated by comparing the proportion of participants with seroinfection between vaccine groups. The log-geometric mean ratios, log-relative risks and their standard errors constituted the input data for evidence synthesis. For serotypes contained in all three vaccines, evidence could be synthesised using a network meta-analysis. For other serotypes, meta-analysis was used. Results from seroefficacy analyses were incorporated into a mathematical model of pneumococcal transmission dynamics to compare the differential impact of pneumococcal conjugate vaccine-10 and pneumococcal conjugate vaccine-13 introduction on invasive pneumococcal disease cases. The model estimated the impact of vaccine introduction over a 25-year time period and an economic evaluation was conducted. Results In total, 47 studies were eligible from 38 countries. Twenty-eight and 12 studies with data available were included in immunogenicity and seroefficacy analyses, respectively. Geometric mean ratios comparing pneumococcal conjugate vaccine-13 versus pneumococcal conjugate vaccine-10 favoured pneumococcal conjugate vaccine-13 for serotypes 4, 9V and 23F at 1 month after primary vaccination series, with 1.14- to 1.54-fold significantly higher immunoglobulin G responses with pneumococcal conjugate vaccine-13. Risk of seroinfection prior to the time of booster dose was lower for pneumococcal conjugate vaccine-13 for serotype 4, 6B, 9V, 18C and 23F than for pneumococcal conjugate vaccine-10. Significant heterogeneity and inconsistency were present for most serotypes and for both outcomes. Twofold higher antibody after primary vaccination was associated with a 54% decrease in risk of seroinfection (relative risk 0.46, 95% confidence interval 0.23 to 0.96). In modelled scenarios, pneumococcal conjugate vaccine-13 or pneumococcal conjugate vaccine-10 introduction in 2006 resulted in a reduction in cases that was less rapid for pneumococcal conjugate vaccine-10 than for pneumococcal conjugate vaccine-13. The pneumococcal conjugate vaccine-13 programme was predicted to avoid an additional 2808 (95% confidence interval 2690 to 2925) cases of invasive pneumococcal disease compared with pneumococcal conjugate vaccine-10 introduction between 2006 and 2030. Limitations Analyses used data from infant vaccine studies with blood samples taken prior to a booster dose. The impact of extrapolating pre-booster efficacy to post-booster time points is unknown. Network meta-analysis models contained significant heterogeneity which may lead to bias. Conclusions Serotype-specific differences were found in immunogenicity and seroefficacy between pneumococcal conjugate vaccine-13 and pneumococcal conjugate vaccine-10. Higher antibody response after vaccination was associated with a lower risk of subsequent infection. These methods can be used to compare the pneumococcal conjugate vaccines and optimise vaccination strategies. For future work, seroefficacy estimates can be determined for other pneumococcal vaccines, which could contribute to licensing or policy decisions for new pneumococcal vaccines. Study registration This study is registered as PROSPERO CRD42019124580. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/03) and is published in full in Health Technology Assessment; Vol. 28, No. 34. See the NIHR Funding and Awards website for further award information. Plain language summary Pneumococcal disease is a serious illness caused by a bacterial infection that can result in death. Children in the United Kingdom receive a vaccine to prevent this disease that protects against 13 different types of pneumococcal diseases. It is very effective, but other vaccines are also available, such as one that contains 10 types of pneumococcal diseases. Vaccines in the United Kingdom are bought by the government and the choice of which vaccine to provide is based on the cost of the vaccine as well as the benefits to our health. However, there is very little information comparing different vaccines and it is often assumed they are the same. We did a large analysis combining all studies of the two main licensed pneumococcal vaccines to determine which vaccine provides better protection against infection and how this affects costs. We used information from studies published in medical journals, and also data from studies done by the companies that own the vaccines. Our results showed that pneumococcal conjugate vaccine-13 vaccine provided better protection than pneumococcal conjugate vaccine-10 for 5 of the 10 serotypes that are contained in both vaccines. When we used these results to model what might have happened had either of these vaccines been introduced into the United Kingdom vaccination programme in 2006, we found that both vaccines caused a rapid decrease in the amount of disease, but that the decrease in disease was faster with pneumococcal conjugate vaccine-13 than pneumococcal conjugate vaccine-10. This resulted in 2808 cases of diseases prevented over a 25-year time frame with pneumococcal conjugate vaccine-13 compared with pneumococcal conjugate vaccine-10. Our methods can be used to compare other vaccines and we recommend this type of study be done in future when making decisions on vaccine product choice. Scientific summary Streptococcus pneumoniae (pneumococcus) causes severe diseases, including bacterial pneumonia, meningitis and sepsis, leading to substantial morbidity and mortality worldwide, with the highest disease burden being in young children and older adults. Three pneumococcal conjugate vaccines (PCVs) have been widely deployed worldwide in the past two decades: PCV7 (Prevnar; Pfizer, headquartered in New York City, New York, USA), PCV10 (Synflorix; GlaxoSmithKline, headquartered in Brentford, London, UK) and PCV13 (Prevenar 13; Pfizer, headquartered in New York City, New York, USA), resulting in substantial reduction in disease. Between 2009 and 2011, PCV7 was gradually replaced by PCV13 and PCV10 and is no longer available. The World Health Organization (WHO) does not preferentially endorse one PCV over another. Both PCV13 and PCV10 have been shown to provide both direct and indirect protection against pneumococcal pneumonia, invasive pneumococcal disease and nasopharyngeal carriage. Although there are 10 common serotypes in these 2 vaccines, the components of the vaccines differ, with different carrier proteins used in the conjugation process, as well as different amounts of polysaccharide, and these differences may contribute to differences in protection. Large randomised controlled trials directly comparing different PCVs with invasive pneumococcal disease as the primary outcome are not feasible. We previously used ‘seroinfection’ as an outcome for analysis of PCVs, where seroinfection is defined as an increase in antibody levels between the primary vaccination series (typically complete at 5–7 months of age) and the booster dose (typically administered at 9–18 months of age). Seroinfection can be regarded as evidence of exposure to the pathogen and a resultant subclinical infection, given antibody responses wane rapidly during this period otherwise. Seroinfection rates for different vaccines can be compared by calculating the relative risk (RR) of seroinfection, referred to herein as ‘seroefficacy’. We meta-analysed data from studies of PCVs to compare the immunogenicity and seroefficacy of PCV10 with PCV13 for each serotype. We aimed to determine if serotype-specific immune responses were higher for either vaccine and whether this resulted in greater protection again seroinfection. In addition, we explored the overall relationship between the higher immune response and protection against seroinfection in infants. Following this, we show how serotype-specific estimates of seroefficacy can be incorporated in vaccine cost-effectiveness models. Objectives The primary objective of the systematic review was to compare the immunogenicity of PCV10 versus PCV13 for each serotype contained in the vaccines. The secondary objectives were: to compare the seroefficacy of PCV10 versus PCV13 for each serotype contained in the vaccines for PCV10 and PCV13 separately, to estimate immunogenicity and seroefficacy in comparison with the older PCV7 vaccine to determine how the comparisons of immunogenicity and efficacy of PCV10 to PCV13 are affected by the co-administration of different routine vaccines. Methods Systematic review We conducted a systematic review identifying studies that compared the immunogenicity of licensed PCVs in trials which randomised children to one of two different PCVs. The PCVs included in the review were PCV7 (Prevnar; Pfizer), PCV10 (Synflorix; GlaxoSmithKline) and PCV13 (Prevenar 13; Pfizer); PCV7 was included even though no longer available, so that we could compare PCV13 and PCV10 indirectly through them each being compared with PCV7 for the same serotypes. Data sources The databases searched were Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials, EMBASE, Global Health and MEDLINE. The trial registers searched were ClinicalTrials.gov (https://clinicaltrials.gov/) and WHO International Clinical Trials Registry Platform (https://trialsearch.who.int/). The search comprised title/abstract keywords and subject headings for pneumococcal vaccines and children. A methodological search filter for randomised controlled trials taken from the Cochrane Handbook was used to limit to randomised controlled trials. Pharmaceutical company websites (GlaxoSmithKline and Pfizer) were also hand-searched for relevant studies. No date or language limits were applied. Study selection Randomised controlled trials were included if they provided direct comparisons of either PCV7, PCV10 or PCV13 among infants and children ˂ 2 years of age, and if they provided estimates of antibody responses [serotype-specific anti-pneumococcal immunoglobulin G (IgG) to PCVs for at least one time point of 1] between 4 and 6 weeks after the primary vaccination series and/or 1 month after a booster vaccination. Individual participant-level data were retrieved if available. Aggregate data from publications were extracted if individual participant data were not available. Risk of bias in results of the included studies was assessed independently by two reviewers using the Cochrane Risk of Bias Tool. Data synthesis Each trial with individual participant-level data available was analysed to obtain the log of the ratio of geometric means (log-GMR) and its standard error (SE) for each serotype and time point of interest. The RR of seroinfection was estimated by comparing the proportion of participants with seroinfection between vaccine groups. When no seroinfection occurred in any group (numerator of absolute risk was 0), a small non-zero value (0.5) was added to both sero-infected and sero-non-infected groups to allow estimation of the RR. The log-GMRs, log-RRs and their SEs constituted the input data for evidence synthesis. Only trials supplying individual