Effectiveness of Pneumococcal Vaccines on Otitis Media in Children: A Systematic Review

ObjectivesWe aimed to determine the effectiveness of pneumococcal vaccines on otitis media (OM) and acute otitis media (AOM) in children.MethodsWe conducted a systematic search in databases PubMed (MEDLINE), Embase, Lilacs, and Web of Science. We included observational studies that evaluated any pneumococcal vaccine – including 7, 10, and 13-valent pneumococcal conjugate vaccines (PCV7, PCV10, and PCV13) and 23-valent polysaccharide vaccines (PPSV23) as the intervention, in children aged less than five years.ResultsOut of the 2112 screened studies, 48 observational studies complied with the eligibility criteria and therefore were included in this review. Of the included studies, 30 (63%) were before-after, eleven (23%) cohort, six (13%) time series, and one (2%) case-control study designs. Vaccine effectiveness (VE) in preventing OM or AOM varied by vaccine type. In children under 24 months VE ranged from 8% and 42.7% (PCV7), 5.6% to 84% (PCV10) and 2.2% to 68% (PCV13). In children aged less than 60 months, VE ranged between 13.2% and 39% for PCV7, 11% to 39% for PCV10 (only children under 48 months), and 39% to 41% (PCV13).ConclusionsOur results demonstrate significant effect of pneumococcal vaccination in decreasing OM or AOM in children under five years old in several countries supporting the public health value of introducing PCVs in national immunization programs.     

The cost-burden of paediatric pneumococcal disease in the UK and the potential cost-effectiveness of prevention using 7-valent pneumococcal conjugate vaccine

We modelled the epidemiology and cost of pneumococcal disease in children in the UK and the cost-effectiveness of immunisation with 7-valent pneumococcal conjugate vaccine (PCV). We estimated the incidence of pneumococcal meningitis, pneumococcal septicaemia, all-cause pneumonia and all-cause otitis media (OM). We further estimated the impact of vaccination with associated costs and outcomes. Vaccine cost was pound 39.25 per dose with a pound 10 administration cost; vaccination schedule and efficacy were taken from a recent trial. We estimated that in each UK annual birth cohort there are 881,146 episodes of these infections and 149 deaths associated with pneumococcal meningitis, pneumococcal septicaemia or all-cause pneumonia and that PCV would prevent 54,384 episodes and 29 deaths. NHS cost per life year gained was estimated at pound 31,512, close to the limit at which PCV would be considered cost-effective.     

Clinical effectiveness of 13-valent and 23-valent pneumococcal vaccination in middle-aged and older adults: The EPIVAC cohort study, 2015–2016

BackgroundClinical benefits using the 23-valent pneumococcal polysaccharide vaccine (PPsV23) or the 13-valent pneumococcal conjugate vaccine (PCV13) in adults are controversial. This study investigated clinical effectiveness for both PPsV23 and PCV13 in preventing pneumonia among middle-aged and older adults.MethodsPopulation-based cohort study involving 2,025,730 persons ≥50 years in Catalonia, Spain, who were prospectively followed between 01/01/2015 and 31/12/2016. Primary outcomes were hospitalisation from pneumococcal or all-cause pneumonia and main explanatory variable was PCV13/PPsV23 vaccination status. Multivariable Cox regression models were used to estimate vaccination effectiveness adjusted for age and baseline-risk conditions.ResultsCohort members were followed for 3,897,151 person-years (17,496 PCV13 vaccinated and 1,551,502 PPsV23 vaccinated), observing 3259 pneumococcal pneumonias (63 in PCV13 vaccinated, 2243 in PPsV23 vaccinated) and 24,079 all-cause pneumonias (566 in PCV13 vaccinated, 17,508 in PPsV23 vaccinated). Global incidence rates (per 100,000 person-years) were 83.6 for pneumococcal pneumonia (360.1 in PCV13 vaccinated, 144.6 in PPsV23 vaccinated) and 617.9 for all-cause pneumonia (3235.0 in PCV13 vaccinated, 1128.5 in PPsV23 vaccinated). In the multivariable analyses, the PCV13 appeared significantly associated with an increased risk of pneumococcal pneumonia (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.17–1.97; p = 0.002) and all-cause pneumonia (HR: 1.76; 95% CI: 1.61–1.92; p < 0.001) whereas the PPsV23 did not alter the risk of pneumococcal pneumonia (HR: 1.08; 95% CI: 0.98–1.19; p = 0.132) and slightly increased the risk of all-cause pneumonia (HR: 1.17; 95% CI: 1.13–1.21; p < 0.001). In stratified analyses focused on specific target population subgroups (i.e., elderly people, at-risk and high-risk individuals), protective effects of vaccination did not emerge either.ConclusionData does not support clinical benefits from pneumococcal vaccination (nor PCV13 neither PPsV23) against pneumonia among Catalonian adults in the current era of universal PCV’s childhood immunisation.     

