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Rates of varicella have decreased substantially in countries implementing routine varicella vaccination. Immunisation is possible with monovalent varicella vaccine or a combined measles-mumps-rubella-varicella vaccine (MMRV). We assessed protection against varicella in naive children administered one dose of varicella vaccine or two doses of MMRV. This study was done in ten European countries with endemic varicella. Healthy children aged 12–22 months were randomised (3:3:1 ratio, by computer-generated randomisation list, with block size seven) to receive 42 days apart (1) two doses of MMRV (MMRV group), or (2) MMR at dose one and monovalent varicella vaccine at dose two (MMR+V group), or (3) two doses of MMR (MMR group; control). Participants and their parents or guardians, individuals involved in assessment of any outcome, and sponsor staff involved in review or analysis of data were masked to treatment assignment. The primary efficacy endpoint was occurrence of confirmed varicella (by detection of varicella zoster virus DNA or epidemiological link) from 42 days after the second vaccine dose to the end of the first phase of the trial. Cases were graded for severity. Efficacy analyses were per protocol. Safety analyses included all participants who received at least one vaccine dose. This trial is registered with ClinicalTrials.gov, number NCT00226499. Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14·2 months, SD 2·5) were vaccinated. In the efficacy cohort of 5285 children, the mean duration of follow-up in the MMRV group was 36 months (SD 8·8), in the MMR+V group was 36 months (8·5) and in the MMR group was 35 months (8·9). Varicella cases were confirmed for 37 participants in the MMRV group (two moderate to severe), 243 in the MMR+V group, and 201 in the MMR group. Second cases occurred for three participants (all in the MMR+V group). Varicella cases were moderate to severe for two participants in the MMRV group, 37 in the MMR+V group (one being a second case that followed a mild first case); and 117 in the MMR group. Efficacy of two-dose MMRV against all varicella was 94·9% (97·5% CI 92·4–96·6), and against moderate to severe varicella was 99·5% (97·5–99·9). Efficacy of one-dose varicella vaccine against all varicella was 65·4% (57·2–72·1), and against moderate to severe varicella (post hoc) was 90·7% (85·9–93·9). The most common adverse event in all groups was injection-site redness (up to 25% of participants). Within 15 days after dose one, 57·4% (95% CI 53·9–60·9) of participants in the MMRV group reported fever of 38°C or more, by contrast with 44·5% (41·0–48·1) with MMR+V, and 39·8% (33·8–46·1) with MMR. Eight serious adverse events were deemed related to vaccination (three MMRV, four MMR+V, one MMR). All resolved within the study period. These results support the implementation of two-dose varicella vaccination on a short course, to ensure optimum protection from all forms of varicella disease. GlaxoSmithKline Vaccines.

The emergence of a novel SARS-CoV-2 B.1.1.7 variant sparked global alarm due to increased transmissibility, mortality, and uncertainty about vaccine efficacy, thus accelerating efforts to detect and track the variant. Current approaches to detect B.1.1.7 include sequencing and RT-qPCR tests containing a target assay that fails or results in reduced sensitivity towards the B.1.1.7 variant. Since many countries lack genomic surveillance programs and failed assays detect unrelated variants containing similar mutations as B.1.1.7, we used allele-specific PCR, and judicious placement of LNA-modified nucleotides to develop an RT-qPCR test that accurately and rapidly differentiates B.1.1.7 from other SARS-CoV-2 variants. We validated the test on 106 clinical samples with lineage status confirmed by sequencing and conducted a country-wide surveillance study of B.1.1.7 prevalence in Slovakia. Our multiplexed RT-qPCR test showed 97% clinical sensitivity and retesting 6,886 SARS-CoV-2 positive samples obtained during three campaigns performed within one month, revealed pervasive spread of B.1.1.7 with an average prevalence of 82%. Labs can easily implement this test to rapidly scale B.1.1.7 surveillance efforts and it is particularly useful in countries with high prevalence of variants possessing only the ΔH69/ΔV70 deletion because current strategies using target failure assays incorrectly identify these as putative B.1.1.7 variants.