participant data were included in seroefficacy analyses. For serotypes contained in all three vaccines, evidence could be synthesised using a network meta-analysis (NMA) of all comparisons. For other serotypes, meta-analysis was used for evidence synthesis. To estimate the overall association between antibody geometric mean ratio (GMR) and RR across all serotypes, we fitted a mixed-effect model regressing study-level RRs of seroinfection on GMRs across serotypes, weighted by the sample size of each study. Fixed effects included GMR, serotype and interactions between GMR and serotype (allowing serotype-specific association), while study was included as a random effect. Mathematical modelling and retrospective economic evaluation To illustrate the use of serotype-specific estimates of seroefficacy in modelling vaccine impact and cost-effectiveness, we developed a serotype-specific mathematical model of pneumococcal transmission dynamics to compare the differential impact of PCV10 and PCV13 introduction on invasive pneumococcal disease cases with vaccine serotypes in England and Wales. The model estimated the impact over a 25-year time period from 2006 to 2030. We subsequently assessed the cost-effectiveness of introducing infant vaccination with PCV13 compared with introducing PCV10 from a healthcare payer perspective in England and Wales. More specifically, we retrospectively estimated the additional threshold price per dose below which PCV13 would be more cost-effective than PCV10 had they both been available at the time of introduction of the PCV vaccine programme in England and Wales in 2006. Results Database registry and hand searches identified 4699 publication records of which 47 studies (78 publication reports) satisfied our eligibility criteria. Nineteen studies (24 publication reports) were excluded from the analysis: 6 studies did not provide individual patient or aggregate data and 13 studies (18 publication reports) were studies with the vaccines of interest, but it was not possible to form a loop within the NMA to provide indirect evidence. The remaining 28 studies (54 publication records) from 2009 to 2023 were included in the NMAs. Twenty-two studies provided individual participant data with a further five studies reporting aggregate data. Immunogenicity Geometric mean ratios for comparisons between PCV13 versus PCV10 for any primary series schedule were higher for PCV13 for serotypes 4, 7F, 9V and 23F at 1 month after primary vaccination series, with 1.14- to 1.54-fold higher IgG responses with PCV13. Additional serotypes contained only in the PCV13 vaccine (3, 6A and 19A) also favoured PCV13 as expected. GMRs were similar for the remaining serotypes (1, 5, 6B, 14, 18C and 19F). GMRs favoured PCV7 over either PCV13 or PCV10 for serotypes 4, 6B, 9V, 14 and 23F. There was no difference in GMRs for serotypes 18C and 19F across three vaccines. At the pre-booster time point, data were available from 18 cohorts. IgG responses were lower with PCV13 compared with PCV10 for all PCV7 serotypes except for serotype 14, with the point estimates of GMRs comparing PCV13 versus PCV10 ranging from 0.44 to 0.78. IgG responses were higher for PCV13 for serotypes 1, 5 and 7F. GMRs comparing PCV13 versus PCV7 showed higher IgG with PCV7 for serotypes 4, 6B, 9V, 14 and 23F and higher IgG with PCV13 for serotype 19F. At 28 days post booster, data were available from 26 cohorts. GMRs favoured PCV13 over PCV10 for serotype 6B, 9V, 14 and 23F and favoured PCV10 over PCV13 for serotype 18C. For serotype 1, 5 and 7F, antibody responses were higher in PCV13 compared with PCV10. PCV7 recipients had higher geometric mean concentrations (GMCs) compared with PCV13 for all PCV7 serotypes except 6B for which there was no difference, and 19F, which favoured PCV13. For PCV13-only serotypes (3, 6A and 19A), GMRs favour PCV13 at all three time points. Substantial heterogeneity and network inconsistency were present for most serotypes at all three time points. To explore potential reasons for the observed heterogeneity, we summarised cohort-level GMRs and RRs for each vaccine comparison. These descriptive analyses revealed a lack of consistency in the direction of study-level estimates within each vaccine comparison, resulting in the significant heterogenicity. There was also no observable pattern in any trial-level variable (region, co-administered vaccines, vaccine schedule), from which one might propose a mechanism that would adequately explain this variation in GMRs. Seroefficacy There were 12 studies (15 cohorts) with available individual participant antibody data at both post-primary and prior to the booster dose, allowing serotype-specific estimation of seroefficacy from a total of 5152 participants. Of these 15 cohorts, 6 compared PCV10 versus PCV7, 3 compared PCV13 versus PCV7 and 6 compared PCV13 versus PCV10. Among PCV7 serotypes, the risk of seroinfection was lower with PCV13 than PCV10 for serotypes 4, 6B, 9V, 18C and 23F, while no difference was seen for serotype 14 and 19F. The RRs of seroinfection (PCV13 vs. PCV10) for PCV7 serotypes ranged from 0.32 (95% CI 0.19 to 0.52) for serotype 4 to 1.28 (95% CI 0.95 to 1.74) for serotype 14. For serotypes 1, 5 and 7F, evidence was summarised from six studies directly comparing PCV13 with PCV10. Comparisons between PCV13 and PCV7 favoured neither vaccine over the other, whereas comparisons between PCV7 and PCV10 favoured PCV7 for serotypes 5, 6B, 9V, 18C and 23F. The I2 and p-values indicated some heterogeneity for all PCV7 serotypes except for serotype 4 and 19F. In the mixed-effects model of all serotypes combined, vaccines that produced the same amount of antibody (GMR = 1) had very similar protection (adjusted RR 0.80, 95% CI 0.41 to 1.58). The model estimate indicates that for each twofold increase in antibody response, the risk of seroinfection was halved (GMR of 2.0; RR 0.46, 95% CI 0.23 to 0.96). Mathematical model and economic evaluation Mathematical model results showed that in the absence of any vaccine programme, an increase in invasive pneumococcal disease cases caused by all five serotypes would be seen over the 25-year time frame. With the introduction of either PCV13 or PCV10 vaccine programmes in 2006, case counts would have decreased, achieving near eradication of all serotypes within the time frame modelled. The decrease in cases was most rapid for serotype 6B and least rapid for serotype 4. The decrease in cases was less rapid for PCV10 than for PCV13 due to the lower seroefficacy. The introduction of an infant PCV13 programme was predicted to avoid an additional 2808 (95% CI 2690 to 2925) cases of invasive pneumococcal disease compared with PCV10 introduction between 2006 and 2030. This includes an estimated 326 cases of meningitis, 578 cases of sepsis, 1770 cases of invasive pneumonia and 30,680 cases of non-invasive pneumonia. Under base-case assumptions, this resulted in discounted healthcare savings of £13 million (95% CI £12 to £14 million). Including non-invasive pneumonia increased the savings to £27 million (95% CI £25 to £29 million). Conclusions In our study, we used a novel methodology to define seroinfection from immunogenicity data to compare the relative efficacy of PCVs in preventing infection. Our results using individual-level data from a global meta-analysis provide the first estimates of the comparative protection afforded by different pneumococcal vaccines and show that for many serotypes, carriage events are less common after PCV13 than PCV10, likely due to a higher antibody response. In addition, we quantify the relationship between the immune response to vaccination and protection against infection, measured serologically, and show that higher antibody responses in infants are associated with greater protection from infection. Licensure of new vaccines is based on non-inferiority comparisons with current vaccines and the proportion of antibody responses above the agreed threshold as a minimum requirement. Once a vaccine meets this ‘at-least-as-good-as’ immunogenicity criteria, it has previously not been clear whether exceeding it is of benefit, and the WHO position paper on pneumococcal vaccines states ‘It is unknown whether a lower serotype-specific GMC of antibody indicates less efficacy’. Our results show that lower protection against subclinical infection does indeed follow from lower antibody production and that two vaccines that produce a similar level of antibody will provide similar levels of protection. The implications of these findings are of greatest importance when a new vaccine roll-out is being considered. Lower antibody production or lower seroefficacy for one vaccine product does not necessarily imply limited effectiveness against invasive pneumococcal diseases when considering vaccines such as PCV10 and PCV13 which are highly effective vaccines in many settings. Instead, lower antibody responses lead to less rapidly observed indirect protection after implementation into a national programme as a smaller proportion of transmission events are blocked by the vaccine. This is evident in the mathematical modelling which showed less rapid decreases in the number of cases of invasive disease when introducing PCV10 compared with PCV13. Implications for practice This evidence of differences in serotype-specific protection can be incorporated into cost-effectiveness models used to compare vaccine products. Cost-effectiveness studies have highlighted the lack of evidence of comparative efficacy for different PCVs, resulting in previous cost-effectiveness models that ignore serotype-specific differences and assume equivalent efficacy for all serotypes covered by different PCVs. Our study fills this evidence gap and allows researchers and policy-makers to use more accurate vaccine-specific models in decision-making. Our cost-effectiveness analysis of a hypothetical scenario showed that introducing infant PCV13 was predicted to avert a higher burden of pneumococcal disease compared with PCV10. This would have realised a small saving of £13 million discounted over 24 years. When considering the introduction of new pneumococcal vaccines into the routine immunisation schedule, we recommend that differences in antibody responses for different vaccines be considered in modelling scenarios as higher antibody responses result in reduced transmission and greater impact on invasive diseases. Vaccine-specific threshold prices can then be determined for cost-effective vaccines. Our analysis showed that due to its higher efficacy against some serotypes, a higher threshold price per dose could be paid for PCV13 while remaining cost-effective. Study registration This study is registered as PROSPERO CRD42019124580. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/148/03) and is published in full in Health Technology Assessment; Vol. 28, No. 34. See the NIHR Funding and Awards website for further award information.

