RESUMO
BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection and hospitalizations among infants, young children, and the elderly. This systematic literature review aimed to summarize the epidemiological and economic burden estimates of RSV infection at any age in Germany. METHODS: We conducted a systematic literature search to identify full-text articles published from 2003 to 2023 and reporting data on the epidemiological or economic burden of RSV in Germany. Based on pre-specified eligibility criteria, data on incidence, rates of hospital and intensive care unit (ICU) admission, clinical manifestation, underlying conditions, seasonality, health care resource use and costs were extracted. RESULTS: After screening 315 full-text articles, we included 42 articles in the review. The characteristics of the included studies were heterogenous regarding study population, setting, age groups and RSV-related outcome measures. The most frequently reported epidemiological outcome measures were RSV detection rate (n = 33), followed by clinical manifestation (n = 19), seasonality (n = 18), and underlying conditions of RSV infection (n = 13). RSV detection rates were reported across heterogenous study populations, ranging from 5.2 to 55.4% in pediatric inpatient cases and from 2.9 to 14% in adult inpatient cases. All articles that reported RSV detection rates across several age groups demonstrated the highest burden in infants and young children. Few articles reported RSV-related outcome measures distinctively for the outpatient setting. Health care resource use, such as hospital length of stay, ICU admission rate and treatment of patients with RSV infection were described in 23 articles, of which only one study quantified associated costs from 1999 to 2003 for children ≤ 3 years. In-hospital ICU admission rates varied between 3.6 and 45%, depending on population characteristics as age and underlying conditions. CONCLUSIONS: This systematic review revealed that RSV imposes substantial disease burden in infants, young children, and the elderly in Germany, whereby infants are particularly affected. To date, there has been limited exploration of the impact of RSV infection on healthy children or the elderly in Germany. Given their notably high reported burden in studies, the medical and economic RSV burden in these groups should move more into focus.
Assuntos
Efeitos Psicossociais da Doença , Hospitalização , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/economia , Alemanha/epidemiologia , Hospitalização/estatística & dados numéricos , Vírus Sincicial Respiratório Humano/isolamento & purificação , Estações do Ano , Lactente , Incidência , Criança , Custos de Cuidados de Saúde/estatística & dados numéricos , Idoso , Unidades de Terapia Intensiva/estatística & dados numéricos , Pré-Escolar , AdultoRESUMO
BACKGROUND: Influenza surveillance systems vary widely between countries and there is no framework to evaluate national surveillance systems in terms of data generation and dissemination. This study aimed to develop and test a comparative framework for European influenza surveillance. METHODS: Surveillance systems were evaluated qualitatively in five European countries (France, Germany, Italy, Spain, and the United Kingdom) by a panel of influenza experts and researchers from each country. Seven surveillance sub-systems were defined: non-medically attended community surveillance, virological surveillance, community surveillance, outbreak surveillance, primary care surveillance, hospital surveillance, mortality surveillance). These covered a total of 19 comparable outcomes of increasing severity, ranging from non-medically attended cases to deaths, which were evaluated using 5 comparison criteria based on WHO guidance (granularity, timing, representativeness, sampling strategy, communication) to produce a framework to compare the five countries. RESULTS: France and the United Kingdom showed the widest range of surveillance sub-systems, particularly for hospital surveillance, followed by Germany, Spain, and Italy. In all countries, virological, primary care and hospital surveillance were well developed, but non-medically attended events, influenza cases in the community, outbreaks in closed settings and mortality estimates were not consistently reported or published. The framework also allowed the comparison of variations in data granularity, timing, representativeness, sampling strategy, and communication between countries. For data granularity, breakdown per risk condition were available in France and Spain, but not in the United Kingdom, Germany and Italy. For data communication, there were disparities in the timeliness and accessibility of surveillance data. CONCLUSIONS: This new framework can be used to compare influenza surveillance systems qualitatively between countries to allow the identification of structural differences as well as to evaluate adherence to WHO guidance. The framework may be adapted for other infectious respiratory diseases.
