RESUMO
Monitoring the real-life effectiveness of respiratory syncytial virus (RSV) products is of major public health importance. This generic protocol for a test-negative design study aims to address currently envisioned approaches for RSV prevention (monoclonal antibodies and vaccines) to study effectiveness of these products among target groups: children, older adults, and pregnant women. The generic protocol approach was chosen to allow for flexibility in adapting the protocol to a specific setting. This protocol includes severe acute respiratory infection (SARI) and acute respiratory infection (ARI), both due to RSV, as end points. These end points can be applied to studies in hospitals, primarily targeting patients with more severe disease, but also to studies in general practitioner clinics targeting ARI.
Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Gravidez , Criança , Humanos , Feminino , Idoso , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Estudos de Casos e Controles , Vacinação , Imunização , Medicamentos GenéricosRESUMO
Several immunization products are currently being developed against respiratory syncytial virus (RSV) for children, pregnant females, and older adults, and some products have already received authorization. Therefore, studies to monitor the effectiveness of these products are needed in the following years. To assist researchers to conduct postmarketing studies, we developed a generic protocol for register-based cohort studies to evaluate immunization product effectiveness against RSV-specific and nonspecific outcomes. To conduct a study on the basis of this generic protocol, the researchers can use any relevant databases or healthcare registers that are available at the study site.
Assuntos
Vírus Sincicial Respiratório Humano , Vacinas , Criança , Feminino , Gravidez , Humanos , Idoso , Anticorpos Monoclonais/uso terapêutico , Estudos de Coortes , Vacinação , Medicamentos GenéricosRESUMO
Annually, increasing numbers of OXA-244-producing Escherichia coli in 13 German federal states prompted us to initiate an outbreak investigation. Whole genome sequencing revealed that among 148 isolates analysed, most belonged to sequence type 38 with 62 isolates forming a genetically distinct cluster. Although no epidemiological link could be identified between cases, ongoing investigations suggest non-healthcare associated transmission. A screening-PCR was developed facilitating early detection of ST38 cluster isolates to identify the source and transmission route.
Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/epidemiologia , Escherichia coli/isolamento & purificação , Sequenciamento Completo do Genoma/métodos , Adolescente , Adulto , Idoso , Antibacterianos/farmacologia , Criança , Pré-Escolar , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Infecções por Escherichia coli/tratamento farmacológico , Proteínas de Escherichia coli/genética , Alemanha/epidemiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , beta-Lactamases/genéticaRESUMO
From June to October 2019, 17 patients (six infected, 11 colonised) with an extensively drug-resistant (XDR) Klebsiella pneumoniae strain were notified from four Western Pomerania medical facilities. The XDR K. pneumoniae produced carbapenemases NDM-1 and OXA-48, and was only susceptible to chloramphenicol, tigecycline and cefiderocol. Synergistic activity was observed for the combination of aztreonam plus ceftazidime-avibactam. Genomic analyses showed all isolates belonged to K. pneumoniae sequence type 307. Control measures and further investigations are ongoing.
Assuntos
Antibacterianos/farmacologia , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/isolamento & purificação , beta-Lactamases , Antibacterianos/uso terapêutico , Proteínas de Bactérias , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Análise de SequênciaRESUMO
BackgroundUnderstanding enterovirus D68 (EV-D68) circulation patterns as well as risk factors for severe respiratory and neurological illness is important for developing preventive strategies. Methods: Between 2010 and 2016, 11,132 respiratory specimens from hospitalised patients in Lyon, France, were screened for EV-D68 by PCR. Phylogenetic relationships of the viral-protein-1 sequences were reconstructed using maximum-likelihood and Bayesian-Markov-Chain-Monte-Carlo approaches. Results: Overall, 171 infections with a biennial pattern were detected, including seven, one, 55, none, 42, one and 65 cases annually during 2010-16. Children (< 16 years-old; n = 150) were mostly affected and 71% (n = 121) of the total patients were under 5 years-old. In 146 patients with medical reviews, 73% (n = 107) presented with acute respiratory distress. Among paediatric patients with medical reviews (n = 133), 55% (n=73) had an asthma/wheezing history, while among adults (n = 13), 11 had underlying diseases. In total, 45 patients had severe infections and 28 patients needed intensive care unit stays. No acute flaccid myelitis (AFM) was detected. We found genotypes A, B1, B2 B3 and D circulating, and no associations between these and clinical presentations. During the study, new genotypes continuously emerged, being replaced over time. We estimated that ancestors of currently circulating genotypes emerged in the late-1990s to 2010. Rises of the EV-D68 effective population size in Lyon coincided with infection upsurges. Phylogenetic analyses showed ongoing diversification of EV-D68 worldwide, coinciding with more infections in recent years and increases of reported AFM paediatric cases. Conclusions: Reinforcement of diagnostic capacities and clinical-based surveillance of EV-D68 infections is needed in Europe to assess the EV-D68 burden.