The duration of protection provided by varicella vaccines is unclear. We assessed the 10-year vaccine efficacy of two doses of a combined measles-mumps-rubella-varicella vaccine (MMRV), one live attenuated varicella vaccine (V) dose given after one measles-mumps-rubella vaccine (MMR) dose (MMR + V), versus two MMR doses (control vaccine) for the prevention of confirmed varicella. This was a phase 3b follow-up of an observer-blinded, randomised, controlled trial. In phase a, children aged 12–22 months (at first vaccination) from Czech Republic (Czechia), Greece, Italy, Lithuania, Norway, Poland, Romania, Russia, Slovakia, and Sweden were randomly assigned by computer-generated randomisation list (3:3:1) to receive two doses of MMRV, one dose of MMR and one dose of varicella vaccine, or two doses of MMR, 42 days apart. Varicella cases were confirmed by detection of viral DNA, or epidemiological link and clinical assessment, by an independent data monitoring committee; disease severity was based on a modified Vázquez scale. Hazard ratios for MMRV and MMR + V versus MMR estimated in the per-protocol cohort using a Cox proportional hazards regression model were used to calculate vaccine efficacy and 95% CI. Serious adverse events were recorded throughout the study in all vaccinated children. Study objectives were secondary and descriptive. The trial is registered at ClinicalTrials.gov, number NCT00226499. Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14·2 months, SD 2·5) were vaccinated. The per-protocol cohort included 2279 children from the MMRV group, 2266 from the MMR + V group, and 744 from the MMR group. From baseline to a median follow-up of 9·8 years, 76 (3%) children in the MMRV group, 469 (21%) in the MMR + V group, and 352 (47%) in the MMR group had varicella. Vaccine efficacy against all varicella was 95·4% (95% CI 94·0–96·4) for MMRV and 67·2% (62·3–71·5) for MMR + V; vaccine efficacy against moderate or severe varicella was 99·1% (97·9–99·6) for MMRV and 89·5% (86·1–92·1) for MMR + V. During phase b, serious adverse events were reported by 290 (15%) of 1961 children in the MMRV group, 317 (16%) of 1978 in the MMR + V group, and 93 (15%) of 641 in the MMR group. There were no treatment-related deaths. The 10-years vaccine efficacy observed, suggests that a two-dose schedule of varicella vaccine provided optimum long-term protection for the prevention of varicella by offering individual protection against all severities of disease and leading to a potential reduction in transmission, as observed in the US experience with universal mass vaccination. GlaxoSmithKline Biologicals.

Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases. European Centre for Disease Prevention and Control.

Slovakia is well-known for tick-borne encephalitis alimentary (TBE) outbreaks in Europe for a long time. Since the first known and largest TBE alimentary outbreak in 1951 (at territory of Slovakia) until today, none of the European countries report a comparable number of TBE alimentary outbreaks with probable and laboratory confirmed food transmission factor as Slovakia. We analyzed TBE outbreak confirmed cases reported in Slovakia from web-based Epidemiological Information System (EPIS) during the period 2007–2016. During years 2007–2016 we recorded 26 TBE alimentary outbreaks. In most outbreaks (22 out of 26) the probable transmission factor of TBE virus was identified within epidemiological context. In 4 outbreaks the transmission factor was laboratory confirmed. The most common probable and confirmed transmission factor of alimentary TBE outbreaks was milk and milk products of goat origin. There should be more effort of laboratory clarification of TBE transmission factor in Slovakia. It is important to be aware of the issue of Slovakia from the point of tourism and prevention, but also due to potential risks of consumption of raw milk and its products that became popular in recent years not only in Slovakia.

Despite the effective National Immunization Programme of Slovakia, some population groups are incompletely vaccinated or unvaccinated. We aimed to describe the measles outbreak spread in Eastern Slovakia between May and October 2018, affecting the Roma communities in relation to the existing immunity gaps. We defined a group of persons living in socially closed communities with low vaccination coverage. Of 439 measles cases (median age: 10 years), 264 (60.1%) were vaccinated, 137 (31.2%) received two doses and 127 (28.9%) one dose of measles vaccines, 155 (35.3%) were unvaccinated and 20 (4.6%) had an unknown vaccination status. Samples from 102 patients (with two-dose vaccination status) were additionally tested for antibodies against rubella and mumps. Of 102 cases, 68 (66.7%) cases had a positive IgM and 23 (22.5 %) IgG antibodies against measles. For rubella, only 20 (19.6%) cases had seropositive IgG levels, for mumps higher positivity was detected in 60 persons (58.8%). We could detect only a small percentage with positive serology results of rubella IgG antibodies across all age groups. We have assumed that rubella antibodies had to be produced following the vaccination. Their absence in the cases with two doses of MMR suggests that these vaccines could not have been administrated despite the fact that this data was included in the medical records. Sequential analysis of two samples showed measles genotype B3. This outbreak can outline the existence of a vulnerable group of the Roma. Low vaccinate coverage represents a serious public health threat.

We assessed the long-term persistence of humoral immunity against diphtheria in adults with childhood vaccination and the immunogenicity of a booster dose considering demographic, behavioural and vaccinating factors. We conducted a trial in 200 healthy Slovak adults aged 24–65 years, immunised against diphtheria in childhood and against tetanus at regular 10–15 year intervals, and receiving a dose of a tetanus-diphtheria toxoid vaccine. The response was determined by ELISA antibody concentrations of paired sera before and at 4 weeks post-vaccination. A seroprotection rate of 21% (95% confidence interval, CI 15.6–27.3%) was found in adults up to 59 years since the last vaccination with seroprotective levels of antibodies against diphtheria ≥0.1 IU/mL and a geometric mean concentration of 0.05 IU/mL. Conversely, seropositive levels ≥0.01 IU/mL were observed in 98% of adults (95% CI 95–99.5%). Booster-induced seroprotection was achieved in 78% of adults (95% CI 71.6–83.5%) clearly depending on pre-booster antibody levels correlating with age and time since the last vaccination. Moreover, only 54.2% of smokers and 53.3% of patients on statins exhibited seroprotection. Booster vaccination against diphtheria was unable to confer seroprotection in all recipients of only childhood vaccination.

