Routine Pneumococcal Conjugate Vaccine Research Articles

Optimization of a high-throughput nanofluidic real-time PCR to detect and quantify of 15 bacterial species and 92 Streptococcus pneumoniae serotypes

Sensitive tools for detecting concurrent colonizing pneumococcal serotypes are needed for detailed evaluation of the direct and indirect impact of routine pneumococcal conjugate vaccine (PCV) immunization. A high-throughput quantitative nanofluidic real-time PCR (Standard BioTools ‘Fluidigm’) reaction-set was developed to detect and quantify 92 pneumococcal serotypes in archived clinical samples. Nasopharyngeal swabs collected in 2009–2011 from South African children ≤ 5 years-old, previously serotyped with standard culture-based methods were used for comparison. The reaction-set within the ‘Fluidigm’ effectively amplified all targets with high efficiency (90–110%), reproducibility (R2 ≥ 0.98), and at low limit-of-detection (< 102 CFU/ml). A blind analysis of 1 973 nasopharyngeal swab samples showed diagnostic sensitivity > 80% and specificity > 95% compared with the referent standard, culture based Quellung method. The qPCR method was able to serotype pneumococcal types with good discrimination compared with Quellung (ROC-AUC: > 0.73). The high-throughput nanofluidic real-time PCR method simultaneously detects 57 individual serotypes, and 35 serotypes within 16 serogroups in 96 samples (including controls), within a single qPCR run. This method can be used to evaluate the impact of current PCV formulations on vaccine-serotype and non-vaccine-serotype colonization, including detection of multiple concurrently colonizing serotypes. Our qPCR method can allow for monitoring of serotype-specific bacterial load, as well as emergence or ongoing transmission of minor or co-colonizing serotypes that may have invasive disease potential.

Influenza and pneumococcus vaccination rates in pediatric dialysis patients in Europe: recommendations vs reality A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group study

Children on dialysis are under increased risk of influenza and invasive pneumococcal disease. Although vaccination against these microorganisms are recommended in dialysis patients and despite the fact that these vaccines can reduce disease burden and rates of hospitalization due to infection, vaccination rates are below expected and desired. We aimed to evaluate influenza and pneumococcal vaccination and infection rates in European pediatric dialysis centers. In 16 centers from 11 countries, 357 pediatric dialysis patients were evaluated retrospectively during 1 year of observation period between 01.01.2014 and 01.01.2015. In all centers, vaccination policy included immunization of dialysis patients with inactive influenza vaccine and pneumococcal conjugate vaccine (PCV). Fifty percent of the centers recommended pneumococcal polysaccharide vaccine following routine PCV series. A significantly higher pneumococcal vaccination rate (43.9%) was seen in peritoneal dialysis (PD) patients compared to those on hemodialysis (HD) (32.9%) (p = 0.035), while the rates for influenza were similar (42.4% and 46.1% respectively, p = 0.496). Among all dialysis patients, 2.2% (n = 8) developed pneumonia and 6.4% (n = 23) was infected by Influenza. Pneumococcic pneumonia rate was 5% for 140 patients who received antipneumococcal vaccine, while only one pneumonia episode was recorded out of 217 unvaccinated patients (p = 0.007). The influenza virus infection rates were similar for patients vaccinated and nonvaccinated (7 % and 6 %, respectively). Although influenza and pneumococcal vaccines are highly recommended in pediatric dialysis patients, vaccination rates were lower than expected. Pneumococcal vaccination rates were higher in PD compared to the patients on HD. The rate of children with influenza infection was higher than pneumonia. The efficacy of influenza and pneumococcal vaccines was highlighted by the low infection rates. Higher pneumonia rates in patients vaccinated against pneumococcus compared to unvaccinated ones might be due to coexisting risk factors.

Incidence and Mortality Trends of Acute Gastroenteritis and Pneumococcal Disease in Children Following Universal Rotavirus and Pneumococcal Conjugate Vaccination in Ecuador.