In patients with severe and recurrent infections, minimal diagnostic workup to test for Inborn Errors of Immunity (IEI) includes a full blood count, IgG, IgA and IgM. Vaccine antibodies against tetanus toxoid are also frequently measured, whereas testing for anti-polysaccharide IgG antibodies and IgG subclasses is not routinely performed by primary care physicians. This basic approach may cause a significant delay in diagnosing monogenic IEI that can present with an impaired IgG response to polysaccharide antigens with or without IgG subclass deficiency at an early stage. Our article reviews genetically defined IEI, that may initially present with an impaired IgG response to polysaccharide antigens, but normal or only slightly decreased IgG levels and normal responses to protein or conjugate vaccine antigens. We summarize clinical, genetic, and immunological findings characteristic for these IEI. This review may help clinicians to identify patients that require extended immunologic and genetic evaluations despite unremarkable basic immunologic findings. We recommend the inclusion of anti-polysaccharide IgG antibodies as part of the initial routine work-up for possible IEI.

Measures to limit SARS-CoV-2 transmission in 2020 reduced other viral infections. Among 7 US children's hospitals, invasive pneumococcal disease cumulative incidence decreased by 46% in 2020 vs 2017-2019. Limited droplet transmission of pneumococci and preceding viral pathogens may be responsible.

We evaluated antibiotic resistance selection in Streptococcus pneumoniae isolates from children participating in an individually randomized trial of single-dose azithromycin versus placebo. After 14 days, the prevalence of resistance to erythromycin, oxacillin, and clindamycin was elevated in the azithromycin versus placebo group. There was no difference at 6 months.

Background Pneumococcal diseases have a clinical and economic impact on the population. Until this year, a 10-valent pneumococcal vaccine (PCV10) used to be applied in Colombia, which does not contain serotypes 19A, 3, and 6A, the most prevalent in the country. Therefore, we aimed to assess the cost-effectiveness of the shift to the 13-valent pneumococcal vaccine (PCV13). Research design and methods A decision model was used for newborns in Colombia between 2022–2025 and adults over 65 years. The time horizon was life expectancy. Outcomes are Invasive Pneumococcal Diseases (IPD), Community-Acquired Pneumonia (CAP), Acute Otitis Media (AOM), their sequelae, Life Gained Years (LYGs), and herd effect in older adults. Results PCV10 covers 4.27% of serotypes in the country, while PCV13 covers 64.4%. PCV13 would avoid in children 796 cases of IPD, 19,365 of CAP, 1,399 deaths, and generate 44,204 additional LYGs, as well as 9,101 cases of AOM, 13 cases of neuromotor disability and 428 cochlear implants versus PCV10. In older adults, PCV13 would avoid 993 cases of IPD and 17,245 of CAP, versus PCV10. PCV13 saves $51.4 million. The decision model shows robustness in the sensitivity analysis. Conclusion PCV13 is a cost-saving strategy versus PCV10 to avoid pneumococcal diseases.

BACKGROUND: Streptococcus pneumoniae is a leading cause of severe infections among children. Despite vaccination, HIV-exposed, uninfected (HEU) children have a higher incidence of invasive pneumococcal disease than HIV-unexposed, uninfected (HUU) children. We sought to compare the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV-13) in HEU and HUU infants. METHODS: We conducted a prospective cohort study of 134 mother-infant dyads in Botswana. Infants received PCV-13 doses at 2, 3, and 4 months through routine clinical care. We measured IgG antibodies specific to vaccine serotypes in sera collected from infants at 0, 5, and 12 months of age. We calculated the proportion of infants with protective IgG levels (≥0.35 µg/mL) to specific pneumococcal serotypes. RESULTS: At birth, fewer than half of infants had protective IgG levels to serotypes 1 (38%), 3 (46%), 4 (33%), 5 (23%), 6B (40%), 7F (44%), 9 V (44%), and 23F (46%). Compared to HUU infants (n = 97), HEU infants (n = 37) had lower antibody concentrations at birth to serotypes 5 (p = 0.046) and 19A (p = 0.008) after adjustment for maternal age and infant birth weight. More than 80% of HEU and HUU infants developed protective antibody levels to each of the 13 vaccine serotypes following PCV-13 vaccination. Median concentrations of antibodies to pneumococcal serotypes declined by 55-93% between 5 and 12 months of age, with fewer than half of infants having protective antibody levels to serotypes 1 (47%), 3 (28%), 9 V (44%), 18C (24%), and 23F (49%) at 12 months of age. CONCLUSIONS: Both HEU and HUU infants developed protective antibody responses to PCV-13 administered in a 3 + 0 schedule. However, antibody concentrations to many pneumococcal serotypes waned substantially by 12 months of age, suggesting that a PCV-13 booster dose in the second year of life may be needed to maintain protective pneumococcal antibody levels in older infants and young children.

