The influenza landscape and vaccination coverage in older adults during the SARS-Cov-2 pandemic: data from Several European Countries and Israel.

INTRODUCTION: The Raise Awareness of Influenza Strategies in Europe (RAISE) group gathered information about the healthcare burden of influenza (hospitalizations, intensive care unit [ICU] admissions, and excess deaths), surveillance systems, and the vaccine coverage rate (VCR) in older adults in 18 European countries and Israel. AREAS COVERED: Published medical literature and official medical documentation on the influenza disease burden in the participating countries were reviewed from 2010/11 until the 2022/23 influenza seasons. Information on the framework for monitoring the disease burden and the provision for ensuring older adults had access to vaccination in their respective countries was provided. Data on influenza VCR in older adults were collected for the 2019/20 to 2022/23 influenza seasons. Data are reported descriptively. EXPERT OPINION: Influenza presents a significant healthcare burden in older adults. Reporting outcomes across participating countries is heterogeneous, highlighting the need for standardized approaches. Although older adults receive free influenza vaccination, vaccine uptake is highly variable among countries. Moreover, hospitalization rates remain high even in countries reporting a high VCR. Increased awareness and education on the burden of disease and the broader use of improved influenza vaccines for older adults may help reduce the disease burden on this population.

Tuberculosis disease in immunocompromised children and adolescents: a pTBnet multi-centre case-control study.

BACKGROUND: In high-resource settings the survival of immunocompromised (IC) children has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools and outcome of IC children with TB in Europe. METHODS: Multicentre, matched case-control study within the Paediatric Tuberculosis Network European Trials Group (ptbnet), capturing TB cases <18 years diagnosed 2000-2020. RESULTS: 417 TB cases were included, comprising 139 children with IC (HIV, inborn errors of immunity, drug-induced immunosuppression and other immunocompromising conditions) and 278 non-IC children as controls. Non-respiratory TB was more frequent among cases than controls (32.4% vs. 21.2%; p = 0.013). IC patients had an increased likelihood of presenting with severe disease (57.6% vs. 38.5%; p < 0.001; OR [95% CI]: 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs. 6.0%; p < 0.001) and QuantiFERON-TB Gold assay (30.0% vs. 7.3%; p < 0.001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs. 49.3%; p = 0.083). Although the mortality in IC children was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs. 6.1%; p = 0.004). CONCLUSIONS: IC children with TB disease in Europe have increased rates of non-respiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in IC patients, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.

Epidemiological changes of acute respiratory infections in children: A single-center experience after COVID-19 lockdown.

BACKGROUND: Since the start of the COVID-19 pandemic, the epidemiology of acute respiratory infections (ARIs) has continually changed, making it difficult to predict. Our study aimed to evaluate epidemiological changes and clinical outcomes of ARIs in pediatric patients in the post-lockdown period. METHODS: A single-center retrospective cross-sectional study was performed in one of the largest pediatric emergency departments in Lithuania during two cold seasons-from October 1, 2021, to April 30, 2022 (Season I) and in the same period in 2022-2023 (Season II). Patients under 18 years of age who had been tested for COVID-19 were enrolled in the study. Additional data about other respiratory pathogens in the study group (specifically influenza A/B, respiratory syncytial virus (RSV) and group A Streptococcus (GAS)), were included. RESULTS: During both seasons of our study, 19,366 children were screened for COVID-19. Positive tests for COVID-19 decreased from 14.5% in Season I to 5.9% in Season II, while at the same time, the rates of other infections increased significantly: influenza from 17.5% to 27.1%, RSV from 8.8% to 27.6%, and GAS from 8.4% to 44%, respectively. In Season II, COVID-19 infection presented in fewer admissions to pediatric intensive care (0.8% vs. 3.7%, p<0.01) and there were no deaths, while influenza presented in a higher proportion of hospitalizations (10.5% vs. 6.1%, p<0.01) and there was one death. The proportion of RSV hospitalizations also increased in Season II (34.6% vs. 44.0%, p<0.01). CONCLUSIONS: The early post-lockdown period saw a decline of COVID-19 and re-emergence of influenza, RSV and GAS infections in children. In Season II, COVID-19 cases became milder contrary to influenza. RSV infection contributed significantly to hospitalizations for respiratory infections in children in both seasons, particularly in Season II. Coinfections were not associated with a more severe course of the disease.

