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.     

Vaccination rates and adherence in premature infants before and after pneumococcal conjugate vaccine schedule change for term infants – A claims database analysis in Germany

BackgroundIn 2015, the German Standing Committee on Vaccination (STIKO) changed the pneumococcal conjugate vaccination (PCV) schedule for mature infants from a 3+1 scheme (2, 3, 4, and 11–14 months of age) to a 2+1 scheme (2, 4, and 11–14 months of age). For premature infants, the 3+1 scheme remained. The aim of this study was to assess vaccination rates, completeness, and timeliness for PCV in premature infants before and after the modified recommendation.MethodsA retrospective claims data analysis using the “Institut für angewandte Gesundheitsforschung Berlin” Research Database was conducted. Premature infants born in 2013 and 2016 with an individual follow-up of 24 months were included. Hexavalent combination (HEXA) vaccination with a consistent 3+1 recommendation for mature and premature infants was analyzed as reference vaccination.ResultsAfter 24 months, the PCV rate for at least one dose remained stable in premature newborns of 2016 compared to 2013, while the HEXA vaccination rate increased slightly. However, a significant decrease of a completed PCV schedule (4 doses) in premature infants was noted, whereas the completeness of HEXA vaccination did not change. The timeliness of PCV in premature newborns increased for the first and the booster PCV, while the timeliness of HEXA immunization did not change from 2013 to 2016.ConclusionAlthough STIKO still recommends a 3+1 PCV schedule for premature infants in Germany, premature infants were vaccinated according to the changed recommendations for mature born infants. A substantial share of premature infants remained unvaccinated, and their vaccinations were often delayed.     

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.     

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A phase III study (V114-033)

BackgroundThis 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.MethodsHealthy 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.ResultsOverall, 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).ConclusionIn 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.     

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.     

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.     

Safety,tolerability, and immunogenicity of V114 pneumococcal vaccine compared with PCV13 in a 2+1 regimen in healthy infants: A phase III study (PNEU-PED-EU-2)

BackgroundThis 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.MethodsHealthy 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.Results1191 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.ConclusionA 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.     

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.     

Effect of pneumococcal conjugate vaccine on prevalence of otitis media with effusion among children in Vietnam

PurposeOtitis media with effusion (OME) is common in young children and is associated with Streptococcus pneumoniae infection. We aimed to determine the impact of pneumococcal conjugate vaccine (PCV) introduction on the prevalence of OME and OME associated with vaccine-type (VT) or non-VT.MethodsPopulation-based cross-sectional surveys were conducted in pre- (2016) and post-PCV periods (2017, 2018, and 2019) at selected communes in Nha Trang, Vietnam. For each survey, we randomly selected 60 children aged 4–11 months and 60 aged 14–23 months from each commune. Nasopharyngeal sample collection and tympanic membrane examination by digital otoscope were performed. S. pneumoniae was detected and serotyped by lytA qPCR and microarray. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using Firth’s logistic regression, stratified by age group.ResultsOver the four surveys, 2089 children had a bilateral ear examination. Compared to pre-PCV, the prevalence of OME reduced in 2018 (OR 0.51, 95 %CI 0.28–0.93) and in 2019 (OR 0.53, 95 %CI 0.29–0.97) among the <12-month-olds, but no significant reduction among the 12–23-month-olds. The prevalence of OME associated with VT pneumococcus decreased in 2018 and 2019 (2018: OR 0.14, 95 %CI 0.03–0.55; 2019: OR 0.20, 95 %CI 0.05–0.69 in the <12-months-olds, 2018: OR 0.05, 95 %CI 0.00–0.44, 2019: OR 0.41, 95 %CI 0.10–1.61 in the 12–23-months-olds). The prevalence of OME associated with non-VT pneumococcus increased in the 12–23-month-olds in 2017 (OR 3.09, 95 %CI 1.47–7.45) and returned to the pre-PCV level of prevalence in 2018 and 2019 (OR 0.94, 95 %CI 0.40–2.43 and 1.40, 95 %CI 0.63–3.49).ConclusionPCV10 introduction was associated with a reduction of OME prevalence in infants but not in older children.     

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.     

