RESUMEN
BackgroundTick-borne encephalitis (TBE) is a severe, vaccine-preventable viral infection of the central nervous system. Symptoms are generally milder in children and adolescents than in adults, though severe disease does occur. A better understanding of the disease burden and duration of vaccine-mediated protection is important for vaccination recommendations.AimTo estimate TBE vaccination coverage, disease severity and vaccine effectiveness (VE) among individuals aged 0-17â¯years in Switzerland.MethodsVaccination coverage between 2005 and 2022 was estimated using the Swiss National Vaccination Coverage Survey (SNVCS), a nationwide, repeated cross-sectional study assessing vaccine uptake. Incidence and severity of TBE between 2005 and 2022 were determined using data from the Swiss disease surveillance system and VE was calculated using a case-control analysis, matching TBE cases with SNVCS controls.ResultsOver the study period, vaccination coverage increased substantially, from 4.8% (95% confidence interval (CI): 4.1-5.5%) to 50.1% (95% CI: 48.3-52.0%). Reported clinical symptoms in TBE cases were similar irrespective of age. Neurological involvement was less likely in incompletely (1-2 doses) and completely (≥â¯3 doses) vaccinated cases compared with unvaccinated ones. For incomplete vaccination, VE was 66.2% (95% CI: 42.3-80.2), whereas VE for complete vaccination was 90.8% (95% CI: 87.7-96.4). Vaccine effectiveness remained high, 83.9% (95% CI: 69.0-91.7) up to 10â¯years since last vaccination.ConclusionsEven children younger than 5â¯years can experience severe TBE. Incomplete and complete vaccination protect against neurological manifestations of the disease. Complete vaccination offers durable protection up to 10â¯years against TBE.
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Encefalitis Transmitida por Garrapatas , Cobertura de Vacunación , Vacunación , Vacunas Virales , Humanos , Encefalitis Transmitida por Garrapatas/prevención & control , Encefalitis Transmitida por Garrapatas/epidemiología , Adolescente , Estudios de Casos y Controles , Suiza/epidemiología , Niño , Estudios Transversales , Masculino , Femenino , Preescolar , Lactante , Vacunación/estadística & datos numéricos , Cobertura de Vacunación/estadística & datos numéricos , Vacunas Virales/administración & dosificación , Incidencia , Eficacia de las Vacunas/estadística & datos numéricos , Virus de la Encefalitis Transmitidos por Garrapatas/inmunología , Recién Nacido , Vigilancia de la PoblaciónRESUMEN
Primary immunodeficiencies in the costimulatory molecule CD27 and its ligand, CD70, predispose for pathologies of uncontrolled Epstein-Barr virus (EBV) infection in nearly all affected patients. We demonstrate that both depletion of CD27+ cells and antibody blocking of CD27 interaction with CD70 cause uncontrolled EBV infection in mice with reconstituted human immune system components. While overall CD8+ T-cell expansion and composition are unaltered after antibody blocking of CD27, only some EBV-specific CD8+ T-cell responses, exemplified by early lytic EBV antigen BMLF1-specific CD8+ T cells, are inhibited in their proliferation and killing of EBV-transformed B cells. This suggests that CD27 is not required for all CD8+ T-cell expansions and cytotoxicity but is required for a subset of CD8+ T-cell responses that protect us from EBV pathology.