Assuntos
Enterovirus Humano D/genética , Enterovirus Humano D/isolamento & purificação , Infecções por Enterovirus/virologia , Infecções Respiratórias/virologia , Proteínas Estruturais Virais/genética , Adolescente , Adulto , Criança , Pré-Escolar , Enterovirus Humano D/classificação , Infecções por Enterovirus/epidemiologia , Infecções por Enterovirus/fisiopatologia , Feminino , França/epidemiologia , Genótipo , Hospitalização , Hospitais Universitários , Humanos , Lactente , Pulmão/virologia , Masculino , Dados de Sequência Molecular , Paralisia/etiologia , Paralisia/virologia , Filogenia , Reação em Cadeia da Polimerase , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/fisiopatologiaRESUMO
c-di-GMP is an attractive target in the fight against bacterial infections since it is a near ubiquitous second messenger that regulates important cellular processes of pathogens, including biofilm formation and virulence. Screening of a combinatorial peptide library enabled the identification of the proline-rich tetrapeptide Gup-Gup-Nap-Arg, which binds c-di-GMP selectively over other nucleotides in water. Computational and CD spectroscopic studies provided a possible binding mode of the complex and enabled the design of a pentapeptide with even higher binding strength towards c-di-GMP. Biological studies showed that the tetrapeptide inhibits biofilm growth by the opportunistic pathogen P. aeruginosa.
Assuntos
GMP Cíclico/análogos & derivados , Peptídeos/metabolismo , Prolina/metabolismo , Pseudomonas aeruginosa/metabolismo , Sistemas do Segundo Mensageiro , Biofilmes/crescimento & desenvolvimento , Dicroísmo Circular , GMP Cíclico/metabolismo , Ligação Proteica , Pseudomonas aeruginosa/crescimento & desenvolvimento , TermodinâmicaRESUMO
Chronic interpersonal traumata systematically result in psychological impairments referred to as complex post-traumatic stress disorder (cPTSD or DESNOS). This diagnosis will be newly established in the ICD-11 system. However, there is need for diagnostic instruments to assess cPTSD. The aim was to develop a screening form to identify patients at risk for cPTSD. The Screening for complex PTSD (SkPTBS) tests a) experience of potential traumatic events, b) related influential features and risk factors, and c) symptoms of cPTSD. 325 patients (mean age 51.5±8.7 years; 62.1% female) filled out the screening instrument at the beginning of their inpatient psychotherapy. The primary criterion for testing SkPTBS validity was the diagnosis of complex PTSD at the end of the inpatient treatment. The proportion of patients with cPTSD was 8.9% (n=29). SkPTBS items were selective, and the scale showed very good reliability (α=0.91). Factor analysis revealed a one-dimensional structure. SkPTBS total values predicted having cPTSD diagnosis and were correlated with global symptom severity (SCL-90-R) and depressive symptoms (BDI-II). There is evidence for high clinical utility of SkPTBS. A revised version was developed.