Molecular characteristics of Neisseria meningitidis carriage strains in university students in Lithuania.

BACKGROUND: Neisseria meningitidis can be carried asymptomatically in the human oropharynx without causing symptoms. Meningococcal carriage is relevant to the epidemiology of invasive meningococcal disease (IMD). No carriage studies have been performed among the general population in Lithuania, whereas the incidence of IMD in Lithuania was among the highest in European countries from 2009 to 2019. RESULTS: We analyzed a total of 401 oropharyngeal samples collected from university students from December 2021 to February 2023 for N. meningitidis carriage using direct swab PCR assays and culture. The overall carriage prevalence based on both or either swab PCR or culture was 4.99%. PCR-based assays were used to characterize 15 carriage isolates, including detection of genogroup, multilocus sequence typing profile, and typing of antigens PorA and FetA. The most common carriage isolates were capsule null locus (cnl), accounting for 46.7%, followed by genogroups B (26.7%) and Y (13.3%). We also performed a molecular characterization of invasive N. meningitidis isolates collected during the COVID-19 pandemic and post-pandemic period to understand better the meningococcal carriage in the context of prevailing invasive strains. Despite the substantial decrease in the incidence of IMD during the 2020-2022 period, clonal complex 32 (CC32) of serogroup B continued to be the most prevalent IMD-causing CC in Lithuania. However, CC32 was not detected among carriage isolates. The most common CCs were CC269, CC198, and CC1136. The antigen peptide variants found in most carried isolates were classified as 'insufficient data' according to the MenDeVAR Index to evaluate the potential coverage by the 4CMenB vaccine. Nearly half of the isolates were potentially covered by the Men-Fhbp vaccine. Resistance to ciprofloxacin was detected only for one cnl isolate. All isolates were susceptible to penicillin and ceftriaxone. Our analysis identified frequent partying (≥ 4 times/month) as a risk factor for meningococcal carriage, whereas smoking, living in a dormitory, and previous COVID-19 illness were not associated with the carriage. CONCLUSIONS: Our study revealed a low prevalence of meningococcal carriage among university students in Lithuania. The carriage isolates showed genetic diversity, although almost half of them were identified as having a null capsule locus.

Molecular characterization of invasive Neisseria meningitidis isolates collected in Lithuania (2009-2019) and estimation of serogroup B meningococcal vaccine 4CMenB and MenB-Fhbp coverage.

Neisseria meningitidis causes invasive meningococcal disease (IMD), which is associated with significant mortality and long-term consequences, especially among young children. The incidence of IMD in Lithuania was among the highest in European Union/European Economic Area countries during the past two decades; however, the characterization of meningococcal isolates by molecular typing methods has not yet been performed. In this study, we characterized invasive meningococcal isolates (n=294) recovered in Lithuania from 2009 to 2019 by multilocus sequence typing (MLST) and typing of antigens FetA and PorA. The more recent (2017-2019) serogroup B isolates (n=60) were genotyped by analyzing vaccine-related antigens to evaluate their coverage by four-component (4CMenB) and two-component (MenB-Fhbp) vaccines using the genetic Meningococcal Antigen Typing System (gMATS) and Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) Index methods, respectively. The vast majority (90.5%) of isolates belonged to serogroup B. MLST revealed a predominance of clonal complex 32 (74.02%). Serogroup B strain P1.19,15: F4-28: ST-34 (cc32) accounted for 64.1% of IMD isolates. The overall level of strain coverage by the 4MenB vaccine was 94.8% (CI 85.9-98.2%). Most serogroup B isolates (87.9%) were covered by a single vaccine antigen, most commonly Fhbp peptide variant 1 (84.5% of isolates). The Fhbp peptides included in the MenB-Fhbp vaccine were not detected among the analyzed invasive isolates; however, the identified predominant variant 1 was considered cross-reactive. In total, 88.1% (CI 77.5-94.1) of isolates were predicted to be covered by the MenB-Fhbp vaccine. In conclusion, both serogroup B vaccines demonstrate potential to protect against IMD in Lithuania.

