Can pneumococcal meningitis surveillance be used to assess the impact of pneumococcal conjugate vaccine on total invasive pneumococcal disease? A case-study from South Africa, 2005–2016

IntroductionSouth Africa introduced seven-valent pneumococcal conjugate vaccine (PCV7) in 2009 and PCV13 in 2011. We aimed to compare the estimated impact of PCV on pneumococcal meningitis (PM) to impact of PCV on total invasive pneumococcal disease (tIPD) based on risk reduction after PCV introduction.MethodsWe conducted national, laboratory-based surveillance for tIPD during 2005–2016. We estimated and compared rates of PCV13 and non-PCV13 serotype disease among tIPD and PM in individuals aged <5 years and ≥5 years, and compared these rates between the 2005–2008 pre-PCV introduction period and two time points after PCV introduction, 2012 and 2016.ResultsWe enrolled 45,853 tIPD cases; 17,251 (38%) were PM. By 2016, IPD caused by all serotypes decreased 55% (95%CI −57% to −53%) for tIPD, and 54% for PM (95%CI −58% to −51%), 0.7% difference between estimates (p = 0.7). No significant differences were observed between PCV7-serotype disease reduction in tIPD and PM in both age groups or the additional 6 serotypes included in PCV13 in <5 year olds in 2012 and 2016. In 2012 there was a significant difference between increases in non-PCV13 serotype disease in those ≥5 years for tIPD and PM (32% greater increase in PM, p < 0.001), but this difference was absent by 2016. There was a significant difference between the estimated decrease in additional PCV13 type disease in 2016 between tIPD and PM for those aged ≥5 years (28% greater reduction in PM, p = 0.008).ConclusionPM showed similar reductions to tIPD seven years after PCV introduction in vaccine serotype disease in those <5 years, and increases in non-vaccine serotype disease in all ages.     

Distribution of serotypes causing invasive pneumococcal disease in older adults from high-income countries and impact of pediatric and adult vaccination policies

BackgroundNeither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs) nor direct vaccination with the 23-valent polysaccharide vaccine have eliminated vaccine serotype invasive pneumococcal disease (IPD) in older adults. Vaccinating older adults with higher-valency PCV15 and PCV20 could address remaining IPD due to pediatric PCV serotypes plus additional IPD due to serotypes included in these vaccines.MethodsWe collected serotype-specific IPD data in older adults (≥65 years in most countries), from national or regional surveillance systems or hospital networks of 33 high-income countries. Data were from official government websites, online databases, surveillance system reports, published literature, and personal communication with in-country investigators. Average percentages of IPD serotypes were calculated.ResultsAmong 52,905 cases of IPD with a serotype identified, PCV13 serotypes accounted for 33.7% of IPD (55.8% and 30.6% for countries with PCV10 and PCV13 in the pediatric NIP), most commonly serotypes 3 (14.9%) and 19A (7.0%). PCV15 and PCV20 would cover an additional 10.4% and 32.9% of older adult IPD beyond PCV13 serotypes (PCV10 countries: 7.7% and 23.3%; PCV13 countries: 10.6% and 34.6%). The most common of these additional serotypes were 8 (9.9%), 22F (7.9%), 12F (4.6%), and 11A (3.3%). PPSV23 policies for older adults were not correlated with lower IPD percentages due to PPSV23 serotypes.ConclusionsVaccinating older adults with higher-valency PCVs, especially PCV20, could substantially reduce the remaining IPD burden in high-income countries, regardless of current PCV use in pediatric NIPs and adult PPSV23 policies.     

Burden of pneumococcal disease due to serotypes covered by the 13-valent and new higher-valent pneumococcal conjugate vaccines in the United States