Assuntos
Programas de Rastreamento , Psicometria/estatística & dados numéricos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Inquéritos e Questionários , Adulto , Idoso , Comorbidade , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Psicoterapia , Reprodutibilidade dos Testes , Fatores de Risco , Estatística como Assunto , Transtornos de Estresse Pós-Traumáticos/terapiaRESUMO
The respiratory mycobiome is an important but understudied component of the human microbiota. Like bacteria, fungi can cause severe lung diseases, but their infection rates are much lower. This study compared the bacterial and fungal communities of sputum samples from a large cohort of 56 adult patients with cystic fibrosis (CF) during nonexacerbation periods and under continuous antibiotic treatment. Molecular fingerprinting based on single-strand conformation polymorphism (SSCP) analysis revealed fundamental differences between bacterial and fungal communities. Both groups of microorganisms were taxonomically classified by identification of gene sequences (16S rRNA and internal transcript spacer), and prevalences of single taxa were determined for the entire cohort. Major bacterial pathogens were frequently observed, whereas fungi of known pathogenicity in CF were detected only in low numbers. Fungal species richness increased without reaching a constant level (saturation), whereas bacterial richness showed saturation after 50 patients were analyzed. In contrast to bacteria, a large number of fungal species were observed together with high fluctuations over time and among patients. These findings demonstrated that the mycobiome was dominated by transient species, which strongly suggested that the main driving force was their presence in inhaled air rather than colonization. Considering the high exposure of human airways to fungal spores, we concluded that fungi have low colonization abilities in CF, and colonization by pathogenic fungal species may be considered a rare event. A comprehensive understanding of the conditions promoting fungal colonization may offer the opportunity to prevent colonization and substantially reduce or even eliminate fungus-related disease progression in CF.
Assuntos
Bactérias/classificação , Biota , Fibrose Cística/complicações , Fungos/classificação , Infecções Respiratórias/microbiologia , Escarro/microbiologia , Adolescente , Adulto , Bactérias/genética , Bactérias/isolamento & purificação , Estudos de Coortes , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Fúngico/química , DNA Fúngico/genética , DNA Intergênico/química , DNA Intergênico/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Feminino , Fungos/genética , Fungos/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Adulto JovemRESUMO
Respiratory syncytial virus (RSV) is the most common cause of acute respiratory infections in young children. Limited data are available on RSV disease burden in primary care and emergency departments (EDs). This review synthesizes the evidence on population-based incidence rates of RSV infections in young children (< 5 years) in primary care and EDs. A systematic literature review was performed in PubMed and Embase. Studies reporting yearly population-based RSV incidence rates in primary care and EDs were included. A total of 4244 records were screened and 32 studies were included, conducted between 1993 and 2019. Studies were mainly performed in high-income countries (n = 27), with 15 studies in North America and 10 studies in Europe. There was significant variability in study methodology and setting among studies, resulting in considerable variability in reported incidence rates. Incidence rates were higher in primary care-ranging from 0.8 to 330 (median = 109) per 1000 population-compared to EDs (7.5-144.0, median = 48). The highest incidence rates were reported in infants. Additionally, incidence rates were higher in high-income countries and in studies using laboratory-confirmed RSV cases compared to studies using bronchiolitis ICD-codes (non-laboratory confirmed). Our study found that a substantial number of children under 5 years of age attend primary care settings and EDs, every year for RSV infections. Due to the considerable heterogeneity in study methodology, it was impossible to draw definitive conclusions regarding factors explaining differences in reported incidence rates. Additionally, more studies in low- and middle-income countries are recommended.
Assuntos
Bronquiolite , Serviço Hospitalar de Emergência , Atenção Primária à Saúde , Infecções por Vírus Respiratório Sincicial , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Lactente , Atenção Primária à Saúde/estatística & dados numéricos , Pré-Escolar , Bronquiolite/epidemiologia , Bronquiolite/virologia , Incidência , Vírus Sincicial Respiratório Humano/isolamento & purificação , Efeitos Psicossociais da Doença , Recém-NascidoRESUMO
OBJECTIVE: To assess the burden of respiratory syncytial virus (RSV)-related bronchiolitis in primary care and at 15 days and 6 months after a primary care visit. STUDY DESIGN: In this test-negative study, children <2 years old with a first episode of bronchiolitis were prospectively enrolled by 45 ambulatory pediatricians in France from February 2021 to April 2023. RSV was assessed with a rapid antigen detection test. The burden of the disease was assessed with a questionnaire, including quality of life (PedsQL 1.0 Infant Scales), at 15-day and 6-month follow-up. Children with a positive RSV test result (RSV+) were compared to those with a negative test result (RSV-). RESULTS: Among the 1591 children enrolled, 750 (47.1%) were RSV+. At 15 days follow-up (data availability: 69%), as compared with RSV- children, RSV+ children more frequently had fever (20.5% vs. 13.7%, P = 0.004) and decreased food intake (27.0% vs. 17.4%, P < 0.001) during the last 3 days. They had higher rates of hospitalization (11.8% vs. 5.8%, P < 0.001), childcare absenteeism (83.5% vs. 66.1%, P < 0.001) and parents who had to stop working to care for them (59.1% vs. 41.0%, P < 0.001) as well as lower quality of life (median PedsQL score 76.2 vs. 78.4, P = 0.03). At 6 months (data availability: 48.5%), the 2 groups did not differ in proportion of medical attendance, hospitalization, antibiotic treatment or quality of life. CONCLUSION: RSV+ children experienced much more severe disease and follow-up family and societal burden than RSV- children. These data may be used as baseline data as RSV prophylaxis is about to be implemented.