Incremental effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia hospitalisation among Australian Indigenous children: A record linkage study

BackgroundThe impact of pneumococcal conjugate vaccines (PCVs) on pneumonia in children is well-documented but data on 23-valent pneumococcal polysaccharide vaccine (PPV23) are lacking. Between 2001 and 2011, Indigenous children in Western Australia (WA) were recommended to receive PPV23 at 18–24 months of age following 3 doses of 7-valent PCV. We evaluated the incremental effectiveness of PPV23 against pneumonia hospitalisation.MethodsIndigenous children born in WA between 2001 and 2012 who received PCV dose 3 by 12 months of age were followed from 18 to 60 months of age for the first episode of pneumonia hospitalisation (all-cause and 3 subgroups: presumptive pneumococcal, other specified causes, and unspecified). We used Cox regression modelling to estimate hazard ratios (HRs) for pneumonia hospitalisation among children who had, versus had not, received PPV23 between 18 and 30 months of age after adjustment for confounders.Results11,120 children had 327 first episodes of all-cause pneumonia hospitalisation, with 15 (4.6%) coded as presumptive pneumococcal, 46 (14.1%) as other specified causes and 266 (81.3%) unspecified. No statistically significant reduction in all-cause pneumonia was seen with PPV23 (HR 1.11; 95% CI: 0.87–1.43), but the direction of the association differed for presumptive pneumococcal (HR 0.47; 95% CI: 0.16–1.35) and specified (HR 0.89; 95% CI: 0.49–1.62) from unspecified causes (HR 1.13; 95% CI: 0.86–1.49). During the baseline period before PPV23 vaccination (12–18 months), all-cause pneumonia risk was higher among PPV23-vaccinated than unvaccinated children (RR: 1.73; 95% CI: 1.30–2.28).ConclusionIn this high-risk population, no statistically significant incremental effect of a PPV23 booster at 18–30 months was observed against hospitalised all-cause pneumonia or the more specific outcome of presumptive pneumococcal pneumonia. Confounding by indication may explain the slight trend towards an increased risk against all-cause pneumonia. Larger studies with better control of confounding are needed to further inform PPV23 vaccination.     

Prevalence of middle ear abnormalities from otitis media in relation with pneumococcal vaccine use in the Inuit population of Nunavik,province of Quebec,Canada

BackgroundOtitis media (OM) constitutes an important public health problem in the Inuit population of Nunavik, Northern Quebec. One of the objectives of the childhood pneumococcal vaccination program is to reduce OM burden. The program was implemented in 2002, and 7-, 10-, and 13-valent conjugate vaccines were used sequentially, with doses offered at 2, 4, 6 and 12–18 months, respectively.ObjectiveTo assess the prevalence of middle ear abnormalities at age 5 years in relation with exposure to different pneumococcal conjugate vaccines.MethodsImmunization cards and audiology screening tests at age 5 years of children born in 1994–2010 were reviewed. Children were classified according to the vaccine schedule recommended for their birth cohort or to the vaccines they actually received. Log-linked binomial regression models were used to assess the relative abnormalities risk according to different vaccination schedules.ResultsAmong 3517 children with complete documentation, the prevalences of minor and major abnormalities were 29% and 18%, respectively. Minor abnormalities frequency was higher in unvaccinated children (34%) and lower in children vaccinated with PCV7 (22%), PCV7 + PCV10 (17%), PCV10 (15%) and PCV10 + PCV13 (18%). No substantial differences among vaccine schedules were observed for major abnormalities.ConclusionsPneumococcal conjugate vaccination was associated with a decreased frequency of middle ear abnormalities although no effect was seen for major abnormalities which may be trigger by OM with early onset.Clinicaltrials.gov registration number: NCT01694329     

