Pneumococcal Conjugate Vaccine In Children Research Articles

Evaluation of the impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia in Ulaanbaatar, Mongolia: study protocol for an observational study

BackgroundCommunity-acquired pneumonia is an important cause of morbidity and mortality in adults. Approximately one-third of pneumonia cases can be attributed to the pneumococcus. Pneumococcal conjugate vaccines (PCVs) protect against colonisation with vaccine-type serotypes. The resulting decrease in transmission of vaccine serotypes leads to large indirect effects. There are limited data from developing countries demonstrating the impact of childhood PCV immunisation on adult pneumonia. There are also insufficient data available on the burden and severity of all-cause pneumonia and respiratory syncytial virus (RSV) in adults from low resource countries. There is currently no recommendation for adult pneumococcal vaccination with either pneumococcal polysaccharide vaccine or PCVs in Mongolia. We describe the protocol developed to evaluate the association between childhood 13-valent PCV (PCV13) vaccination and trends in adult pneumonia.MethodsPCV13 was introduced into the routine childhood immunisation schedule in Mongolia in a phased manner from 2016. In March 2019 we initiated active hospital-based surveillance for adult pneumonia, with the primary objective of evaluating trends in severe hospitalised clinical pneumonia incidence in adults 18 years and older in four districts of Ulaanbaatar. Secondary objectives include measuring the association between PCV13 introduction and trends in all clinically-defined pneumonia, radiologically-confirmed pneumonia, nasopharyngeal carriage of S. pneumoniae and pneumonia associated with RSV or influenza. Clinical questionnaires, nasopharyngeal swabs, urine samples and chest radiographs were collected from enrolled patients. Retrospective administrative and clinical data were collected for all respiratory disease-related admissions from January 2015 to February 2019.DiscussionEstablishing a robust adult surveillance system may be an important component of monitoring the indirect impact of PCVs within a country. Monitoring indirect impact of childhood PCV13 vaccination on adult pneumonia provides additional data on the full public health impact of the vaccine, which has implications for vaccine efficiency and cost-effectiveness. Adult surveillance in Mongolia will contribute to the limited evidence available on the burden of pneumococcal pneumonia among adults in low- and middle-income countries, particularly in the Asia-Pacific region. In addition, it is one of the few examples of implementing prospective, population-based pneumonia surveillance to evaluate the indirect impact of PCVs in a resource-limited setting.

The Burden of Invasive Bacterial Disease and the Impact of 10-Valent Pneumococcal Conjugate Vaccine in Children

Background Despite the availability of vaccines, invasive bacterial diseases remain a public health concern and cause childhood morbidity and mortality. We investigated the characteristics of etiological agents causing bacterial meningitis in children <5 years in the years pre- (2010–2012) and post- (2014–2019) 10-valent pneumococcal conjugate vaccine (PCV10) introduction in Zambia.MethodsStreptococcus pneumoniae (Spn), Haemophilus influenzae (Hi), and Neisseria meningitidis (Nm) from cerebrospinal fluid (CSF) were identified by microbiological culture and/or real-time polymerase chain reaction.ResultsDuring the surveillance period, a total of 3811 children were admitted with suspected meningitis, 16% (598 of 3811) of which were probable cases. Bacterial meningitis was confirmed in 37% (221 of 598) of the probable cases. Spn pneumoniae, Hi, and Nm accounted for 67% (148 of 221), 14% (31 of 221), and 19% (42 of 221) of confirmed cases, respectively. Thirty-six percent of pneumococcal meningitis was caused by 10-valent pneumococcal conjugate vaccine (PCV10) serotypes, 16% 13-valent pneumococcal conjugate vaccine and 39% by nonvaccine serotype (NVS). There was an association between the introduction of PCV10 vaccination and a decrease in both Spn meningitis and the proportion of PVC10 serotypes in the postvaccination period. Antimicrobial susceptibility of 47 Spn isolates revealed 34% (16 of 47) penicillin resistance. The 31 serotyped Hi accounted for 74% type b (Hib) and 10% type a (Hia). All 42 serogrouped Nm belonged to serogroup W.ConclusionsThere was a decline in pneumococcal meningitis and proportion of PCV10 serotypes in the postvaccination period. However, the serotype replacement with non-PCV10 serotypes and penicillin resistance warrant continued surveillance to inform policy.