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Linfocitos T CD8-positivos/inmunología , Infecciones por Virus de Epstein-Barr/inmunología , Herpesvirus Humano 4/inmunología , Inmunidad Celular , Fosfoproteínas/inmunología , Transactivadores/inmunología , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Animales , Linfocitos B/inmunología , Transformación Celular Viral/genética , Transformación Celular Viral/inmunología , Infecciones por Virus de Epstein-Barr/genética , Herpesvirus Humano 4/genética , Humanos , Ratones , Ratones Endogámicos NOD , Ratones Transgénicos , Fosfoproteínas/genética , Transactivadores/genética , Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/genéticaRESUMEN
Approximately 28% of the human population have been exposed to Mycobacterium tuberculosis (MTB), with the overwhelming majority of infected individuals not developing disease (latent TB infection (LTBI)). While it is known that uncontrolled HIV infection is a major risk factor for the development of TB, the effect of underlying LTBI on HIV disease progression is less well characterized, in part because longitudinal data are lacking. We sorted all participants of the Swiss HIV Cohort Study (SHCS) with at least 1 documented MTB test into one of the 3 groups: MTB uninfected, LTBI, or active TB. To detect differences in the HIV set point viral load (SPVL), linear regression was used; the frequency of the most common opportunistic infections (OIs) in the SHCS between MTB uninfected patients, patients with LTBI, and patients with active TB were compared using logistic regression and time-to-event analyses. In adjusted models, we corrected for baseline demographic characteristics, i.e., HIV transmission risk group and gender, geographic region, year of HIV diagnosis, and CD4 nadir. A total of 13,943 SHCS patients had at least 1 MTB test documented, of whom 840 (6.0%) had LTBI and 770 (5.5%) developed active TB. Compared to MTB uninfected patients, LTBI was associated with a 0.24 decreased log HIV SPVL in the adjusted model (p < 0.0001). Patients with LTBI had lower odds of having candida stomatitis (adjusted odds ratio (OR) = 0.68, p = 0.0035) and oral hairy leukoplakia (adjusted OR = 0.67, p = 0.033) when compared to MTB uninfected patients. The association of LTBI with a reduced HIV set point virus load and fewer unrelated infections in HIV/TB coinfected patients suggests a more complex interaction between LTBI and HIV than previously assumed.
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Infecciones por VIH/complicaciones , Tuberculosis Latente/complicaciones , Tuberculosis Latente/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones Oportunistas Relacionadas con el SIDA/etiología , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Adulto , Linfocitos T CD4-Positivos , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Infecciones por VIH/metabolismo , VIH-1/patogenicidad , Humanos , Interferón gamma , Tuberculosis Latente/metabolismo , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/patogenicidad , Infecciones Oportunistas/complicaciones , Riesgo , Tuberculosis/complicaciones , Tuberculosis/diagnóstico , Carga Viral/inmunologíaRESUMEN
Immunological memory equips our immune system to respond faster and more effectively against reinfections. This acquired immunity was originally attributed to long-lived, memory T and B cells with body wide access to peripheral and secondary lymphoid tissues. In recent years, it has been realized that both innate and adaptive immunity to a large degree depends on resident immune cells that act locally in barrier tissues including tissue-resident memory T cells (Trm). Here, we will discuss the phenotype of these Trm in mice and humans, the tissues and niches that support them, and their function, plasticity, and transcriptional control. Their unique properties enable Trm to achieve long-lived immunological memory that can be deposited in nearly every organ in response to acute and persistent infection, and in response to cancer. However, Trm may also induce substantial immunopathology in allergic and autoimmune disease if their actions remain unchecked. Therefore, inhibitory and activating stimuli appear to balance the actions of Trm to ensure rapid proinflammatory responses upon infection and to prevent damage to host tissues under steady state conditions.
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Enfermedades Autoinmunes/inmunología , Hipersensibilidad/inmunología , Inflamación/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T/inmunología , Animales , Plasticidad de la Célula , Humanos , Memoria Inmunológica , RatonesRESUMEN
Tick-Borne Encephalitis - Viral Transmission and Considerations for Vaccination Abstract. Tick-Borne encephalitis virus (TBEV) is a flavivirus transmitted to humans primarily through the bite of infected Ixodes ticks. Infection with TBEV results in Tick-Borne Encephalitis (TBE), an acute disease of the Central Nervous System (CNS) that can lead to significant long-term sequalae. Over the last decades the geographic range of TBEV and the incidence of TBE have substantially increased. TBEV is now endemic through much of Central Europe, including parts of Germany, Austria, and Switzerland, and is recognized as an increasing public health problem. While there are no specific therapies for TBE, two vaccines are licensed and available in Europe, Encepur® and FSME-Immun®. Both are considered safe and effective. Following vaccination, the generation of virus-neutralizing antibodies is often considered an indicator of protection against disease. While recent evidence suggests that cell-mediated immune responses likely also play important roles in protection, cell-mediated immunity following infection and vaccination remains poorly characterized. As with many vaccines, the initial response to TBE vaccination is influenced by several factors. Here, we review how age, immunosuppression, adherence to recommended vaccination schedules, and the use of single vaccine type during priming may impact immunity following TBE vaccination. We further discuss vaccination coverage and disease prevention, as well as factors impacting individual vaccine uptake.