Background The incidence of certain vaccine-preventative diseases, such as influenza, herpes zoster and pneumococcal infection, continues to be high despite the availability of vaccines, resulting in a substantial health and economic burden on society, particularly among older adults aged ≥65 years. Methods A cost calculator was developed to assess the cost of illness of influenza, herpes zoster and pneumococcal disease in France. Direct medical costs related to diagnosis and treatment in the older adult population in both inpatient and outpatient settings were modelled over a 1-year time horizon. Scenario analyses were conducted to determine the impact of hospitalizations on the results by considering only influenza-attributed diagnoses. Results In France, influenza has the highest incidence, followed by herpes zoster and pneumococcal disease. Similarly, influenza poses the greatest cost burden among all older adults, while pneumococcal disease poses the greatest cost burden among those aged 65–74 years. When considering only influenza-attributed diagnoses, the number of inpatient visits and associated costs was reduced by 63% in the overall older adult population. In the low-incidence season, the number of inpatient visits and associated costs were reduced by 69%, while in the high-incidence season, the number of inpatient visits and associated costs increased by 63%. Conclusion Influenza remains a leading vaccine-preventable disease among older adults in France, resulting in a substantial economic burden that could be prevented by increasing vaccine uptake. [ABSTRACT FROM AUTHOR]

BackgroundWhile secondary pneumococcal pneumonia occurs less commonly after coronavirus disease 2019 (COVID-19) than after other viral infections, it remains unclear whether other interactions occur between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Streptococcus pneumoniae.MethodsWe probed potential interactions between these pathogens among adults aged ≥65 years by measuring associations of COVID-19 outcomes with pneumococcal vaccination (13-valent conjugate vaccine [PCV13] and 23-valent pneumococcal polysaccharide vaccine [PPSV23]). We estimated adjusted hazard ratios (aHRs) using Cox proportional hazards models with doubly robust inverse-propensity weighting. We assessed effect modification by antibiotic exposure to further test the biologic plausibility of a causal role for pneumococci.ResultsAmong 531 033 adults, there were 3677 COVID-19 diagnoses, leading to 1075 hospitalizations and 334 fatalities, between 1 March and 22 July 2020. Estimated aHRs for COVID-19 diagnosis, hospitalization, and mortality associated with prior PCV13 receipt were 0.65 (95% confidence interval [CI], .59-.72), 0.68 (95% CI, .57-.83), and 0.68 (95% CI, .49-.95), respectively. Prior PPSV23 receipt was not associated with protection against the 3 outcomes. COVID-19 diagnosis was not associated with prior PCV13 within 90 days following antibiotic receipt, whereas aHR estimates were 0.65 (95% CI, .50-.84) and 0.62 (95% CI, .56-.70) during the risk periods 91-365 days and >365 days, respectively, following antibiotic receipt.ConclusionsReduced risk of COVID-19 among PCV13 recipients, transiently attenuated by antibiotic exposure, suggests that pneumococci may interact with SARS-CoV-2.

BackgroundPeople with HIV (PWH) are at increased risk for invasive pneumococcal disease (IPD). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for use in US children in 2010 and for PWH aged 19 years or older in 2012. We evaluated the population-level impact of PCV13 on IPD among PWH and non-PWH aged 19 years or older.MethodsWe identified IPD cases from 2008 to 2018 through the Active Bacterial Core surveillance platform. We estimated IPD incidence using the National HIV Surveillance System and US Census Bureau data. We measured percent changes in IPD incidence from 2008 to 2009 to 2017-2018 by HIV status, age group, and vaccine serotype group, including serotypes in recently licensed 15-valent (PCV15) and 20-valent (PCV20) PCVs.ResultsIn 2008-2009 and 2017-2018, 8.4% (552/6548) and 8.0% (416/5169) of adult IPD cases were among PWH, respectively. Compared with non-PWH, a larger proportion of IPD cases among PWH were in adults aged 19-64 years (94.7%-97.4% vs. 56.0%-60.1%) and non-Hispanic Black people (62.5%-73.0% vs. 16.7%-19.2%). Overall and PCV13-type IPD incidence in PWH declined by 40.3% (95% confidence interval: -47.7 to -32.3) and 72.5% (95% confidence interval: -78.8 to -65.6), respectively. In 2017-2018, IPD incidence was 16.8 (overall) and 12.6 (PCV13 type) times higher in PWH compared with non-PWH; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2%, and 16.5% of IPD in PWH, respectively.ConclusionsDespite reductions post-PCV13 introduction, IPD incidence among PWH remained substantially higher than among non-PWH. Higher-valent PCVs provide opportunities to reduce remaining IPD burden in PWH.

Streptococcus pneumoniae can co-infect persons who have viral respiratory tract infections. However, research on S. pneumoniae infections that are temporally associated with SARS-CoV-2 infections is limited. We described the epidemiology and clinical course of patients who had invasive pneumococcal disease (IPD) and temporally associated SARS-CoV-2 infections in Alaska, USA, during January 1, 2020–December 23, 2021. Of 271 patients who had laboratory-confirmed IPD, 55 (20%) had a positive SARS-CoV-2 test result. We observed no major differences in age, race, sex, or underlying medical conditions among IPD patients with and without SARS-CoV-2. However, a larger proportion of IPD patients with SARS-CoV-2 died (16%, n = 9) than for those with IPD alone (4%, n = 9) (p

Innate-like T cells, including invariant natural killer T cells, mucosal-associated invariant T cells, and γδ T cells, are present in various barrier tissues, including the lung, where they carry out protective responses during infections. Here, we investigate their roles during pulmonary pneumococcal infection. Following infection, innate-like T cells rapidly increase in lung tissue, in part through recruitment, but T cell antigen receptor activation and cytokine production occur mostly in interleukin-17-producing NKT17 and γδ T cells. NKT17 cells are preferentially located within lung tissue prior to infection, as are CD103+ dendritic cells, which are important both for antigen presentation to NKT17 cells and γδ T cell activation. Whereas interleukin-17-producing γδ T cells are numerous, granulocyte-macrophage colony-stimulating factor is exclusive to NKT17 cells and is required for optimal protection. These studies demonstrate how particular cellular interactions and responses of functional subsets of innate-like T cells contribute to protection from pathogenic lung infection.

Pneumococcal conjugate vaccines reduce the burden of invasive pneumococcal disease, but the sustained effect of these vaccines can be diminished by an increase in disease caused by non-vaccine serotypes. To describe pneumococcal serotype epidemiology in Botswana following introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in July 2012, we performed molecular serotyping of 268 pneumococcal strains isolated from 221 children between 2012 and 2017. The median (interquartile range) age of the children included in this analysis was 6 (3,12) months. Fifty-nine percent of the children had received at least one dose of PCV-13 and 35% were fully vaccinated with PCV-13. While colonization by vaccine serotypes steadily declined following PCV-13 introduction, 25% of strains isolated more than 3 years after vaccine introduction were PCV-13 serotypes. We also observed an increase in colonization by non-vaccine serotypes 21 and 23B, which have been associated with invasive pneumococcal disease and antibiotic resistance in other settings.

IntroductionStreptococcus pneumoniae is a leading cause of pneumonia among children. However, owing to diagnostic limitations, the protection conferred by pneumococcal conjugate vaccines (PCVs) against pediatric pneumonia attributable to vaccine-serotype pneumococci remains unknown.MethodsWe analyzed data on vaccination and nasopharyngeal pneumococcal detection among children

Background: Streptococcus pneumoniae (pneumococcus) is a human nasopharyngeal tract coloniser responsible for invasive pneumococcal disease, which is largely vaccine preventable. Vaccination is recommended from birth for all, and through adulthood for those with risk conditions. Aims: To describe the clinical and serotype analysis of pneumococcus bacteraemia over a 10‐year period. Methods: A 10‐year (February 2011–December 2020) retrospective review was performed on all adult (age ≥18 years) pneumococcus bacteraemia presenting to the four public hospitals in Western Sydney, Australia. Comorbidities and risk factors were recorded. Results: Three hundred unique episodes of S. pneumoniae bloodstream infection (SPBI) were identified during the study period. The median age for SPBI was 63 years with 31.7% aged 70 years or older. A 94.7% had one or more risks factors for SPBI. Pneumonia was reported in 80% of all SPBI, whereas meningitis was reported in 6% and infective endocarditis in <1%. Asplenia was noted in 2.4%. Seven‐ and 30‐day mortality was 6.6% and 11.9%, with a higher 30‐day mortality in those aged ≥70 years (24.4%). The serotype distribution showed 7‐valent conjugate vaccine covered 11.0% of all isolates, whereas 13‐valent conjugate vaccine (13vPCV) and a 23‐valent polysaccharide vaccine (23vPPV) covered 41.7% and 69.0% respectively. Immunisation details were available for 110 individuals, of whom, only 7.3% had received pneumococcal vaccination. Conclusions: Most patients with pneumococcal bacteraemia had age‐ or comorbidity‐related risk factors but were not vaccinated. Two‐thirds of cases occurred in people aged <70 years. 13vPCV and 23vPPV covered 41.7% and 69.0% of bacteraemic isolates. [ABSTRACT FROM AUTHOR]