Influenza and Respiratory Syncytial Virus Infections in Pediatric Patients during the COVID-19 Pandemic: A Single-Center Experience.

The overlap of coronavirus disease 2019 (COVID-19) with other common respiratory pathogens may complicate the course of the disease and prognosis. The aim of the study was to evaluate the rates, characteristics, and outcomes of pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), influenza A/B infections, and their coinfections. A single-center prospective cross-sectional study was performed at the pediatric emergency department in Vilnius from 1 October 2021 to 30 April 2022. In total, 5127 children were screened for SARS-CoV-2, RSV, and influenza A/B. SARS-CoV-2 PCR tests were positive for 21.0% of children (1074/5127). The coinfection rate of respiratory viruses (RSV, influenza A) in patients with COVID-19 was 7.2% (77/1074). Among the 4053 SARS-CoV-2 negative patients, RSV was diagnosed in 405 (10.0%) patients and influenza A/B in 827 (20.4%) patients. Patients with COVID-19 and coinfection did not have a more severe clinical course than those with RSV or influenza infection alone. RSV and SARS-CoV-2 primarily affected younger patients (up to 2 years), while the influenza was more common in older children (4-10 years). Patients infected with RSV were more severely ill, reflected by higher hospitalization proportion and need for respiratory support.

COVID-19 in Hospitalised Children and Adolescents: Review of the First Pandemic Year at Vilnius University Hospital Santaros Klinikos.

Background: Since the start of the pandemic with SARS-CoV-2 virus, very little data was known about clinical features and outcomes of COVID-19 in children and adolescents not only in Lithuania, but also in other European countries. This study was started in collaboration with 82 participating healthcare institutions across 25 European countries, using a well-established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet). This multinational, multicentre cohort study was performed during the first wave of the pandemic, between April 1 and April 24, 2020. Each participating country was allowed to continue further research individually encompassing brighter time limits and using the same methodology. We present here data of children hospitalised at Vilnius University Hospital Santaros Klinikos (VUH SK) during the first year of the pandemic. Materials and methods: We included all paediatric patients with PCR confirmed SARS-CoV-2 infection who were hospitalised at VUH SK. The study was performed between March 12, 2020 and March 12, 2021. A standardised data collection spreadsheet was used to record epidemiological, clinical and treatment data. Results: A total of 104 patients were included in the study. The median age of participants was 5 years (IQR 1.0-11.0, range 0-17 years). Males accounted for 50 (48%) of all patients. The average duration of hospitalisation was 3 days. Ten (9.6%) patients had pre-existing medical conditions. Among all hospitalised patients 16 (15%) were asymptomatic, 5 (4.8%) were treated in intensive care unit (ICU). The most common symptoms among COVID-19 patients were pyrexia 71 (68%) followed by upper respiratory tract infection 49 (47%) and gastrointestinal symptoms 33 (32%). Among the entire cohort only 3 (3%) patients required oxygen support, but none of them was started on continuous positive airway pressure (CPAP), mechanical ventilation or extracorporeal membrane oxygenation (ECMO). None of the patients admitted to ICU needed inotropic support. There was no fatal outcome. Conclusions: Our data indicate that COVID-19 may affect children of any age. The COVID-19 disease was usually mild in hospitalized children and adolescents. The most common clinical findings of COVID-19 were pyrexia and symptoms of upper respiratory tract infection. Severe COVID-19 disease cases when oxygen support or treatment in ICU was required were very rare. No patient received antiviral drugs for Covid-19 treatment. There was no fatal outcome due to COVID-19 in our study population.

Bacille Calmette-Guérin Vaccine-induced Osteomyelitis in Immunocompetent Children: A 10-year Case Series in Lithuania.