The addition of pneumococcal conjugate vaccines (PCVs) to the United States (US) national immunization program led to significant reductions in incidence, mortality, and associated sequelae caused by pneumococcal disease (PD) in children and adults through direct and indirect protection. However, there remains clinical and economic burden due to PD caused by serotypes not included in the current 13-valent PCV (PCV13) formulation. To address this unmet need, 15-valent PCV (PCV15) and 20-valent PCV (PCV20), containing additional serotypes to PCV13, were recently approved in the US for adults and are anticipated for pediatrics in the near future. The study objective was to estimate the annual number of cases, deaths, and economic burden of PD due to serotypes included in PCV13, PCV15, and PCV20 for both US pediatric and adult populations. An Excel-based model was developed to calculate clinical and economic outcomes using published age-group specific serotype coverage; incidence of invasive PD, community-acquired pneumonia, and acute otitis media; case fatality rates; and disease-related costs. The results showed that across all age groups, the estimated annual PD cases and associated deaths covered by PCV13 serotypes were 914,199 and 4320, respectively. Compared with PCV13 serotypes, the additional 2 and 7 serotypes covered by PCV15 and PCV20 were attributed with 550,475 and 991,220 annual PD cases, as well as 1425 and 3226 annual deaths, respectively. This clinical burden translates into considerable economic costs ranging from $903 to $1,928 million USD that could be potentially addressed by PCV15 and PCV20. The additional serotypes included in PCV20 contribute substantially to the clinical and economic PD burden in the US pediatric and adult populations. Despite the success of the PCV13 pediatric national immunization program and increased adult uptake of PCV13 and 23-valent polysaccharide vaccine, broader PCV serotype coverage is needed across all ages to further reduce pneumococcal disease burden.     

Persistent serotype 3 and 19A invasive pneumococcal diseases in adults in vaccine era: Serotype-dependent difference in ceftriaxone susceptibility

BackgroundInvasive pneumococcal disease (IPD) is associated with substantial morbidity and mortality in children and elderly populations. Serotype distribution and antibiotic susceptibility of IPD isolates are changing with the implementation of pneumococcal vaccination and increasing antibiotic use worldwide. We aimed to determine serotype distribution, antibiogram, and molecular epidemiology of pneumococci in the late stage of PCV13 era.MethodsProspective multicenter IPD surveillance study was conducted for adults aged ≥ 19 years from July 2019 to June 2021. Clinical and epidemiologic data were collected. In addition, antibiotic susceptibility test, serotype identification and multi-locus sequence typing (MLST) was taken for pneumococcal isolates.ResultsA total of 160 IPD cases were collected with mean age of 65.1 years (male, 72.5%). Serotyping was taken for 116 available pneumococcal isolates. PCV13 and PPSV23 serotypes were 32.8% (n = 38) and 56.0% (n = 65), respectively. Serotype 3 (13.8%) and 19A (9.5%) were the most common causative agents of IPD, followed by serogroup 11 (6.9%), 23A (6.9%), 10A (4.3%), and 15B (4.3%). Notably, 32.5% of invasive pneumococcal isolates were non-susceptible to ceftriaxone. Serotypes 11A, 11E and 19A pneumococci showed high ceftriaxone non-susceptible rate (80%, 100% and 81.8% respectively), and they were related to sequence type (ST) 166 and ST320. In comparison, most serotype 3 isolates were ceftriaxone susceptible and related to ST180.ConclusionsPCV serotypes, especially 3 and 19A, are still prevalent in adult IPDs, suggesting that individual PCV13 immunization would be necessary for the elderly people and chronically ill patients. Ceftriaxone non-susceptible rate was remarkably high in invasive pneumococcal isolates.     

Long-term impact of pneumococcal conjugate vaccines for children on adult pneumococcal pneumonia in Japan: Two multicenter observational studies from 2011 to 2020

BackgroundPediatric pneumococcal conjugate vaccines (PCVs) introduction has directly and indirectly reduced pneumococcal pneumonia and invasive disease caused by PCV-covered serotypes among children and adults globally. In Japan, both PCV7 and PCV13 were introduced into the national immunization program (NIP) for children in 2013. However, the long-term impact of PCV use in children on adult pneumococcal pneumonia in Japan remains unclear.MethodsWe assessed serotypes isolated from adult pneumococcal pneumonia patients (in- and outpatients) in two multicenter observational studies in Japan: 2011–2014 and 2016–2020. The latter study period was divided into two periods to evaluate changes after PCV introduction in children. The Quellung reaction was used to determine serotypes. We evaluated trends of individual and vaccine-covered serotypes over three periods and assessed the difference in changes by patient group before and after the introduction of pediatric PCVs.ResultsA total of 650 patients were enrolled: 224, 322, and 104 in 2011–2014, 2016–2017, and 2018–2020, respectively. The median age was 73 years; 59.7% (388/650) were male; 86.9% (565/650) had comorbidities; and 10.2% (66/650) were nursing-home residents. The proportion of PCV13 serotypes decreased from 52.7% in 2011–2014 to 30.4% in 2016–2017 (p <0.001) after PCV13 introduction for children. However, PCV13, PCV15, and PCV20 serotypes still accounted for 38.5, 43.3, and 59.6% of total pneumococcal pneumonia in 2018–2020, respectively. Decline of PCV13 serotypes was more marked in patients aged ≥65 (-23.5%; p <0.001) than those aged <65 (-12.3%; p = 0.104) from 2011–2014 to 2016–2020. The proportion of PPSV23 non-PCV13 serotypes didn’t change over time.ConclusionsThe proportion of adult pneumococcal pneumonia caused by PCV13 serotypes in Japan declined after pediatric PCVs introduction into NIP, possibly due to indirect effects of pediatric PCVs. However, use of new PCVs in Japanese adults may potentially prevent additional pneumococcal pneumonia cases. Now, pneumococcal vaccination strategy for older adults requires discussion.     

Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay

Objective(s)In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017.MethodsS. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16–49, 50–64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)].Results11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50–64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP.Conclusion(s)Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.     

Decline in pneumococcal nasopharyngeal carriage in children 6–23 months with respiratory illnesses following pneumococcal conjugate vaccine implementation

BackgroundFollowing pneumococcal conjugate vaccines (PCVs) implementation, worldwide, pneumococcal carriage rates remained stable, indicating full replacement of vaccine-serotypes (VT) with non-VT. However, data are scarce regarding PCV impact on pneumococcal carriage rates in healthy vs. sick children. We assessed pneumococcal carriage rates dynamics in healthy and sick children 6–23 months, following PCV introduction.MethodsThis is a prospective, population-based surveillance conducted during the years 2009–2017, in southern Israel. Three groups were defined as follows: Children without respiratory infection signs (the healthy/non-respiratory group); Children who had a chest radiography at the hospital (the Hosp-CXR group); and children with community-acquired alveolar pneumonia (CAAP).Rate ratios (RRs; 95% CI) were calculated, comparing between late-13-valent PCV (PCV13) period (2016–2017) and early-PCV period (2009–2010). Rate ratios were adjusted for antibiotic administration, seasonality and ethnicity, and separate calculations were performed for 6–11 and 12–23 month old children.ResultsOverall, 51% of 8627 nasopharyngeal cultures were positive.In 2009–2010 (early-PCV period), the overall carriage rate was 55%; serotypes included in the PCV13 carriage rates were 28%, 31% and 38% in the healthy/non-respiratory, Hosp-CXR, and CAAP groups, respectively.Overall carriage rates in healthy/non-respiratory episodes were stable (~54%) when comparing between 2016 and 17 and 2009–10 (RR = 0.98; 0.84–1.15). In contrast, rates significantly declined for Hosp-CXR (RR = 0.78; 0.63–0.98) and CAAP (RR = 0.65; 0.47–0.89). These trends were driven by ~ 80% VT reductions, coupled with non-VT increase.ConclusionsFollowing 7-valent PCV/ PCV13 introduction, pneumococcal carriage rates declined in respiratory diseases, but not in healthy children and children without respiratory infections. These trends suggest that a reduction in pneumococcal carriage rates during respiratory infections indicates a decline in respiratory infections caused by VT, while carriage rates in non-respiratory cases reflect non-VT predominance, that have low disease potential for respiratory disease.     

Immunogenicity of PCV24, an expanded pneumococcal conjugate vaccine,in adult monkeys and protection in mice

Invasive pneumococcal disease (IPD) is responsible for serious illnesses such as bacteremia, sepsis, meningitis, and pneumonia in young children, older adults, and persons with immunocompromising conditions and often leads to death. Although the most recent pneumococcal conjugate vaccines (PCVs) have been designed to target serotypes identified as the primary causative agents of IPD, the epidemiological landscape continues to change stressing the need to develop new PCVs. We have developed an investigational 24-valent PCV (PCV24) including serotypes 1, 2, 3, 4, 5, 6A, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F all conjugated to CRM197 and evaluated this vaccine in adult monkeys. PCV24 was shown to be immunogenic and induced functional antibody for all vaccine serotypes. Of the serotypes common to PCV13 and V114 (PCV15), PCV24 had a similar immunogenic response with the exceptions of 23F which had higher IgG GMCs for PCV13 and V114, and 7F which had higher GMCs for PCV13. Functional antibody responses were similar for the serotypes in common between PCV24, PCV13 and V114 vaccines, with the exception of serotype 7F which was greater for PCV13. Overall, this study shows that PCV24 provided similar immunogenicity as the lower valent vaccines in adult monkeys with no apparent serotype interference. In addition, PCV24 also provided protection against pneumococcal infection in a mouse challenge model.     

