Increase in tympanostomy tube placements despite pneumococcal vaccination, a population-based study.

AIM: The aim was to estimate the impact of the 10-valent pneumococcal vaccine (PHiD-CV) on tympanostomy tube placements (TTP) in children under five years of age in Iceland. METHODS: This population-based observational cohort study followed 11 consecutive birth-cohorts 2005-2015 from birth until their fifth birthday. Population registries were merged using national identification numbers. The risk of TTP was compared between birth-cohorts adjusted for the number of previous otitis media diagnoses and antimicrobial prescriptions. A Cox regression model was applied and the hazard ratio (HR) of TTP was estimated between each birth-cohort and the last vaccine non-eligible birth-cohort. The vaccine impact of PHiD-CV10 on TTP was estimated as 1-HR ×100%. RESULTS: In total, 51 247 children were followed for 210 724 person-years, of which 14 351 underwent 20 373 procedures. The estimated vaccine impact on TTP was -6% (95% CI -16% to 2.7%). Children in the vaccine-eligible cohorts had fewer previous otitis media diagnoses and had been prescribed fewer antimicrobials prior to the procedure than children in the vaccine non-eligible cohorts. CONCLUSION: Despite high uptake of PHiD-CV10, tympanostomy procedures increased in Iceland during the study period. Vaccine-eligible children had milder disease prior to the procedure. The reason underlying these findings are speculative.

Reduction in All-Cause Acute Otitis Media in Children <3 Years of Age in Primary Care Following Vaccination With 10-Valent Pneumococcal Haemophilus influenzae Protein-D Conjugate Vaccine: A Whole-Population Study.

Background: The 10-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced in Iceland in 2011, without catch-up. The aim of this study was to estimate vaccine impact (VI) on acute otitis media (AOM). Methods: In this whole-population study, all primary care visits due to AOM from 2005 to 2015 in children <3 years of age were included. Birth cohorts were grouped as vaccine noneligible (VNEC) or vaccine eligible (VEC). Crude incidence rates (IRs) were compared between the VNEC and VEC. A Cox regression model for repeated events was used to model the individual-level data. VI was calculated as (hazard ratio [HR] - 1) × 100%. Results: Included were 53150 children, with 140912 person-years of follow-up and 58794 AOM episodes. Both IR and the mean number of episodes differed significantly between VNEC and VEC; 43 compared to 38 episodes per 100 person-years and 1.61 episodes per child compared to 1.37. IR was significantly reduced in all age brackets, with the largest reduction in children <4 months of age (40% [95% confidence interval {CI}, 31%-49%). The VI on all-cause AOM was 22% (95% CI, 12%-31%). The impact was mediated through its effect on the first (HR, 0.84 [95% CI, .82-.86]) and second (HR, 0.95 [95% CI, .93-.98]) episodes. Conclusions: The impact of PHiD-CV10 on all-cause AOM was considerable, mediated mainly by preventing the first two episodes of AOM. A decrease in the IR of AOM in children too young to receive direct vaccine protection was demonstrated, suggesting herd effect.

Effect of Vaccination on Pneumococci Isolated from the Nasopharynx of Healthy Children and the Middle Ear of Children with Otitis Media in Iceland.

Vaccination with pneumococcal conjugate vaccines (PCVs) disrupts the pneumococcal population. Our aim was to determine the impact of the 10-valent PCV on the serotypes, genetic lineages, and antimicrobial susceptibility of pneumococci isolated from children in Iceland. Pneumococci were collected between 2009 and 2017 from the nasopharynges of healthy children attending 15 day care centers and from the middle ears (MEs) of children with acute otitis media from the greater Reykjavik capital area. Isolates were serotyped and tested for antimicrobial susceptibility. Whole-genome sequencing (WGS) was performed on alternate isolates from 2009 to 2014, and serotypes and multilocus sequence types (STs) were extracted from the WGS data. Two study periods were defined: 2009 to 2011 (PreVac) and 2012 to 2017 (PostVac). The overall nasopharyngeal carriage rate was similar between the two periods (67.3% PreVac and 61.5% PostVac, P = 0.090). Vaccine-type (VT) pneumococci decreased and nonvaccine-type (NVT) pneumococci (serotypes 6C, 15A, 15B/C, 21, 22F, 23A, 23B, 35F, and 35B) significantly increased in different age strata post-PCV introduction. The total number of pneumococci recovered from ME samples significantly decreased as did the proportion that were VTs, although NVT pneumococci (6C, 15B/C, 23A, and 23B) increased significantly. Most serotype 6C pneumococci were multidrug resistant (MDR). Serotype 19F was the predominant serotype associated with MEs, and it significantly decreased post-PCV introduction: these isolates were predominantly MDR and of the Taiwan19F-14 PMEN lineage. Overall, the nasopharyngeal carriage rate remained constant and the number of ME-associated pneumococci decreased significantly post-PCV introduction; however, there was a concomitant and statistically significant shift from VTs to NVTs in both collections of pneumococci.

