Welcome to the ESPID 2021 Meeting Calendar

Background

In 2015, 4CMenB (Bexsero®) was added to the UK infant vaccination schedule to protect infants against invasive meningococcal disease with capsular group B meningococcus. 4CMenB is efficacious but reactogenic, and has led to an increase in infant hospital admissions for infection screens due to vaccine related fever. This study investigated the innate immune response to vaccination in infants and its relationship to the increased reactogenicity of the current 4CMenB containing schedule.

Methods

4-month-old infants were randomised to receive pre-2015 vaccinations alone or alongside 4CMenB (current schedule). Plasma protein expression was profiled using mass spectrometry (LC-MS/MS) and Luminex® multiplex bead-based immunoassays to measure high and low abundance proteins respectively. Plasma from thirty infants was profiled at baseline and 4-hours (n=13) or 24-hours (n=17) post vaccination. Foldchanges were determined using paired Wilcox-tests (Luminex data) and linear models (mass-spectrometry data). Results with FDR<0.05 were deemed significant.

Results

Compared with baseline samples, 4 and 29 proteins were differentially expressed at 4-hours and 24-hours after vaccination respectively. Eight proteins correlated with neutrophil counts and/or post-vaccine temperature. Differentially expressed proteins were enriched in 30 REACTOME pathways; enriched terms included neutrophil degranulation, haemostasis, retinoid metabolism and lipid metabolism.

Seven proteins were more highly expressed at 4-hours (Apolipoprotein-A1, Apolipoprotein-A2, and Apolipoprotein-C1) and 24-hours (CRP, serum amyloid-A2, G-CSF and IL-6) post vaccination in the 4CMenB group, potentially reflecting the increased reactogenicity of the current vaccine schedule.

Proteomic and transcriptomic data were integrated to create networks summarising the innate immune response to vaccination.

Conclusions

This is the first study investigating the effect of vaccination on the plasma proteome. These findings provide new insights into the immune response to vaccination and vaccine reactogenicity, potentially informing the design of less reactogenic vaccines and vaccine schedules.

Clinical Trial Registration

EudraCT number 2014-000126-38

Background

Following the 13-valent pneumococcal conjugate vaccine (PCV13) implementation in infants worldwide, overall and vaccine-type invasive pneumococcal disease (IPD) rates declined in children, with variable indirect impact on IPD rates in adults.

Methods

A population-based, prospective, nationwide active surveillance of overall 8,614 IPD cases in Israel, during 2004-2019 (for adults, 2009-2019). PCV7/PCV13 were implemented in July 2009/November 2010, respectively, with >90% uptake in children <2 years. The 23-valent pneumococcal polysaccharide vaccine uptake among >65 years was ~75%. Overall, PCV13 serotypes (VT13) and non-VT13 serotypes (NVT) incidence rates ratios were calculated, comparing the pre-PCV (2004-2008 for children; 2009-2011 for adults) and late-PCV13 (2016-2019) periods, for different age groups. For pre-PCV episodes in which serotypes were missing, extrapolation was conducted.

Results

IPD rates declined by 67% in children <5 and 5-17 years. For adults, rates significantly declined only in the 18-44 years (by 53%) (Fig.). VT13 rates significantly declined; range 94% in <5 years to 60% in ≥85 years. NVT rates significantly increased in <5, 50-64 and ≥65 years; VT13 serotypes 3, 14 and 19A, and NVT serotypes 8 and 12F were predominant in 2016-2019. During 2016-2019, VT13, PCV15 additional serotypes (22F, 33F) and PCV20 additional serotypes (8, 10A, 11A, 12F, 15B/C, 22F, 33F) caused 19.2%, 7.4% and 39.2% of IPD.

Conclusions

Continuous monitoring of circulating serotypes in all age groups is essential for the development of new vaccination strategies.

Background

After introducing pneumococcal vaccination, the epidemiology of community-acquired pneumonia (CAP) in children has changed. Thus, the prevalence of non-pneumococcal bacteria, such as Staphylococcus aureus, may be increasing. Pneumococcal 13-valent vaccination was implemented in the Regional Immunization program of Madrid in 2010. We aimed to describe the epidemiology of pediatric S. aureus CAP (SA-CAP) in recent years and to compare them with the characteristics of Streptococcus pneumoniae CAP (SP-CAP).

Methods

Retrospective multicenter study including patients <17 years with bacterial CAP (S. aureus, S. pneumoniae, and Streptococcus pyogenes) admitted in 5 tertiary hospitals in Madrid (Spain) during 2008-18. For comparisons, S. pneumoniae CAP (SP-CAP) were randomly selected with a ratio 2:1 SA-CAP, comparing 34 SA-CAP with 68 SP-CAP. The annual rate of cases/10,000 admissions/year was analyzed.