Epidemiology of community-acquired pneumonia in the era of extended serotype-covering multivalent pneumococcal conjugate vaccines

BackgroundSouth Korea has been providing 10-valent pneumococcal conjugate vaccine/(PCV10)/13-valent pneumococcal conjugate vaccine (PCV13) to children and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to older adults as part of a national immunization program.MethodsFrom September 2015 to August 2017, a prospective cohort study was conducted for adults aged ≥19 years with community-acquired pneumonia (CAP) at four university hospitals. All-cause and pneumococcal CAP incidence and mortality rates were evaluated on the basis of hospital catchment population. Serotype distribution of pneumococcal CAP was also evaluated.ResultsAmong 2669 patients with CAP, 252 cases (9.4%) were pneumococcal CAP cases. The annual incidences of all-cause and pneumococcal CAP were 194.3 cases and 18.3 cases respectively, per 100,000 persons. Serotyped Streptococcus pneumoniae was identified in 107 cases (42.5%) through culture or a serotype-specific urinary antigen detection assay. Pneumococcal CAP caused by the PCV13 and PPSV23 serotypes were 50 cases (46.7% of serotyped pneumococcal CAP and 19.8% of pneumococcal CAP), and 83 cases (77.6% of serotyped pneumococcal CAP and 32.9% of pneumococcal CAP), respectively. The most prevalent serotype was 3 (n = 21, 19.6% of serotyped pneumococcal CAP), followed by 19A (n = 10, 9.3% of serotyped pneumococcal CAP) and 11A (n = 10, 9.3% of serotyped pneumococcal CAP). Compared with non-pneumococcal CAP patients, pneumococcal CAP patients were more likely to have a higher CURB-65 scores (P = 0.002). The overall 30-day mortality rate of pneumococcal CAP was higher than that of non-pneumococcal CAP (6.3% versus 5.6%; odds ratio [OR], 1.15; 95% confidence interval [CI], 0.67–1.96), but this trend was reversed in patients aged 65–74 years (4.2% versus 8.6%; OR, 0.47; 95% CI, 0.14–1.54).ConclusionsThe disease burden of PCV13-serotype pneumococcal CAP remains significantly high in Korean adults, particularly among elderly people, even after a high uptake of pediatric PCVs.     

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

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

Lack of effectiveness of 13-valent pneumococcal conjugate vaccination against pneumococcal carriage density in Papua New Guinean infants

BackgroundPapua New Guinea (PNG) introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2014, with administration at 1, 2, and 3 months of age. PCV13 has reduced or eliminated carriage of vaccine types in populations with low pneumococcal carriage prevalence, carriage density and serotype diversity. This study investigated PCV13 impact on serotype-specific pneumococcal carriage prevalence, density, and serotype diversity in PNG infants, who have some of the highest reported rates of pneumococcal carriage and disease in the world.MethodsNasopharyngeal swabs were collected at 1, 4 and 9 months of age from PCV13-vaccinated infants (n = 57) and age-/season-matched, unvaccinated infants (at approximately 1 month, n = 53; 4 months, n = 57; 9 months, n = 52). Serotype-specific pneumococcal carriage density and antimicrobial resistance genes were identified by qPCR and microarray.ResultsPneumococci were present in 89% of swabs, with 60 different serotypes and four non-encapsulated variants detected. Multiple serotype carriage was common (47% of swabs). Vaccine type carriage prevalence was similar between PCV13-vaccinated and unvaccinated infants at 4 and 9 months of age. The prevalence of non-vaccine type carriage was also similar between cohorts, with non-vaccine types present in three-quarters of samples (from both vaccinated and unvaccinated infants) by 4 months of age. The median pneumococcal carriage density was high and similar at each age group (~7.0 log₁₀ genome equivalents/mL). PCV13 had no effect on overall pneumococcal carriage density, vaccine type density, non-vaccine type density, or the prevalence of antimicrobial resistance genes.ConclusionPNG infants experience dense and diverse pneumococcal colonisation with concurrent serotypes from 1 month of age. PCV13 had no impact on pneumococcal carriage density, even for vaccine serotypes. The low prevalence of vaccine serotypes, high pneumococcal carriage density and abundance of non-vaccine serotypes likely contribute to the lack of PCV13 impact on carriage in PNG infants. Indirect effects of the infant PCV programs are likely to be limited in PNG. Alternative vaccines with broader coverage should be considered.     

