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Pneumococcal conjugate vaccine 10 (PCV10) and pneumococcal conjugate vaccine 13 (PCV13), are used in childhood immunization programs worldwide, but direct comparisons of impacts against invasive pneumococcal disease (IPD) in equivalent populations have not been performed. We compared the vaccines (prevaccination 2007-2009 vs postvaccination 2013-2016) in Sweden, where the 21 counties use either PCV10 or PCV13 (introduced 2009-2010). All IPD episodes (n = 16992) were recorded in Sweden during 2005-2016. Of 14 186 isolates from 2007-2016, 13 468 (94.9%) were characterized with serotyping and 12 235 (86.2%) with antibiotic susceptibility. Poisson models assessed changes in incidence over time. Invasive pneumococcal disease incidences decreased between 2005 and 2016 in vaccinated children (by 68.5%), and in the whole population (by 13.5%), but not among the elderly (increased by 2%) due to a substantial increase in nonvaccine types (NVTs). In 2016, NVTs constituted 72% of IPD cases in the elderly. Serotype 6A declined in PCV10 and PCV13 counties, whereas serotype 19A increased in PCV10 counties. There was no effect against serotype 3. Cross-protection was found between 6B and 6A but not between 19F and 19A. Serotype 6C increased in PCV10 counties, but not in PCV13 counties, suggesting cross-protection with 6A, which is included in PCV13. In the elderly, the increase in NVTs, excluding 6C, was more pronounced in PCV13 counties. The overall impact of IPD incidences was not statistically different irrespective of vaccine used. The incidence of serotypes, where the effect of the vaccines differed, will influence the cost-effectiveness of which vaccine to use in immunization programs. The dominance of NVTs suggests a limited effect of current pediatric PCVs against IPD in the elderly.

Brazil introduced 10-valent pneumococcal conjugate vaccine (PCV10) into its immunization program in 2010. We assessed antimicrobial susceptibility of Streptococcus pneumoniae (Spn) obtained from a national surveillance system for invasive pneumococcal diseases (IPD) before/after PCV10 introduction. Antimicrobial non-susceptible isolates were defined as intermediate or resistant. Minimum inhibitory concentrations (MICs) to penicillin and ceftriaxone were analyzed by year. Antimicrobial susceptibility rates were assessed for each three-year-period using the pre-PCV10-period as reference. Susceptibility of vaccine-types was evaluated for 2017–2019. 11,380 isolates were studied. Spn with penicillin ≥ 0.125 mg/L and ceftriaxone ≥ 1.0 mg/L decreased in the three-years after PCV10 introduction (2011–2013: penicillin, 28.1–22.5%; ceftriaxone, 11.3%-7.6%) versus pre-PCV10-years (2007–2009: penicillin, 33.8–38.1%; ceftriaxone, 17.2%-15.6%). After 2013, the proportion of Spn with those MICs to penicillin and ceftriaxone increased to 39.4% and 19.7% in 2019, respectively. Non-susceptibility to penicillin and ceftriaxone increased in 2014–2016, and again in 2017–2019 especially among children < 5 years with meningitis (penicillin, 53.9%; ceftriaxone, 28.0%); multidrug-resistance reached 25% in 2017–2019. Serotypes 19A, 6C and 23A were most associated with antimicrobial non-susceptibility. Antimicrobial non-susceptible Spn decreased in the three-years after vaccination but subsequently increased and was associated with non-PCV10-types. Antimicrobial susceptibility surveillance is fundamental for guiding antibiotic therapy policies.