Results

236/313(75.4%) bacterial pneumonia were SP-CAP, and 34/313(10.9%) SA-CAP. The annual rate of SP-CAP decreased from 14.7/10,000 admissions (2008) to 7.7/10,000 admissions (2018)(p<0.001), whereas the annual rate of SA-CAP remained stable(Figure). SP-CAP median age was higher (2.9[IQR: 1.7-4.6]years) than SA-CAP (0.7[IQR: 0.5-2.6]years)(p<0.001). Initial empiric treatment was more frequently inadequate in SA-CAP (50% vs. 1.5%,p<0.001). Viral coinfections were more commonly detected among SA-CAP(26.5% vs. 7.4%,p=0.008). A higher percentage of patients with SA-CAP required respiratory support. However, lung complications were more common among SP-CAP: pleural effusion(64.7 vs. 47.1%,p=0.088),p=0.088) and lung necrosis(32.4% vs. 5.9%,p=0.003).

Conclusions

The prevalence of SP-CAP in children decreased from 2008 to 2018, whereas S. pyogenes CAP prevalence slightly increased. Interestingly, in this population, unlike other studies, admitted SP-CAP had a higher severity than SA-CAP. Indeed, two patients with SP-CAP (2.9%) died vs. none SA-CAP.

Background

To investigate the impact of universal varicella vaccination (UVV) on potential exposure to antibiotics and antivirals and associated costs for the treatment of varicella among US children.

Methods

A decision tree model of vaccination, varicella infections and treatment decisions was developed. 10 million replications were run using probabilistic sampling. Results were extrapolated to the 2017 population of 73.5 million US children ≤18 years in cross-section of one year. Parameters (vaccination and complications rates, treatment costs) were populated from literature. Expert opinion helped determine correct treatment for each vignette. Treatment decision likelihood were estimated using online survey results where 153 Health care professionals made treatment recommendations for 8 patient varicella vignettes.

Results

In a scenario with no UVV, our model estimated 1,053,087 antibiotic and 1,705,841 antiviral prescriptions would be dispensed annually to treat varicella. Under existing UVV in US, antibiotic and antiviral prescriptions were reduced by 95% and 93% respectively leading to $87 million annual cost-savings. Treatment in unvaccinated children (4%) under UVV accounted for 61% of antibiotic and antiviral prescriptions costing $18 million annually. While vaccination offers significant protection, breakthrough cases of varicella result in 16,961 antibiotic and 50,824 antiviral prescriptions annually.

Conclusions

Our model estimated substantial reduction in antibiotic and antiviral use among US children for treatment of varicella due to UVV. Antibiotics and antivirals are frequently used for managing varicella infection among unvaccinated children, sometimes inappropriately. Strategies to improve vaccination coverage and education to improve management of cases may further reduce clinical and economic burden of varicella in U.S.

Background

Pneumococcal conjugate vaccine (7 valent, PCV7) was first introduced in the UK in 2006 as a 2+1 (2, 4 and 12 months) schedule. A 13 valent vaccine (PCV13) replaced PCV7 in 2010. Recently the schedule changed to a 1+1 (3, 12 months) schedule for children born 1^st January 2020 onwards. We present baseline data from a cross-sectionalpneumococcal carriage study in 6-12 month olds in the Thames Valley region.

Methods

Nasopharyngeal swabs were taken from healthy 6-12 month olds in 2017/20 who had received a full primary course (two doses) of PCV13. A subset of participants provided a blood sample (finger or heel-prick). Molecular serotyping by microarray analysis was performed on ‘sweeps’ of selective culture plates from swabs with pneumococcal-presumptive growth, based on optochin susceptibility and bile solubility. Serum concentrations of total anti-capsular immunoglobulin G (IgG) for PCV13 serotypes were identified by luminescent microsphere.

Results

In total 615 children were swabbed, 274 (44.6%, 95% CI 40.6-48.6) of whom were carrying pneumococcus. PCV13 serotypes 3 (5, 0.8%), 19A(6, 1.0%), and 19F (3, 0.5%) were detected however, the majority (95.6%) of detected isolates (comprising >30 different serotypes) were non-vaccine types, most commonly 23B (34, 5.5%), 11A (31, 5.0%), 21 (31, 5.0%), 15B (28, 4.6%), and 10A (23, 3.7%).