Under-Vaccination in Pediatric Liver Transplant Candidates with Acute and Chronic Liver Disease-A Retrospective Observational Study of the European Reference Network TransplantChild.

Infection is a serious concern in the short and long term after pediatric liver transplantation. Vaccination represents an easy and cheap opportunity to reduce morbidity and mortality due to vaccine-preventable infection. This retrospective, observational, multi-center study examines the immunization status in pediatric liver transplant candidates at the time of transplantation and compares it to a control group of children with acute liver disease. Findings show only 80% were vaccinated age-appropriately, defined as having received the recommended number of vaccination doses for their age prior to transplantation; for DTP-PV-Hib, less than 75% for Hepatitis B and two-thirds for pneumococcal conjugate vaccine in children with chronic liver disease. Vaccination coverage for live vaccines is better compared to the acute control group with 81% versus 62% for measles, mumps and rubella (p = 0.003) and 65% versus 55% for varicella (p = 0.171). Nevertheless, a country-specific comparison with national reference data suggests a lower vaccination coverage in children with chronic liver disease. Our study reveals an under-vaccination in this high-risk group prior to transplantation and underlines the need to improve vaccination.

A phase 4 study of the safety of the 13-valent pneumococcal conjugate vaccine in children 6 to 17 years of age in India

PurposeThe 13-valent pneumococcal conjugate vaccine (PCV13) was recently approved in India for the prevention of pneumococcal disease in children aged 6 to 17 years based on global data as well as immunogenicity and safety findings from a phase 3 study. The current phase 4 study in India further evaluated the safety profile of PCV13 in this age group to support the positive benefit-risk profile of PCV13. MethodsHealthy male and female children aged 6 to 17 years in India were administered a single intramuscular injection of PCV13. Through 7 days after PCV13 administration, local reactions and systemic events were recorded daily by caregivers in an electronic diary. Adverse events (AEs) were collected from the provision of informed consent through 28–42 days postvaccination. ResultsOne hundred subjects enrolled in and completed the study. After PCV13 vaccination, 73.9% and 57.8% of subjects reported local reactions and systemic events, respectively. The majority of reactogenicity events were mild to moderate in severity, with injection site pain and fatigue the most frequently reported local reaction and systemic event, respectively. Six subjects reported 7 AEs, all of which were considered unrelated to PCV13. One subject reported a serious AE (acute hepatitis), which was considered unrelated to PCV13 and ultimately resolved. No subjects withdrew because of AEs, and there were no deaths. ConclusionPCV13 vaccination was well tolerated with an acceptable safety profile in healthy subjects aged 6 to 17 years in India. This work further supports the safety profile of PCV13 for prevention of pneumococcal disease in this age group in India.

The impact of childhood pneumococcal conjugate vaccine immunisation on all-cause pneumonia admissions in Hong Kong: A 14-year population-based interrupted time series analysis