•Since 2010, PCV10 and PCV13 became available for use in children.•This meta-analysis assessed the impact PCV10 and PCV13 in pneumonia hospitalization among children.•Novel PCVs reduced hospitalization for pneumonia in children <24months and 24–59months.•Reduction was more pronounced for radiologically confirmed pneumonia with respect to clinically confirmed pneumonia.•None of the studies included in this meta-analysis had been designed to directly compare the impact of PCV10 and PCV13. This systematic review and meta-analysis aimed at summarizing available data on the impact of PCV10 and PCV13 in reducing the incidence of CAP hospitalizations in children aged <5years. A systematic search of the literature was conducted. We included time-series analyses and before-after studies, reporting the incidence of hospitalization for pneumonia in the periods before and after the introduction of PCV10 or PCV13 into the immunization program. Pooled estimates of Incidence Rate Ratio (IRR) were calculated by using a random-effects meta-analytic model. Results were stratified according to age-groups (<24months and 24–59months) and case definitions of pneumonia (clinically and radiologically confirmed pneumonia). A total of 1533 potentially relevant articles were identified. Of these, 12 articles were included in the analysis. In children aged <24months, the meta-analysis showed a reduction of 17% (95%CI: 11–22%, p-value<0.001) an of 31% (95%CI: 26–35%, p-value<0.001) in the hospitalization rates respectively for clinically and radiologically confirmed pneumonia, respectively, after the introduction of the novel PCVs. In children aged 24–59months, the meta-analysis showed a reduction of 9% (95%CI: 5–14%, p-value<0.001) and of 24% (95%CI: 12–33%, p-value<0.001) in the hospitalization rates for clinically and radiologically confirmed pneumonia, respectively, after the introduction of the novel PCVs. High heterogeneity was detected among studies evaluating the hospitalization rate for clinically and radiologically confirmed pneumonia. The results of this study revealed a significant impact of PCV10 and PCV13 in reducing the hospitalizations for pneumonia, particularly in children aged <24months and for radiologically confirmed disease. Further appropriately designed studies, comparing the impact of PCV10 and PCV13, are needed in order to obtain solid data on which to establish future immunization strategies.

•Robust PCV13 effect against 6C invasive disease and carriage in children.•PCV13 effects against 6A and 6C invasive disease in children were nearly identical.•Indirect effect of PCV13 in adults of countries with rapid PCV7-PCV13 transition.•No evidence of PCV10 effect against 6C invasive disease or carriage.•Effect of 6A-containing PCVs against 6C should be considered in decision-making. The cross-protection of pneumococcal conjugate vaccines (PCV) against serotype 6C is not clearly documented, although 6C represents a substantial burden of pneumococcal disease in recent years. A systematic review by the World Health Organization that covered studies through 2016 concluded that available data were insufficient to determine if either PCV10 (which contains serotype 6B but not 6A) or PCV13 (containing serotype 6A and 6B) conferred protection against 6C. We performed a systematic review of randomized controlled trials and observational studies published between January 2010 – August 2022 (Medline/Embase), covering the direct, indirect, and overall effect of PCV10 and PCV13 against 6C invasive pneumococcal disease (IPD), non-IPD, nasopharyngeal carriage (NPC), and antimicrobial resistance (AMR). Of 2548 publications identified, 112 were included. Direct vaccine effectiveness against 6C IPD in children ranged between 70 and 85 % for ≥ 1 dose PCV13 (n = 3 studies), was 94 % in fully PCV13 vaccinated children (n = 2), and −14 % for ≥ 1 dose of PCV10 (n = 1). Compared to PCV7, PCV13 efficacy against 6C NPC in children was 66 % (n = 1). Serotype 6C IPD rates or NPC prevalence declined post-PCV13 in most studies in children (n = 5/6) and almost half of studies in adults (n = 5/11), while it increased post-PCV10 for IPD and non-IPD in all studies (n = 6/6). Changes in AMR prevalence were inconsistent. In contrast to PCV10, PCV13 vaccination consistently protected against 6C IPD and NPC in children, and provided some level of indirect protection to adults, supporting that serotype 6A but not 6B provides cross-protection to 6C. Vaccine policy makers and regulators should consider the effects of serotype 6A-containing PCVs against serotype 6C disease in their decisions.

The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in March 2015 in Bangladesh. In this study, we aimed to estimate the impact of PCV10 on invasive pneumococcal disease (IPD) identified by blood cultures and severe pneumonia identified clinically and its effectiveness on invasive disease caused by vaccine serotypes. We conducted population-based surveillance among children aged 2- <24 months between April 2012 through March 2019 in Mirzapur, a rural sub-district of Bangladesh. We compared incidence of IPD and severe pneumonia before (April 2012 to March 2015) and after (April 2015 to March 2019) the introduction of PCV10. Vaccine effectiveness was measured using an indirect cohort analysis of data from four sentinel sites in which PCV10 vaccination status was compared between children with IPD caused by vaccine serotype vs. non-vaccine serotypes. We identified 24 IPD cases by blood culture and 1,704 severe pneumonia hospitalizations during the surveillance period. IPD incidence in under-2-year-old children fell 25 % (95 % CI: −1.2 % to 76 %; p-value = 0.59) from 106 cases per 100,000 child-years at baseline to 79.3 in April 2018- March 2019. Vaccine serotype-IPD incidence was lower (77 % reduction, 95 % CI: −0.45 % to 96 %; p-value = 0.068) in April 2018 - March 2019 than in the pre-vaccine period (85.7 cases to 19.8/100,000 child-years). A significant decline of 54.0 % (95 % CI: 47.0 % to 59.0 %; p-value < 0.001) was observed in hospitalizations due to severe pneumonia. From indirect cohort analysis, the effectiveness of PCV10 against vaccine serotype IPD was 37 % (95 % CI: −141.0 % to 83.5 %; p = 0.5) after the 1st dose and 63.1 % (95 % CI: −3.3 % to 85.9 %, p = 0.0411) after the 2nd or the 3rd dose. This study demonstrates that PCV10 introduction prevented hospitalizations with severe pneumonia and provided individual protection against vaccine serotypes.