Cost-effectiveness of 13-valent pneumococcal conjugate vaccine in Switzerland

The 7-valent pneumococcal conjugate vaccine (PCV7) has been shown to be highly cost-effective. The 13-valent pneumococcal conjugate vaccine (PCV13) offers seroprotection against six additional serotypes. A decision-analytic model was constructed to estimate direct medical costs and clinical effectiveness of PCV13 vaccination on invasive pneumococcal disease (IPD), pneumonia, and otitis media relative to PCV7 vaccination. The option with an one-dose catch-up vaccination in children of 15-59 months was also considered. Assuming 83% vaccination coverage and considering indirect effects, 1808 IPD, 5558 pneumonia and 74,136 otitis media cases could be eliminated from the entire population during a 10-year modelling period. The PCV13 vaccination programme would lead to additional costs (+€26.2 Mio), but saved medical costs of -€77.1 Mio due to cases averted and deaths avoided, overcompensate these costs (total cost savings -€50.9 Mio). The national immunisation programmes with PCV13 can be assumed cost saving when compared with the current vaccine PCV7 in Switzerland.     

The pharmacoeconomics of pneumococcal conjugate vaccines in Latin America

Streptococcus pneumoniae continues to be the most important causative agent of invasive bacterial infections in children and is the most common cause of vaccine-preventable deaths in children less than 5 years of age. Due to some conditions in the Latin America region, economic assessments of pneumococcal conjugate vaccines (PCVs) have unique characteristics. First, distribution of S. pneumoniae serotypes, and thus coverage by vaccines that incorporate certain serotypes, varies within the region and compared with other parts of the world. Second, the mortality rate of pneumococcal infections in developing countries is significantly higher than in the US and Europe. Third, the economies of the Latin American region are very different from those of developed countries. For these reasons, the Pan American Health Organization (PAHO) is promoting the need for economic valuation studies of the impact of pneumococcal vaccines Latin America. Given the importance of pneumonia in the burden of pneumococcal disease in Latin America, the number of pneumonia cases prevented by the vaccine has a large impact on the economic valuation of PCVs, due to a strong correlation with numbers of deaths averted, quality-adjusted life-years (QALYs) gained or disability-adjusted life-years (DALYs) avoided. In terms of cost, analysis of impact on acute otitis media (short-term) and sequelae (long-term) show a significant and important expenditure avoided by vaccination. Cost-effectiveness is significantly modified by vaccine cost, mortality due to pneumonia, vaccine efficacy/effectiveness and herd immunity. Finally the validity of certain assumptions based on the uncertainty of the data should be considered in economic assessments of new PCVs. These include assumptions related to the impact on otitis media, estimates of efficacy/effectiveness based on measured antibody levels and the extrapolation to PCV10 and PCV13 of previous experience with PCV7.     

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.     

Cost-effectiveness analysis of pneumococcal vaccination for infants in China

BackgroundAlthough China has a high burden of pneumococcal disease among young children, the government does not administer publicly-funded pneumococcal conjugate vaccines (PCV) through its Expanded Program on Immunization (EPI). We evaluated the cost-effectiveness of publicly-funded PCV-7, PCV-10, and PCV-13 vaccination programs for infants in China.MethodsUsing a Markov model, we simulated a cohort of 16 million Chinese infants to estimate the impact of PCV-7, PCV-10, and PCV-13 vaccination programs from a societal perspective. We extrapolated health states to estimate the effects of the programs over the course of a lifetime of 75 years. Parameters in the model were derived from a review of the literature.ResultsWe found that PCV-7, PCV-10, and PCV-13 vaccination programs would be cost-effective compared to no vaccination. However, PCV-13 had the lowest incremental cost-effectiveness ratio ($11,464/QALY vs $16,664/QALY for PCV-10 and $18,224/QALY for PCV-7) due to a reduction in overall costs. Our sensitivity analysis revealed that the incremental cost-effectiveness ratios were most sensitive to the utility of acute otitis media, the cost of PCV-13, and the incidence of pneumonia and acute otitis media.ConclusionsThe Chinese government should take steps to reduce the burden of pneumococcal diseases among young children through the inclusion of a pneumococcal conjugate vaccine in its EPI. Although all vaccinations would be cost-effective, PCV-13 would save more costs to the healthcare system and would be the preferred strategy.     

