Epidemiology of reported cases of leptospirosis in the EU/EEA, 2010 to 2021.

BackgroundLeptospirosis is a zoonotic disease caused by bacteria of the genus Leptospira. Humans are infected by exposure to animal urine or urine-contaminated environments. Although disease incidence is lower in Europe compared with tropical regions, there have been reports of an increase in leptospirosis cases since the 2000s in some European countries.AimWe aimed to describe the epidemiology of reported cases of leptospirosis in the European Union/European Economic Area (EU/EEA) during 2010-2021 and to identify potential changes in epidemiological patterns.MethodsWe ran a descriptive analysis of leptospirosis cases reported by EU/EEA countries to the European Centre for Disease Prevention and Control with disease during 2010-2021. We also analysed trends at EU/EEA and national level.ResultsDuring 2010-2021, 23 countries reported 12,180 confirmed leptospirosis cases corresponding to a mean annual notification rate of 0.24 cases per 100,000 population. Five countries (France, Germany, the Netherlands, Portugal and Romania) accounted for 79% of all reported cases. The highest notification rate was observed in Slovenia with 0.82 cases per 100,000 population. Overall, the notification rate increased by 5.0% per year from 2010 to 2021 (95% CI: 1.2-8.8%), although trends differed across countries.ConclusionThe notification rate of leptospirosis at EU/EEA level increased during 2010-2021 despite including the first 2 years of the COVID-19 pandemic and associated changes in population behaviours. Studies at (sub)national level would help broaden the understanding of differences at country-level and specificities in terms of exposure to Leptospira, as well as biases in diagnosis and reporting.

Impact of nirsevimab prophylaxis on paediatric respiratory syncytial virus (RSV)-related hospitalisations during the initial 2023/24 season in Luxembourg.

After Luxembourg introduced nirsevimab immunisation against respiratory syncytial virus (RSV), estimated neonatal coverage was 84% (1,277 doses/1,524 births) in 2023. That year, paediatric RSV-related hospitalisations, especially concerning infants < 6 months old (n = 72) seemed to decrease compared to the same period in 2022 (n = 232). In 2023, hospitalised children's mean age increased (14.4 months vs 7.8 months in 2022; p < 0.001) and hospital-stay length decreased (3.2 days vs 5.1 days; p < 0.001). In infants < 6 months old, intensive-care unit admissions appeared to drop (n = 28 vs 9). This suggests that nirsevimab prophylaxis reduced severe RSV infections, particularly in infants < 6 months old, thereby alleviating healthcare strain.

A Molecular and Epidemiological Investigation of a Large SARS-CoV-2 Outbreak in a Long-Term Care Facility in Luxembourg, 2021.

In spring 2021, a long-term care facility (LTCF) of 154 residents in Luxembourg experienced a large severe, acute respiratory-syndrome coronavirus 2 (SARS-CoV-2) outbreak a few days after a vaccination campaign. We conducted an outbreak investigation and a serosurvey two months after the outbreak, compared attack rates (AR) among residents and staff, and calculated hospitalization and case-fatality rates (CFR). Whole genome sequencing (WGS) was performed to detect variants in available samples and results were compared to genomes published on GISAID. Eighty-four (55%) residents and forty-five (26%) staff members tested positive for SARS-CoV-2; eighteen (21%) residents and one (2.2%) staff member were hospitalized, and twenty-three (CFR: 27%) residents died. Twenty-seven (21% of cases) experienced a reinfection. Sequencing identified seventy-seven cases (97% of sequenced cases) with B.1.1.420 and two cases among staff with B.1.351. The outbreak strain B.1.1.420 formed a separate cluster from cases from other European countries. Convalescent and vaccinated residents had higher anti-SARS-CoV-2 IgG antibody concentrations than vaccinated residents without infection (98% vs. 52%, respectively, with >120 RU/mL, p < 0.001). We documented an extensive outbreak of SARS-CoV-2 in an LTCF due to the presence of a specific variant leading to high CFR. Infection in vaccinated residents increased antibody responses. A single vaccine dose was insufficient to mitigate the outbreak.