The Bacille Calmette-Guérin (BCG)-induced osteomyelitis is an extremely rare systemic adverse reaction after BCG vaccination in immunocompetent children and the correct diagnosis is frequently missed. We present 4 clinical cases of BCG-induced osteomyelitis reported over a 10-year period in a high-TB incidence country Lithuania. A brief review of clinical, management and treatment features of the disease is given.

Expert panel diagnosis demonstrated high reproducibility as reference standard in infectious diseases.

OBJECTIVE: If a gold standard is lacking in a diagnostic test accuracy study, expert diagnosis is frequently used as reference standard. However, interobserver and intraobserver agreements are imperfect. The aim of this study was to quantify the reproducibility of a panel diagnosis for pediatric infectious diseases. STUDY DESIGN AND SETTING: Pediatricians from six countries adjudicated a diagnosis (i.e., bacterial infection, viral infection, or indeterminate) for febrile children. Diagnosis was reached when the majority of panel members came to the same diagnosis, leaving others inconclusive. We evaluated intraobserver and intrapanel agreement with 6 weeks and 3 years' time intervals. We calculated the proportion of inconclusive diagnosis for a three-, five-, and seven-expert panel. RESULTS: For both time intervals (i.e., 6 weeks and 3 years), intrapanel agreement was higher (kappa 0.88, 95%CI: 0.81-0.94 and 0.80, 95%CI: NA) compared to intraobserver agreement (kappa 0.77, 95%CI: 0.71-0.83 and 0.65, 95%CI: 0.52-0.78). After expanding the three-expert panel to five or seven experts, the proportion of inconclusive diagnoses (11%) remained the same. CONCLUSION: A panel consisting of three experts provides more reproducible diagnoses than an individual expert in children with lower respiratory tract infection or fever without source. Increasing the size of a panel beyond three experts has no major advantage for diagnosis reproducibility.

Burden of varicella in Central and Eastern Europe: findings from a systematic literature review.

INTRODUCTION: Vaccination against varicella rapidly reduces disease incidence, resulting in reductions in both individual burden and societal costs. Despite these benefits, there is no standardization of varicella immunization policies in Europe, including countries in Central and Eastern Europe (CEE). AREAS COVERED: This systematic literature review identified publications on the epidemiology of varicella, its associated health and economic burden, and vaccination strategies within the CEE region, defined as Albania, Bosnia-Herzegovina, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Serbia, Slovakia, and Slovenia. Twenty-six studies were identified from a search of PubMed, Embase®, and MEDLINE® biomedical literature databases, supplemented by gray literature and country-specific/global websites. EXPERT COMMENTARY: Limited information exists in published studies on the burden of varicella in CEE. The wide variability in incidence rates between countries is likely explained by a lack of consistency in reporting systems. Funded universal varicella vaccination (UVV) in CEE is currently available only in Latvia as a one-dose schedule, but Hungary together with Latvia are introducing a two-dose strategy in 2019. For countries that do not provide UVV, introduction of vaccination is predicted to provide substantial reductions in cases and rates of associated complications, with important economic benefits.

Prescription of antibiotics in Riga and Vilnius tertiary children's hospitals.

OBJECTIVES: The aim of this study was to compare the use of antibiotics among hospitalised children in Riga (Latvia) and in Vilnius (Lithuania) at two tertiary paediatric centres. METHODS: A point prevalence survey (PPS) was conducted using validated and standardised Antibiotic Resistance and Prescribing in European Children (ARPEC) project methodology during November 2012. All inpatients less than 18 years old were included in the study. All data were recorded for patients with active antimicrobial prescriptions at 8 am on the day of the survey. Data were entered into the ARPEC-webPPS programme and were validated online for accuracy. RESULTS: The proportion of patients receiving antimicrobial therapy was statistically different: 128 (37.0%) patients in Riga and 83 (26.3%) in Vilnius. The most common age group in Riga and Vilnius was 1-5 years. The most commonly used antibiotic classes for the treatment and prophylaxis of infection were third-generation cephalosporins (38; 25.5% prescriptions) in Riga and second-generation cephalosporins (16; 19.8%) in Vilnius. Parenteral use of antimicrobials was higher in Riga than in Vilnius: 111 (74.5%) prescriptions to paediatric patients in Riga and 45 (55.6%) prescriptions in Vilnius. CONCLUSIONS: The PPS identified differences in antibiotic use in both hospitals and problem areas for improvement: high use of third-generation cephalosporins for paediatric patients (in Riga) and predominant use of parenteral antibiotics. Further collaboration between both centres is needed because sharing audit data and antimicrobial stewardship initiatives may encourage further changes in practice at both institutions.