Assuntos
Atenção Primária à Saúde , Qualidade de Vida , Infecções por Vírus Respiratório Sincicial , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , França/epidemiologia , Lactente , Atenção Primária à Saúde/estatística & dados numéricos , Feminino , Masculino , Estudos Prospectivos , Seguimentos , Efeitos Psicossociais da Doença , Vírus Sincicial Respiratório Humano , Bronquiolite/virologia , Bronquiolite/epidemiologia , Recém-Nascido , Inquéritos e Questionários , Antivirais/uso terapêuticoRESUMO
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI) in infants and young children worldwide. Using routine statutory health insurance claims data including patients from all regions of Germany, we investigated the health-care resource use and costs associated with RSV prophylaxis with palivizumab in Germany. In the database, infants from the birth cohorts 2015-2019 eligible for palivizumab immunization were identified using codes of the 10th revision of the International Classification of Diseases (ICD-10). Health-care resource use and costs related to immunization were determined by inpatient and outpatient administrations. Over the study period, only 1.3% of infants received at least one dose of palivizumab in their first year of life. The mean number of doses per immunized infant was 4.6. From a third-party payer perspective, the mean costs of palivizumab per infant who received at least one dose in the first year of life was 5,435 in the birth cohorts 2015-2019. Despite the substantial risk of severe RSV infection, we found low rates of palivizumab utilization. Novel preventive interventions, featuring broader indications and single-dose administration per season, contribute to mitigating the burden of RSV disease across a more extensive infant population.
Assuntos
Antivirais , Palivizumab , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/economia , Alemanha/epidemiologia , Palivizumab/administração & dosagem , Palivizumab/uso terapêutico , Lactente , Feminino , Masculino , Vírus Sincicial Respiratório Humano/imunologia , Antivirais/economia , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Custos de Cuidados de Saúde/estatística & dados numéricos , Recém-Nascido , Vacinação/estatística & dados numéricos , Vacinação/economia , Imunização/estatística & dados numéricos , Coorte de Nascimento , Pré-EscolarRESUMO
OBJECTIVES: We aimed to study whether the percentwise age distribution of RSV cases changes over time during annual epidemics. METHODS: We used surveillance data (2008-2019) from the Netherlands, Lyon (France), Portugal, Singapore, Ecuador, South Africa, and New Zealand. In each country, every season was divided into "epidemic quarters", i.e. periods corresponding to each quartile of RSV cases. Multinomial logistic regression models were fitted to evaluate whether the likelihood of RSV cases being aged <1 or ≥5 years (vs. 1 to <5) changed over time within a season. RESULTS: In all countries, RSV cases were significantly more likely to be aged <1 year in the 4th vs. 1st epidemic quarter; the relative risk ratio [RRR] ranged between 1.35 and 2.56. Likewise, RSV cases were significantly more likely to be aged ≥5 years in the 4th vs. 1st epidemic quarter (except in Singapore); the RRR ranged from 1.75 to 6.70. The results did not change when stratifying by level of care or moving the lower cut-off to 6 months. CONCLUSIONS: The age profile of RSV cases shifts within a season, with infants and adolescents, adults, and the elderly constituting a higher proportion of cases in the later phases of annual epidemics. These findings may have implications for RSV prevention policies with newly approved vaccines.