Age-specific associations between underlying health conditions and hospitalisation, death and in-hospital death among confirmed COVID-19 cases: a multi-country study based on surveillance data, June to December 2020.

BackgroundUnderlying conditions are risk factors for severe COVID-19 outcomes but evidence is limited about how risks differ with age.AimWe sought to estimate age-specific associations between underlying conditions and hospitalisation, death and in-hospital death among COVID-19 cases.MethodsWe analysed case-based COVID-19 data submitted to The European Surveillance System between 2 June and 13 December 2020 by nine European countries. Eleven underlying conditions among cases with only one condition and the number of underlying conditions among multimorbid cases were used as exposures. Adjusted odds ratios (aOR) were estimated using 39 different age-adjusted and age-interaction multivariable logistic regression models, with marginal means from the latter used to estimate probabilities of severe outcome for each condition-age group combination.ResultsCancer, cardiac disorder, diabetes, immunodeficiency, kidney, liver and lung disease, neurological disorders and obesity were associated with elevated risk (aOR: 1.5-5.6) of hospitalisation and death, after controlling for age, sex, reporting period and country. As age increased, age-specific aOR were lower and predicted probabilities higher. However, for some conditions, predicted probabilities were at least as high in younger individuals with the condition as in older cases without it. In multimorbid patients, the aOR for severe disease increased with number of conditions for all outcomes and in all age groups.ConclusionWhile supporting age-based vaccine roll-out, our findings could inform a more nuanced, age- and condition-specific approach to vaccine prioritisation. This is relevant as countries consider vaccination of younger people, boosters and dosing intervals in response to vaccine escape variants.

Surveillance of Indoor Air Concentration of Volatile Organic Compounds in Luxembourgish Households.

Exposure to air pollution is a well-known health risk. For instance, volatile and very volatile organic compounds (VOCs and VVOCs) are known to cause respiratory, haematologic or immune diseases, and even cancer. Based on the Luxembourgish indoor pollution surveillance program, we performed an exploratory analysis for the period 2014-2019, in order (1) to evaluate the prevalence of VOCs and VVOCs in households, and (2) to estimate the risks of lifelong exposure to selected VOCs on the health of the adult population. The database included 715 indoor air samples from 159 different households. Observed VOC and VVOC levels were similar to those in neighbouring countries. Our health impact assessment identified some health risks associated with the observed concentrations in Luxembourg. Furthermore, this study shows the major public health importance of having a national indoor pollution surveillance system in place. Highlights: (1) This study provides an overview of the domestic indoor pollution in Luxembourg. (2) (V)VOCs levels in Luxembourg were similar to those in neighbouring countries. (3) The results clearly show the importance of having a surveillance system in place.

Investigation of an international outbreak of multidrug-resistant monophasic Salmonella Typhimurium associated with chocolate products, EU/EEA and United Kingdom, February to April 2022.

An extensive multi-country outbreak of multidrug-resistant monophasic Salmonella Typhimurium infection in 10 countries with 150 reported cases, predominantly affecting young children, has been linked to chocolate products produced by a large multinational company. Extensive withdrawals and recalls of multiple product lines have been undertaken. With Easter approaching, widespread product distribution and the vulnerability of the affected population, early and effective real-time sharing of microbiological and epidemiological information has been of critical importance in effectively managing this serious food-borne incident.

Risk reduction of severe outcomes in vaccinated COVID-19 cases: an analysis of surveillance data from Estonia, Ireland, Luxembourg and Slovakia, January to November 2021.

Despite high COVID-19 vaccine coverage in the EU/EEA, there are increasing reports of SARS-CoV-2 infections and hospitalisations in vaccinated individuals. Using surveillance data from Estonia, Ireland, Luxembourg and Slovakia (January-November 2021), we estimated risk reduction of severe outcomes in vaccinated cases. Increasing age remains the most important driver of severity, and vaccination significantly reduces risk in all ages for hospitalisation (adjusted relative risk (aRR): 0.32; 95% confidence interval (CI): 0.26-0.39) and death (aRR: 0.20; 95% CI: 0.13-0.29).

Characteristics of SARS-CoV-2 variants of concern B.1.1.7, B.1.351 or P.1: data from seven EU/EEA countries, weeks 38/2020 to 10/2021.