BackgroundNine years after the introduction of pneumococcal conjugate vaccine (PCV) in the United States, Hong Kong (HK) introduced the vaccine to its universal childhood immunisation programme in 2009. We aimed to assess the impact of childhood PCV immunisation on all-cause pneumonia (ACP) admissions among the overall population of HK. MethodsIn this population-based interrupted time series analysis, we used territory-wide population-representative electronic health records in HK to evaluate the vaccine impact. We identified hospitalised patients with a diagnosis of pneumonia from any cause between 2004 and 2017. We applied segmented Poisson regression to assess the gradual change in the monthly incidence of ACP admissions between pre- and post-vaccination periods. Negative outcome control, subgroup and sensitivity analyses were used to test the robustness of the main analysis. FindingsOver the 14-year study period, a total of 587,607 ACP episodes were identified among 357,950 patients. The monthly age-standardised incidence of ACP fluctuated between 33.42 and 87.44 per 100,000-persons. There was a marginal decreasing trend in pneumonia admissions after PCV introduction among overall population (incidence rate ratio [IRR]: 0·9965, 95% confidence interval [CI]: 0·9932–0·9998), and older adults (≥65 years, IRR: 0·9928, 95% CI: 0·9904–0·9953) but not in younger age groups. InterpretationThere was a marginally declining trend of overall ACP admissions in HK up to eight years after childhood PCV introduction. The significance disappeared when fitting sensitivity analyses. The results indicate the complexities of using non-specific endpoints for measuring vaccine effect and the necessity of enhancing serotype surveillance systems for replacement monitoring. FundingHealth and Medical Research Fund, Food and Health Bureau of the Government of Hong Kong (Reference number: 18171272).

Cost-effectiveness analysis of domestic 13-valent pneumococcal conjugate vaccine for children under 5 years of age in mainland China

ABSTRACT Background: The first Chinese domestic 13-valent pneumococcal conjugate vaccine (WoAnxin®, PCV-13) is available for children aged 2 months to 5 years and is more economical than import vaccine with equal safety and immunogenicity. However, the cost-effectiveness of this new PCV-13 for children <5 years in mainland China is not clear. Methods: In the present study, we developed a Markov model under societal perspective to evaluate the incremental cost-effectiveness ratios (ICERs) of five birth cohorts of 100,000 Chinese infants across four alternative vaccination programs:1) no vaccination; 2) vaccinate 4 doses of new PCV-13 for children aged 2 to 6 months; 3) vaccinate 3 doses of new PCV-13 for children aged 7 to 11 months; 4) vaccinate 2 doses of new PCV-13 for children aged 12 to 23 months; 5) vaccinate 1 dose of new PCV-13 for children aged 2 to 5 years. We conducted one-way and probability sensitivity analysis to determine the uncertainty of the model findings. Results: We found that with awillingness-to-pay (WTP) threshold of three-times Chinese per-capita gross domestic product (GDP) all vaccination programs were cost-effective compared to no vaccination and children aged 2 to 5 years received 1 dose of new PCV-13 would incur the lowest additional cost of US$2417 per quality-adjusted-life-years (QALYs) compare with other vaccination programs ($15394/QALYs for 4 doses program, $9292/QALYs for 3 doses program, $4445/QALYs for 2 doses program). Conclusions: According to our results, China should give priority to incorporating new PCV-13 into its national immunization program.

PIN25 The IMPACT of Childhood Pneumococcal Conjugate Vaccine Immunisation on Pneumonia Admissions in Hong Kong: A Population-Based Interrupted Time Series Analysis from 2004-2017

PIN25 The IMPACT of Childhood Pneumococcal Conjugate Vaccine Immunisation on Pneumonia Admissions in Hong Kong: A Population-Based Interrupted Time Series Analysis from 2004-2017

Evaluation of the effectiveness of pneumococcal conjugate vaccine for children in Korea with high vaccine coverage using a propensity score matched national population cohort