In 2019, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in the Croatian immunization programme, a first for this European PCV-naïve country. This study aimed to evaluate the impact of PCV10 on pneumococcal serotype distribution among asymptomatic children and children with pneumonia and/or acute otitis media. Cross-sectional studies were conducted before and after the PCV10 introduction, with nasopharyngeal swabs collected from 1500 healthy children under 48 months of age. An additional 324 children under 18 years with pneumonia and/or acute otitis media, from whom Streptococcus pneumoniae was isolated, were also included. Isolates were identified by conventional methods, serotyped by Quellung reaction, and tested for antimicrobial susceptibility using disk diffusion and gradient test methods. We report prevalence, absolute risk (prevalence) difference (RD) and relative risk (prevalence) ratio (RR) differences between exposed and control children. Carriage prevalence among healthy children increased from 19.9% to 28.7%, primarily due to a rise in non-vaccine serotypes (NVT). Adjusted probabilities for serotypes 6C (RR 3.18; 95% CI, 1.43–7.06), 11A (RR 2.8; 95% CI, 1.22–6.39), 19A (RR 4.18; 95% CI, 1.18–14.9) and 23A (RR 3.93; 95% CI, 1.87–8.24) were significantly higher in healthy exposed children. Prevalences of these serotypes were also higher in exposed children with pneumonia/acute otitis media. In this cohort, serotype 3 increased (RR 4.6; 95% CI, 2.02–10.3), becoming the leading post-PCV10 isolate in the overall studied population. Serotypes 3 and 19A were almost entirely responsible for complicated pneumonia cases for which the probability increased by 21-fold. Antimicrobial susceptibility remained similar across periods. In the early post-vaccine period significant increase of PCV10 vaccine-related serotypes (6C, 19A) was observed. Continued monitoring is also essential due to concerning rise of serotype 3 in patients with mucosal infections and a higher risk for complicated pneumonia.

Background Invasive pneumococcal disease (IPD), caused by Streptococcus pneumoniae , remains a major global health concern, particularly for children. Among more than 100 pneumococcal serotypes, 19A is known for its multidrug resistance (MDR) and increased incidence following PCV7/PCV10 introduction in many countries. Bangladesh introduced PCV10 in 2015 considering the low burden of 19A in the country. Methods Utilizing our IPD surveillance from 2004 to 2023, we investigated the hospital incidence of serotype 19A before and after PCV10 introduction among < 5 years old children in Bangladesh. Whole-genome sequencing was done for 153 serotype 19A isolates from IPD, otitis media, carriage, and urine samples. We used phylogenetic and BEAST analyses to investigate population structure, circulating subtypes, global pneumococcal sequence clusters (GPSCs), sequence types (STs), and antimicrobial resistance genes, and compared them with global 19A genomes. Results Our findings indicate no increase in hospital IPD incidence due to serotype 19A following PCV10 introduction. The MDR 19A-ST320 lineage (GPSC1) remains absent in Bangladesh. ST12888 (GPSC84) became dominant in the post-PCV10 introduction (from 15% to 70%). GPSC84 carries the capsular locus of 19A subtype-I (19A-I), which emerged independently from the standard 19A locus. Macrolide resistance is increasing within the 19A-I/GPSC84 lineage and is estimated to have originated between 2007 and 2011. Conclusions This study presents the first comprehensive genomic analysis of the serotype 19A population in Bangladesh, supporting the decision to introduce PCV10 in Bangladesh based on local pneumococcal serotype burden data. However, the rapid evolution within the local 19A population highlights the need for continuous epidemiological and genomic surveillance to support effective vaccination programs.