We compared 19,207 cases of SARS-CoV-2 variant B.1.1.7/S gene target failure (SGTF), 436 B.1.351 and 352 P.1 to non-variant cases reported by seven European countries. COVID-19 cases with these variants had significantly higher adjusted odds ratios for hospitalisation (B.1.1.7/SGTF: 1.7, 95% confidence interval (CI): 1.0-2.9; B.1.351: 3.6, 95% CI: 2.1-6.2; P.1: 2.6, 95% CI: 1.4-4.8) and B.1.1.7/SGTF and P.1 cases also for intensive care admission (B.1.1.7/SGTF: 2.3, 95% CI: 1.4-3.5; P.1: 2.2, 95% CI: 1.7-2.8).

Antimicrobial Susceptibility of Pseudomonas aeruginosa Isolated from Cystic Fibrosis Patients in Northern Europe.

Pseudomonas aeruginosa is a major cause of morbidity and mortality in cystic fibrosis patients. This study compared the antimicrobial susceptibilities of 153 P. aeruginosa isolates from the United Kingdom (UK) (n = 58), Belgium (n = 44), and Germany (n = 51) collected from 118 patients during routine visits over the period from 2006 to 2012. MICs were measured by broth microdilution. Genes encoding extended-spectrum ß-lactamases (ESBL), metallo-ß-lactamases, and carbapenemases were detected by PCR. Pulsed-field gel electrophoresis and multilocus sequence typing were performed on isolates resistant to ≥3 antibiotic classes among the penicillins/cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, and polymyxins. Based on EUCAST/CLSI breakpoints, susceptibility rates were ≤30%/≤40% (penicillins, ceftazidime, amikacin, and ciprofloxacin), 44 to 48%/48 to 63% (carbapenems), 72%/72% (tobramycin), and 92%/78% (colistin) independent of patient age. Sixty percent of strains were multidrug resistant (MDR; European Centre for Disease Prevention and Control criteria). Genes encoding the most prevalent ESBL (BEL, PER, GES, VEB, CTX-M, TEM, SHV, and OXA), metallo-ß-lactamases (VIM, IMP, and NDM), or carbapenemases (OXA-48 and KPC) were not detected. The Liverpool epidemic strain (LES) was prevalent in UK isolates only (75% of MDR isolates). Four MDR sequence type 958 (ST958) isolates were found to be spread over the three countries. The other MDR clones were evidenced in ≤3 isolates and localized in a single country. A new sequence type (ST2254) was discovered in one MDR isolate in Germany. Clonal and nonclonal isolates with different susceptibility profiles were found in 20 patients. Thus, resistance and MDR are highly prevalent in routine isolates from 3 countries, with meropenem, tobramycin, and colistin remaining the most active drugs.

TLR3 deficiency in herpes simplex encephalitis: high allelic heterogeneity and recurrence risk.

OBJECTIVE: To determine the proportion of children with herpes simplex encephalitis (HSE) displaying TLR3 deficiency, the extent of TLR3 allelic heterogeneity, and the specific clinical features of TLR3 deficiency. METHODS: We determined the sequence of all exons of TLR3 in 110 of the 120 patients with HSE enrolled in our study who do not carry any of the previously described HSE-predisposing mutations of TLR3 pathway genes (TLR3, UNC93B1, TRIF, TRAF3, and TBK1). All the new mutant TLR3 alleles detected were characterized experimentally in-depth to establish the causal relationship between the genotype and phenotype. RESULTS: In addition to the 3 previously reported TLR3-deficient patients from the same cohort, 6 other children or young adults with HSE carry 1 of 5 unique or extremely rare (minor allele frequency <0.001) missense TLR3 alleles. Two alleles (M374T, D592N) heterozygous in 3 patients are not deleterious in vitro. The other 3 are deleterious via different mechanisms: G743D+R811I and L360P heterozygous in 2 patients are loss-of-function due to low levels of expression and lack of cleavage, respectively, and R867Q homozygous in 1 patient is hypomorphic. The 3 patients' fibroblasts display impaired TLR3 responses and enhanced herpes simplex virus 1 susceptibility. Overall, TLR3 deficiency is therefore found in 6 (5%) of the 120 patients studied. There is high allelic heterogeneity, with 3 forms of autosomal dominant partial defect by negative dominance or haploinsufficiency, and 2 forms of autosomal recessive defect with complete or partial deficiency. Finally, 4 (66%) of the 6 TLR3-deficient patients had at least 1 late relapse of HSE, whereas relapse occurred in only 12 (10%) of the total cohort of 120 patients. CONCLUSIONS: Childhood-onset HSE is due to TLR3 deficiency in a traceable fraction of patients, in particular the ones with HSE recurrence. Mutations in TLR3 and TLR3 pathway genes should be searched and experimentally studied in children with HSE, and patients with proven TLR3 deficiency should be followed carefully.