Pneumonia hospitalization after introduction of pneumococcal conjugate vaccine in Japan: Descriptive study using a nationwide claims database

BackgroundThe pneumococcal conjugate vaccine (PCV) was introduced to children in Japan in February 2010 for PCV7 and February 2013 for PCV13. This study aimed to investigate the changes in child pneumonia hospitalization in Japan, before and after the introduction of PCV.MethodsWe utilized the JMDC Claims Database, an insurance claims database in Japan, with a cumulative population of approximately 10.6 million as of 2022. We extracted data of approximately 3.16 million children below 15 years of age from January 2006 to December 2019, and evaluated the number of pneumonia hospitalizations per 1,000 persons per year. The primary analysis was a comparison of three categories according to PCVs: before PCV7, before PCV13, and after PCV13 (2006–2009, 2010–2012, and 2013–2019). The secondary analysis was an interrupted time series (ITS) analysis, assessing the slope change in pneumonia hospitalizations per month, with PCV introduction as an intervening factor.ResultsThe cases of pneumonia hospitalizations during the study period was 19,920 (0.6 %); 25 % of these were 0–1 years, 48 % were 2–4 years, 18 % were 5–9 years, and 9 % were 10–14 years. Pneumonia hospitalizations per 1000 population was 6.10 before PCV7 and 4.03 after PCV13, representing a 34 % decrease (p < 0.001). The reduction by age group was –30.1 % in 0–1 years, –20.3 % in 2–4 years, –41.7 % in 5–9 years, and –52.9 % in 10–14 years, significant reduction in all groups. ITS analysis showed a further reduction of –0.17 % per month after the introduction of PCV13 than that before PCV7 (p = 0.006).ConclusionOur study estimated 4–6 pneumonia hospitalizations per 1000 pediatric population in Japan, with a 34 % decrease after the introduction of PCV. This study examined the nationwide effectiveness of PCV, further studies are needed in all age groups.     

A systematic review of pneumococcal conjugate vaccine impact on pneumococcal nasopharyngeal colonisation density in children under 5 years of age

BackgroundHigh pneumococcal carriage density has been associated with severe pneumonia in some settings. The impact of pneumococcal conjugate vaccines (PCVs) on pneumococcal carriage density has been variable. The aim of this systematic literature review is to describe the effect of PCV7, PCV10 and PCV13 on pneumococcal colonisation density in children under five years old.MethodsWe included peer reviewed English literature published between 2000 and 2021 to identify relevant articles using Embase, Medline and PubMed. Original research articles of any study design in countries where PCV has been introduced/studied were included. Quality (risk) assessment was performed using tools developed by the National Heart Brain and Lung Institute for inclusion in this review. We used a narrative synthesis to present results.ResultsTen studies were included from 1941 articles reviewed. There were two randomised controlled trials, two cluster randomised trials, one case control study, one retrospective cohort study and four cross sectional studies. Three studies used semiquantitative culture methods to determine density while the remaining studies used quantitative molecular techniques. Three studies reported an increase in density and three studies found a decrease in density among vaccinated compared with unvaccinated children. Four studies found no effect. There was considerable heterogeneity in the study populations, study design and laboratory methods.ConclusionThere was no consensus regarding the impact of PCV on pneumococcal nasopharyngeal density. We recommend the use of standardised methods to evaluate PCV impact on density.     