OBJECTIVE Patients with sickle cell disease (SCD) are at increased risk for invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Immunization and antimicrobial prophylaxis may prevent this complication, and landmark clinical trials support discontinuation of antimicrobial prophylaxis at age 5 years. However, antimicrobial prophylaxis continues in some patients indefinitely. The objective of this study was to evaluate the incidence of culture-positive IPD and other infections in the setting of penicillin prophylaxis in the pediatric SCD population. METHODS This was a single-center, retrospective cohort study of patients with SCD who continued antimicrobial prophylaxis with penicillin, compared with those whose antimicrobial prophylaxis was discontinued. Included patients were aged 5 to 18 years during the study period and had no history of IPD or surgical splenectomy. Patient charts were reviewed for demographics, immunizations, penicillin prescription history, and microbiologic culture data. RESULTS Antimicrobial prophylaxis continued beyond age 5 years in 65% of patients, a higher percentage of whom had hemoglobin SS or S beta-zero disease. No patients whose antimicrobial prophylaxis was discontinued experienced IPD; 1 patient who continued antimicrobial prophylaxis died of S pneumoniae sepsis. Rates of other infections were comparable between groups (21% in prophylaxis versus 18% in no prophylaxis). CONCLUSIONS These results support appropriate de-prescribing of antimicrobial prophylaxis in patients with SCD who are not at high risk for IPD. Further multicenter studies are needed to evaluate consequences of antimicrobial prophylaxis with alternative agents on antibiotic resistance, examine provider rationale for continuation of antimicrobial prophylaxis, and assess quality of life effects (e.g., medication adherence, adverse drug reactions) of antimicrobial prophylaxis. [ABSTRACT FROM AUTHOR]

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Influenza is associated with primary viral and secondary bacterial pneumonias; however, the dynamics of this relationship in populations with varied levels of pneumococcal vaccination remain unclear. We conducted nested matched case-control studies in 2 prospective cohorts of Nicaraguan children aged 2-14 years: 1 before pneumococcal conjugate vaccine introduction (2008-2010) and 1 following introduction and near universal adoption (2011-2018). The association between influenza and pneumonia was similar in both cohorts. Participants with influenza (across types/subtypes) had higher odds of developing pneumonia in the month following influenza infection. These findings underscore the importance of considering influenza in interventions to reduce global pneumonia burden.

The hypothetical molecule 4-dimethylaminopyridinium salicylate monohydrate was synthesized and investigated leveraging FT-IR spectra, UV visible, NMR and quantum chemical calculations and also compared with its precursor molecules 4-dimethylamino pyridine and salicylic acid in the present work. To explore the impingement of hydrogen bonding on molecule the geometrical parameters, interaction energies, and vibrational spectra are employed. Natural Bond Orbital analysis indicated the existence of intermolecular hydrogen bonding N–H...O contact, which is mediated by a hyperconjugative interaction between the carbonyl oxygen atom donor and the pyridine ring N–H acceptor. The stretching wavenumber of hydrogen bond donor O–H and hydrogen bond acceptor C–O is red shifted due to elongation in respective bond lengths, according to vibrational analysis. The presence of intermolecular charge transfer from electron-rich pyridine to electron-deficient salicylate is revealed by FMO analysis, and this is corroborated by charge transfer due to excitation. A molecular docking simulation was also executed to better understand the structure-activity relation and further antibacterial tests confirmed that the compound inhibits the bacterial pathogens. [ABSTRACT FROM AUTHOR]

• In healthy Japanese infants/toddlers, V114 given subcutaneously was well tolerated. • The V114 safety profile was comparable to that of PCV13. • V114 elicited immune responses to all 15 serotypes in healthy infants/toddlers. • V114 was non-inferior for the 13 PCV13 serotypes after the three-dose infant series. • V114-elicited immune responses were higher than PCV13 for serotypes 22F and 33F. This phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in Japanese infants. V114 contains all 13 serotypes in PCV13 plus additional serotypes 22F and 33F. Healthy Japanese infants were randomized to receive three primary doses of V114 or PCV13 (dose 1 at 2–6 months of age; doses 2 and 3 ≥ 27 days after prior dose), plus a toddler dose at 12–15 months of age. Adverse events (AEs) were collected on Days 1–14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-dose 3, pre-dose 4, and 30 days post-dose 4. Primary objectives included non-inferiority of V114 to PCV13 for the 13 shared serotypes based on serotype-specific IgG response rates (IgG ≥ 0.35 μg/mL) and geometric mean concentration (GMC) ratios, and for serotypes 22F and 33F based on IgG response rates and compared with the lowest response of any serotype in the PCV13 group, at 30 days post-dose 3. Overall, 694 infants were randomized to V114 (n = 347) or PCV13 (n = 347). Proportions of participants with solicited and serious AEs were comparable between vaccination groups. V114 met non-inferiority criteria for all 13 shared serotypes, based on difference in proportion of responders (lower bound of two-sided 95 % confidence interval [CI] > −10.0) and IgG GMC ratios (V114/PCV13, lower bound of two-sided 95 % CI > 0.5) at 30 days post-dose 3. The non-inferiority criterion based on IgG response rates was met for serotype 22F, but narrowly missed for serotype 33F (90.9 %, lower bound of two-sided 95 % CI −10.6). In Japanese infants, a four-dose series of V114 was generally well tolerated. Compared with PCV13, V114 provided non-inferior immune responses to the 13 shared serotypes and higher immune responses to serotype 22F and 33F post-primary series. Trial registration: ClinicalTrials.gov : NCT04384107; EudraCT 2019-003644-68. [ABSTRACT FROM AUTHOR]

BackgroundReduced-dose pneumococcal conjugate vaccine (PCV) schedules are under consideration in countries where children are recommended to receive 3 doses. Whereas PCV-derived protection against vaccine-serotype colonization is responsible for herd effects of vaccination, dose-specific PCV effectiveness against colonization endpoints is not known. We aimed to assess the performance of differing PCV schedules against vaccine-serotype colonization in children.MethodsFrom 2009-2016, we monitored pneumococcal carriage in southern Israel, where children should receive PCV at ages 2 months, 4 months, and 12 months (2 primary [p] +1 booster [b] schedule). We analyzed nasopharyngeal swabs and vaccination histories from 5928 children aged 0-59 months without symptoms of diseases potentially attributable to pneumococci. Matching individuals on age, sex, ethnicity, visit timing, and recent antibiotic receipt, we measured schedule-specific 7-valent PCV (PCV7) and 13-valent PCV (PCV13) effectiveness against vaccine-serotype colonization in a modified case-control framework. We sampled from the distribution of all possible case-control match assignments for statistical analyses.ResultsReceiving 2 primary-series PCV13 doses conferred 53% (95% confidence interval [CI], 32-67%) protection against PCV13-serotype colonization at ages ≤12 months; 1 primary-series dose was not protective. A 2p+1b PCV13 series conferred 40% (95% CI, 4-67%) and 62% (95% CI, 33-83%) protection against PCV13-serotype colonization at ages 13-24 months and 25-59 months, respectively. Estimates suggested greater PCV13-conferred protection against PCV7-targeted serotypes than the 6 PCV13-only serotypes. As compared to children receiving 2p+1b PCV13 dosing, those receiving 1p+1b and 2p+0b schedules experienced 2.05-fold (95% CI, 1.12-5.00) and 3.33-fold (95% CI, 2.28-4.93) greater odds, respectively, of vaccine-serotype pneumococcal colonization at ages 13-24 months.ConclusionsOur results demonstrate real-world effectiveness of 2p+1b PCV dosing against vaccine-serotype colonization. Reduced-dose schedules may confer lower protection against vaccine-serotype carriage during and beyond the first year of life.

BackgroundMany upper respiratory pathogens cause similar symptoms. In China, routine molecular tests for upper respiratory pathogens are not widely performed and antibiotics abuse in treating upper respiratory tract infections (URTIs) is a major public health concern.MethodsWe performed qualitative real-time PCR tests to detect common upper respiratory tract pathogens including 9 viruses and 3 bacteria in 1221 nasopharyngeal swabs from patients with fever and influenza-like symptoms in a Chinese city. A quantitative real-time PCR was also performed to measure the bacterial density of the colonizing Streptococcus pneumoniae in these samples.ResultsWe found very diverse pathogens including 81.7% viruses, 11.6% bacteria and 6.7% mixed viruses and bacteria. S. pneumoniae colonization was found in 8.0% of the cases but most of them had low bacterial density (Mean = 3.9 log cfu/ml). We also discovered an increase of S. pneumoniae colonization frequency (but not the density) in patients with detectable upper respiratory tract pathogens, in a pathogen variety-dependent manner.ConclusionsOur study provided strong evidence against empiric antibiotic use for treating URTIs, and highlighted a strong need for improving the diagnostic capacity for URTIs by using more molecular testing in China.

This phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in healthy infants. V114 contains all 13 serotypes in PCV13 and additional serotypes 22F and 33F. Healthy infants were randomized to two primary doses and one toddler dose (2+1 regimen) of V114 or PCV13 at 3, 5, and 12 months of age; diphtheria, tetanus, pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib), hepatitis B (HepB) vaccine was administered concomitantly. Adverse events (AEs) were collected on Days 1–14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-primary series, immediately prior to toddler dose, and 30 days post-toddler dose. Primary objectives included non-inferiority of V114 to PCV13 for 13 shared serotypes and superiority of V114 to PCV13 for serotypes 22F and 33F. 1191 healthy infants were randomized to V114 (n = 595) or PCV13 (n = 596). Proportions of participants with solicited AEs and serious AEs were comparable between groups. V114 met non-inferiority criteria for 13 shared serotypes, based on difference in proportions with serotype-specific IgG ≥0.35 μg/mL (lower bound of two-sided 95% confidence interval [CI] >−10.0) and IgG geometric mean concentration (GMC) ratios (lower bound of two-sided 95% CI >0.5) at 30 days post-toddler dose. V114 met superiority criteria for serotypes 22F and 33F, based on response rates (lower bound of two-sided 95% CI >10.0) and IgG GMC ratios (lower bound of two-sided 95% CI >2.0) at 30 days post-toddler dose. Antibody responses to DTaP-IPV-Hib-HepB met non-inferiority criteria, based on antigen-specific response rates. A two-dose primary series plus toddler dose of V114 was well-tolerated in healthy infants. Compared with PCV13, V114 provided non-inferior immune responses to 13 shared serotypes and superior immune responses to additional serotypes 22F and 33F. [ABSTRACT FROM AUTHOR]

In the coming XXI century, infectious diseases still retain their importance both in medical and social terms, this problem is very relevant for rheumatology, where comorbid infections (CI) have a significant impact on both the course of the main immuno-inflammatory rheumatic disease (IIRD) and mortality. One of the leading places in the structure of serious CI in patients with IIRD is occupied by pneumonia, which is a weighty argument in favor of the vaccination of these patients from pneumococcal infection. The article presents generalized data on the use of 23-valent pneumococcal polysaccharide vaccine (PPV-23) in patients with IIRD who received inpatient and outpatient treatment at the V.A. Nasonova Research Institute of Rheumatology for the last 10 years. It has been shown that the vaccination of PPV-23 in patients with IIRD is characterized by high preventive efficacy (>90%), is safe and does not increase the risk of exacerbation of the disease. The sufficient immunogenicity of vaccination is evidenced by a significant increase in the levels of pneumococcal antibodies in the blood serum and the coefficient of post-vaccination response. The use of glucocorticoids (methylprednisolone, prednisolone) has no significant effect on the effectiveness, immunogenicity and safety of PPV-23 vaccination. The possibility of vaccination of PPV-23 with any activity of the process in patients with rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis (ankylosing spondylitis, psoriatic arthritis) with the condition of adequate therapy has been demonstrated. In order to develop clearer indications for vaccination, to determine time intervals for revaccination, to evaluate the effectiveness and safety of new pneumococcal vaccines, as well as to study the effect on the results of immunization of various anti-rheumatic drugs in patients with IIRD, further multicenter large-scale studies are needed.

Pneumococcal diseases have a clinical and economic impact on the population. Until this year, a 10-valent pneumococcal vaccine (PCV10) used to be applied in Colombia, which does not contain serotypes 19A, 3, and 6A, the most prevalent in the country. Therefore, we aimed to assess the cost-effectiveness of the shift to the 13-valent pneumococcal vaccine (PCV13). A decision model was used for newborns in Colombia between 2022–2025 and adults over 65 years. The time horizon was life expectancy. Outcomes are Invasive Pneumococcal Diseases (IPD), Community-Acquired Pneumonia (CAP), Acute Otitis Media (AOM), their sequelae, Life Gained Years (LYGs), and herd effect in older adults. PCV10 covers 4.27% of serotypes in the country, while PCV13 covers 64.4%. PCV13 would avoid in children 796 cases of IPD, 19,365 of CAP, 1,399 deaths, and generate 44,204 additional LYGs, as well as 9,101 cases of AOM, 13 cases of neuromotor disability and 428 cochlear implants versus PCV10. In older adults, PCV13 would avoid 993 cases of IPD and 17,245 of CAP, versus PCV10. PCV13 saves $51.4 million. The decision model shows robustness in the sensitivity analysis. PCV13 is a cost-saving strategy versus PCV10 to avoid pneumococcal diseases. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to identify the risk factors for pneumococcal disease. Methods: The study was performed using insurance claims data from the residents of 12 Japanese municipalities. Based on recorded diagnoses, we identified chronic medical conditions in each patient between April 2015 and March 2016 and examined the subsequent occurrence of a pneumococcal disease from April 2016 onward. Cox proportional hazards models were used to estimate the hazard ratio of each chronic medical condition for a pneumococcal disease occurrence. Results: The study was conducted on 732,235 patients, of whom, 61,306 (8.4%) were aged 0-18 years, 184,367 (25.2%) were aged 19-49 years, 126,078 (17.2%) were aged 50-64 years, and 360,484 (49.2%) were aged ≥65 years. A higher number of conditions was associated with a higher incidence of pneumococcal disease. Significant risk factors for pneumococcal disease in all patients included chronic heart disease, chronic lung disease, diabetes mellitus, cancer, and chronic renal disease. Furthermore, chronic lung disease, diabetes mellitus, aspiration pneumonia, and immunosuppressant use were risk factors among patients aged 50-64 years. Conclusions: Persons aged 50-64 years with multiple chronic medical conditions or with specific conditions are at a higher risk of developing pneumococcal disease, indicating a need to consider their inclusion in routine vaccination programs.

This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12–15 months of age. Diphtheria, tetanus, and pertussis–inactivated poliovirus (DTaP–IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP–IPV at 1-month post-dose 3 (PD3). On days 1–14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP–IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic.

Background:Despite concerns that antimicrobial treatment of prevalent infections may select for drug-resistant bacteria, the effects of antimicrobial treatment on colonization dynamics have not been well quantified. Methods:We measured impacts of antimicrobial treatment on nasopharyngeal carriage of penicillin-susceptible Streptococcus pneumoniae (PSSP) and penicillin-nonsusceptible (PNSP) lineages at the end of treatment and 15, 30, and 60 days after treatment in a previously conducted randomized, double-blinded, placebo-controlled trial of amoxicillin-clavulanate for stringently defined acute otitis media. Results:In intention-to-treat analyses, immediate treatment with amoxicillin-clavulanate reduced PSSP carriage prevalence by 88% (95% confidence interval [CI], 76%-96%) at the end of treatment and by 27% (-3%-49%) after 60 days but did not alter PNSP carriage prevalence. By the end of treatment, 7% of children who carried PSSP at enrollment remained colonized in the amoxicillin-clavulanate arm, compared with 61% of PSSP carriers who received placebo; impacts of amoxicillin-clavulanate persisted at least 60 days after treatment among children who carried PSSP at enrollment. Amoxicillin-clavulanate therapy reduced PSSP acquisition by >80% over 15 days. Among children who carried PNSP at enrollment, no impacts on carriage prevalence of S. pneumoniae, PSSP, or PNSP were evident at follow-up visits. Conclusions:Although the absolute risk of carrying PNSP was unaffected by treatment, antimicrobial therapy conferred a selective impact on colonizing pneumococci by accelerating clearance and delaying acquisition of PSSP.

