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.
Summary Background 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. Methods 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. Findings 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. Interpretation These results support the implementation of two-dose varicella vaccination on a short course, to ensure optimum protection from all forms of varicella disease. Funding GlaxoSmithKline Vaccines.
The number of cases of
Candida auris
infection or carriage and of countries reporting cases and outbreaks increased in the European Union and European Economic Area during 2020 and 2021. Eight ...countries reported 335 such cases in 2020 and 13 countries 655 cases in 2021. Five countries experienced outbreaks while one country reported regional endemicity. These findings highlight the need for adequate laboratory capacity and surveillance for early detection of
C. auris
and rapid implementation of control measures.
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.
Antimicrobial agents used to treat infections are life-saving. Overuse may result in more frequent adverse effects and emergence of multidrug-resistant microorganisms. In 2016-17, we performed the ...second point-prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals. We included 1,209 hospitals and 310,755 patients in 28 of 31 European Union/European Economic Area (EU/EEA) countries. The weighted prevalence of antimicrobial use in the EU/EEA was 30.5% (95% CI: 29.2-31.9%). The most common indication for prescribing antimicrobials was treatment of a community-acquired infection, followed by treatment of HAI and surgical prophylaxis. Over half (54.2%) of antimicrobials for surgical prophylaxis were prescribed for more than 1 day. The most common infections treated by antimicrobials were respiratory tract infections and the most commonly prescribed antimicrobial agents were penicillins with beta-lactamase inhibitors. There was wide variation of patients on antimicrobials, in the selection of antimicrobial agents and in antimicrobial stewardship resources and activities across the participating countries. The results of the PPS provide detailed information on antimicrobial use in European acute care hospitals, enable comparisons between countries and hospitals, and highlight key areas for national and European action that will support efforts towards prudent use of antimicrobials.
Antimicrobials are commonly prescribed and contribute to the development of antimicrobial resistance in long-term care facilities (LTCFs). In 2010, the European Centre for Disease Prevention and ...Control initiated point prevalence surveys (PPS) of healthcare-associated infections and antimicrobial use in European LTCFs, performed by external contractors as the Healthcare-Associated infections in Long-Term care facilities (HALT) projects. Here, we investigated prevalence and characteristics of antimicrobial use and antimicrobial stewardship indicators in European LTCFs in 2016-17. Twenty-four European Union/European Economic Area (EU/EEA) countries, the former Yugoslav Republic of Macedonia and Serbia participated in the third PPS in European LTCFs. Overall, 4.9% (95% confidence interval: 4.8-5.1) of LTCF residents in the EU/EEA participating countries received at least one antimicrobial. The most commonly reported Anatomical Therapeutic Chemical (ATC) groups were beta-lactam antibacterials/penicillins (J01C), other antibacterials (J01X) (e.g. glycopeptide antibacterials, polymyxins), quinolones (J01M), sulfonamides and trimethoprim (J01E), and other beta-lactams (J01D). Urinary tract infections and respiratory tract infections were the main indications for antimicrobial prescription. This PPS provides updated and detailed information on antimicrobial use in LTCFs across the EU/EEA that can be used to identify targets for future interventions, follow-up of these interventions and promote prudent use of antimicrobials in European LTCFs.
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.
The number of cases of Candida auris infection or carriage and of countries reporting cases and outbreaks increased in the European Union and European Economic Area during 2020 and 2021. Eight ...countries reported 335 such cases in 2020 and 13 countries 655 cases in 2021. Five countries experienced outbreaks while one country reported regional endemicity. These findings highlight the need for adequate laboratory capacity and surveillance for early detection of C. auris and rapid implementation of control measures.
To provide valuable local data on the economic burden of rotavirus gastroenteritis (RVGE) for decision making on introduction of rotavirus vaccination in Central European countries.
We conducted a ...retrospective patient hospital chart review during the winter RVGE peak in the Czech Republic (n = 109), Hungary (n = 109), Poland, (n = 112), and Slovakia (n = 115) to estimate resource use and associated costs from the payer’s perspective in children younger than 5 years with severe RVGE requiring hospitalization. Microcosting analysis was used to estimate the average costs of treating RVGE inpatients including pre- and posthospitalization costs.
The average cost of treatment was €476, €316, €741, and €594 in the Czech Republic, Hungary, Poland, and Slovakia, respectively. Extrapolating these costs to the total number of RVGE hospitalizations gives annual cost estimates of €2.1 million, €1.5 million, €13.2 million, and €1.5 million, respectively. The main component of expenditure in all the four countries is the hospital stay, but wide variation among countries was observed (total cost of treating RVGE in hospital was almost 2.5-fold higher in Poland than in Hungary). In countries with diagnosis related group (DRG) costs available, the best agreement between real resource-use–driven costs and the DRG cost was found in the Czech Republic and Hungary, with differences of only €22 and €33, respectively. In Poland, the microcosting indicated higher overall costs incurred in hospital than the DRG cost, with a difference exceeding €190.
Hospitalization of children with RVGE represents a substantial economic burden for the national health systems in these countries.
We collected data from 10 EU/EEA countries on 240 COVID-19 outbreaks occurring from July-October 2021 in long-term care facilities with high vaccination coverage. Among 17,268 residents, 3,832 ...(22.2%) COVID-19 cases were reported. Median attack rate was 18.9% (country range: 2.8-52.4%), 17.4% of cases were hospitalised, 10.2% died. In fully vaccinated residents, adjusted relative risk for COVID-19 increased with outbreak attack rate. Findings highlight the importance of early outbreak detection and rapid containment through effective infection prevention and control measures.
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