Impact of the 10-valent pneumococcal conjugate vaccine on antimicrobial prescriptions in young children: a whole population study.

BACKGROUND: Antimicrobial resistance is a public-health threat and antimicrobial consumption is the main contributor. The ten-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced into the Icelandic vaccination program in 2011. The aim was to estimate the vaccine impact of PHiD-CV10 on outpatient antimicrobial prescriptions in children. METHODS: Eleven Icelandic birth-cohorts (2005-2015) were followed from birth until three years of age or to the end of the study period (December 31, 2016). Birth-cohorts were grouped as vaccine non-eligible (VNEC, 2005-2010) or vaccine eligible (VEC, 2011-2015). Data on primary care visits for respiratory infections and antimicrobial prescriptions were extracted from two national registers. Using national identification numbers, prescriptions were linked to physician visits if filled within three days of the visit. Incidence rates and incidence rate ratios between VNEC and VEC were calculated. An Andersen-Gill model was used to model the individual level data, accounting for repeated events and censoring. Vaccine impact was calculated as (1 - Hazard Ratio) × 100%. RESULTS: Included were 53,510 children who contributed 151,992 person-years of follow-up and filled 231,660 antimicrobial prescriptions. The incidence rate was significantly lower in the VEC compared to the VNEC, 144.5 and 157.2 prescriptions per 100 person-years respectively (IRR 0.92, 95%CI 0.91-0.93). Children in VEC were more likely to have filled zero (IRR 1.16 (95%CI 1.10-1.23) and 1-4 (IRR 1.08 95%CI 1.06-1.11) prescriptions compared to children in VNEC. The vaccine impact of PHiD-CV10 against all-cause antimicrobial prescriptions was 5.8% (95%CI 1.6-9.8%).When only considering acute otitis media-associated prescriptions, the vaccine impact was 21.8% (95%CI 11.5-30.9%). CONCLUSION: The introduction of PHiD-CV10 lead to reduced antimicrobial use in children, mainly by reducing acute otitis media episodes. This intervention therefore reduces both disease burden and could slow the spread of antimicrobial resistance.

Glucocorticoids in the treatment of non-infectious superior ophthalmic vein thrombosis - Three cases and a review of the literature.

Purpose: Superior ophthalmic vein thrombosis (SOVT) is a rare clinical entity, which can have a septic and an aseptic cause. Aseptic SOVT is typically treated with anticoagulation. Glucocorticoids are reserved for cases with concurrent orbital inflammation.We present three cases of SOVT due to carotid cavernous fistula not responding to standard treatment, subsequently successfully treated with glucocorticoids. Observations: Three patients with various degrees of proptosis, ophthalmoplegia, orbital stasis and reduced vision are presented. One patient was confirmed to have isolated SOVT, while the other two had associated cavernous sinus thrombosis. All patients had underlying carotid-cavernous fistula without signs of infection. All patients were initially treated with parenteral anticoagulation. Two patients were treated with intraocular pressure-reducing medication. One of whom underwent canthotomy-cantholysis. Two patients experienced a gradual worsening of symptoms during treatment with anticoagulation, while one patient improved before deteriorating. All patients received additional treatment with glucocorticoids consisting of a three-day treatment with intravenous methylprednisolone 500 mg, followed by oral glucocorticoids resulting in total regression of symptoms. Two patients regained 20/20 vision, with some vision field defects, while the third patient regained 20/25 vision. Conclusion and importance: The addition of glucocorticoids in the treatment of aseptic SOVT can lead to improvement of symptoms and a potentially better prognosis. However, the risk of complications of glucocorticoid treatment must be carefully considered on a case-by-case basis.

Impact of the 10-valent pneumococcal conjugate vaccine on hospital admissions in children under three years of age in Iceland.