Cost-effectiveness of pneumococcal conjugate vaccine: An update after 7 years of use in the United States

Seven-valent pneumococcal conjugate vaccine (PCV7) has been in routine use in the United States since 2000 and data have indicated direct and indirect effects of the vaccine. We simulated the effects of PCV7 on children vaccinated during 2000–2006, incorporating direct and indirect effects on incidence of invasive pneumococcal disease (IPD), hospitalized pneumonia and otitis media. Before accounting for indirect effects, PCV7 cost $201,000 per life-year saved. After incorporating indirect effects on IPD, cost per life-year saved was $10,400. The presence of modest additional indirect effects against hospitalized pneumonia and otitis media in children may have resulted in overall cost savings.     

Burden and cost of hospital admissions for vaccine-preventable paediatric pneumococcal disease and non-typable Haemophilus influenzae otitis media in New Zealand

Introduction

Streptococcus pneumoniae (Sp.) is a leading cause of paediatric bacterial meningitis, pneumonia and acute otitis media, as is non-typable Haemophilus influenzae (NTHi) for acute otitis media. In 2008, a 7-valent conjugated pneumococcal vaccine (PCV7) was included in the New Zealand (NZ) childhood immunization schedule.

Objective

To estimate the potentially vaccine-preventable annual hospital admissions and cost to the NZ Government of paediatric admissions for pneumococcal disease and NTHi otitis media prior to the immunization programme.

Methods

Admissions (2000–7) and deaths (2000–5) in children aged <20 years with pneumococcal meningitis or bacteraemia, pneumonia or otitis media were identified in national datasets and linked by unique patient identifiers. New episodes of illness were defined as admissions occurring >30 days after discharge from a previous admission. Informed by the literature, pneumococcal pneumonia episodes were estimated at 33% of all-cause pneumonia admissions; Sp. and NTHi otitis media episodes were estimated jointly at 72% of otitis media admissions. Each episode was assigned a single diagnosis according to the following hierarchy: meningitis > bacteraemia > pneumonia > otitis media. Incidence rates for episodes were determined for 2000–7 (meningitis, bacteraemia and pneumonia) and 2006–7 (otitis media). Annual DRG-based costs for pneumococcal meningitis, bacteraemia, pneumonia and otitis media were estimated as (episode rate) × (DRG cost weight per episode) × (2007 population) × (national price per cost weight).

Results

Episode rates for pneumococcal meningitis, bacteraemia and pneumonia were stable in 2000–7, highest in the second 6 months of life and declined steeply over the first 5 years of life. Mean rates per 100 000 in 2000–7 were 18.4, 27.6 and 464 for pneumococcal meningitis, bacteraemia and pneumonia, respectively, for children aged <2 years; 8.4, 14.9 and 295 for children aged <5 years (including those aged <2 years); and 2.2, 4.4 and 97 for children aged <20 years (including those aged <5 years). Mean rates per 100 000 in 2006–7 for Sp. and NTHi otitis media combined were 631 (surgical) and 197 (medical) for children aged <2 years; 691 and 116 for children aged <5 years; and 281 and 35 for children aged <20 years. Pacific Island and indigenous Māori children generally had higher rates than European/other children. Rates increased with socioeconomic disadvantage, across all diagnoses. The annual cost to Government of pneumococcal disease and NTHi otitis media admissions for children aged <20 years was estimated at New Zealand dollars ($NZ)9.95 million (range 7.7–12.2 million) [about $US7.1 million]. Most of this cost was shared between pneumococcal pneumonia (48%) and otitis media (45%), and 78% was incurred in the first 2 years of life. Estimated annual paediatric mortality rates per 100 000 for children aged <5 years were 0.48, 0.30 and 0.54 for pneumococcal meningitis, bacteraemia and pneumonia, respectively. The analysis predicted four or five pneumococcal deaths per year (range 1–8) for children aged <5 years.

Conclusions

Prior to the introduction of a national Sp. immunization programme, hospital admissions for Sp. disease and NTHi otitis media in NZ cost about $NZ10 million annually, mostly for children aged <2 years and particularly for those living in relative socioeconomic deprivation and for Pacific Island and Māori children. There were about five pneumococcal deaths annually. With adjustment for local serotypes, vaccine serotype coverage and uptake, immunization with any of the three available pneumococcal vaccines would reduce this burden substantially.     