Significant impact of pneumococcal conjugate vaccination on pediatric parapneumonic effusion: Italy 2006–2018

Etiology and serotyping of parapneumonic effusion (PPE) and the impact of vaccination was evaluated over a 12-year period, before and after the PCV13 introduction (2011) for Italian children From 0 to 16 years of age.Five hundred and two children were evaluated; 226 blood and 356 pleural fluid samples were obtained and tested using Realtime-PCR and culture. In the pre-PCV13 era S. pneumoniae was the most frequent pathogen identified (64/90; 71.1%) with a large predominance of serotypes 1 (42.4%), 3 (23.7%), 7F (5.1%) and 19A (11.9%).The impact of vaccination, calculated on children 0–8 years of age, demonstrated a significant reduction of PPE: with an incidence rate of 2.82 (95%CL 2.32–3.41) in the pre-PCV13 era and an age-standardized rate (ASR) of 0.66 (95% CL 0.37–1.99) in the post-PCV13 era, p < 0.0001. No increase in non-PCV13 serotypes was recorded. S. pneumoniae remained the most frequent pathogen identified in the post-PCV13 era in unvaccinated children with an unchanged serotype distribution: respectively 26/66 (39.4%), 25/66 (37.9%), 5/66 (7.6%), and 4/66 (6.1%) for 1, 3, 7F and 19A. On the other hand 7F and 19A disappeared in vaccinated children and serotype 1 and 3 decreased by 91.8% and 31.5%, respectively. Realtime PCR was significantly more sensitive than culture both in pleural fluid (79.7% vs 12.5%) and in blood (17.8% vs 7.4%).In conclusion, our findings indicate that routine immunization with PCV13 has significantly reduced the burden of childhood PPE in vaccinated children, without increasing PPE due to other bacteria and without serotype shift. Moreover, the impact of PCV13 may be underestimated due to the increase in pneumococcal surveillance in Italy. Data has also shown that Real-time PCR is an essential tool to better define the etiology of PPE and to monitor vaccination plans. Longer studies will be necessary to evaluate the role of herd protection in PPE prevention.     

Reduced risk of serious pneumococcal infections up to 10 years after a dose of pneumococcal conjugate vaccine in established arthritis

BackgroundTo examine rates of serious pneumococcal infections up to 10 years after vaccination with 7-valent conjugated pneumococcal vaccine (PCV7) in patients with arthritis compared to non-vaccinated arthritis patients.MethodsIn total, 595 adult arthritis patients (rheumatoid arthritis; RA = 342, 80 % women and spondylarthropathy; SpA = 253, 45 % women) received one dose of PCV7. Mean age/disease duration were 62/16 and 51/14 years, respectively. For each patient, 4 matched reference subjects were identified.At vaccination, 420 patients received bDMARDs (anti-TNF = 330, tocilizumab = 15, abatacept = 18, anakinra = 1, rituximab = 56). Methotrexate was given as monotherapy (n = 86) or in combination with bDMARD (n = 220). 89 SpA patients received NSAIDs without DMARD.The Skåne Healthcare Register was searched for ICD-10 diagnostic codes for pneumococcal infections (pneumonia, lower respiratory tract infection, septicemia, meningitis, septic arthritis) between January 2000 and December 2018. Frequency of infections after vs before vaccination were calculated (relative risks). Relative risk ratio (RRR) and relative risk reduction (1-RRR) were calculated comparing patients vs non-vaccinated references. Kaplan-Meier and Cox regression were used to investigate time to first event and predictors of infections.ResultsAmong vaccinated RA and SpA patients, there was a significant relative risk reduction of pneumonia and all serious infections; 53% and 46%, respectively. There was no significant difference in time to first pneumonia or all serious infections after vaccination between patients and references. Higher age, RA diagnosis and concomitant prednisolone were associated with infections.ConclusionOne dose of pneumococcal conjugate vaccine may decrease risk of serious pneumococcal infection up to 10 years in patients with arthritis receiving immunomodulating treatment.     

Cost-effectiveness of continuing pneumococcal conjugate vaccination at age 65 in the context of indirect effects from the childhood immunization program

The findings and conclusions in this report are those of the authors and do not necessarily represent the official positon of the Centers for Disease Control and Prevention.BackgroundContinued indirect effects provided by the childhood pneumococcal conjugate vaccine (13-valent pneumococcal conjugate vaccine [PCV13]) program in the United States have decreased disease in the adult population, reducing the potential direct effects of vaccinating older adults.ObjectiveWe examined the incremental cost-effectiveness of continuing to recommend PCV13 in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) at age 65 compared to a strategy that only included a recommendation for PPSV23 at age 65.MethodsWe used a probabilistic model following a cohort of 65 year olds in 2019. We used vaccination coverage and disease incidence estimates for healthy adults and adults with chronic medical conditions. We incorporated continued indirect effects from the childhood PCV13 program on adult disease incidence.ResultsIn the base case scenario, continuing to recommend PCV13 at age 65 cost $561,682 per quality-adjusted life year (QALY) gained. In a scenario where PPSV23 provided modest protection against non-invasive pneumococcal pneumonia, costs increased to $2.3 million per QALY. These estimates are larger than our prior estimates for cost-effectiveness of this recommendation in the context of predicted indirect effects due to new data indicating PCV13 provided limited impact on serotype 3, the major cause of the remaining PCV13-type disease. Under our prior assumptions about PCV13 effectiveness against serotype 3 disease, the cost of continuing the recommendation is $207,607 per QALY.ConclusionIndirect effects from the childhood PCV13 program have dramatically increased the cost per QALY of continuing to recommend PCV13 at age 65 after only a few years.     