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Virus de la Encefalitis Transmitidos por Garrapatas , Encefalitis Transmitida por Garrapatas , Vacunas Virales , Humanos , Encefalitis Transmitida por Garrapatas/epidemiología , Encefalitis Transmitida por Garrapatas/prevención & control , Vacunación , Alemania , Europa (Continente)/epidemiologíaRESUMEN
Following infection, tissue-resident memory T cells (Trm) are thought to be left behind at sites of antigen encounter to protect affected tissues against subsequent reinfection. In this issue of the European Journal of Immunology, however, Pascutti et al. demonstrate that both murine and human CD8+ Trm specific to seven different pathogens, including systemic, skin, and lung tissue-localized pathogens, accumulate in the bone marrow (BM). These cells have a CD69+ phenotype, develop independently of local antigen, and require IL-15, Blimp-1, and Hobit for their differentiation and maintenance. Following restimulation, these cells expand and rapidly produce cytokines. While some of these responses may protect the BM from infection, the consideration that some of these pathogens or their antigens might never reach the BM suggests additional functional roles of BM Trm, possibly in supporting hematopoietic functions via cytokine production following infection. It will be further interesting to determine whether BM Trm contribute to the circulating effector pool following reinfection with tissue-localized or systemic pathogens and whether these cells can be elicited by vaccination.
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Linfocitos T CD8-positivos , Memoria Inmunológica , Animales , Antígenos , Humanos , Pulmón , Ratones , FenotipoRESUMEN
Viral respiratory tract infections (VRTI) remain a leading cause of morbidity and mortality among infants and young children. In mice, optimal protection to VRTI is mediated by recruitment of effector T cells to the lungs and respiratory tract, and subsequent establishment of tissue resident memory T cells (Trm), which provide long-term protection. These critical processes of T cell recruitment to the respiratory tract, their role in disease pathogenesis, and establishment of local protective immunity remain undefined in pediatric VRTI. In this study, we investigated T cell responses in the upper respiratory tract (URT) and lower respiratory tract (LRT) of infants and young children with VRTI, revealing developmental regulation of T cell differentiation and Trm generation in situ. We show a direct concurrence between T cell responses in the URT and LRT, including a preponderance of effector CD8+ T cells that was associated with disease severity. During infant VRTI, there was an accumulation of terminally differentiated effector cells (effector memory RA+ T cells) in the URT and LRT with reduced Trm in the early neonatal period, and decreased effector memory RA+ T cell and increased Trm formation with age during the early years of childhood. Moreover, human infant T cells exhibit increased expression of the transcription factor T-bet compared with adult T cells, suggesting a mechanism for preferential generation of effector over Trm. The developmental regulation of respiratory T cell responses as revealed in the present study is important for diagnosing, monitoring, and treating VRTI in the critical early life stages.
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Linfocitos T CD8-positivos/inmunología , Memoria Inmunológica/inmunología , Infecciones del Sistema Respiratorio/inmunología , Virosis/inmunología , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Pulmón/inmunología , Pulmón/virología , Activación de Linfocitos/inmunología , Masculino , Infecciones del Sistema Respiratorio/virología , Factores de Transcripción/inmunologíaRESUMEN
Influenza A virus is a significant cause of morbidity and mortality worldwide, particularly among young children and the elderly. Current vaccines induce neutralizing antibody responses directed toward highly variable viral surface proteins, resulting in limited heterosubtypic protection to new viral serotypes. By contrast, memory CD4 T cells recognize conserved viral proteins and are cross-reactive to multiple influenza strains. In humans, virus-specific memory CD4 T cells were found to be the protective correlate in human influenza challenge studies, suggesting their key role in protective immunity. In mouse models, memory CD4 T cells can mediate protective responses to secondary influenza infection independent of B cells or CD8 T cells, and can influence innate immune responses. Importantly, a newly defined, tissue-resident CD4 memory population has been demonstrated to be retained in lung tissue and promote optimal protective responses to an influenza infection. Here, we review the current state of results regarding the generation of memory CD4 T cells following primary influenza infection, mechanisms for their enhanced efficacy in protection from secondary challenge including their phenotype, localization, and function in the context of both mouse models and human infection. We also discuss the generation of memory CD4 T cells in response to influenza vaccines and its future implications for vaccinology.