Assuntos
Epidemias , Infecções por Vírus Respiratório Sincicial , Estações do Ano , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Lactente , Adolescente , Pré-Escolar , Criança , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Masculino , Feminino , Recém-Nascido , Distribuição por Idade , Vírus Sincicial Respiratório Humano/isolamento & purificação , Fatores Etários , Idoso de 80 Anos ou mais , Nova Zelândia/epidemiologia , Singapura/epidemiologiaRESUMO
BACKGROUND: Galicia (Spain) was one of the first regions worldwide to incorporate nirsevimab for universal respiratory syncytial virus (RSV) prophylaxis in infants into its immunisation programme. The NIRSE-GAL longitudinal population-based study aimed to assess nirsevimab effectiveness in preventing hospitalisations (ie, admittance to hospital). METHODS: The 2023-24 immunisation campaign with nirsevimab in Galicia began on Sept 25, 2023, and concluded on March 31, 2024. The campaign targeted three groups: infants born during the campaign (seasonal group), infants younger than 6 months at the start of the campaign (catch-up group), and infants aged 6-24 months with high-risk factors at the start of the campaign (high-risk group). Infants in the seasonal group were offered immunisation on the first day of life before discharge from hospital. Infants in the catch-up and high-risk groups received electronic appointments to attend a public hospital or health-care centre for nirsevimab administration. For this interim analysis, we used data collected from Sept 25 to Dec 31, 2023, from children born up to Dec 15, 2023. Data were retrieved from public health registries. Nirsevimab effectiveness in preventing RSV-associated lower respiratory tract infection (LRTI) hospitalisations; severe RSV-related LRTI requiring intensive care unit admission, mechanical ventilation, or oxygen support; all-cause LRTI hospitalisations; and all-cause hospitalisations was estimated using adjusted Poisson regression models. Data from five past RSV seasons (2016-17, 2017-18, 2018-19, 2019-20, and 2022-23), excluding the COVID-19 pandemic period, were used to estimate the number of RSV-related LRTI hospitalisations averted along with its IQR. The number needed to immunise to avoid one case in the 2023-24 season was then estimated from the averted cases. Nirsevimab safety was routinely monitored. The NIRSE-GAL study protocol was registered on ClinicalTrials.gov (NCT06180993), and follow-up of participants is ongoing. FINDINGS: 9408 (91·7%) of 10 259 eligible infants in the seasonal and catch-up groups received nirsevimab, including 6220 (89·9%) of 6919 in the catch-up group and 3188 (95·4%) of 3340 in the seasonal group. 360 in the high-risk group were offered nirsevimab, 348 (97%) of whom received it. Only infants in the seasonal and catch-up groups were included in analyses to estimate nirsevimab effectiveness and impact because there were too few events in the high-risk group. In the catch-up and seasonal groups combined, 30 (0·3%) of 9408 infants who received nirsevimab and 16 (1·9%) of 851 who did not receive nirsevimab were hospitalised for RSV-related LRTI, corresponding to an effectiveness of 82·0% (95% CI 65·6-90·2). Effectiveness was 86·9% (69·1-94·2) against severe RSV-related LRTI requiring oxygen support, 69·2% (55·9-78·0) against all-cause LRTI hospitalisations, and 66·2% (56·0-73·7) against all-cause hospitalisations. Nirsevimab effectiveness against other endpoints of severe RSV-related LRTI could not be estimated because of too few events. RSV-related LRTI hospitalisations were reduced by 89·8% (IQR 87·5-90·3), and the number needed to immunise to avoid one RSV-related LRTI hospitalisation was 25 (IQR 24-32). No severe adverse events related to nirsevimab were registered. INTERPRETATION: Nirsevimab substantially reduced infant hospitalisations for RSV-associated LRTI, severe RSV-associated LRTI requiring oxygen, and all-cause LRTI when given in real-world conditions. These findings offer policy makers and health authorities robust, real-world, population-based evidence to guide the development of strategies for RSV prevention. FUNDING: Sanofi and AstraZeneca. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.
Assuntos
Anticorpos Monoclonais Humanizados , Antivirais , Hospitalização , Infecções por Vírus Respiratório Sincicial , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Lactente , Espanha/epidemiologia , Hospitalização/estatística & dados numéricos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Estudos Longitudinais , Feminino , Masculino , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Recém-Nascido , Vírus Sincicial Respiratório Humano/imunologia , Pré-Escolar , Programas de ImunizaçãoRESUMO
Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.