Prevalence,capsular types,antimicrobial resistance and risk factors associated with pneumococcal carriage among children after long-term 10-valent pneumococcal conjugate vaccine use in Brazil

BackgroundThe 10-valent pneumococcal conjugate vaccine (PCV10) was introduced for childhood vaccination in Brazil’s National Immunization Program in 2010. After nine years of PCV10 use, we investigated the carriage prevalence, capsular types, antimicrobial resistance and risk factors among children living in Niterói city, RJ, Brazil.MethodsBetween September and December 2019, we conducted a cross-sectional study and recruited children under 6 years of age. Antimicrobial susceptibility was evaluated by the disk-diffusion method and MICs to beta-lactams and macrolides were determined by E-test®. Capsular types were deduced by multiplex PCR. Logistic regression was used to predict risk factors for pneumococcal carriage.ResultsSeventy-five (17.4%) of the 430 children were pneumococcal carriers. The most frequent capsular types were 6C/D (14.7%), 11A/D (13.3%), and 23B (9.3%). PCV10 serotypes represented 5.3%. All isolates were susceptible to levofloxacin, linezolid, rifampicin, and vancomycin. Penicillin non-susceptible pneumococci (PNSP) made up 37.3%, with penicillin and ceftriaxone MICs ranging from 0.12 to 4.0 μg/ml and 0.064–4.0 μg/ml, respectively. Of the 19 (25.3%) erythromycin-resistant (ERY-R) isolates (macrolide MICs of 6 to >256 μg/ml), most had the cMLS_B phenotype (84.2%) and carried the erm(B) gene (73.7%). We detected 17 (22.6%) multidrug-resistant (MDR) isolates, strongly associated with serotype 6C/D. Presence of any symptoms, chronic diseases, childcare center attendance, living with young siblings, slum residence, and unstable income were predictors of pneumococcal carriage.ConclusionsLong-term universal childhood use of PCV10 has nearly eliminated carriage with PCV10 serotypes, but the high frequency of MDR isolates, especially associated with serotype 6C/D, remains a concern. Replacing PCV10 with PCV13 should reduce the proportion of ERY-R isolates and PNSP by at least 14% and 18%, respectively.     

A trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in populations of adults ≥65 years of age with different prior pneumococcal vaccination

IntroductionA 20-valent pneumococcal conjugate vaccine, PCV20, was developed to expand protection against vaccine-preventable pneumococcal disease. PCV20 contains the components of the 13-valent pneumococcal conjugate vaccine, PCV13, and includes capsular polysaccharide conjugates for 7 additional serotypes. Thus, PCV20 may cover those additional serotypes in individuals previously vaccinated with PCV13 or provide benefits of immunization with a conjugate vaccine to individuals previously immunized with a pneumococcal polysaccharide vaccine. This study described the safety and immunogenicity of PCV20 in adults ≥65 years of age with prior pneumococcal vaccination.MethodsThis phase 3, multicenter, randomized, open-label study was conducted in the United States and Sweden. Adults ≥65 years of age were enrolled into 1 of 3 cohorts based on their prior pneumococcal vaccination history (23-valent pneumococcal polysaccharide vaccine [PPSV23], PCV13, or both PCV13 and PPSV23). Participants were randomized 2:1 within their cohort to receive a single dose of PCV20 or PCV13 in those with prior PPSV23 only, and PCV20 or PPSV23 in those with prior PCV13 only; all participants with prior PCV13 and PPSV23 received PCV20. Safety was assessed by prompted local reactions within 10 days, systemic events within 7 days, adverse events (AEs) within 1 month, and serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) within 6 months after vaccination. Immune responses 1 month after PCV20 were assessed.ResultsThe percentages of participants reporting local reactions, systemic events, and AEs after PCV20 administration were similar across cohorts and comparable with the PCV13 and PPSV23 control groups. SAE and NDCMC rates were low in all groups. Robust immune responses, including opsonophagocytic antibody responses, to the 20 vaccine serotypes were observed 1 month after PCV20 regardless of prior pneumococcal vaccination.ConclusionsPCV20 was well tolerated and immunogenic in adults ≥65 years of age previously vaccinated with different pneumococcal vaccine regimens.Clinicaltrials.gov NCT03835975.     