ObjectivesThis study was performed to evaluate the vaccine effectiveness (VE) of protein conjugated pneumococcal vaccines (PCV) in children with regard to all-cause pneumonia (ACP), pneumococcal pneumonia (PP), invasive pneumococcal disease (IPD), and acute otitis media (AOM), in a country where the unvaccinated group is very small. MethodsChildren born between 2013 and 2015 were identified in the national population registry for retrospective observation. Vaccination history from the National Immunization Program registry and medical records from the National Health Insurance System were linked together to set up a cohort. VE based on original and propensity score matched cohorts were estimated and compared. ResultsA total of 990 224 children were included and 98% were vaccinated. The crude incidence of ACP, PP, and AOM for the original cohort was heavily skewed to the vaccinated group. Adjusting for age, sex, comorbidity, and healthcare utilization rate, the vaccine was found to be effective against PP (VE 60.15%, 95% confidence interval (CI) 21.21–79.85%) and AOM (VE 19.13%, 95% CI 13.42–24.46%). The propensity score matched cohort showed VE against ACP (5.95%, 95% CI 0.88–11.57%), PP (48.61%, 95% CI 23.60–65.43%), and AOM (33.21%, 95% CI 31.01–35.33%). ConclusionsThe direct effect of the PCV program was confirmed for ACP, PP, and AOM. The propensity score matched cohort is a feasible solution for measuring and tracing nationwide VE in countries with a very high level of vaccine coverage.

Signal Detection of Adverse Events Following Pneumococcal Vaccines from the Korea Adverse Event Reporting System Database, 2005-2016.

PurposeWe aimed to analyze the surveillance reports of adverse events (AEs) due to different types of pneumococcal vaccines, in addition to detecting and validating signals of pneumococcal vaccines by comparing AEs with labels.Materials and MethodsWe analyzed the percentages of AEs according to vaccine type [pneumococcal polysaccharide vaccines (PPSVs) and pneumococcal conjugate vaccines (PCVs)] in children and adults using data from the Korea Adverse Event Reporting System (KAERS) database from 2005 to 2016. A signal was defined as an AE that met all three indices of data mining: proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). We validated the detected signals by calculating sensitivity, specificity, as well as positive and negative predictive values of the signals against label information.ResultsOf the 39933 AE reports on vaccination, 5718 (7.0%) were related to pneumococcal vaccine. The most frequent AE after vaccination with PPSV was fever (23.9%) in children and injection-site reaction in adults. The most frequent AE after vaccination with PCV in children was pharyngitis (26.2%). In total, 13 AEs met all three indices for signal detection. Among these, hypotension, apathy, sepsis, and increased serum glutamic oxaloacetic transaminase level were not listed on vaccine labels. In validation analysis, PRR and ROR performed slightly better than IC for adults who were vaccinated with PPSVs.ConclusionOverall, 13 new signals of PPSVs, including four signals not listed on the labels, were detected. Further research based on additional AE reports is required to confirm the validity of these signals for children.

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

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

2705. Serotype Replacement Following Childhood Pneumococcal Conjugate Vaccination Programs in British Columbia, Canada

BackgroundPneumococcal conjugate vaccines have substantially reduced the incidence of invasive pneumococcal disease (IPD); however, the impact of the vaccine on non-vaccine serotypes (NVT) remains unclear. We evaluated the effect of PCV13 use in British Columbia, Canada.MethodsThe annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) was calculated using provincial laboratory surveillance data. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–10) and pre-PCV7 (2002–03) baselines using Poisson regression for non-conjugate vaccine type IPD.ResultsA total of 4,490 cases were reported over the 14 year period. The overall annual incidence increased from 5.73 cases per 100,000 population in 2002 to 7.90 cases per 100,000 population in 2015. Compared with baseline, PCV7 reduced VT-IPD (IRR: 0.49; 95% CI: 0.42–0.56), but the additional 6 serotypes in the PCV13 vaccine caused 214% increase in IPD (IRR: 2.65; 95% CI: 2.12–3.39). The majority of this increase is related to an increase in NVT disease (IRR: 3.17; 95% CI: 2.62–3.87) such as 23B, 23A, 9N, 20, 33F, 15C, 17F and 6C. IPD from PCV13 vaccine serotypes 19A and 7F which emerged after PCV7 continue to be high.ConclusionThe introduction of PCV13 has a modest impact on IPD rates, due to inadequate control of serotypes 19A and 7F, and, of concern, IPD rates continue to escalate due to serotype replacement by non-vaccine serotypes.Disclosures All authors: No reported disclosures.