IntroductionEcuador introduced routine infant rotavirus (RV) vaccination in 2008 and pneumococcal conjugate vaccination (PCV) in 2011 to manage disease and mortality in children caused by gastroenteritis (GE) and by pneumonia (PNE) and invasive pneumococcal disease (IPD), respectively.MethodsThis retrospective ecological database study described vaccination coverage as well as the trends in incidence and mortality in the pre- versus post-vaccination periods and used time-trend analysis models to assess the impact of vaccination.ResultsRV vaccination coverage of the second dose was between 79–97% from 2008 to 2016. GE incidence and mortality showed a declining trend before vaccination which continued in the post-vaccination period. The model estimated a statistically significant decrease of 72.4% for GE mortality and 51.2% for GE incidence in the post-vaccination period. PCV vaccination coverage remained above 80% (second dose) and 40% (third dose) after 2011. PNE mortality showed a declining trend before vaccination and a continued decline after vaccination, while PNE incidence was more variable (sharp increase from 2005–2009 then decrease and eventual stabilisation). The model estimated a statistically significant decline of 41.1% for PNE mortality and a stable PNE incidence in the post- versus pre-vaccination period. IPD incidence and mortality yearly data showed large variability by year and low numbers, making it difficult to discern a trend. The model estimated a statistically significant reduction of 51.1% for IPD mortality and 31.5% for IPD incidence in the post- versus pre-vaccination period.ConclusionAfter the first 9 years of routine RV vaccination and 6 years of routine PCV vaccination in Ecuador, significant decreases in incidence and mortality in children < 5 years of age due to GE and pneumococcal disease have been observed.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00531-6.

Influenza and pneumococcus vaccination rates in pediatric dialysis patients in Europe: recommendations vs reality A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group study.

Children on dialysis are under increased risk of influenza and invasive pneumococcal disease. Although vaccination against these microorganisms are recommended in dialysis patients and despite the fact that these vaccines can reduce disease burden and rates of hospitalization due to infection, vaccination rates are below expected and desired. We aimed to evaluate influenza and pneumococcal vaccination and infection rates in European pediatric dialysis centers. In 16 centers from 11 countries, 357 pediatric dialysis patients were evaluated retrospectively during 1 year of observation period between 01.01.2014 and 01.01.2015. In all centers, vaccination policy included immunization of dialysis patients with inactive influenza vaccine and pneumococcal conjugate vaccine (PCV). Fifty percent of the centers recommended pneumococcal polysaccharide vaccine following routine PCV series. A significantly higher pneumococcal vaccination rate (43.9%) was seen in peritoneal dialysis (PD) patients compared to those on hemodialysis (HD) (32.9%) (p = 0.035), while the rates for influenza were similar (42.4% and 46.1% respectively, p = 0.496). Among all dialysis patients, 2.2% (n = 8) developed pneumonia and 6.4% (n = 23) was infected by Influenza. Pneumococcic pneumonia rate was 5% for 140 patients who received antipneumococcal vaccine, while only one pneumonia episode was recorded out of 217 unvaccinated patients (p = 0.007). The influenza virus infection rates were similar for patients vaccinated and nonvaccinated (7 % and 6 %, respectively). Although influenza and pneumococcal vaccines are highly recommended in pediatric dialysis patients, vaccination rates were lower than expected. Pneumococcal vaccination rates were higher in PD compared to the patients on HD. The rate of children with influenza infection was higher than pneumonia. The efficacy of influenza and pneumococcal vaccines was highlighted by the low infection rates. Higher pneumonia rates in patients vaccinated against pneumococcus compared to unvaccinated ones might be due to coexisting risk factors.