Recommendations for tick-borne encephalitis vaccination from the Central European Vaccination Awareness Group (CEVAG).

Tick-borne encephalitis (TBE) is a viral neurological zoonotic disease transmitted to humans by ticks or by consumption of unpasteurized dairy products from infected cows, goats, or sheep. TBE is highly endemic in areas of Central and Eastern Europe and Russia where it is a major public health concern. However, it is difficult to diagnose TBE as clinical manifestations tend to be relatively nonspecific and a standardized case definition does not exist across the region. TBE is becoming more important in Europe due to the appearance of new endemic areas. Few Central European Vaccination Awareness Group (CEVAG) member countries have implemented universal vaccination programmes against TBE and vaccination coverage is not considered sufficient to control the disease. When implemented, immunization strategies only apply to risk groups under certain conditions, with no harmonized recommendations available to date across the region. Effective vaccination programmes are essential in preventing the burden of TBE. This review examines the current situation of TBE in CEVAG countries and contains recommendations for the vaccination of children and high-risk groups. For countries at very high risk of TBE infections, CEVAG strongly recommends the introduction of universal TBE vaccination in children > 1 y of age onwards. For countries with a very low risk of TBE, recommendations should only apply to those traveling to endemic areas. Overall, it is generally accepted that each country should be free to make its own decision based on regional epidemiological data and the vaccination calendar, although recommendations should be made, especially for those living in endemic areas.

The unpredictable diversity of co-circulating rotavirus types in Europe and the possible impact of universal mass vaccination programmes on rotavirus genotype incidence.

This article reviews the incidence of group A rotavirus (RV) types isolated from children with acute gastroenteritis (AGE) in European countries during the last 5-10 years, with the aim of establishing an overview of RV diversity before the introduction of universal mass vaccination (UMV) programmes against RV disease in most European countries. Consistent with findings from previous surveys, a high degree of diversity of co-circulating RV types exists in different locations of Europe, and over different RV seasons. Whilst RV UMV can potentially change the diversity of co-circulating genotypes, there are at present insufficient data for Europe to come to firm conclusions. Even in countries outside Europe, with several years of RV surveillance following the introduction of RV UMV (Brazil, Australia, USA), it is not clear whether changes observed in the diversity of particular RV types are due to natural fluctuations or immunological pressure exerted by RV UMVs. Consequently, it will be very difficult for European countries that have RV UMVs to conclude whether incidence changes of RV types in children with AGE are driven by immune pressures from vaccination or simply reflect natural temporal and spatial fluctuations. Whilst the monitoring of co-circulating RV strains should be continued, it should be acknowledged that the licensed monovalent and pentavalent RV vaccines are similarly effective in developed countries and that levels of RV type-specific neutralising antibodies after RV vaccination are only partially correlated with the degree of protection achieved; therefore, the significance of RV diversity for RV vaccination may be less important than is often assumed.

Adult vaccination in 11 Central European countries - calendars are not just for children.

As Europe's population ages, disease morbidity and treatment costs in the adult population are likely to rise substantially, making this a pertinent time to review and revise preventive strategies such as vaccination. Vaccine uptake remains a problem for adults and there is a lack of coordinated programmes for vaccination of adults. Countries in Western Europe have begun to identify the need to increase adult vaccination, but the situation in Central European countries remains poorly identified and inadequately described. This paper summarises the evidence to support the development of an adult vaccination calendar in the Central European Vaccination Awareness Group (CEVAG) member countries (Bulgaria, Croatia, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Romania, Slovakia, Slovenia and Turkey). CEVAG recommends the introduction of an adult vaccination calendar, which should include vaccination against diseases that represent a large burden in adults in terms of mortality and morbidity. This calendar could be modified to meet the priorities of individual countries.