All-cause otitis media (OM) incidence has declined in numerous settings following introduction of pneumococcal conjugate vaccines (PCVs) despite increases in carriage of nonvaccine pneumococcal serotypes escaping immune pressure. To understand the basis for the declining incidence, we assessed the intrinsic capacity of pneumococcal serotypes to cause OM independently and in polymicrobial infections involving nontypeable Haemophilus influenzae (NTHi) using samples obtained from middle ear fluid and nasopharyngeal cultures before PCV7/13 rollout. Data included samples from OM episodes (11,811) submitted for cultures during a 10-year prospective study in southern Israel and nasopharyngeal samples (1,588) from unvaccinated asymptomatic children in the same population. We compared data representing pneumococcal serotype diversity across carriage and disease isolates with and without NTHi coisolation. We also measured associations between the pneumococcal phenotype and the rate of progression from colonization to OM in the presence and absence of NTHi. Whereas pneumococcal serotype diversity was lower in single-species OM than in single-species colonization, levels of serotype diversity did not differ significantly between colonization and OM in mixed-species episodes. Serotypes differed roughly 100-fold in progression rates, and those differences were attenuated in polymicrobial episodes. Vaccine serotype pneumococci had higher rates of progression than nonvaccine serotypes. While serotype invasiveness was a weak predictor of the OM progression rate, efficient capsular metabolic properties-traditionally thought to serve as an advantage in colonization-predicted an enhanced rate of progression to complex OM. The lower capacity of nonvaccine serotypes to cause OM may partially account for reductions in all-cause OM incidence despite serotype replacement in carriage following rollout of PCVs.

Austrian syndrome corresponds to the triad of meningitis, pneumonia, and endocarditis caused by Streptococcus pneumoniae, there is no global or local incidence given the infrequency of entity. Scarce cases are published in Latin America, with none of them in Colombia. A case of Austrian syndrome by penicillin-resistant S. pneumoniae in an immunocompetent patient is presented. Aortic valve is the most frequent site involved in Austrian syndrome; this patient had an unusual localization of the vegetation on the right coronary artery ostium. The prognosis is poor with a mortality rate of 30% or higher, this patient survived despite systemic complications. Vaccination status impacts in prevention and severity of cases because responsible serotypes are often included in available vaccines. The patient had a serotype covered by available vaccines; however, her vaccination status was unknown. Thus, we present the first case reported in Colombia of Austrian syndrome by a penicillin-resistant S. pneumoniae, in a patient with no identified comorbidities or toxicological history, with a successful evolution. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae (the pneumococcus) is the leading cause of pneumonia and bacterial meningitis. A number of recent studies indicate an association between the incidence of pneumococcal disease and exposure to air pollution. Although the epidemiological evidence is substantial, the underlying mechanisms by which the various components of air pollution (particulate matter and gases such as NO2 and SO2) can increase susceptibility to pneumococcal infection are less well understood. In this review, we summarize the various effects air pollution components have on pneumococcal pathogenesis and transmission; exposure to air pollution can enhance host susceptibility to pneumococcal colonization by impairing the mucociliary activity of the airway mucosa, reducing the function and production of key antimicrobial peptides, and upregulating an important pneumococcal adherence factor on respiratory epithelial cells. Air pollutant exposure can also impair the phagocytic killing ability of macrophages, permitting increased replication of S. pneumoniae. In addition, particulate matter has been shown to activate various extra- and intracellular receptors of airway epithelial cells, which may lead to increased proinflammatory cytokine production. This increases recruitment of innate immune cells, including macrophages and neutrophils. The inflammatory response that ensues may result in significant tissue damage, thereby increasing susceptibility to invasive disease, because it allows S. pneumoniae access to the underlying tissues and blood. This review provides an in-depth understanding of the interaction between air pollution and the pneumococcus, which has the potential to aid the development of novel treatments or alternative strategies to prevent disease, especially in areas with high concentrations of air pollution. [ABSTRACT FROM AUTHOR]

The potential impact of new pneumococcal conjugate vaccines (PCVs) is assessed by using immune responses to predict their effectiveness against invasive pneumococcal disease (IPD). This analysis predicted the serotype-specific effectiveness against IPD of a new 15-valent PCV (V114) for the serotypes shared with a 13-valent PCV (PCV13), in a US pediatric population given a 3 + 1 dosing regimen. Beginning with the known serotype-specific antibody concentrations after vaccination with placebo, 7-valent PCV (PCV7) and PCV13, reverse cumulative distribution curves were used, along with published serotype-specific vaccine effectiveness of PCV7 and PCV13, to derive a protective antibody concentration (Cp) for each PCV13 serotype in V114. Serotype-specific effectiveness was predicted using the Cp estimates and the respective serotype-specific antibody concentrations of placebo and V114 recipients in recent pediatric clinical trials. Predicted serotype-specific V114 effectiveness values ranged from 86% to 99% for PCV7 serotypes and from 59% to 97% for (non-PCV7) PCV13 serotypes. V114 serotype-specific effectiveness against IPD in a US pediatric population was predicted to be largely comparable to that of PCV7 and PCV13 for shared serotypes, with models suggesting likelihood of high overall benefit gained from increased serotype 3 effectiveness, and additional protection against serotypes 22 F and 33 F. [ABSTRACT FROM AUTHOR]

Streptococcus pneumoniae (pneumococcus) remains a significant cause of both mild infections such as otitis media, sinusitis, and bronchitis and more severe manifestations such as bacteremia, pneumonia, and invasive pneumococcal disease. Several key serotypes have been targeted in vaccine development due to their association with increased infectivity. Pneumococcal vaccines are available in two formulations, the unconjugated purified polysaccharide (PPSV) and the conjugated formulation (PCV), which leads to a more robust and prolonged immune response. There have been dramatic reductions in mortality attributed to invasive pneumococcal disease over the past 2 decades due to improved vaccination rates and improved serotype coverage with the existing arsenal of vaccines (PCV13 and PPSV23). Utilizing both conjugate and purified polysaccharide modalities in series has produced greater and lasting immunity. The development of both the PCV15 and the PCV20 vaccines provides an opportunity to use conjugated vaccines against a wider spectrum of pneumococcal serotypes. National guidelines have been updated to incorporate the new pneumococcal vaccines into clinical practice. [ABSTRACT FROM AUTHOR]

Competing Interests: Declaration of competing interest Elaine Yuen Phin Lee is an employee of the University of Hong Kong, Hong Kong SAR, China and reports that her institution received payment from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Andy Cheuk Nam Hwang has no conflict of interest to report. Dong Wang, Boshu Ru, Jessica Weaver, Meghan White, Yiyun Chen, and Craig S. Roberts are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may hold shares in Merck & Co., Inc., Rahway, NJ, USA. Kim S. J. Lao and Tsz K. Khan are employees of MSD (Asia). Kate Ching-Ching Chan received a research grant from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Use of pneumococcal conjugate vaccines (PCVs) has greatly reduced the incidence of invasive pneumococcal disease (IPD). V114 (VAXNEUVANCE™, Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA) is a 15-valent PCV currently approved in adults in the United States, containing the 13 serotypes in licensed PCV13 and 2 additional serotypes (22F and 33F) which are important contributors to residual pneumococcal disease. This study quantified the health and economic burden of IPD attributable to V114 serotypes in hypothetical birth cohorts from Korea and Hong Kong. A Markov model was used to estimate the case numbers and costs of IPD in unvaccinated birth cohorts over 20 years. The model was applied to 3 scenarios in Korea (pre-PCV7, pre-PCV13, and post-PCV13) and to 2 scenarios in Hong Kong (pre-PCV7 and post-PCV13). For Korea, the model predicted 62, 26, and 8 IPD cases attributable to V114 serotypes in the pre-PCV7, pre-PCV13, and post-PCV13 scenarios, respectively. Costs of V114-type IPD fell from $1.691 million pre-PCV7 to $.212 million post-PCV13. For Hong Kong, the model estimated 62 V114-associated IPD cases in the pre-PCV7 scenario and 46 in the post-PCV13 scenario. Costs attributed to all V114 serotypes were $2.322 million and $1.726 million in the pre-PCV7 and post-PCV13 periods, respectively. Vaccine-type serotypes are predicted to cause continuing morbidity and cost in Korea (19A) and Hong Kong (3 and 19A). New pediatric pneumococcal vaccines must continue to protect against serotypes in licensed vaccines to maintain disease reduction, while extending coverage to non-vaccine serotypes.