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Linfocitos T CD4-Positivos/inmunología , Memoria Inmunológica , Gripe Humana/inmunología , Animales , Citocinas/biosíntesis , Humanos , Vacunas contra la Influenza/inmunología , Tejido Linfoide/inmunología , RatonesRESUMEN
Tick-borne Encephalitis (TBE) is a severe disease of the Central Nervous System (CNS) caused by the tick-borne encephalitis virus (TBEV). The generation of protective immunity after TBEV infection or TBE vaccination relies on the integrated responses of many distinct cell types at distinct physical locations. While long-lasting memory immune responses, in particular, form the basis for the correlates of protection against many diseases, these correlates of protection have not yet been clearly defined for TBE. This review addresses the immune control of TBEV infection and responses to TBE vaccination. Potential correlates of protection and the durability of protection against disease are discussed, along with outstanding questions in the field and possible areas for future research.
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Virus de la Encefalitis Transmitidos por Garrapatas , Encefalitis Transmitida por Garrapatas , Humanos , Sistema Nervioso Central , VacunaciónRESUMEN
BACKGROUND: A significant proportion of the global population has been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at some point since the onset of the pandemic. Although most individuals who develop coronavirus disease 2019 (COVID-19) recover without complications, about 6% have persistent symptoms, referred to as post-COVID-19 condition (PCC). Intervention studies investigating treatments that potentially alleviate PCC-related symptoms and thus aim to mitigate the global public health burden and healthcare costs linked to PCC are desperately needed. The PYCNOVID trial investigates the effects of Pycnogenol®, a French maritime pine bark extract with anti-inflammatory and antioxidative properties, versus placebo on patient-reported health status in people with PCC. METHODS: This is a single-center, placebo-controlled, quadruple blind, randomized trial. We aim to randomly assign 150 individuals with PCC (1:1 ratio) to receive either 200 mg Pycnogenol® or placebo daily for 12 weeks. Randomization is stratified for duration of PCC symptoms (≤ 6 months versus > 6 months) and presence of symptomatic chronic disease(s). The primary endpoint is perceived health status at 12 weeks (EuroQol-Visual Analogue Scale) adjusted for baseline values and stratification factors. Secondary endpoints include change in self-reported PCC symptoms, health-related quality of life, symptoms of depression and anxiety, cognitive function, functional exercise capacity, physical activity measured with accelerometry, and blood biomarkers for endothelial health, inflammation, coagulation, platelet function, and oxidative stress. Investigators, study participants, outcome assessors, and data analysts are blinded regarding the intervention assignment. Individuals with PCC were involved in the design of this study. DISCUSSION: This is the first trial to investigate the effects of Pycnogenol® versus placebo on patient-reported health status in people with PCC. Should the trial proof clinical effectiveness, Pycnogenol® may serve as a therapeutic approach to mitigate symptoms associated with PCC. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov. :NCT05890534, June 6, 2023.
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Flavonoides , Extractos Vegetales , Humanos , Extractos Vegetales/uso terapéutico , Extractos Vegetales/efectos adversos , Flavonoides/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Calidad de Vida , COVID-19 , Resultado del Tratamiento , SARS-CoV-2/efectos de los fármacos , Estado de Salud , Tratamiento Farmacológico de COVID-19 , Síndrome Post Agudo de COVID-19 , Adulto , Femenino , Masculino , Antioxidantes/uso terapéutico , Antioxidantes/efectos adversos , Antiinflamatorios/uso terapéutico , Antiinflamatorios/efectos adversosRESUMEN
OBJECTIVES: The correlate(s) of protection against SARS-CoV-2 remain incompletely defined. Additional information regarding the combinations of antibody and T cell-mediated immunity which can protect against (re)infection is needed. METHODS: We conducted a population-based, longitudinal cohort study including 1044 individuals of varying SARS-CoV-2 vaccination and infection statuses. We assessed spike (S)- and nucleocapsid (N)-immunoglobulin(Ig)G and wildtype, Delta, and Omicron-neutralizing antibody (N-Ab) activity. In a subset of 328 individuals, we evaluated S, membrane (M), and N-specific T cells. Three months later, we reassessed Ab (n = 964) and T cell (n = 141) responses and evaluated factors associated with protection from (re)infection. RESULTS: At the study start, >98% of participants were S-IgG seropositive. N-IgG and M/N-T-cell responses increased over time, indicating viral (re)exposure, despite existing S-IgG. Compared to N-IgG, M/N-T cells were a more sensitive measure of viral exposure. High N-IgG titers, Omicron-N-Ab activity, and S-specific-T-cell responses were all associated with a reduced likelihood of (re)infection over time. CONCLUSION: Population-level SARS-CoV-2 immunity is S-IgG-dominated, but heterogeneous. M/N-T-cell responses can distinguish previous infection from vaccination, and monitoring a combination of N-IgG, Omicron-N-Ab, and S-T-cell responses may help estimate protection against SARS-CoV-2 (re)infection.