Exploring the acceptability of the available pneumococcal conjugate vaccines in Canadian health care professionals and immunization experts

BackgroundIn children, the 13 and 10-valent pneumoccocal conjugate vaccines (PCV13/10) are currently approved for the prevention of invasive pneumococcal disease (IPD). Acceptability is a key consideration in the implementation of a vaccine program and it is recognized that health professional’s attitudes and opinions towards vaccines are independent predictors of the success of an immunization program. We aimed to survey the beliefs and attitudes for the two available PCVs in health care professionals and immunization experts.FindingsWe interviewed 21 members of Canadian immunization committees and/or participants working in frontline healthcare delivery. Overall, participants predominantly preferred PCV-13 over PCV10. For most, AOM should not be taken into considerations in decisions for pneumococcal vaccination programs implementation. AOM was considered an important endpoint of the program but an ineffective measure of program success due to the lack of surveillance for the condition. Recent evidence pertaining to PCV10 cross-protection against 19A did not affect preference but had an impact on perceptions regarding pricing.ConclusionTo consider implementing any changes to the current program, most participants would require more evidence regarding PCV10 cross-protection and effectiveness against OM. Decreasing vaccine price was cited as a positive outcome of funding both vaccines.     

Impacts of Catch-Up Immunization program with the 13-Valent pneumococcal Conjugate vaccine in Taiwan: Focus on age-stratified differences and high-risk population (2001–2015)

BackgroundTaiwan commenced a national catch-up immunization program with a 13-valent pneumococcal conjugate vaccine (PCV13) in 2013 for children aged 2–5 years old and in 2014 for children aged 1–5 years old. However, real-world nationwide evidence of both the direct protection and indirect protection of all-cause pneumonia and pneumococcal pneumonia has been scarce, especially among high-risk populations, defined as patients with chronic diseases or immunosuppression. The aim of this study was to examine the impact of the national PCV13 catch-up program on all-cause pneumonia and pneumococcal pneumonia among overall and high-risk populations using interrupted time series analysis.MethodsUsing the National Health Insurance Research Database (NHIRD) from January 2001 to December 2015, we assessed the impact of this catch-up program by interrupted time-series analyses age-stratified (0–1, 2–4, 5–9, 10–17, 18–34, 35–49, 50–64, 65 + years old) incidence of pneumococcal pneumonia and all-cause pneumonia (100,000 person-quarter) among the overall and high-risk populations.ResultsThe impact of this program was most profound on the incidence of pneumococcal pneumonia in children aged 2–4 years old (level change ?10.56 per 100,000 person-quarters, p = 0.04; trend change ?2.93, p less than 0.01). Indirect protection among unvaccinated children (0–1 years old: trend change ?1.19, p = 0.01; 5–9 years old: trend change ?1.04, p = 0.03; 10–17 years old: level change ?1.42 per 100,000 person-quarters, p = 0.03) was also found. The incidence of all-cause pneumonia also decreased in children aged 2–4 (level change ?234.91 per 100,000 person-quarter, p = 0.058) and 5–9 years old (level change ?173.96 per 100,000 person-quarter, p = 0.0424). However, we did not find a significant impact among most high-risk populations.ConclusionsOur study suggests that the introduction of this catch-up program with PCV13 was associated with significant declines in the incidence of pneumococcal pneumonia and all-cause pneumonia in vaccinated children, and indirect protection from the program was also found in unvaccinated children.     

Ten year public health impact of 13-valent pneumococcal conjugate vaccination in infants: A modelling analysis

Pneumococcal disease is a substantial contributor to illness and death in young children globally. The introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 had a significant impact in preventing pneumococcal disease in both vaccinated children and unvaccinated individuals (through herd effect). A higher valent PCV13 replaced PCV7 in late 2009. This analysis was undertaken to assess how many cases and deaths have been averted over the last decade since PCV13 introduction. A model estimated the number of infants vaccinated annually with PCV13, as well as the number of cases and deaths of invasive pneumococcal disease, pneumococcal pneumonia, and acute otitis media cases averted.PCV13 vaccination was estimated to have prevented 175.2 million cases of all pneumococcal diseases and 624,904 deaths globally between 2010 and 2019. These results demonstrate the substantial public health impact of PCV13 and highlight the importance of increasing the global reach of PCV programs.     