Incidence trends of parapneumonic pleural effusions/empyema in children 2009 to 2018 from health insurance data: Only temporal reduction after the introduction of PCV13

BackgroundRecently, emergence of a higher proportion of serotype 3 in children with parapneumonic pleural effusion/empyema (PPE/PE) were observed in Germany despite general immunization with 13-valent pneumococcal conjugate vaccine (PCV13) since 2009. The impact of PCV13 on the overall incidence of PPE/PE in children is unclear.MethodsAnnual incidence of PPE/PE in children were determined using secondary health care data for 2009–2018, provided by the Barmer statutory health insurer, serving about 11% of the German population. Temporal trends of the annual incidence were modelled applying generalized additive models.ResultsOverall incidence of PPE/PE in children ( ≤18 years) in the ten-year observation period was 18.17 per 100,000. The 0–1 year olds showed the highest incidence (43.09 per 100 000). PPE/PE incidence decreased from 2009 until 2013 (nadir 2013 was 15.36; 95% CI: 13.41–17.31). Since 2013, the data show an annual increase. The nadir of incidence for the 2–5 year olds (15.85; 95% CI: 11.27–20.43) and the 6–18 year olds (12.29; 95% CI: 10.23–14.36) was also in 2013, whereas for the 0–1 year olds it was found in 2014 (32.66; 95% CI: 23.79–41.54). The GAM across all age groups showed a nearly U-shaped curve between time and incidence of PPE/PE by calendar year (p-non-linear = 0.0017). The model confirms the nadir in the year 2013.DiscussionWe found a nonlinear temporal trend of PPE/PE incidence in children with a decrease from 2009 to 2013 and a subsequent increase until 2018. The former might be explained by a quasi elimination of serotype 1, the latter by an increase in the proportion of serotype 3 as demonstrated in German surveillance data of pediatric PPE/PE cases generated during the same observation period.     

The increasing age of respiratory syncytial virus-related hospitalisation during COVID-19 pandemic in Lyon was associated with reduced hospitalisation costs

BackgroundPreventive measures applied during the COVID-19 pandemic have modified the age distribution, the clinical severity and the incidence of Respiratory Syncytial Virus (RSV) hospitalisations during the 2020/21 RSV season. The aim of the present study was to estimate the impact of these aspects on RSV-associated hospitalisations (RSVH) costs stratified by age group between pre-COVID-19 seasons and 2020/21 RSV season.MethodsWe compared the incidence, the median costs, and total RSVH costs from the national health insurance perspective in children < 24 months of age during the COVID-19 period (2020/21 RSV season) with a pre-COVID-19 period (2014/17 RSV seasons). Children were born and hospitalised in the Lyon metropolitan area. RSVH costs were extracted from the French medical information system (Programme de Médicalisation des Systémes d’Information).ResultsThe RSVH-incidence rate per 1000 infants aged < 3 months decreased significantly from 4.6 (95 % CI [4.1; 5.2]) to 3.1 (95 % CI [2.4; 4.0]), and increased in older infants and children up to 24 months of age during the 2020/21 RSV season. Overall, RSVH costs for RSVH cases aged below 2 years old decreased by €201,770 (31 %) during 2020/21 RSV season compared to the mean pre-COVID-19 costs.ConclusionsThe sharp reduction in costs of RSVH in infants aged < 3 months outweighed the modest increase in costs observed in the 3–24 months age group. Therefore, conferring a temporal protection through passive immunisation to infants aged < 3 months should have a major impact on RSVH costs even if it results in an increase of RSVH in older children infected later in life. Nevertheless, stakeholders should be aware of this potential increase of RSVH in older age groups presenting with a wider range of disease to avoid any bias in estimating the cost-effectiveness of passive immunisation strategies.     

Non-immunization associated with increased risk of sudden unexpected death in infancy: A national case–control study

ObjectiveIn the context of vaccine scepticism, our study aimed to analyse the association between immunization status and the occurrence of sudden unexpected death in infancy (SUDI).Study design: A multi-centre case–control study was conducted between May 2015 and June 2017 with data from the French national SUDI registry (OMIN) for 35 French regional SUDI centres. Cases were infants under age 1 year who died from SUDI and who were registered in OMIN. Controls, matched to cases by age and sex at a 2:1 ratio, were infants admitted to Nantes University Hospital. All immunization data for diphtheria (D), tetanus (T), acellular pertussis (aP), inactivated poliovirus (IPV), Haemophilus influenzae b (Hib), hepatitis B (HB) and 13-valent pneumococcal conjugate vaccine (PCV13) were collected by a physician. Cases and controls were considered immunized if at least one dose of vaccine was administered.ResultsA total of 91 cases and 182 controls were included. The median age was 131 days (interquartile range 98–200.0) and the sex ratio (M/F) was about 1.1. For all vaccines combined (D-T-aP-IPV-Hib and PCV13), 22 % of SUDI cases versus 12 % of controls were non-immunized, which was significantly associated with SUDI after adjustment for potential adjustment factors (adjusted odds ratio 2.01 [95 % confidence interval 1.01–3.98, p = 0,047]).ConclusionsNon-immunization for D-T-aP-IPV-Hib-HB and PCV13 was associated with increased risk of SUDI. This result can be used to inform the general public and health professionals about this risk of SUDI in case of vaccine hesitancy.     

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.     