Rubella revisited: where are we on the road to disease elimination in Central Europe?

Rubella is a contagious viral disease with few complications except when contracted by pregnant women. Rubella infection in pregnancy can result in miscarriage, stillbirth or an infant born with congenital rubella syndrome (CRS) which comprises deafness, heart disease, cataracts and other permanent congenital manifestations. Clinical diagnosis of rubella is difficult due to overlapping symptoms with many other diseases and confirmation of rubella is not possible without laboratory testing. Effective vaccination programmes are critical to the elimination of rubella and prevention of CRS. Such programmes have been successful in several countries in Europe and around the world. However, rubella outbreaks still occur due to suboptimal vaccine coverage and in the past 10 years rubella has been reported in Central European countries such as Romania and Poland. Over the past decade the elimination of rubella and prevention of congenital rubella infection in Europe has been a high priority for the WHO European Regional Office. In 2010 the WHO regional committee for Europe renewed its commitment to the elimination of rubella and prevention of CRS with a new target of 2015. This paper examines the current situation for rubella and CRS in Central Europe and describes the different rubella vaccination programmes in the region. The Central European Vaccination Advisory Group (CEVAG) recommends that two doses of measles, mumps and rubella vaccine, MMR, should be given to all children. The first dose should be given between 12 and 15 months of age. The second dose can be given between the ages of 21 months and 13 years with the exact age of administration of the second dose depending on the situation specific to each country. All suspected rubella cases should be laboratory-confirmed and monitoring systems to detect and investigate cases of CRS should be strengthened.

Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for influenza vaccination in children.

BACKGROUND: Influenza vaccination in infants and children with existing health complications is current practice in many countries, but healthy children are also susceptible to influenza, sometimes with complications. The under-recognised burden of disease in young children is greater than in elderly populations and the number of paediatric influenza cases reported does not reflect the actual frequency of influenza. DISCUSSION: Vaccination of healthy children is not widespread in Europe despite clear demonstration of the benefits of vaccination in reducing the large health and economic burden of influenza. Universal vaccination of infants and children also provides indirect protection in other high-risk groups in the community. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for the vaccination of infants and children against influenza. The aim of CEVAG is to encourage the efficient and safe use of vaccines to prevent and control infectious diseases. SUMMARY: CEVAG recommends the introduction of universal influenza vaccination for all children from the age of 6 months. Special attention is needed for children up to 60 months of age as they are at greatest risk. Individual countries should decide on how best to implement this recommendation based on their circumstances.

Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for 2009 pandemic influenza A(H1N1) vaccination.

The 2009 influenza A(H1N1) pandemic is markedly different from seasonal influenza with the disease affecting the younger population and a larger than expected number of severe or fatal cases has been seen in pregnant women, obese people and in people who were otherwise healthy. In Europe, influenza activity caused by the 2009 influenza A(H1N1) virus has passed the winter peak with nearly all countries now reporting lower influenza activity. However, although the rate of 2009 pandemic influenza A(H1N1) is declining, fatal cases continue to be reported and the future is hard to predict. The most effective protection against influenza is vaccination and increasing vaccine coverage is the only way to eliminate uncertainties regarding possible future waves of 2009 pandemic influenza A(H1N1). Recommendations have been developed for several central European countries but there is no clear or uniform definition with respect to priority groups or age groups who should receive vaccination. This paper contains the Central European Vaccination Advisory Group (CEVAG) guidance statement on recommendations for the vaccination of adults and children against 2009 pandemic influenza A(H1N1). CEVAG recommends vaccination of all health-care workers, pregnant women, children > or = 6 months and <2 years of age and people with chronic medical conditions as a first priority.