Efficacy,safety and immunogenicity of a pneumococcal protein-based vaccine co-administered with 13-valent pneumococcal conjugate vaccine against acute otitis media in young children: A phase IIb randomized study

BackgroundNative American populations experience a substantial burden of pneumococcal disease despite use of highly effective pneumococcal conjugate vaccines (PCVs). Protein-based pneumococcal vaccines may extend protection beyond the serotype-specific protection elicited by PCVs.MethodsIn this phase IIb, double-blind, controlled trial, 6–12 weeks-old Native American infants randomized 1:1, received either a protein-based pneumococcal vaccine (dPly/PhtD) containing pneumolysin toxoid (dPly, 10 µg) and pneumococcal histidine triad protein D (PhtD, 10 µg) or placebo, administered along with 13-valent PCV (PCV13) at ages 2, 4, 6 and 12–15 months. Other pediatric vaccines were given per the routine immunization schedule. We assessed vaccine efficacy (VE) against acute otitis media (AOM) and acute lower respiratory tract infection (ALRI) endpoints. Immunogenicity, reactogenicity and unsolicited adverse events were assessed in a sub-cohort and serious adverse events were assessed in all children.Results1803 infants were randomized (900 dPly/PhtD; 903 Control). VE against all episodes of American Academy of Pediatrics (AAP)-defined AOM was 3.8% (95% confidence interval: −11.4, 16.9). Point estimates of VE against other AOM outcomes ranged between 2.9% (−9.5, 14.0) and 5.2% (−8.0, 16.8). Point estimates of VE against ALRI outcomes ranged between −4.4% (−39.2, 21.8) and 2.0% (−18.3, 18.8). Point estimates of VE tended to be higher against first than all episodes but the confidence intervals included zero. dPly/PhtD vaccine was immunogenic and had an acceptable reactogenicity and safety profile after primary and booster vaccination in Native American infants.ConclusionsThe dPly/PhtD vaccine was immunogenic and well tolerated, however, incremental efficacy in preventing AAP-AOM over PCV13 was not demonstrated.Clinical trials registrationNCT01545375 (www.clinicaltrials.gov)     

Serotype distribution of Streptococcus pneumoniae isolated from children hospitalized in Beijing children’s hospital (2013–2019)

BackgroundStreptococcus pneumoniae can cause many infectious diseases among children, and relevant vaccines have not been scheduled into the National Immunization Program in China. The serotype distribution of Streptococcus pneumoniae is essential information used to evaluate the value of pneumococcal vaccines and formulate immunization strategies.MethodsStreptococcus pneumoniae isolates, identified as the disease pathogens, were collected from children hospitalized in Beijing Children’s Hospital from 2013 to 2019. The serotype was detected by the Quellung reaction.ResultsA total of 903 isolates of Streptococcus pneumoniae were collected, among which 809 were from non-invasive infections and 94 were from invasive infections. The non-invasive isolates were mainly isolated from respiratory secretions (49.4%) and bronchoalveolar lavage fluid (38.9%), while invasive isolates were from venous blood (5.4%), cerebrospinal fluid (2.8%) and pleural effusion (2.8%). The leading serotypes were 19F (36.0%), 19A (13.6%), 23F (9.4%), 14 (8.9%), 6A (6.9%), and 6B (5.3%). The overall coverage rates of 10-, 13-, 15-, 20-valent pneumococcal conjugate vaccines (PCV10, PCV13, PCV15, PCV20) and 23-valent pneumococcal polysaccharide vaccine (PPV23) as well as Pneumosil (a 10-valent pneumococcal conjugate vaccine) were 61.6%, 83.2%, 83.4%, 88.0%, 82.4% and 81.6%, respectively. The coverage rates of PCV13, PCV15 and PPV23 in isolates from invasive infections were significantly higher than those from non-invasive infections. The coverage rates of Pneumosil, either on the whole or among different age groups or different infections, were significantly higher than those of PCV10.ConclusionsSerotypes 19F, 19A, 23F, 14, 6A and 6B were the most common types among the isolates. As for pneumococcal vaccines available now, the coverage rate of PCV13 was high, especially in isolates from invasive infections. The promotion of PCV13 or further high valent vaccines might be of greater benefit in preventing pneumococcal infections than other pneumococcal vaccines in children.     