Timeliness of immunisations in preterm infants in the Netherlands

BackgroundIn the Netherlands, preterm infants receive the immunisations at the same chronological age as recommended for term infants without correction for gestational age (GA). The aim of this paper was to describe the timeliness of the routine Dutch national immunisation schedule in preterm infants in their first year of life and to evaluate possible determinants of delay.MethodsPreterm infants were prospectively recruited between October 2015 and October 2017 and stratified according to GA (<28, 28–32 and 32–36 weeks). Data from the baseline parental questionnaire, monthly parental questionnaires and medical records were used to determine the immunisation age and proportion of infants timely receiving the first immunisations (between 42 and 63 days). Results were compared between the GA and birth weight (BW) groups. Determinants associated with timeliness of immunisation were studied by multivariate logistic regression analysis.ResultsTimely start of immunisation occurs in 60.5% of preterm infants in the Netherlands. The proportion of infants receiving the first immunisation on time was lowest for the group with GA <28 weeks (37%). The mean age of the first immunisation across all GA groups was 62.7 days (range 33–118) and differed significantly between GA group <28 weeks and the other two GA groups of 28–32 and 32–36 weeks (p < 0.001). Similar results were seen when stratified by BW. Multivariate analysis showed that low socioeconomic status (SES) and prolonged hospitalisation beyond 37 weeks each negatively influenced timeliness of the first immunisation.ConclusionThese findings indicate that start of immunisations was often delayed in prematures and differs for different GA groups, being lowest (37%) in infants <28 weeks GA. Lower SES and prolonged hospital stay beyond 37 weeks GA are important determinants of timeliness. Efforts to improve timeliness should focus most on counselling parents in lower SES.     

Effects of rotavirus vaccine on all-cause acute gastroenteritis and rotavirus hospitalizations in Israel: A nationwide analysis

BackgroundIn December 2010, the pentavalent rotavirus vaccine (RotaTeq) was added to the national immunization program in Israel. The study aim was to examine national reductions in all-cause acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) hospitalizations among children aged 0–59 months following the introduction of universal rotavirus immunization in Israel.MethodsWe extracted data from the Israel National Hospital Discharge Database. Hospitalization rates were calculated by dividing the annual number of all-cause AGE and RVGE hospitalizations by the number of children aged 0–59 months residing Israel. To assess rate reductions, we compared the mean hospitalization rate for the pre-vaccine years (2002–2008) with that for the universal vaccination years (2011–2017). Interrupted time-series analyses were undertaken. During 2008–2010 rotavirus vaccines were partially available.ResultsA total of 131,116 AGE hospitalizations were reported, of which 13,111 (10.0%) were coded as RVGE hospitalizations. The average annual all-cause AGE hospitalization rate during the pre-vaccine period was 147.9 (95% CI 146.7–149.0) per 10,000 children aged 0–59 months, and declined by 38.7–53.0% during the universal vaccination years. The average annual pre-vaccine RVGE hospitalization rate was 16.9 (95% CI 16.5–17.3) per 10,000 children, and declined by 89.1% during 2016–2017.Findings from interrupted time-series analyses showed significant impact of introducing universal rotavirus immunization on the declines of all-cause AGE and RVGE hospitalizations rates. A multivariable Autoregressive Integrated Moving Average model showed that the variable “immunization period” was a significant predictor of RVGE hospitalizations (t = 7.3, p < 0.001) for the universal vaccination years.The declines in hospitalizations rates of all-cause AGE were lower among Arab children compared to Jewish children, but the declines in RVGE rates were similar between the groups.ConclusionsNational hospitalization data demonstrated substantial and consistent reductions in all-cause AGE and RVGE hospitalizations following the implementation of universal rotavirus vaccination program.     

Pertussis burden and acellular pertussis vaccine effectiveness in high risk children

BackgroundPertussis hospitalisation is more common among infants born prematurely, who have significant comorbidities, or are Indigenous, but acellular pertussis (aP) vaccine effectiveness (VE) estimates in these sub-groups are lacking. We measured aP VE by Indigenous status, and policy-relevant categories of prematurity and comorbidity, in a population-based Australian cohort.MethodsPerinatal, disease notification, hospitalisation, mortality, and vaccination data were linked to birth records in two Australian states (Western Australia and New South Wales) 2001–2012, with follow-up to the end of 2013. Children followed to 18 months of age were stratified by Aboriginality, prematurity (<32 vs 32–<37 weeks gestation) and comorbidities identified from hospital discharge coding. Rates, rate ratios and VE were calculated for first episode of hospitalised and non-hospitalised pertussis notifications using adjusted Cox proportional hazards models.ResultsAmong >1,300,000 children, 63,867 (4·9%) were Aboriginal, 47,721 (3·6%) had at least one comorbidity and 3,771 first episodes of notified pertussis occurred <18 months of age; of these, 1,207 (32.0%) had an associated pertussis-coded hospitalisation. For hospitalised pertussis in Aboriginal and non-Aboriginal children, there was significant protection post dose 1 (VE 51% v 25%), 2 (VE 69% v 74%) and 3 (VE 76% v 80%). For children with co-morbidities, VE for hospitalised pertussis was low and non-significant post dose 1 (0%) and 2 (30%). Post dose 3, VE was significant for hospitalised pertussis (70%; 95% CI 29–87) but not for non-hospitalised pertussis (24%; 95% CI ?49 to 61).ConclusionsFor most Aboriginal and non-Aboriginal children, improved timeliness of current infant doses and higher antenatal coverage should further improve protection against pertussis of any severity. For children at highest risk of severe pertussis (born <32 weeks gestation or with significant medical comorbidities), our data suggest that additional measures-such as extra doses of pertussis-containing vaccines and/or vaccines with improved immunogenicity–are needed for protection.     