Thirteen-Valent Pneumococcal Conjugate Vaccine in Children With Acute Lymphoblastic Leukemia: Protective Immunity Can Be Achieved on Completion of Treatment.

Children with acute lymphoblastic leukemia (ALL) are at increased risk of developing invasive pneumococcal disease. This study describes the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) during and after chemotherapy. Children with ALL were allocated to study groups and received a single dose of PCV13: group 1, maintenance chemotherapy; group 2, end of chemotherapy; group 3, 6 months after chemotherapy. A protective vaccine response was defined as at least 10 of 12 serotypes (or >83% of serotypes with data) achieving postvaccination serotype-specific immunoglobulin G ≥0.35 µg/mL and ≥4-fold rise, compared to prevaccination at 1 and 12 months. One hundred eighteen children were recruited. Only 12.8% (5/39; 95% confidence interval [CI], 4.3%-27.4%) of patients vaccinated during maintenance (group 1) achieved a protective response at 1 month postvaccination and none had a protective response at 12 months. For group 2 patients, 59.5% (22/37; 95% CI, 42.1%-75.3%) achieved a response at 1 month and 37.9% (11/29; 95% CI, 20.7%-57.7%) maintained immunity at 12 months. For group 3 patients, 56.8% (21/37; 95% CI, 39.5%-72.9%) achieved a protective response at 1 month and 43.3% (13/30; 95% CI, 25.5%-62.6%) maintained immunity at 12 months. This study demonstrated that the earliest time point at which protective immunity can be achieved in children with ALL is on completion of chemotherapy. This is earlier than current recommendations and may improve protection during a period when children are most susceptible to infection. EudraCT 2009-011587-11.

Cost-effectiveness of introducing the pneumococcal conjugate vaccine for children under 5 years in the Islamic Republic of Iran.

Pneumococcal disease caused by Streptococcus pneumoniae results in considerable mortality and morbidity. Pneumococcal conjugate vaccines (PCV), such as PCV-13, can prevent invasive pneumococcal disease and avoid disability and death. The cost of introducing PCV-13 in childhood immunization schedules should be assessed against the cost of pneumococcal diseases for each community. This study aimed to evaluate the cost-effectiveness of introducing PCV-13 in the national immunization programme for children under 5 years in the Islamic Republic of Iran. The TRIVAC decision support model was used to estimate total costs of introducing PCV-13 and the disability- adjusted life years (DALYs) averted. The main pneumococcal diseases were considered-pneumonia, meningitis, acute otitis media, and non-pneumonia, non-meningitis infections-in terms of hospital admissions, outpatient visits and deaths. Local data were used to estimate costs. Pneumococcal disease is estimated to affect 18 713 211 children under 5 years (519 412 pneumonia, 18 148 116 acute otitis media, 6884 meningitis, and 38 799 non-pneumonia, non-meningitis) in 10 years (2014-2023) without use of the vaccine. Introduction of PCV-13 would prevent 4 900 084 cases of pneumococcal disease (190 849 pneumonia, 4 692 450 acute otitis media, 2529 meningitis, and 14 256 non-pneumonia, non-meningitis). Pneumococcal infection would cause 287 950 hospital admissions and 29 399 deaths; vaccination could avert 105 802 hospital admissions and 9997 deaths. The incremental cost-effectiveness was estimated to be US$ 1890 and US$ 1538 per averted DALY for the government and society respectively. According to WHO-recommended thresholds for interpreting cost-effectiveness, introduction of PCV-13 for children under 5 years in the Islamic Republic of Iran would be cost-effective.

Impact of Childhood Pneumococcal Conjugate Vaccine on Nonnotified Clinically Suspected Invasive Pneumococcal Disease in Australia.