Pneumococcal aetiology and serotype distribution in paediatric community-acquired pneumonia.

Community-acquired pneumonia (CAP) is a major cause of morbidity in children. This study estimated the proportion of children with pneumococcal CAP among children hospitalised with CAP in Belgium and describes the causative serotype distribution after implementation of the 7-valent pneumococcal conjugate vaccine. Children 0-14 years hospitalised with X-ray-confirmed CAP were prospectively enrolled in a multicentre observational study. Acute and convalescent blood samples were collected. Pneumococcal aetiology was assessed by conventional methods (blood or pleural fluid cultures with Quellung reaction capsular typing or polymerase chain reaction [PCR] in pleural fluid), and recently developed methods (real-time PCR in blood and World Health Organization-validated serotype-specific serology). A total of 561 children were enrolled. Pneumococcal aetiology was assessed by conventional methods in 539, serology in 171, and real-time PCR in blood in 154. Pneumococcal aetiology was identified in 12.2% (66/539) of the children by conventional methods alone but in 73.9% by the combination of conventional and recently developed methods. The pneumococcal detection rate adjusted for the whole study population was 61.7%. Serotypes 1 (42.3%), 5 (16.0%), and 7F(7A) (12.8%) were predominant. In conclusion, Streptococcus pneumoniae remains the predominant bacteria in children hospitalised for CAP in Belgium after implementation of 7-valent pneumococcal conjugate vaccine, with non-vaccine-serotypes accounting for the majority of cases. The use of recently developed methods improves diagnosis of pneumococcal aetiology.

Acute otitis media in young children - what do parents say?

OBJECTIVES: The Ear infections Attitudes Research study investigated parental attitudes and awareness towards acute otitis media (AOM) and evaluated the burden of AOM for affected children, their families, and parental work capabilities. METHODS: This study, conducted via online interviews in October-November 2010, included parents (N=2867) from 12 countries, whose children aged ≤3.5 years had experienced ≥1 professionally diagnosed AOM episode in the last 6 months (AOM-experienced group; N=1438) or had never experienced any professionally diagnosed AOM episode (non AOM-experienced group; N=1429). The interviews consisted of questions with multiple-choice, five-point scaled or free-text answers. Answers to multiple-choice questions were presented as frequencies of particular responses and those to scaled questions as mean values or percentages of parents considering each aspect as applicable. RESULTS: Parents considered that the main AOM burdens for affected children were pain (mean values on five-point scales: 4.4 and 4.5), disturbed sleep (4.3 and 4.3) and irritability (4.2 and 4.0) and for their families, sleepless nights (4.2 and 3.8) and worries about the child's recovery (4.1 and 4.3) and about potential long-term implications (4.0 and 4.3) in the AOM-experienced and non AOM-experienced groups, respectively. During their child's most recent AOM episode, 95% of parents in the AOM-experienced group used antibiotics, 76% reported that their doctors prescribed antibiotics for immediate use, 13% were advised to return for antibiotic prescription if symptoms did not abate and 9% received a prescription for antibiotics to use if symptoms did not improve. Both reported prescription and usage rates for antibiotics were higher than expected. When their child had AOM, 73% of parents had to be absent from work or rearrange their working hours. Among those who took leave from work, 67% stayed at home for 2-7 days. CONCLUSIONS: Parents perceive AOM to be a burden for their child and families, particularly the pain and disturbed sleep due to AOM, and this disease had a significant effect on parents' ability to attend work. Given how common AOM is, this loss of workdays may lead to substantial financial burden for families and the society. Antibiotics were almost invariably used in all countries despite current guidelines.