Herd immunity alters the conditions for performing dose schedule comparisons: an individual-based model of pneumococcal carriage

BackgroundThere is great interest in the use of reduced dosing schedules for pneumococcal conjugate vaccines, a strategy premised on maintaining an acceptable level of protection against disease and carriage of the organism. We asked about the practicality of measuring differential effectiveness against carriage in a population with and without widespread use of the vaccine for infants.MethodsWe adapted an existing transmission-dynamic, individual-based stochastic model fitted to the prevaccine epidemiology of pneumococcal carriage in the United States, and compared the observed vaccine-type carriage prevalence in different arms of a simulated trial with one, two, or three infant doses plus a 12-month booster. Using these simulations, we calculated vaccine efficacy that would be estimated at different times post-enrollment in the trial and calculated required sample sizes to see a difference in carriage prevalence.ResultsIn a pneumococcal conjugate vaccine (PCV)-naïve population, the difference in vaccine-type (VT) pneumococcal carriage prevalence between trial arms was less than 7% and varied with sampling time. In a population already receiving routine PCV administration, VT pneumococcal prevalence is nearly indistinguishable between trial arms. Relative efficacy of different dosing schedules was strongly dependent on the time between enrollment and sampling, with maximal prevalence differences reached 1–3 years post-enrollment. Moreover, vaccine efficacy estimates were typically slightly higher in trials in communities already receiving vaccination. Despite this, much larger sample sizes—by more than an order of magnitude—are required for a vaccine trial conducted in a population receiving routine PCV administration as compared to in a PCV-naïve population.ConclusionsThese findings highlight some underappreciated aspects of clinical trials of pneumococcal conjugate vaccines with efficacy endpoints, such as the context- and time-dependence of efficacy estimates. They support the wisdom of conducting comparative dose schedule trials of conjugate vaccine effects on carriage in vaccine-naïve populations.

Paediatric community‐acquired bacteraemia, pneumococcal invasive disease and antibiotic resistance fell after the pneumococcal conjugate vaccine was introduced

This study examined the impact of the routine pneumococcal conjugate vaccination (PCV) on childhood community-acquired bacteraemia (CAB) and antibiotic resistance patterns in Israeli children. Israel added the PCV vaccine to its national immunisation programme in July 2009. We retrospectively analysed the medical records of all patients with CAB under 18years at three children's hospitals in Tel Aviv and Jerusalem from 2007 to 2015. The microbiological data, clinical presentation, pneumococcal serotype distribution, antibiotic susceptibility and outcomes of infections were compared before and after the vaccine was introduced. There were 511904 emergency department visits and 125922 children were hospitalised. Of those, 238 had CAB before vaccination was introduced (mean age 17months) and 316 had CAB after the introduction (mean age 21months). Emergency department presentations for CAB fell from 141.8 to 91.8 per 100000 visits: a relative risk reduction (RRR) of 35%. Hospitalisations for CAB decreased from 430 to 337 per 100000 admissions: an RRR of 22%. Hospitalisations due to Staphylococcus aureus increased significantly and penicillin nonsusceptible blood Streptococcus pneumoniae isolates decreased significantly. Introducing national pneumococcal conjugate vaccination significantly changed the epidemiology of CAB, with reduced antibiotic-resistant Streptococcus pneumoniae and increased hospitalisation rates for Staphylococcus aureus infections.

Clinical features and inflammatory markers in pediatric pneumonia: a prospective study.

With relatively high specificity and likelihood ratio CRP, WBC count and hypoxemia may be beneficial in ruling in a positive chest radiograph in suspected pneumonia and bacterial etiology in proven pneumonia, but with low sensitivity, the clinical utility is limited. What is Known: • Pneumonia is recommended to be a clinical diagnosis, and neither clinical features nor inflammatory markers can reliably distinguish etiology. • The etiology of pneumonia has changed after routine pneumococcal conjugate vaccine. What is New: • High CRP and WBC counts were associated with infiltrates in children with suspected pneumonia and with bacterial infection in proven pneumonia. • In the post-pneumococcal vaccination era, viral etiology is expected, and in cases of pneumonia with low CRP and WBC counts, a watch-and-wait strategy for antibiotic treatment may be applied.