No previous studies have reported long-term follow-up of ten-valent pneumococcal conjugate vaccine (PCV10) program impact on pneumococcal meningitis (PM). We assessed the effects of infant PCV10 program on PM incidence, mortality and serotype distribution in children and adults during 7 years after introduction. We conducted a population-based observational study. A case of PM was defined as isolation of Streptococcus pneumoniae from cerebrospinal fluid or, a patient with S. pneumoniae isolated from blood and an ICD-10 hospital discharge diagnosis of bacterial meningitis within 30 days before or after positive culture date.We compared age- and serotype-specific incidence and associated 30-day mortality rates in 2011–2017 (PCV10 period) with those in 2004–2010 (pre-PCV10 baseline) by using Poisson regression models. Absolute rate differences and 95% confidence intervals (CIs) were calculated from the parameter estimates by using delta method. During the PCV10 period, the overall incidence of PCV10 serotype meningitis decreased by 68% (95%CI 57%-77%), and the overall PM incidence by 27% (95%CI: 12%-39%). In age groups 0–4, 50–64, and ≥ 18 years, the overall PM incidence was reduced by 64%, 34% and 19%, respectively. In adults ≥ 65 years of age, a 69% reduction in PCV10 serotypes was offset by 157% (56%-342%) increase in non-PCV10 serotypes. The overall PM-related mortality rate decreased by 42% (95%CI 4%-65%). Overall case fatality proportion (CFP) was 16% in pre-PCV10 period and 12% in PCV10 period (p = 0.41); among persons 50–64 years the CFP decreased from 25% to 10% (p = 0.04). We observed substantial impact and herd protection for vaccine-serotype PM and associated mortality after infant PCV10 introduction. However, in older adults ≥ 65 years of age, PM burden remains unchanged due to serotype replacement.

Pneumococcal conjugate vaccines reduce pneumococcal colonization via serotype-specific immunoglobulin G (IgG) at mucosal surfaces. The infant immunization schedule with the ten-valent pneumococcal conjugate vaccine (PCV10) changed from a 3 + 1 schedule (2–3-4–11 months) to a 2 + 1 schedule (2–4–11 months) in The Netherlands in 2013. We compared anti-pneumococcal IgG concentrations in saliva between the schedules. IgG was measured using a fluorescent bead-based multiplex immunoassay at the ages of 6 (post-primary) and 12 (post-booster) months in 51 infants receiving the 3 + 1 schedule and 68 infants receiving the 2 + 1 schedule. Post-primary IgG geometric mean concentrations (GMCs) were comparable between schedules for all vaccine serotypes. Post-booster IgG GMCs were significantly lower after the 2 + 1 schedule for serotypes 4 (p = 0.035), 7F (p = 0.048) and 23F (p = 0.0056). This study shows small differences in mucosal IgG responses between a 3 + 1 and a 2 + 1 PCV10 schedule. Future studies should establish correlates of protection against pneumococcal colonization for mucosal antibodies.

•Pneumococcal carriage rates and the frequency of physical contact differed by ethnicity.•Contact with older children and toddlers was positively associated with vaccine-type carriage.•Unvaccinated older children may become a vaccine-type carriage reservoir post-PCV10.•Ethnic differences in social contact did not explain ethnic differences in carriage.•Pneumococcal density was not associated with ethnicity, contact, or PCV10 status. Pneumococcal carriage is a prerequisite for pneumococcal disease. Little is known about whether social contact frequency and intensity are associated with pneumococcal carriage. In Fiji, indigenous iTaukei have higher prevalence of pneumococcal carriage compared with Fijians of Indian Descent (FID). We hypothesised that contact differences may contribute to ethnic differences in pneumococcal carriage prevalence and density. In 2015, young infants (5–8 weeks), toddlers (12–23 months), children (2–6 years), and caregivers from Suva and surrounding areas, participated in a cross-sectional survey (n = 2014), three years post pneumococcal conjugate vaccine introduction. Demographic and contact data, and nasopharyngeal swabs were collected. Pneumococci were detected, and quantified using quantitative real-time PCR, with molecular serotyping by microarray. Associations between ethnicity, contact, and pneumococcal carriage and density were estimated using multivariable generalised estimating equation regression models. iTaukei participants had larger household sizes, higher pneumococcal carriage rates, more contacts, and more frequent contacts of longer duration, compared with FID. The odds of vaccine-type carriage increased by 28% (95% CI 8–53%) P < 0.01 in association with physical contact with 7–14 year old children. iTaukei ethnicity was associated with vaccine-type carriage (aOR) 1.73; 95% CI 1.06–2.82, P = 0.03) and non-vaccine type carriage (aOR 5.98; 95% CI 4.47–8.00, P < 0.01). Ethnicity and contact were not associated with pneumococcal density. iTaukei had greater frequency and intensity of contact compared with FID. Physical contact was associated with pneumococcal carriage. Observed differences in pneumococcal nasopharyngeal carriage prevalence between iTaukei and FID were not explained by differences in social contact patterns by ethnicity.