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COVID-19 , Linfocitos T , Humanos , Anticuerpos Neutralizantes , Suiza/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Estudios Longitudinales , SARS-CoV-2 , Inmunidad Celular , Reinfección , Inmunoglobulina G , Anticuerpos AntiviralesRESUMEN
BACKGROUND: Although monitoring of vaccination program performance is usually evaluated by measurement of vaccine coverage, timely uptake is rarely part of this assessment. This study aims to examine the timeliness of the administration of a measles-containing-vaccine (MCV) for 2-year-old children between 2005 and 2019. METHODS: We used data from the Swiss National Vaccination Coverage Survey 2005-2019 for the study. We defined timely vaccinated as a vaccination administered within the recommended age specified in the Swiss National Vaccination Schedule, with an added tolerance period of 30.4 days for both MCV 1 and 2 doses. The median delay time was estimated by Kaplan-Meier survival curve and examined using log-rank test. A Cox hazard ratio was used to identify factors associated with delay. RESULTS: 81% (95% CI:79-82%) of toddlers were timely vaccinated for MCV1 and 82% (95% CI:81-83%) for MCV2 in survey period 2017-2019. Between 2005 and 2019, the median age of vaccinated children ranged between 12.2 and 12.5 and 18.3-22.0 months for MCV1 and MCV2 with median delay of 44 and 38 days, respectively, at the national level. Children in the French-, Italian- and German-speaking regions were vaccinated earlier between 2005 and 2019 for MCV1 (vaccination coverage range before 10 months of age: 1.7-45.9%, 1.2-35.3% and 1.4-15.0%, respectively). Nationality, linguistic regions, and survey periods were the strongest predictive factors related to prolonged delay time. CONCLUSION: Overall adherence to recommendations has improved over time, as MCV coverage has significantly increased over the years with differences across linguistic regions. Vaccinations were administered earlier and with shorter delay time.
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Vacuna Antisarampión , Sarampión , Adolescente , Adulto , Niño , Preescolar , Humanos , Programas de Inmunización , Esquemas de Inmunización , Lactante , Sarampión/prevención & control , Persona de Mediana Edad , Encuestas y Cuestionarios , Suiza , Vacunación , Adulto JovenRESUMEN
OBJECTIVE: To estimate effectiveness of tickborne encephalitis (TBE) vaccination by time interval (<5, 5-10 and 10+years) postvaccination. DESIGN: A retrospective, matched case-control study PARTICIPANTS: Cases-all adult (age 18-79) TBE cases in Switzerland reported via the national mandatory disease reporting surveillance system from 2006 to 2020 (final n=1868). Controls-community controls from a database of randomly selected adults (age 18-79) participating in a 2018 cross-sectional study of TBE vaccination in Switzerland (final n=4625). PRIMARY OUTCOME MEASURES: For cases and controls, the number of TBE vaccine doses received and the time since last vaccination were determined. Individuals were classified as being 'unvaccinated' (0 doses), 'incomplete' (1-2 doses) or 'complete' (3+ doses). Individuals with 'complete' vaccination were further classified by time since the last dose was received (<5 years, 5-10 years or 10+ years). A conditional logistic regression model was used to calculate vaccine effectiveness (VE: 100 × [1-OR]) for each vaccination status category. RESULTS: VE for incomplete vaccination was 76.8% (95% CI 69.0% to 82.6%). For complete vaccination, overall VE was 95.0% (95% CI 93.5% to 96.1%). When the most recent dose was received <5 years prior VE was 91.6% (95% CI 88.4% to 94.0%), 95.2% (95% CI 92.4% to 97.0%) when the most recent dose was received 5-10 years prior, and 98.5% (95% CI 96.8% to 99.2%) when the most recent dose was received 10+ years prior. CONCLUSIONS: That VE does not decrease among completely vaccinated individuals over 10+ years since last vaccination supports the longevity of the protective response following complete TBE vaccination. Our findings support the effectiveness of 10-year TBE booster intervals currently used in Switzerland.