Impact of pneumococcal conjugate vaccine in children morbidity and mortality in Peru: Time series analyses

Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available.We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru.We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged <1year, as well as weekly rates for pneumonia and AOM recorded in RENACE were estimated.After PCV introduction, we observed significant vaccine impact in morbidity and mortality in children aged <1year. Vaccine effectiveness was 26.2% (95% CI 16.9–34.4) for AOM visits, 35% (95% CI 8.6–53.8) for mortality due to pneumonia, and 20.6% (95% CI 10.6–29.5) for weekly cases of pneumonia hospitalization and outpatient visits notified to RENACE. We used secondary data sources which are usually developed for other non-epidemiologic purposes. Despite some data limitations, our results clearly demonstrate the overall benefit of PCV vaccination in Peru.

Invasive Pneumococcal Disease, Comorbidities, and Polysaccharide Vaccine Use in Children Aged 5-15 Years in England and Wales

In the United Kingdom, the 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended in addition to routine pneumococcal conjugate vaccination for at-risk children aged ≥2 years. This study describes the epidemiology, serotype distribution, clinical characteristics, vaccination status, and reasons for nonvaccination in children aged 5-15 years with invasive pneumococcal disease (IPD). Public Health England conducts enhanced national surveillance of IPD in England and Wales. In 2012, general practitioners (GPs) were contacted to complete a questionnaire for children aged 5-15 years with laboratory-confirmed IPD diagnosed during 2 epidemiological years, July 2009-June 2011. During 2009-2011, 447 IPD episodes occurred in 439 children (incidence, 2.2/100 000), and GPs of 423 of the 439 (96.4%) children completed the questionnaire. Comorbidity was reported in 124 (29.3%); a third each were immunocompromised or had chronic respiratory disease or other comorbidities. Pneumonia was the most common presentation (332/439 [75.6%]), and IPD-related case fatality was 1.8% (8/439). Only 26.6% (33/124) of children with comorbidities had received PPV23, and development of PPV23-type IPD was not associated with prior PPV23 vaccination (adjusted odds ratio [AOR], 1.09; 95% confidence interval [CI], .36-3.32; P = .88), even when analysis was restricted to the extra 11 PPV23 serotypes not contained in the 13-valent pneumococcal conjugate vaccine (AOR, 1.70; 95% CI, .30-9.76; P = .55). GPs of eligible but unvaccinated cases with comorbidities were mostly unaware that the child required PPV23 and/or expected pediatricians to inform them to administer the vaccine. Only a quarter of children with comorbidities who developed IPD had received PPV23 prior to infection. Among PPV23-vaccinated children with comorbidities, however, there was no evidence of protection against PPV23 serotypes.

Invasive Pneumococcal Disease after Routine Pneumococcal Conjugate Vaccination in Children, England and Wales

We assessed known risk factors, clinical presentation, and outcome of invasive pneumococcal disease (IPD) in children 3-59 months of age after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in England and Wales. During September 2006-March 2010, a total of 1,342 IPD episodes occurred in 1,332 children; 14.9% (198/1,332) had comorbidities. Compared with IPD caused by PCV7 serotypes (44/248; 17.7%), comorbidities were less common for the extra 3 serotypes in the 10-valent vaccine (15/299; 5.0%) but similar to the 3 additional PCV13 serotypes (45/336; 13.4%) and increased for the 11 extra serotypes in 23-valent polysaccharide vaccine (PPV23) (39/186; 21.0%) and non-PPV23 serotypes (38/138; 27.5%). Fifty-two (3.9%) cases resulted from PCV7 failure; 9 (0.7%) case-patients had recurrent IPD. Case-fatality rate was 4.4% (58/1,332) but higher for meningitis (11.0%) and children with comorbidities (9.1%). Thus, comorbidities were more prevalent in children with IPD caused by non-PCV13 serotypes and were associated with increased case fatality.