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 phase 3, randomized,controlled, open-label study to evaluate the persistence up to 5 years of 1 or 2 doses of meningococcal conjugate vaccine MenACWY-TT given with or without 13-valent pneumococcal conjugate vaccine in 12–14-month-old children

BackgroundImmunogenicity and safety up to 5 years after administration of 1 or 2 doses of quadrivalent meningococcal serogroup A, C, W, and Y tetanus toxoid conjugate vaccine (MenACWY-TT) given alone or with 13-valent pneumococcal conjugate vaccine (PCV13) in children was investigated.MethodsThis phase 3 study randomized healthy 12–24-month-olds to MenACWY-TT at Month 0 (ACWY1d), MenACWY-TT at Months 0 and 2 (ACWY2d), MenACWY-TT and PCV13 at Month 0 (Co-Ad), or PCV13 at Month 0 and MenACWY-TT at Month 2 (PCV13/ACWY). Immune responses 1, 3, and 5 years after primary vaccination were evaluated with serum bactericidal activity using rabbit complement (rSBA) titers ≥ 1:8 and geometric mean titers (GMTs). Evaluation of serious adverse events up to 5 years after primary vaccination are reported.ResultsOf the 802 children randomized in the study, 619 completed the study through Year 5. Immune responses after vaccination declined over time but were higher 5 years after vaccination compared with levels before vaccination. At Year 5, the percentages of children with rSBA titers ≥ 1:8 across all serogroups were 20.5 %?58.6 %, 28.4 %?65.8 %, 23.9 %?52.8 %, and 19.4 %?55.8 % in the ACWY1d, ACWY2d, Co-Ad, and PCV13/ACWY groups, respectively. Comparable antibody persistence at Year 5 was observed for participants receiving 1 or 2 doses of MenACWY-TT, although GMTs were elevated in those who received 2 versus 1 dose. The percentage of children with protective antibody titers at Year 5 was similar in participants who received PCV13 and MenACWY-TT compared with that observed for participants who only received 1 or 2 MenACWY-TT doses. No new safety concerns were identified during the study period.ConclusionAntibody responses persisted in the majority of children up to 5 years after primary vaccination with MenACWY-TT administered in a 1- or 2-dose regimen with or without PCV13, with no new safety concerns identified.ClinicalTrials.gov Identifier NCT01939158; EudraCT number 2013–001083-28.     

Impact of the National Perinatal Hepatitis B Prevention Programme in the Republic of Korea: A retrospective registry-based cohort study

IntroductionHepatitis B is a major preventable cause of morbidity and mortality from chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. We aimed to evaluate the performance and outcomes of the Korean Perinatal Hepatitis B Prevention Programme (PHBPP) and to investigate the impact of the current post-exposure immunoprophylaxis protocol.MethodsA retrospective cohort study was performed based on electronic data registry of infants born to hepatitis B virus (HBV)-infected mothers between July 2002 and 2013.ResultsDuring the study period, 159,983 Korean infants were registered with the PHBPP, with an overall programme coverage of 92.8%. Despite receiving timely post-exposure immunoprophylaxis, 8.6% of infants born to mothers aged <25 years and hepatitis B e antigen (HBeAg)-positive, and 0.7% of infants born to mothers aged ≥25 years and HBeAg-negative were infected. An estimated 14,123 infants were directly protected from perinatal HBV transmission by the PHBPP during the 11.5-year period, at a cost of 1157 US dollars per case averted. The incidence of paediatric hepatocellular carcinoma declined dramatically during the period.ConclusionsA substantial number of infants have been prevented from hepatitis B since the PHBPP was launched in the Republic of Korea. Continued efforts to promote the programme, an integrated approach to maximising its coverage, a risk-stratified strategy, and innovations in logistics could further reduce perinatal HBV transmission.