INTRODUCTION: Pneumococcus is an important respiratory pathogen. The 10-valent pneumococcal vaccine (PHiD-CV) was introduced into the Icelandic vaccination programme in 2011. The aim was to estimate the impact of PHiD-CV on paediatric hospitalisations for respiratory tract infections and invasive disease. METHODS: The 2005-2015 birth-cohorts were followed until three years of age and hospitalisations were recorded for invasive pneumococcal disease (IPD), meningitis, sepsis, pneumonia and otitis media. Hospitalisations for upper- and lower respiratory tract infections (URTI, LRTI) were used as comparators. The 2005-2010 birth-cohorts were defined as vaccine non-eligible cohorts (VNEC) and 2011-2015 birth-cohorts as vaccine eligible cohorts (VEC). Incidence rates (IR) were estimated for diagnoses, birth-cohorts and age groups, and incidence rate ratios (IRR) between VNEC and VEC were calculated assuming Poisson variance. Cox regression was used to estimate the hazard ratio (HR) of hospitalisation between VNEC and VEC. RESULTS: 51,264 children were followed for 142,315 person-years, accumulating 1,703 hospitalisations for the respective study diagnoses. Hospitalisations for pneumonia decreased by 20% (HR 0.80, 95%CI:0.67-0.95) despite a 32% increase in admissions for LRTI (HR 1.32, 95%CI:1.14-1.53). Hospital admissions for culture-confirmed IPD decreased by 93% (HR 0.07, 95%CI:0.01-0.50) and no hospitalisations for IPD with vaccine-type pneumococci were observed in the VEC. Hospitalisations for meningitis and sepsis did not change. A decrease in hospital admissions for otitis media was observed, but did not coincide with PHiD-CV introduction. CONCLUSION: Following the introduction of PHiD-CV in Iceland, hospitalisations for pneumonia and culture confirmed IPD decreased. Admissions for other LRTIs and URTIs increased during this period.

Pneumococcal vaccination: Direct and herd effect on carriage of vaccine types and antibiotic resistance in Icelandic children.

BACKGROUND: Since the introduction of pneumococcal conjugate vaccines, vaccine type pneumococcal carriage and disease has decreased world-wide. The aim was to monitor changes in the nasopharyngeal carriage of pneumococci, the distribution of serotypes and antimicrobial resistance in children before and after initiation of the 10-valent pneumococcal vaccination in 2011, in a previously unvaccinated population. METHODS: Repeated cross-sectional study at 15day-care centres in greater Reykjavik area. Nasopharyngeal swabs were collected yearly in March from 2009 to 2015. The swabs were selectively cultured for pneumococci, which were serotyped using latex agglutination and/or PCR and antimicrobial susceptibility determined. Two independent studies were conducted. In study 1, on total impact, isolates from children aged <4years were included. The vaccine-eligible-cohort (birth-years: 2011-2013, sampled in 2013-2015) was compared with children at the same age born in 2005-2010 and sampled in 2009-2012. In study 2 on herd effect, isolates from older non-vaccine-eligible children (3.5-6.3years) were compared for the periods before and after the vaccination (2009-2011 vs 2013-2015. Vaccine impact was determined using 1-odds-ratio. RESULTS: Following vaccination, the vaccine impact on vaccine type acquisition was 94% (95% CI: 91-96%) in study 1 and 56% (95% CI: 44-65%) in study 2. The impact on serotype 6A was 33% (95% CI: -9%; 59%) in study 1 and 42% (95% CI: 10-63%) in study 2 with minimal effect on 19A. The non-vaccine serotypes/groups 6C, 11, 15 and 23B were the most common serotypes/groups after vaccination. Isolates from the vaccine-eligible-cohort had lower penicillin MICs, less resistance to erythromycin and co-trimoxazole and less multi resistance than isolates from the control-group. CONCLUSIONS: The efficacy of the vaccination on vaccine serotypes was high, and a milder effect on vaccine-associated-serotype 6A was observed for the vaccine-eligible-cohort. There was a significant herd effect on vaccine types in older non-vaccine-eligible children. Overall antimicrobial non-susceptibility was reduced.

Decreased Incidence of Respiratory Infections in Children After Vaccination with Ten-valent Pneumococcal Vaccine.

INTRODUCTION: Respiratory tract infections (RTIs) and antibiotic usage are common in children, increasing the risk of antibacterial resistance. The introduction of protein-conjugated pneumococcal vaccines has led to reduction in pneumococcal infections. In 2011, pneumococcal protein-conjugated vaccine-10 was introduced into the national childhood vaccination in Iceland, a population not earlier vaccinated against pneumococcus, with 95% vaccine uptake in the first year. The aim of the study was to evaluate the number of children visiting the Children's Hospital Iceland for RTIs before and after the introduction of the vaccine. METHODS: Admissions and visits to the Children's Hospital because of RTIs were recorded, and children aged 3 months to 2 years in the nonvaccine eligible cohort (born 2008-2010) were compared with the vaccine eligible cohort (born in 2011). Statistical analysis was done using large sample Z test and incidence rate ratios (IRRs) were calculated. RESULTS: A significant reduction in incidence rate was found when comparing the nonvaccine eligible cohort with the vaccine eligible cohort, both for acute otitis media (AOM) (IRR: 0.76; 95% confidence interval: 0.67-0.87; P < 0.0001) and for pneumonia (IRR: 0.77; 95% confidence interval: 0.64-0.95; P < 0.01). CONCLUSION: A significant reduction in hospital visits because of AOM and pneumonia in children vaccinated with pneumococcal protein-conjugated vaccine-10 was established. The abrupt and significant reduction of AOM is unusually clear. This reduction was noted very early after initiation of the vaccination.