Assuntos
Antivirais , Hospitalização , Infecções por Vírus Respiratório Sincicial , Humanos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Lactente , Hospitalização/estatística & dados numéricos , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Vírus Sincicial Respiratório Humano/imunologia , Feminino , Masculino , Infecções Respiratórias/prevenção & controle , Programas de Imunização , Recém-Nascido , Pré-Escolar , Palivizumab/uso terapêutico , Palivizumab/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagemRESUMO
BACKGROUND: The significant annual burden caused by seasonal influenza has led to global calls for increased influenza vaccination coverage rates (VCRs). We aimed to estimate the proportion of the German population at high risk of serious illness from influenza due to chronic conditions and to estimate age-specific VCRs of people with/without chronic conditions. METHODS: Using health insurance claims data covering nine influenza seasons (2010-2019), we assessed up to 7 million insured individuals per season across all German regions. Individuals were classified according to age and presence of chronic health conditions. VCRs were estimated using outpatient healthcare utilization documentation. RESULTS: In the 2018-2019 influenza season, 47.3% of individuals had ≥1 chronic condition. Most common were circulatory disorders, accounting for more than a third of individuals with ≥1 condition. Prevalence of chronic diseases, and therefore the proportion of high-risk individuals, increased slightly over time across most age groups. A downward trend in influenza VCRs was observed in all age groups until the 2017-2018 season, followed by a noticeable increase in the 2018-2019 season. Highest VCRs occurred among individuals of ≥60 years, with a 38.5% VCR for this age group in the 2018-2019 season. Several factors, including age, chronic condition type, and geographical location, affected VCRs. CONCLUSIONS: Influenza VCRs in individuals at high risk of severe complications from influenza infection are insufficient. Our results suggest that intensified public health efforts are necessary to reach the World Health Organization vaccination coverage target of 75%.
Assuntos
Vacinas contra Influenza , Influenza Humana , Humanos , Cobertura Vacinal , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Prevalência , Vacinação , Alemanha/epidemiologia , Doença Crônica , Estações do Ano , Seguro Saúde , Análise de DadosRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) causes respiratory tract disease in seasonal waves, primarily in infants and young children. This study aims to quantify the number of RSV-related hospitalizations in children ≤2 years of age and to determine corresponding resource use and costs in Germany. METHODS: We retrospectively analyzed population-wide hospital data from the Institute for the Hospital Remuneration System (InEK) from 2019 to 2022. RSV cases were identified using the RSV-specific 10th revision of the International Classification of Diseases (ICD-10) codes J12.1, J20.5, and J21.0. The RSV-associated proportion of all hospitalizations caused by severe acute respiratory infections (SARIs), clinical manifestations, length of stay (LOS), intensive care unit (ICU) admissions, ventilation rates, and hospitalization costs were retrieved. RESULTS: We identified 98,220 hospitalizations (26,052, 15,407, 31,362, and 25,399 in 2019, 2020, 2021, and 2022, respectively) with a principal RSV diagnosis in children aged ≤2 years in Germany. The majority of RSV hospitalizations (73,178) occurred in infants (<1 year), with annual incidence rates ranging from 14.9 to 28.6 per 1000 population. Fifty-eight percent of all SARI hospitalizations in this age group were attributable to RSV. In children aged ≤2 years, mean LOS was 4.5 days, 6.1% of cases were admitted to ICU, and 5.3% of cases were ventilated. Mean hospitalization costs per case ranged from 3001 to 3961 over the study period. CONCLUSIONS: RSV causes substantial disease burden and is a leading cause of SARI-related hospital admissions of children ≤2 years of age in Germany. Our results confirm the need to explore and evaluate strategies to prevent RSV in infants and young children.
Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Lactente , Humanos , Criança , Pré-Escolar , Estudos Retrospectivos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/terapia , Pacientes Internados , HospitalizaçãoRESUMO
We aimed to estimate the respiratory syncytial virus positivity rate among ambulatory children with bronchiolitis according to the bronchiolitis epidemic period as defined by the French Public Health Institute. The positivity rate was 28.9% during the nonepidemic period and 50.6% during the epidemic period, which suggests continuous virus circulation between bronchiolitis annual peaks.