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Encefalitis Transmitida por Garrapatas , Vacunas Virales , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Estudios Transversales , Encefalitis Transmitida por Garrapatas/epidemiología , Encefalitis Transmitida por Garrapatas/prevención & control , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Suiza/epidemiología , Vacunación , Eficacia de las Vacunas , Adulto JovenRESUMEN
To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection.
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COVID-19 , SARS-CoV-2 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Humanos , Inmunidad Celular , Inmunidad Humoral , Inmunoglobulina G , Glicoproteína de la Espiga del CoronavirusRESUMEN
BACKGROUND: The incidence of influenza and influenza-like illnesses in Switzerland is generally high. Although related direct medical costs can be substantial, especially if hospitalisations occur, several studies suggested that indirect costs due to the loss of productivity may represent an even higher economic burden. The aim of this study was to assess the costs arising from lost productivity due to influenza and influenza-like illnesses in Switzerland. METHODS: Analyses were based on data collected in 2016 and 2017 by the Swiss Sentinel Surveillance Network of the Swiss Federal Office of Public Health (SFOPH). The available information covered details on the physicians collecting the data, patients' characteristics, symptoms, treatments, and inability to work (in terms of physician-recorded workdays lost for own sickness or caregiving). The cost of lost productivity, estimated using the human capital approach, was calculated as the number of workdays lost due to influenza-like illnesses multiplied by the mean salary for one working day. Salary differences across sex, age and region were considered. Extrapolation to the national level was performed by adjusting for the size of the Swiss population, the age and sex distribution, the regional distribution, the number of Sentinel general physician contacts and the specialisation of the physician. RESULTS: At the Swiss national level, the estimated total yearly number of cases of inability to work due to influenza and influenza-like illnesses was 101,287 in 2016 and 86,373 in 2017. In subgroups defined by year, gender, region and age class, numbers of cases per 100,000 inhabitants ranged from 12 to 2396. The total number of workdays lost in Switzerland, considering degree of employment and visit day, were estimated to be 324,118 in 2016 and 278,121 in 2017. The number of workdays lost was generally higher in men (53.7% of the total in 2016 and 55.6% of the total in 2017) than women. The estimated total costs due to inability to work, calculated using a human capital approach and including the caregiving costs, were CHF 115 million in 2016 and CHF 103 million in 2017, equivalent to CHF 1.4 million per 100,000 inhabitants. CONCLUSION: The costs of lost productivity due to influenza and influenza-like illnesses in Switzerland are substantial and may vary considerably between different years, regions and age classes. As the present analyses could not consider all causes of lost productivity (e.g., short-term inability to work not requiring a physician consultation, hospitalisations, early retirement, premature death), the total indirect costs due to influenza or influenza-like illnesses can be expected to be higher than the presented estimates.