Long-term effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae in children in Brazil

Brazil introduced the 10-valent pneumococcal vaccine (PCV10) to the routine national immunization program (NIP) in March 2010. In 2017, we investigated the effects of PCV10 on nasopharyngeal carriage of vaccine-types (VT) and non-vaccine-types (NVT) of Streptococcus pneumoniae (Spn) among children living in São Paulo city. We also compared the prevalence of VT and NVT with previous carriage surveys performed in 2010 (baseline) and 2013.MethodThe carriage survey was conducted among 531 children, aged 12 months to <24 months, recruited from public Primary Health Units during the immunization campaign, using previous surveys methodology, except for qPCR, which was performed in the 2017 survey only.ResultsNo statistical difference was found in the prevalence of Spn either by culture (59.7%) or by qPCR (61.2%). Spn carriage increased from 40.3% (baseline) to 59.7% (2017 survey) (p < 0.001). Colonization by VT isolates significantly decreased by 90.9% (19.8–1.8%) and 95.5% (19.8–0.9%) in the 2013 and 2017 surveys, respectively, compared to that at baseline. NVT isolates increased significantly by 128% (19.6–44.8%) and 185% (19.6–55.9%) in the respective post-PCV10 surveys, most led to high prevalence of serotypes 6C (27%), 15B (9.8%), 19A (9.2%), 15A (6.0%), and 16F (5.7%). In 2017, reduction in serotype 6A (4.2–0.6%, p < 0.001) and increase in serotype 19A (1.8–6.0%, p = 0.001) were found; serotype 3 isolate was not detected in the present survey. We identified the emergence of 19A isolates CC320, associated with high penicillin (MIC ≥ 2.0 mg/L) and cefotaxime (MIC ≥ 1.0 mg/L) values.ConclusionAfter 7 years of PCV10 introduction in the NIP, colonization by VT among toddlers decreased substantially to a residual level, along with substantial serotype replacement by novel serotypes not present in any current conjugated pneumococcal vaccine and serotype 19A. The present findings can assist policy decisions in Brazil.     

Immunogenicity and safety of 7-valent pneumococcal conjugate vaccine (PCV7) in children aged 2–5 years in China

BackgroundThe widespread use of pneumococcal conjugate vaccines (PCVs) has significantly decreased pneumococcal disease worldwide. However, China has not adopted PCVs in their national immunization schedules and had only approved these vaccines for children aged 2–15 months by 2020.MethodsIn an open-label trial, enrolled healthy children aged 2–5 years old were randomized 1:1 and divided into a 7-valent pneumococcal conjugate vaccine (PCV7) group and a Haemophilus influenzae type b conjugate vaccine (Hib) group. Children in the PCV7 group received a single dose of PCV7, and the Hib group received a single dose of Hib vaccine. Blood samples were collected before and 6 months after vaccination. Immunogenicity and safety of PCV7 were assessed at prespecified time points.ResultsSix months after a single dose of PCV7, children in the PCV7 group for all 7 serotypes, IgG mean concentrations (GMCs) and opsonophagocytic geometric mean titres (GMTs) were significantly higher (P < .001) than at baseline, and the proportion of IgG ≥ 0.35 µg/mL ranged from 90.0% to 100%. Although the antibody level increased with age, preexisting antibodies did not induce hyporesponsiveness to PCV7. In the Hib group, the antibody levels were not significantly different or had changed slightly at 6 months. PCV7 was well tolerated in all age groups, and no serious adverse events (AEs) emerged during this study.ConclusionsA single dose of PCV7 was immunogenic and safe for Chinese children aged 2–5 years, and the preexisting antibodies against the PCV7 serotypes did not change the response to vaccination. The findings supported the effectiveness of PCV7 in this age group. PCVs with broader serotype coverage are expected to expand pneumococcal disease protection.