Assuntos
Bronquiolite , Epidemias , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Criança , Humanos , Lactente , Infecções por Vírus Respiratório Sincicial/epidemiologia , Pacientes Ambulatoriais , Bronquiolite/epidemiologiaRESUMO
We report on a new three-color FRET system which we were able to verify in peptides as well as in synthetic DNA. All three chromophores could be introduced by a building block approach avoiding postsynthetic labeling. Additional features are robustness, matching spectroscopic properties, high-energy transfer, and sensitivity. The system was investigated in detail on a set of peptides as well as an array of tailored oligonucleotides. The detailed analysis of the experimental data and comparison with theoretical considerations were in excellent agreement. It is shown that in the case of polypeptides specific interaction with the fluorescence probes has to be considered. In contrast with DNA, the fluorescence probes did not show any indications of such interactions. The novel three-color FRET toolbox revealed the potential for applications studying fundamental processes of three interacting molecules in life science applications.
Assuntos
DNA/análise , Transferência Ressonante de Energia de Fluorescência/métodos , Corantes Fluorescentes/química , Proteínas/análise , Oligonucleotídeos/química , Peptídeos/químicaRESUMO
Resistance of Aspergillus fumigatus to triazoles has been reported increasingly in Europe. As few data are available from Southern France, the objectives of this study were to assess the burden of A. fumigatus isolates with azole resistance from clinical specimens in Lyon, and explore the resistance mechanisms involved. In this retrospective cross-sectional study, 221 consecutive A. fumigatus isolates from respiratory samples were identified from an 8-month period from 195 patients attending the Pulmonary Medicine Departments of Lyon University Hospitals. Morphological identification was confirmed by sequence analysis of the ß-tubulin gene. All samples were tested for susceptibilities to itraconazole, voriconazole, posaconazole and isavuconazole using concentration gradient strips, and the results were confirmed using the EUCAST broth microdilution method. Resistance mechanisms were investigated by sequencing the cyp51A gene and its promoter, and by expression analysis of cyp51 and genes encoding several efflux transporters. Four isolates exhibited azole resistance. Three isolates presented with polymorphisms in an intronic region of cyp51A, and one isolate had F46Y, M172V and E427K polymorphisms. No mutations were identified in the cyp51A promoter, but significant induction of cyp51A and cyp51B gene expression was observed for all four and three isolates, respectively. Significant induction of atrF and cdr1B gene expression was observed for two and three isolates, respectively. No significant induction of MDR1/2/3/4, MFS56 and M85 gene expression was observed. To conclude, the observed prevalence of azole resistance was 2.1%. Significant induction of expression of the cyp51 genes and two genes encoding efflux transporters was evidenced, underlying the diversity of resistance mechanisms to be explored.
Assuntos
Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Infecções Respiratórias/tratamento farmacológico , Triazóis/farmacologia , Aspergillus fumigatus/isolamento & purificação , Estudos Transversais , Sistema Enzimático do Citocromo P-450/genética , França , Proteínas Fúngicas/genética , Hospitais Universitários , Humanos , Itraconazol/farmacologia , Testes de Sensibilidade Microbiana , Nitrilas/farmacologia , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Piridinas/farmacologia , Infecções Respiratórias/microbiologia , Estudos Retrospectivos , Tubulina (Proteína)/genética , Voriconazol/farmacologiaRESUMO
Acute flaccid myelitis (AFM) was increasingly detected in recent years, coinciding with upsurges of enterovirus D68 (EV-D68) infections. We reviewed the evidence for a causal relationship between both. Based on reported cases, we provide case definitions for AFM caused by EV-D68 infections to enable a standard procedure for affected patients. Current case definitions are focussing on epidemiological aspects but clinical case definitions are still missing. We propose the following case definitions to be used in clinical practice in order to mirror clinical realities and facilitate a common systematic approach in case management: A possible case is defined as a person presenting with either acute myelitis/paralysis or Guillain-Barré Syndrome (GBS), particularly during periods of EV-D68 circulation. A probable case is defined as a person presenting with symptoms of either acute myelitis/paralysis or GBS and at least one of the following criteria: i) MRI abnormality representing with T2 hyperintensity in spinal cord grey matter with or without hyperintensity at dorsal brain stem, ii) investigations showing an axonal neuropathy including reduced compound motor action potentials with normal conduction velocities and absence of conduction blocks compatible with anterior horn cell disease or iii) detection of enteroviruses in a respiratory specimen obtained from the lower respiratory tract during periods of EV-D68 circulation. A confirmed case is defined as a person presenting with acute flaccid myelitis/paralysis, MRI abnormality and detection of enterovirus-D68-specific nucleic acids in a respiratory specimen using a validated PCR assay targeting the VP1 gene with subsequent sequencing and typing.