• PCV10 and PCV13 protect similarly against invasive disease due to vaccine serotypes. • PCV13 provides direct protection against serotype 3 and vaccine-related serotype 6C. • PCV10 does not provide significant protection against vaccine-related serotypes 19A and 6C. • PCV13 effectiveness declined with time after booster, in particular for serotypes 3 and 19A. • Multinational networks are crucial for the evaluation of PCV15/ PCV20 that may be introduced. Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010–11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet). We compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012–2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose. The PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0–88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8–96.1) < 12 months to 85.1% (72.0–92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7–94.7) against fatal PCV13 IPD, 64.5% (43.7–77.6), 83.2% (73.7–89.3) and 85.1% (67.6–93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3–94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4–92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2–96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and −14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively. PCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines. [ABSTRACT FROM AUTHOR]

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Abstract Background The pneumococcal conjugate vaccine PCV7 was introduced in Southwest Sweden in the child vaccination program in 2009, followed by PCV13 in 2010 and PCV10 in 2015. In this retrospective cohort study we assessed the pneumococcal serotype distribution in relation to predisposing factors, clinical manifestations and outcome during seven years after PCV introduction. Methods Clinical data from 1278 patients with 1304 episodes of invasive pneumococcal disease (IPD) between January 2009 and December 2015 in Region Västra Götaland, Sweden, were retrospectively collected from medical records. Pneumococcal isolates were serotyped by gel diffusion and/or Quellung reactions performed at the Public Health Agency in Sweden. Associations between serotypes and clinical characteristics were statistically evaluated by use of Fisher’s exact test, Mann-Whitney U test and Logistic regression analysis, whereas IPD episodes caused by serotypes over time were analyzed by Mantel-Haenszel chi-square test. Results With the exception of serotype 3, the prevalence of PCV13 serotypes decreased during the study period, from 76% (n = 157) of all IPD episodes in 2009 to 25% (n = 42) in 2015 (p

The evaluation of the public health impact of a vaccination program is essential in monitoring its policy relevance. Vaccine impact (VI) is usually assessed in a before-after design, in which data on disease burden without vaccination program is required from a historical reference period. It takes into account the indirect effects and therefore aims to describe the public health performance of the vaccination program in the population. Vaccine effectiveness (VE), measured in parallel settings, quantifies the benefit for an individual of being vaccinated but does not address the indirect effects of a vaccination program. The motivation of this paper is to gain insight into patterns of how VI and VE have manifested under large-scale use of a ten-valent pneumococcal conjugate vaccine in Finnish children. We construct a simple pseudo-dynamic model that mimics typical post-vaccination trends in the incidences of pneumococcal carriage and invasive disease in children when the proportion of vaccine-type carriage decreases. In the context of the model, we define the parameters of interest for VI and VE and explore how their expected values evolve over time. For comparison, we demonstrate the application of VI and VE estimation by using register data.

BackgroundPneumococcal conjugate vaccines (PCVs) are being used worldwide. A key question is whether the impact of PCVs on pneumonia is similar in low- and high-income populations. However, most low-income countries, where the burden of disease is greatest, lack reliable data that can be used to evaluate the impact. Data from middle-income countries that have both low- and high-income subpopulations can provide a proxy measure for the impact of the vaccine in low-income countries.MethodsWe evaluated the impact of PCV10 on hospitalizations for all-cause pneumonia in Brazil, a middle-income country with localities that span a broad range of human development index (HDI) levels. We used complementary time series and spatiotemporal methods (synthetic controls and hierarchical Bayesian spatial regression) to test whether the decline in pneumonia hospitalizations associated with vaccine introduction varied across the socioeconomic spectrum.ResultsWe found that the declines in all-cause pneumonia hospitalizations in children and young and middle-aged adults did not vary substantially across low and high HDI subpopulations. Moreover, the estimated declines seen in infants and young adults were associated with higher levels of uptake of the vaccine at a local level.ConclusionsThese results suggest that PCVs have an important impact on hospitalizations for all-cause pneumonia in both low- and high-income populations.

BackgroundReductions in otitis media (OM) burden following rollout of pneumococcal conjugate vaccines (PCVs) have exceeded predictions of vaccine impact. In settings with active surveillance, reductions in OM caused by vaccine-targeted pneumococcal serotypes have co-occurred with reductions in OM caused by other pathogens carried in the upper-respiratory tract of children. To understand these changes, we investigated the progression of vaccine-targeted and non-vaccine pneumococcal serotypes from carriage to OM before and after vaccine rollout.MethodsNasopharyngeal carriage prevalence of pneumococcus was monitored in prospective studies of Bedouin and Jewish children

BackgroundPneumococcal conjugate vaccines (PCVs) prevent invasive pneumococcal disease and pneumonia. However, some low-and middle-income countries have yet to introduce PCV into their immunization programs due, in part, to lack of certainty about the potential impact. Assessing PCV benefits is challenging because specific data on pneumococcal disease are often lacking, and it can be difficult to separate the effects of factors other than the vaccine that could also affect pneumococcal disease rates.MethodsWe assess PCV impact by combining Bayesian model averaging with change-point models to estimate the timing and magnitude of vaccine-associated changes, while controlling for seasonality and other covariates. We applied our approach to monthly time series of age-stratified hospitalizations related to pneumococcal infection in children younger 5 years of age in the United States, Brazil, and Chile.ResultsOur method accurately detected changes in data in which we knew true and noteworthy changes occurred, i.e., in simulated data and for invasive pneumococcal disease. Moreover, 24 months after the vaccine introduction, we detected reductions of 14%, 9%, and 9% in the United States, Brazil, and Chile, respectively, in all-cause pneumonia (ACP) hospitalizations for age group 0 to

Rates of invasive pneumococcal disease have declined since widespread introduction of pneumococcal conjugate vaccines (PCVs) in the United States. We evaluated the impact of immunization status and recent antibiotic use on an individual child's risk of colonization. This study extends previously reported data from children

ObjectivesExternal validity, or generalisability, is the measure of how well results from a study pertain to individuals in the target population. We assessed generalisability, with respect to socioeconomic status, of estimates from a matched case-control study of 13-valent pneumococcal conjugate vaccine effectiveness for the prevention of invasive pneumococcal disease in children in the USA.DesignMatched case-control study.SettingThirteen active surveillance sites for invasive pneumococcal disease in the USA.ParticipantsCases were identified from active surveillance and controls were age and zip code matched.Outcome measuresSocioeconomic status was assessed at the individual level via parent interview (for enrolled individuals only) and birth certificate data (for both enrolled and unenrolled individuals) and at the neighbourhood level by geocoding to the census tract (for both enrolled and unenrolled individuals). Prediction models were used to determine if socioeconomic status was associated with enrolment.ResultsWe enrolled 54.6% of 1211 eligible cases and found a trend toward enrolled cases being more affluent than unenrolled cases. Enrolled cases were slightly more likely to have private insurance at birth (p=0.08) and have mothers with at least some college education (p

When a new vaccine is introduced, it is critical to monitor trends in disease rates to ensure that the vaccine is effective and to quantify its impact. However, estimates from observational studies can be confounded by unrelated changes in healthcare utilization, changes in the underlying health of the population, or changes in reporting. Other diseases are often used to detect and adjust for these changes, but choosing an appropriate control disease a priori is a major challenge. The "synthetic controls" (causal impact) method, which was originally developed for website analytics and social sciences, provides an appealing solution. With this approach, potential comparison time series are combined into a composite and are used to generate a counterfactual estimate, which can be compared with the time series of interest after the intervention. We sought to estimate changes in hospitalizations for all-cause pneumonia associated with the introduction of pneumococcal conjugate vaccines (PCVs) in five countries in the Americas. Using synthetic controls, we found a substantial decline in hospitalizations for all-cause pneumonia in infants in all five countries (average of 20%), whereas estimates for young and middle-aged adults varied by country and were potentially influenced by the 2009 influenza pandemic. In contrast to previous reports, we did not detect a decline in all-cause pneumonia in older adults in any country. Synthetic controls promise to increase the accuracy of studies of vaccine impact and to increase comparability of results between populations compared with alternative approaches.