Evaluation of a WHO-validated serotype-specific serological assay for the diagnosis of pneumococcal etiology in children with community-acquired pneumonia.

BACKGROUND: The etiologic diagnosis of community-acquired pneumonia (CAP) remains challenging in children because blood cultures have low sensitivity. Novel approaches are needed to confirm the role of Streptococcus pneumoniae. METHODS: In this study, pneumococcal etiology was determined by serology using a subset of blood samples collected during a prospective multicentre observational study of children <15 years of age hospitalized in Belgium with radiogram-confirmed CAP. Blood samples were collected at admission and 3-4 weeks later. Pneumococcal (P)-CAP was defined in the presence of a positive blood or pleural fluid culture. Serotyping of S. pneumoniae isolates was done with the Quellung reaction. Serological diagnosis was assessed for 9 serotypes using World Health Organization-validated IgG and IgA serotype-specific enzyme-linked immunosorbent assays (ELISAs). RESULTS: Paired admission/convalescent sera from 163 children were evaluated by ELISA (35 with proven P-CAP and 128 with nonproven P-CAP). ELISA detected pneumococci in 82.8% of patients with proven P-CAP. The serotypes identified were the same as with the Quellung reaction in 82% and 59% of cases by IgG ELISA and IgA ELISA, respectively. Overall, ELISA identified a pneumococcal etiology in 55% of patients with nonproven P-CAP. Serotypes 1 (51.6%), 7F (19%) and 5 (15.7%) were the most frequent according to IgG ELISA. CONCLUSIONS: In conclusion, the serological assay allows recognition of pneumococcal origin in 55% of CAP patients with negative culture. This assay should improve the diagnosis of P-CAP in children and could be a useful tool for future epidemiological studies on childhood CAP etiology.

The burden of childhood pneumonia in the developed world: a review of the literature.

BACKGROUND: Estimates of the disease burden from childhood pneumonia are available for most developed countries, but they are based mainly on models. Measured country-specific pneumonia burden data are limited to a few nations and differ in case definitions and case ascertainment methods. This review describes pneumonia disease burden in developed countries. METHODS: We reviewed studies describing childhood pneumonia incidence in North America, Europe, Australia, New Zealand and Japan. Available estimates suggest that each year in developed countries there are up to 2.6 million cases of pneumonia, including 1.5 million hospitalized cases and around 3000 pneumonia deaths (compared with approximately 640 annual deaths from meningitis) in children <5 years of age. RESULTS: Data to inform policy decisions would be improved by information on burden and etiology of severe pneumonia, population-based incidence of ambulatory visits and hospitalizations and prevalence of complications and sequelae.

Effectiveness of rotavirus vaccination in prevention of hospital admissions for rotavirus gastroenteritis among young children in Belgium: case-control study.

OBJECTIVE: To evaluate the effectiveness of rotavirus vaccination among young children in Belgium. DESIGN: Prospective case-control study. SETTING: Random sample of 39 Belgian hospitals, February 2008 to June 2010. PARTICIPANTS: 215 children admitted to hospital with rotavirus gastroenteritis confirmed by polymerase chain reaction and 276 age and hospital matched controls. All children were of an eligible age to have received rotavirus vaccination (that is, born after 1 October 2006 and aged ≥ 14 weeks). MAIN OUTCOME MEASURE: Vaccination status of children admitted to hospital with rotavirus gastroenteritis and matched controls. RESULTS: 99 children (48%) admitted with rotavirus gastroenteritis and 244 (91%) controls had received at least one dose of any rotavirus vaccine (P<0.001). The monovalent rotavirus vaccine accounted for 92% (n=594) of all rotavirus vaccine doses. With hospital admission as the outcome, the unadjusted effectiveness of two doses of the monovalent rotavirus vaccine was 90% (95% confidence interval 81% to 95%) overall, 91% (75% to 97%) in children aged 3-11 months, and 90% (76% to 96%) in those aged ≥ 12 months. The G2P[4] genotype accounted for 52% of cases confirmed by polymerase chain reaction with eligible matched controls. Vaccine effectiveness was 85% (64% to 94%) against G2P[4] and 95% (78% to 99%) against G1P[8]. In 25% of cases confirmed by polymerase chain reaction with eligible matched controls, there was reported co-infection with adenovirus, astrovirus and/or norovirus. Vaccine effectiveness against co-infected cases was 86% (52% to 96%). Effectiveness of at least one dose of any rotavirus vaccine (intention to vaccinate analysis) was 91% (82% to 95%). CONCLUSIONS: Rotavirus vaccination is effective for the prevention of admission to hospital for rotavirus gastroenteritis among young children in Belgium, despite the high prevalence of G2P[4] and viral co-infection.