A retrospective study of clinical Streptococcus pneumoniae isolates from four health facilities in South-West Nigeria

Nigeria is currently one of the highest pneumococcal disease burdened countries not implementing routine pneumococcal conjugate vaccine (PCV) immunization and having limited clino-biological data on Streptococcus pneumoniae. This retrospective study provides phenotypic and genotypic data on 15 isolates of S. pneumoniae recovered from clinical samples provided by 75 bacteremia, asthma, pneumonia, otitis media, meningitis, severe malaria and sickle cell anaemia (SCA) patients, attending health facilities within the south-West region of the country. The recovered S. pneumoniae isolates were serotyped and had their antibiotic susceptibilities determined by disk diffusion and MIC assays. They were further analyzed for disparity by SDS-PAGE and RAPD analysis coupled with genotyping for ply and lyt genes to query virulence. Empirical antibiotic prescription and demographic data were also extracted from the patients’ medical records with consent. The 15 recovered S pneumoniae isolates belonged to 5 distinct serotypes: 19F (n = 6), 5 (n = 3) and 2 each of 6B, 9V and 23F. More isolates were recovered from children than adults and from invasive diseases than non-invasive ones. However, serotype 9V isolates (adults only) were distinctively invasive and genotyping revealed some levels of clonal diversity and virulence among the multi-drug resistant strains. All the strains were within the vaccine coverage of PCV-13. Key words: Streptococcus pneumoniae, serotypes, antibiotic susceptibility, random amplified polymorphic DNA (RAPD), pneumococcal conjugate vaccine coverage, Nigeria

Health Care Utilization for Pneumonia in Young Children After Routine Pneumococcal Conjugate Vaccine Use in the United States

To estimate the effect of 7-valent pneumococcal conjugate vaccine (PCV7) on rates of pneumonia-related health care utilization and costs in children younger than 2 years. Retrospective population study. Approximately 40 large employers each year, from 1997 to 2004. Enrollees in the MarketScan databases collected by Thomson Medstat. Pneumococcal conjugate vaccine immunization program. Rates of International Classification of Diseases, Ninth Revision-coded hospitalizations and ambulatory visits due to all-cause and pneumococcal pneumonia and their medical expenditures. Comparing the rates in 2004 with those in the baseline period of 1997 to 1999 among children younger than 2 years, hospitalizations due to all-cause pneumonia declined from 11.5 to 5.5 per 1000 children (52.4% decline; P < .001) and ambulatory visits due to all-cause pneumonia declined from 99.3 to 58.5 per 1000 children (41.1% decline; P < .001). Rates of hospitalizations due to pneumococcal pneumonia declined from 0.6 to 0.3 per 1000 children (57.6% decline; P < .001) and rates of ambulatory visits declined from 1.7 to 0.9 per 1000 children (46.9% decline; P < .001). Projecting from these data to the US population, the total estimated direct medical expenditures for all-cause pneumonia-related hospitalizations and ambulatory visits in young children were reduced from an annual average of $688.2 million during the period of 1997 to 1999 to $376.7 million in 2004 (45.3% decline and approximately $310 million decrease). In children younger than 2 years, the age group targeted for vaccination, pneumonia-related health care utilization in a privately insured population declined substantially following PCV7 introduction. These results suggest that PCV7 may play an important role in reducing the burden of pneumonia, resulting in major savings in medical care cost.

Assessing costs and cost effectiveness of pneumococcal disease and vaccination within Kaiser Permanente

Objective: To review studies of the costs of pneumococcal disease and the cost effectiveness of pneumococcal conjugate vaccination conducted in association with the Kaiser Permanente Pneumococcal conjugate Efficacy Trial. Results: for each birth cohort of 3.8 million infants, routine pneumococcal conjugate vaccination program for healthy infants would prevent more than 12 000 (78% of potential) meningitis and bacteremia cases, 53 000 (69% of potential) pneumonia cases, and 1 million (8% of potential) otitis media episodes. Before accounting for vaccine costs, the vaccination program would reduce the costs of pneumococcal disease by $342 million in medical and $415 million in work-loss and other costs. Vaccination of healthy infants would result in net savings for society if the vaccine cost less than $46 per dose, and net savings for the health care payer if the vaccine cost less than $18 per dose.