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Gripe Humana , Costo de Enfermedad , Costos y Análisis de Costo , Femenino , Hospitalización , Humanos , Gripe Humana/epidemiología , Masculino , Vigilancia de Guardia , Suiza/epidemiologíaRESUMEN
Streptococcus pneumoniae, or pneumococcus, is a common, opportunistic pathogen which can cause severe disease, particularly in adults 65+. In Switzerland, vaccination is recommended for children under 5 and for adults with health predispositions; vaccination of healthy adults 65+ is not recommended. In 2020 we conducted a nationwide, cross-sectional survey of vaccination records to evaluate pneumococcal vaccination coverage and factors affecting uptake among adults 18-85. We found that nationwide coverage was 4.5% without significant regional differences. Coverage was comparable between men and women and between those aged 18-39 (3.0%) and 40-64 (3.2%). Coverage was significantly higher among those 65-85 (9.6%). While 2.7% of individuals reporting no health predisposition were vaccinated, 14.8% with asthma or chronic pulmonary disease, 27.1% with immunosuppression, 12.9% with diabetes, 11.6% with heart, liver, or kidney disease, and 25.9% with >1 health risk were vaccinated. Adjusted odds of vaccination for all health predispositions except heart, liver, or kidney disease were significantly increased. Among unvaccinated individuals "not enough information about the topic" and "not suggested by a doctor/healthcare provider" were the major reasons for abstaining from vaccination. Respondents reporting a health predisposition were significantly less likely to report "not at increased risk due to chronic health conditions or age" as a reason for not being vaccinated (3.7% vs. 29.1%) and were more likely to report willingness to be vaccinated in the future compared to those not-at-risk (54.2% vs. 39.9%). Our results indicate that pneumococcal vaccination coverage in Switzerland is low among both individuals 65-85 and among those with predisposing health risks. It appears that at-risk individuals are aware of their increased risk, but feel they do not have enough information on the topic to seek vaccination, or have not been recommended a vaccination by their physician.
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Streptococcus pneumoniae , Cobertura de Vacunación , Adulto , Niño , Enfermedad Crónica , Estudios Transversales , Femenino , Humanos , Masculino , Suiza/epidemiología , VacunaciónRESUMEN
The goal of this study was to evaluate timeliness of Tick-borne Encephalitis vaccination uptake among adults in Switzerland. In this cross-sectional survey, we collected vaccination records from randomly selected adults 18-79 throughout Switzerland. Of 4,626 participants, data from individuals receiving at least 1 TBE vaccination (n = 1875) were evaluated. We determined year and age of first vaccination and vaccine compliance, evaluating dose timeliness. Participants were considered "on time" if they received doses according to the recommended schedule ± a 15% tolerance period. 45% of participants received their first TBE vaccination between 2006 and 2009, which corresponds to a 2006 change in the official recommendation for TBE vaccination in Switzerland. 25% were first vaccinated aged 50+ (mean age 37). More than 95% of individuals receiving the first dose also received the second; ~85% of those receiving the second dose received the third. For individuals completing the primary series, 30% received 3 doses of Encepur, 58% received 3 doses of FSME-Immun, and 12% received a combination. According to "conventional" schedules, 88% and 79% of individuals received their second and third doses "on time", respectively. 20% of individuals receiving Encepur received their third dose "too early". Of individuals completing primary vaccination, 19% were overdue for a booster. Among the 31% of subjects receiving a booster, mean time to first booster was 7.1 years. We estimate that a quarter of adults in Switzerland were first vaccinated for TBE aged 50+. Approximately 80% of participants receiving at least one vaccine dose completed the primary series. We further estimate that 66% of individuals completing the TBE vaccination primary series did so with a single vaccine type and adhered to the recommended schedule.
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Encefalitis Transmitida por Garrapatas/prevención & control , Esquemas de Inmunización , Motivación , Vacunación , Vacunas Virales/administración & dosificación , Adolescente , Adulto , Anciano , Estudios Transversales , Encefalitis Transmitida por Garrapatas/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
For both targeted and non-targeted exposures, the cellular responses to ionizing radiation have predominantly been measured in two-dimensional monolayer cultures. Although convenient for biochemical analysis, the true interactions in vivo depend upon complex interactions between cells themselves and the surrounding extracellular matrix. This study directly compares the influence of culture conditions on radiation induced cytotoxicity following exposure to low-LET ionizing radiation. Using a three-dimensional (3D) human mammary epithelial tissue model, we have found a protective effect of 3D cell culture on cell survival after irradiation. The initial state of the cells (i.e., 2D versus 3D culture) at the time of irradiation does not alter survival, nor does the presence of extracellular matrix during and after exposure to dose, but long term culture in 3D which offers significant reduction in cytotoxicity at a given dose (e.g. approximately 4-fold increased survival at 5Gy). The cell cycle delay induced following exposure to 2 and 5Gy was almost identical between 2D and 3D culture conditions and cannot account for the observed differences in radiation responses. However the amount of apoptosis following radiation exposure is significantly decreased in 3D culture relative to the 2D monolayer after the same dose. A likely mechanism of the cytoprotective effect afforded by 3D culture conditions is the down regulation of radiation induced apoptosis in 3D structures.