Impact of rotavirus vaccines on rotavirus disease.

Rotaviruses are the most common cause of acute gastroenteritis in young children worldwide. Both licensed rotavirus vaccines (Rotarix™ [RV1] and RotaTeq™ [RV5]) are effective and safe. Studies from countries that have included RV1 or RV5 in the national immunization programs have demonstrated their safety and sustained efficacy under real-life circumstances. A significant decline in acute gastroenteritis-related deaths among Latin American children was observed after the introduction of RV1 and RV5 vaccines. Both vaccines were able to decrease the number of cases of rotavirus acute gastroenteritis and of severe rotavirus diseases. Vaccination was also associated with a dramatic reduction in hospitalizations and outpatient visits for all-cause acute gastroenteritis. Indirect protection after infant mass vaccination has been strongly suggested. Moreover, postlicensure safety studies assessed rare adverse events (rates <1 in 50,000), such as intussusception.

Antibiotic therapy for pediatric community-acquired pneumonia: do we know when, what and for how long to treat?

Community-acquired pneumonia (CAP) is a common cause of morbidity among children in developed countries and accounts for an incidence of 10-40 cases per 1000 children in the first 5 years of life. Given the clinical, social and economic importance of CAP, there is general agreement that prompt and adequate therapy is essential to reduce the impact of the disease. The aim of this discussion paper is to consider critically the available data concerning the treatment of uncomplicated pediatric CAP and to consider when, how and for how long it should be treated. This review has identified the various reasons that make it difficult to establish a rational approach to the treatment of pediatric CAP, including the definition of CAP, the absence of a pediatric CAP severity score, the difficulty of identifying the etiology, limited pharmacokinetic (PK)/pharmacodynamic (PD) studies, the high resistance of the most frequent respiratory pathogens to the most widely used anti-infectious agents and the lack of information concerning the changes in CAP epidemiology following the introduction of new vaccines against respiratory pathogens. More research is clearly required in various areas, such as the etiology of CAP and the reasons for its complications, the better definition of first- and second-line antibiotic therapies (including the doses and duration of parenteral and oral antibiotic treatment), the role of antiviral treatment and on how to follow-up patients with CAP. Finally, further efforts are needed to increase vaccination coverage against respiratory pathogens and to conduct prospective studies of their impact.

Impact of pneumococcal conjugate vaccination on otitis media: a systematic review.

Acute otitis media (AOM) is a leading cause of visits to physicians and of antibiotic prescriptions for young children. We systematically reviewed studies on all-cause AOM episodes and physician visits in which impact was attributed to pneumococcal conjugate vaccines, either as efficacy or effectiveness. Of 18 relevant publications found, most used the 7-valent pneumococcal conjugate vaccine (7vCRM). The efficacy of 7vCRM against all-cause AOM episodes or visits was 0%-9% in randomized trials and 17%-23% in nonrandomized trials. In observational database studies, physician visits for AOM were already declining in the 3-5 years before 7vCRM introduction (mean change, -15%; range, +14% to -24%) and continued to decline afterward (mean, -19%; range, +7% to -48%). This vaccine provides some protection against OM, but other factors have also contributed to the recent decline in OM incidence. Future effectiveness studies should thus use better-controlled methods to estimate the true impact of vaccination on AOM.