Vaccines are biologic medical products, the biological activity and characteristics of which are significantly different from common drugs and other medical products. The process of determining the dosing (vaccination) schedule for a particular vaccine is based on different principles and rules than other drugs. The dosing schedule for drugs is based on the essential pharmacological properties: pharmacokinetics and pharmacodynamics. When determining the schedule for vaccines, the pharmacokinetic and pharmacodynamic principles cannot be applied: sero-conversion and sero-protectivity of the biologically active component of the vaccine need to be applied. As opposed to drugs and medical products the dosing (vaccination) schedule in the Summary of Product Characteristics (SPC) is often provided in several versions, sometimes with a supplement referring to official (national) recommendations. In relation to the large variability vaccination schedules in the European Union (EU), it is not realistic to test each vaccination schedule in clinical studies. Requiring clinical trials for each vaccination schedule used only for the needs of regulators is more of an ethical issue than a scientific one. The European Centre for Disease Prevention and Control (ECDC), which is the Scientific Panel on Childhood Immunisation Schedule (SPACIS), accepts all the schedules used in EU countries as valid. A review of the literature on immunisation schedules for primary series and booster doses choosing the following key words: immunisation, vaccination schedule, primary, booster, timing, vaccination delay.

Mandelic acid (MA) is an important metabolite of styrene. In humans, measurement of its concentration in urine provides an important assessment of the overall level of styrene exposure in workers of the reinforced plastic manufacturing industry. The aim of our study was to investigate in these workers the relationship between MA concentration and styrene exposure time and intensity as well as its dependence on work occupation. The concentration of MA in the urine samples of 35 employees was analyzed with HPLC (high performance liquid chromatography). Out of 35 workers, 11 performed laminating, 11 milling and finalizing, 6 laying-up and spraying-up, and 7 worked in background support. Urinal samples were obtained twice a day over the course of three weeks, at the beginning and the end of the work shift. We found a significant increase in MA concentrations during a work shift in all tested days (Wilcoxon test p < 0.05). Employees working in elevated atmospheric concentrations of styrene (93.77-159.88 mg/m3) had significantly higher MA concentrations in urine compared to other groups at both the beginning and the end of the shift (Kruskal Wallis test p < 0.001) (p < 0.001). Only samples from laminating workers exceeded the biological limit of MA concentration (640 mg/L) at the end of the shift. Normalisation of MA concentration to body mass index (BMI, normal range: 21.7 +/- 3.2 kg/m2) refined differences within groups (Kruskal-Wallis analysis p < 0.001). The accumulation of MA at the end of the work shift for measured time period was not significant for the measured time period (Friedman analysis p > 0.11). Our results confirmed that MA is a sensitive metabolic marker of styrene exposure without cumulative effect. However, normalization of MA concentrations to BMI can improve the accuracy of styrene exposure estimates in certain groups of employees.

In 2011–12, the European Centre for Disease Prevention and Control (ECDC) held the first Europe-wide point-prevalence survey of health-care-associated infections in acute care hospitals. We analysed paediatric data from this survey, aiming to calculate the prevalence and type of health-care-associated infections in children and adolescents in Europe and to determine risk factors for infection in this population. Point-prevalence surveys took place from May, 2011, to November, 2012, in 1149 hospitals in EU Member States, Iceland, Norway, and Croatia. Patients present on the ward at 0800 h on the day of the survey and who were not discharged at the time of the survey were included. Data were collected by locally trained health-care workers according to patient-based or unit-based protocols. We extracted data from the ECDC database for all paediatric patients (age 0–18 years). We report adjusted prevalence for health-care-associated infections by clustering at the hospital and country level. We also calculated risk factors for development of health-care-associated infections with use of a generalised linear mixed-effects model. We analysed data for 17 273 children and adolescents from 29 countries. 770 health-care-associated infections were reported in 726 children and adolescents, corresponding to a prevalence of 4·2% (95% CI 3·7–4·8). Bloodstream infections were the most common type of infection (343 [45%] infections), followed by lower respiratory tract infections (171 [22%]), gastrointestinal infections (64 [8%]), eye, ear, nose, and throat infections (55 [7%]), urinary tract infections (37 [5%]), and surgical-site infections (34 [4%]). The prevalence of infections was highest in paediatric intensive care units (15·5%, 95% CI 11·6–20·3) and neonatal intensive care units (10·7%, 9·0–12·7). Independent risk factors for infection were age younger than 12 months, fatal disease (via ultimately and rapidly fatal McCabe scores), prolonged length of stay, and the use of invasive medical devices. 392 microorganisms were reported for 342 health-care-associated infections, with Enterobacteriaceae being the most frequently found (113 [15%]). Infection prevention and control strategies in children should focus on prevention of bloodstream infections, particularly among neonates and infants. None.