Streptococcus pneumoniae as cause of acute otitis media (AOM) in Slovak children in the pneumococcal conjugate vaccine era (2008–2019)

AimLittle data is available on pneumococcal serotypes and their antimicrobial resistance in the pneumococcal conjugate vaccination era in young children with acute otitis media (AOM). Here such data is provided from Slovakia, a country with sequential introduction and parallel-use of the three commercially available pneumococcal conjugate vaccines (PCVs; PCV7; PCV13; PCV10).MethodsThis observational study takes advantage of the fact that tympanocentesis is the standard of care in children with AOM in Slovakia. Over the 12 year observation period, participating pediatric ENT specialists sent samples taken during tympanocentesis from children with AOM to their local MEDIRIX laboratories for identification of bacteria. Pneumcoccal isolates were serotyped and tested for antimicrobial resistance. Incidence data could be calculated from 1 region.ResultsStudy participation and completeness of typing increased over time. Based on testing of 1,131 isolates over 12 years, PCV7-serotypes rapidly waned after PCV7 introduction in 2009 and had virtually disappeared in 2014. The maximum fraction of PCV10-only isolates (1, 5, 7F) was 2.7 % (2009) whereas the additional 3 PCV-serotypes (3, 6A, 19A) in PCV13 represented the largest proportion of pneumococcal AOM cases as of 2010. This finding remained unchanged during the period of highest PCV10-market share (2012–2017) and even until the end of the observation period (2019). The fraction of untypeable pneumococci (<6 %) and non-PCV13-serotypes (16–34 %) increased 2012–2017, but decreased again thereafter. Serotype 19A evolved as the most relevant (multidrug-) resistant pneumococcal serotype, again particularly during the time with high sales of PCV10 (2012–2017). Incidence data from the Bratislava region document a huge impact of PCV use (77 % vaccine uptake: mainly PCV13) on AOM in children < 6 years. Serotypes 19A and 3 remain the only relevant pneumococcal serotypes in young Slovakian children with AOM.ConclusionsAs AOM is one of the most common bacterial infections in children < 6 years, the observed benefits of PCVs in reducing vaccine serotypes have been tremendous. With sequential / parallel-use of PCVs, serotypes 3 and (MDR-) 19A today make the largest proportion (about 2/3) of pneumococcal AOM in Slovakia. This data will help to further guide the choice of pneumococcal conjugate vaccines for pediatricians and parents.     

Effectiveness of a 3 + 0 pneumococcal conjugate vaccine schedule against invasive pneumococcal disease among a birth cohort of 1.4 million children in Australia

BackgroundMost studies use indirect cohort or case-control methods to estimate vaccine effectiveness (VE) of 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) against invasive pneumococcal disease (IPD). Neither method can measure the benefit vaccination programs afford the unvaccinated and many studies were unable to estimate dose-specific VE. We linked Australia’s national immunisation register with health data from two states to calculate IPD incidence by vaccination status and VE for a 3 + 0 PCV schedule (doses at 2, 4, 6 months, no booster) among a cohort of 1.4 million births.MethodsBirths records for 2001–2012 were probabilistically linked to IPD notifications, hospitalisations, deaths, and vaccination history (available until December 2013). IPD rates in vaccinated and unvaccinated children <2 years old were compared using Cox proportional hazards models (adjusting for potential confounders), with VE = (1 − adjusted hazard ratio) × 100. Separate models were performed for all-cause, PCV7, PCV13 and PCV13-non-PCV7 serotype-specific IPD, and for Aboriginal and non-Aboriginal children.ResultsFollowing introduction of universal PCV7 in 2005, rates of PCV7 serotype and all-cause IPD in unvaccinated children declined 89.5% and 61.4%, respectively, to be similar to rates in vaccinated children. Among non-Aboriginal children, VEs for 3 doses were 94.2% (95%CI: 81.9–98.1) for PCV7 serotype-specific IPD, 85.6% (95%CI: 60.5–94.8) for PCV13-non-PCV7 serotype-specific IPD and 80.1% (95%CI: 59.4–90.3) for all-cause IPD. There were no statistically significant differences between the VEs for 3 doses and for 1 or 2 doses against PCV13 and PCV13-non-PCV7 serotype-specific IPD, or between Aboriginal and non-Aboriginal children.ConclusionOur population-based cohort study demonstrates that >90% coverage in the first year of a universal 3 + 0 PCV program provided high population-level protection, predominantly attributable to strong herd effects. The size of the cohort enabled calculation of robust dose-specific VE estimates for important population sub-groups relevant to vaccination policies internationally.