A subset of 249 children provided a blood sample. Geometric mean antibody concentrations against PCV13 serotypes ranged from 0.26µg/ml (95% CI 0.22-0.31) (6B) to 2.31µg/ml (95% CI 2.08-2.56) (7F). The proportion of samples with IgG ≥0.35µg/ml ranged from 38.6% (23F) to 97.2% (7F).

Conclusions

Following a two-dose priming schedule there is a low prevalence of vaccine serotype carriage. These data provide an important baseline for comparison with carriage and seroprevalence data after a single priming dose.

Funded by Pfizer Ltd.

Clinical Trial Registration

Clinicaltrials.gov identifier NCT03102840

ClinicalTrials.gov Identifier: NCT01996007

Background

Hemolytic uremic syndrome (HUS) is typically a complication of enterocolitis from Shiga toxin-producing Escherichia coli. Streptococcus pneumoniae-associated HUS (SP-HUS) is less frequent, accounting for ~5% of HUS cases in children. This study describes the epidemiology of pediatric SP-HUS in Canada.

Methods

The Canadian Immunization Monitoring Program, ACTive (IMPACT) is a national, sentinel surveillance network for vaccine-preventable diseases. It includes 12 pediatric hospitals and ~90% of tertiary care pediatric beds across Canada. All IMPACT invasive pneumococcal disease (IPD) cases from 1991-2019 were retrospectively analyzed to describe SP-HUS occurrence according to pneumococcal conjugate vaccine (PCV13) history and SP serotype. Fisher’s Exact Test compared serotype prevalence among SP-HUS and non-HUS IPD cases.

Results

From total 6,757 IPD cases, 30 SP-HUS cases (0.44%) were identified. Among SP-HUS patients with known serotypes (25/30), serotypes 3 (9/25, 36%) and 19A (32%) were more prevalent in SP-HUS cases than in non-HUS IPD cases (p<0.01).

PCV13 serotypes occurred in 88% (22/25) of SP-HUS cases, of which 77% (17/22) occurred pre-PCV13 availability. Among the 5 SP-HUS cases occurring post-PCV13, 1 was not immunized and became ill with a vaccine preventable serotype, 1 had unknown vaccine history, and 3 were vaccine failures including serotypes 3 (n=2) and 19A (n=1).

Conclusions

Two PCV13 serotypes (3, 19A) were significantly more prevalent in SP-HUS cases compared to non-HUS IPD and were identified in all vaccine failure SP-HUS cases. Future study will examine if serotypes 3 and 19A are also more prevalent among SP-HUS cases in other geographic regions and if PCV13 is less effective against these serotypes. Further research will also identify vaccine failures in non-HUS IPD cases and compare them to those of SP-HUS.

Background

In the United States, persons 16-23 years-of-age are recommended to receive serogroup B meningococcal (MenB) vaccine series. We estimated series completion rates for the two licensed MenB vaccines that have different dosing schedules: MenB-4C (2-doses administered at least one month apart) and MenB-FHbp (2-doses administered at 0 and 6 months).

Methods

This retrospective analysis of insurance claims data, included 16-23 year-olds who received a MenB vaccination (index date) on/after 01/01/2017 in the MarketScan Commercial Claims Encounters (through 11/30/2018) Multi-State Medicaid Databases (9/30/2018), and were continuously enrolled for 6 months prior and 15 months post-index date. Kaplan-Meier curves estimated time to 2-dose completion and chi-squared tests assessed statistical significance. For individuals who did not complete their series, potential missed opportunities for series completion were identified as preventive care or vaccine administrative office visits during 15-months follow-up.

Results

Among 156,080 eligible commercially insured individuals, 61% of those who initiated MenB-4C and 50% of those who initiated MenB-FHbp completed the 2-dose series within 15 months (p-value <0.0001) (Fig 1a). For 57,082 eligible Medicaid beneficiaries, completion rates were 48% and 34% for MenB-4C and MenB-FHbp, respectively (p-value <0.0001) (Fig 1b). For both vaccines combined, completion rates were 57% and 45% for Commercial and Medicaid, respectively. Of the 67,523 commercially insured individuals who did not complete their series, 40% had at least one missed opportunity for series completion (35% for Medicaid).

Conclusions

While 2-dose completion rates are higher among those who initiate MenB-4C compared to MenB-FHbp, overall MenB vaccine completion rates are suboptimal. To ensure full benefits of MenB vaccination, it is critical to improve completion rates and reduce potential missed opportunities.

ACKNOWLEDGEMENTS: Business & Decision Life Sciences (Coordinator: Quentin Rayée).