Finnish studies have shown a significant impact of 10-valent pneumococcal conjugate vaccine (PCV10) on nonnotified clinically suspected invasive pneumococcal disease (IPD). We used a similar vaccine probe design to estimate PCV7 and PCV13 impact in Australian children. Season and age-matched pre-PCV7 cohorts (born in 2002-2004) were compared with PCV7-early and PCV7-late, and PCV13-eligible cohorts. Using linked notification and hospitalization data, we calculated relative rate reductions (RRRs) and absolute rate reductions (ARRs) for notified IPD, and nonnotified clinically suspected IPD or unspecified sepsis (first hospitalization with an International Classification of Diseases 10th Revision-Australian Modification code: A40.3/G00.1/M00.1 or A40.9/A41.9/A49.9/G00/I30.1/M00, respectively). Significant reductions in all outcomes were observed comparing PCV7-early and PCV7-late and PCV13-eligible to pre-PCV7 cohorts. RRRs were high for both notified and nonnotified clinically suspected IPD (range 71%-91%), but ARRs were lower for nonnotified (5-6/100,000 person-years) than for notified cases (59-70/100,000 person-years). RRRs for the combined outcome of nonnotified clinically suspected IPD or unspecified sepsis were lower at 21%-24% for PCV7-eligible cohorts and 36% for the PCV13-eligible cohort, but ARRs were considerable due to the high pre-PCV7 rates (ARR 37-31/100,000 person-years for PCV7-early and PCV7-late cohorts and 54/100,000 person-years for PCV13). This study provides a quantitative estimate of the total burden of IPD preventable by PCV7 and PCV13 vaccination programs in Australia. ARRs (compared with prevaccination) were significant but smaller than in Finland (122/100,000 for the combined outcome) and longer-term follow-up is required to determine the additional impact of PCV13 above that seen for PCV7. Country-specific studies are needed to accurately estimate the burden of pneumococcal disease preventable by vaccination and cost-effectiveness of PCV vaccination programs.

Childhood Pneumococcal Conjugate Vaccination Benefits Adults

A 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the early 2000s and was followed by a 13-valent version (PCV-13). Because these

Molecular typing, antibiotic susceptibility, and biofilm production in nonencapsulated Streptococcus pneumoniae isolated from children in Japan

The prevalence of nonencapsulated Streptococcus pneumoniae (NESp) has increased with the introduction of pneumococcal conjugate vaccines in children; however, the bacteriological characteristics of NESp have not been sufficiently clarified. In this study, NESp strains isolated from the nasopharyngeal carriage of children from four nursery schools in Japan were analyzed for molecular type, antibiotic susceptibility, and biofilm productivity. A total of 152 putative S. pneumoniae strains were identified by optochin-susceptibility analysis, of which 21 were not serotypeable by slide agglutination, quellung reaction, or multiplex PCR. Among these 21 strains, three were lytA-negative and, therefore, not S. pneumoniae. The remaining 18 strains were positive for lytA, ply, pspK, and bile solubility and were confirmed as NESp. Therefore, the isolation rate of NESp in the S. pneumoniae strains in this study was 12.0% (18/149). Molecular-typing analyses classified five strains as two existing sequence types (STs; ST7502 and ST7786), and 13 strains formed four novel STs. Horizontal spread was suspected, because strains with the same ST were often isolated from the same nursery school. The NESp isolates were generally susceptible to most antimicrobials, with the exception of macrolides; however, all isolates possessed more than one abnormal penicillin-binding protein gene. Furthermore, NESp strains were more effective than encapsulated counterparts at forming biofilms, which showed obvious differences in morphology. These data indicated that NESp strains should be continuously monitored as emerging respiratory pathogens.

The duopoly of ten-valent and 13-valent pneumococcal conjugate vaccines: do they differ?

The duopoly of ten-valent and 13-valent pneumococcal conjugate vaccines: do they differ?

Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination

BackgroundPneumococcal conjugate vaccines (PCVs) have the potential to prevent pneumococcal disease through direct and indirect protection. This multicentre European study estimated the indirect effects of 5-year childhood PCV10 and/or PCV13...

Register-Based Ecologic Evaluation of Safety Signals Related to Pneumococcal Conjugate Vaccine in Children.

Background:In clinical trials of Pneumococcal Conjugate Vaccines (PCV), some adverse events have been reported more frequently in the PCV vaccinated. Ten-valent PCV (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in September 2010.Objective:We conducted an ecologic register-based study to investigate further the reported adverse events after PCV.Methods:This study included data obtained from the Finnish nationwide, population-based registers. First diagnoses of febrile seizures, breath-holding, urticarial rash, asthma and Kawasaki’s disease were included as outcomes obtained from the hospital discharge register. Data from Finnish Population Register during 2000-2014 for children age from 3 months to 10 years were used to estimate annual incidence rates. Incidence rate ratios of the outcomes were calculated between the target cohort of children eligible for PCV10 during 2010-2014 and a reference cohort before the NVP introduction (2004-2008).Results:No increases in the incidence of the adverse events after PCV10 introduction were found except for urticarial rash (incidence rate 2.48 vs. 1.60/1000 pyrs; incidence rate ratio, 1.54;95% CI 1.42-1.67). This increase was seen also in the unvaccinated older age groups in the post-vaccination era. The higher incidence of urticarial rash after the PCV10 introduction was due to the inclusion of diagnoses made in general medicine specialty in the discharge register because of a concomitant administrative change.Conclusion:The results do not support public health concerns related to the previously reported adverse events. Concomitant changes in health care administration and coding introduced bias, which was controlled after further evaluation of the data. We consider this register-based approach with real-world data feasible in the signal validation process after any signal detection.

Changes in the Nature and Severity of Invasive Pneumococcal Disease in Children Before and After the Seven-valent and Thirteen-valent Pneumococcal Conjugate Vaccine Programs in Calgary, Canada.

Since the introduction of childhood pneumococcal conjugate vaccines, invasive pneumococcal disease (IPD) incidence has decreased in children and the predominant serotypes causing disease have changed. This study describes changes in the clinical features of IPD in children (<18 years) before and after the conjugate vaccine introduction. The Calgary Area Streptococcus pneumoniae Epidemiology Research study collects information on all IPD cases in Calgary, Alberta, Canada. Descriptive and regression analyses were used to compare IPD in the pre-vaccine (January 2000 to August 2002), post-7-valent protein-polysaccharide conjugate vaccine (September 2002 to June 2010) and post-13-valent protein-polysaccharide conjugate vaccine (PCV13) (July 2010 to December 2015) periods; intensive care unit and inpatient admissions were outcome measures. The incidence of IPD in children (<18 years) decreased from an average of 17 cases/100,000/yr in 2000-2001 to 4 cases/100,000/yr in 2015. The median age of children presenting with IPD shifted from 2.0 years (interquartile range: 2.5) in the pre-vaccine period to 3.9 years (interquartile range: 6.2) in the post-PCV13 period. The proportion of children with a comorbidity that is an indication for pneumococcal vaccination did not change. Invasive disease with focus (meningitis, pneumonia, empyema, peritonitis) compared with invasive disease with bacteremia only increased from 44.6% in pre-vaccine to 64.0% and 61.4% in the post-7-valent protein-polysaccharide conjugate vaccine and post-PCV13 periods, respectively (P = 0.017). Having IPD in the post-PCV13 period compared with the pre-vaccine period was associated with an increased odds of hospitalization [Odds ratio (OR): 2.9; 95% Confidence Interval (CI): 1.4-6.2]. Clinical features of IPD have changed since pneumococcal conjugate vaccines were introduced, with a shift toward more focal infections requiring hospitalization. Although overall IPD cases have declined, disease that does occur appears to be more severe.