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Técnicas de Cultivo de Célula , Células Epiteliales/efectos de la radiación , Glándulas Mamarias Humanas/efectos de la radiación , Ciclo Celular/efectos de la radiación , Línea Celular , Supervivencia Celular/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Radiación IonizanteRESUMEN
BACKGROUND: Overall incidence and geographic range of Tick-borne Encephalitis (TBE), a vaccine preventable infection, have steadily increased in Switzerland over the last 50 years. While fully subsidized vaccination has been recommended in many areas for well over a decade, vaccine coverage and variables associated with vaccination compliance among Swiss adults are poorly understood. METHODS: In 2018 we conducted a national, cross-sectional survey of vaccination cards evaluating TBE vaccination coverage and compliance among adults (18-79) in Switzerland. RESULTS: Nationwide TBE vaccination coverage was 41.7% (range 14.3% to 60.3%) for 1 dose and 32.9% (range 8.4% to 50.4%) for a complete primary series (3 doses). There was a significant correlation between average disease incidence by canton (2009-2018) and vaccine coverage at both 1 and 3 doses. Of the overall population, 9.5% had received at least one TBE booster vaccination with large regional coverage variation. We estimated that 23% of adults in Switzerland would be protected from infection based on their vaccination history and 135 (95% CI: 112-162) TBE cases were prevented in 2018. Individuals reporting previous experience with tick-associated health problems, those frequently in nature or those with "high" perceived risk of contracting TBE, were significantly more likely to have received at least one vaccine dose, indicating a positive impact of awareness on vaccination compliance. We also calculated a TBE incidence rate of 6.83/100,000 among the unvaccinated adult population in Switzerland and estimated vaccine effectiveness at 91.5% (95% CI: 90.9-92.0%). CONCLUSIONS: These findings provide an important reference for TBE vaccination levels in Switzerland and further suggest that public health interventions promoting knowledge of TBE health impacts and risk factors may be beneficial in improving TBE vaccination coverage but should be tailored to account for heterogeneity in vaccine uptake.
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Encefalitis Transmitida por Garrapatas , Vacunas Virales , Adulto , Animales , Estudios Transversales , Encefalitis Transmitida por Garrapatas/epidemiología , Encefalitis Transmitida por Garrapatas/prevención & control , Humanos , Suiza/epidemiología , Vacunación , Cobertura de VacunaciónRESUMEN
BACKGROUND: Tick-borne encephalitis (TBE) is increasing in Europe. We aimed to evaluate the immunogenicity and safety of TBE-vaccination. METHODS: This systematic review was registered at PROSPERO (#CRD42020155737) and conducted in accordance with PRISMA guidelines. We searched CINAHL, Cochrane, Embase, PubMed, and Scopus using specific terms. Original articles, case reports and research abstracts in English, French, German and Italian were included for screening and extracting (JER; PS). RESULTS: Of a total of 2464 records, 49 original research publications were evaluated for immunogenicity and safety. TBE-vaccines showed adequate immunogenicity, good safety and interchangeability in adults and children with some differences in long-term protection (Seropositivity in 90.6-100% after primary vaccination; 84.9%-99.4% at 5 year follow up). Primary conventional vaccination schedule (days 0, 28, and 300) demonstrated the best immunogenic results (99-100% of seropositivity). Mixed brand primary vaccination presented adequate safety and immunogenicity with some exceptions. After booster follow-ups, accelerated conventional and rapid vaccination schedules were shown to be comparable in terms of immunogenicity and safety. First booster vaccinations five years after primary vaccination were protective in adults aged <50 years, leading to protective antibody levels from at least 5 years up to 10 years after booster vaccination. In older vaccinees, > 50 years, lower protective antibody titers were found. Allergic individuals showed an adequate response and immunosuppressed individuals a diminished response to TBE-vaccination. CONCLUSIONS: The TBE-vaccination is generally safe with rare serious adverse events. Schedules should, if possible, use the same vaccine brand (non-mixed). TBE-vaccines are immunogenic in terms of antibody response but less so when vaccination is started after the age of 50 years. Age at priming is a key factor in the duration of protection.