Assuntos
Influenza Humana , Europa (Continente)/epidemiologia , França/epidemiologia , Humanos , Influenza Humana/epidemiologia , Reino Unido/epidemiologia , Organização Mundial da SaúdeRESUMO
OBJECTIVES: In Germany, routine influenza vaccination with quadrivalent influenza vaccines (QIV) is recommended and reimbursed for individuals ≥60 years of age and individuals with underlying chronic conditions. The present study examines the cost-effectiveness of a possible extension of the recommendation to include strategies of childhood vaccination against seasonal influenza using QIV. METHODS: A dynamic transmission model was used to examine the epidemiological impact of different childhood vaccination strategies. The outputs were used in a health economic decision tree to calculate the costs per quality-adjusted life year (QALY) gained from a societal and a third-party payer (TPP) perspective. Strain-specific epidemiology, vaccine uptake, and vaccine efficacy data from the 10 non-pandemic seasons from 2003/2004 to 2013/2014 were used, and cost data were drawn mainly from a health insurance claims data analysis and supplemented by estimates from literature. Uncertainty is explored via scenario, deterministic, and probabilistic sensitivity analyses. RESULTS: Vaccinating 2- to 9-year-olds with QIV assuming a vaccine uptake of 40% is cost-saving with a benefit-cost ratio of 1.66 from a societal perspective and an incremental cost-effectiveness ratio of 998/QALY from a TPP perspective. Lower and higher vaccine uptakes show marginal effects, while extending the target group to 2- to 17-year-olds further increases the health benefits while still being below the willingness-to-pay (WTP) threshold. Assuming no vaccine-induced herd protection has a negative effect on the cost-effectiveness ratio, but childhood vaccination remains cost-effective. CONCLUSION: Routine childhood vaccination against seasonal influenza in Germany is most likely to be cost-saving from a societal perspective and highly cost-effective from a TPP perspective.
Assuntos
Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/economia , Influenza Humana/prevenção & controle , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Alemanha/epidemiologia , Gastos em Saúde , Humanos , Programas de Imunização/economia , Lactente , Vacinas contra Influenza/imunologia , Influenza Humana/economia , Influenza Humana/epidemiologia , Pessoa de Meia-Idade , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Adulto JovemRESUMO
BACKGROUND: Seasonal influenza contributes substantially to the burden of communicable diseases in Europe, especially among paediatric populations and the elderly. The aim of the present study was to estimate the incidence of seasonal influenza in Germany, the probabilities of related complications and the economic burden of influenza per case and on a population level for different age groups. METHODS: Claims data from 2012 to 2014 from > 8 million insured of a large German sick-ness fund were analysed. A matched case control study was used on a sub-sample of 100,000 influenza cases to calculate complication rates for ear infections/acute otitis media (AOM) and community-acquired pneumonia (CAP) as well as resource use and costs for seven age groups. RESULTS: Incidence of seasonal influenza varies between the years and is highest among infants and children 2 to 5 years of age. AOM is more likely in the younger age groups with up to 14% more patients in the influenza group than in the control group. CAP is more frequently observed in the younger age groups and in influenza patients 60 years and older. The manifestation of one influenza complication (AOM or CAP) significantly in-creases the occurrence of a second complication (AOM or CAP). The economic burden per case is highest in infants (251.91) and persons over 60 years of age (131.59). CONCLUSION: The burden of influenza is highest among infants and young children, which is also reflected in the economic burden. Influenza related costs per case are nearly double for infants compared to persons over 60 years of age.
Assuntos
Efeitos Psicossociais da Doença , Influenza Humana/economia , Influenza Humana/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Lactente , Recém-Nascido , Revisão da Utilização de Seguros , Masculino , Pessoa de Meia-Idade , Estações do Ano , Adulto JovemRESUMO
BACKGROUND: Epidemiological studies suggest that reduced exposure to varicella might lead to an increased risk for herpes zoster (HZ). Reduction of exposure to varicella is a consequence of varicella vaccination but also of demographic changes. We analyzed how the combination of vaccination programs and demographic dynamics will affect the epidemiology of varicella and HZ in Germany over the next 50 years. METHODS: We used a deterministic dynamic compartmental model to assess the impact of different varicella and HZ vaccination strategies on varicella and HZ epidemiology in three demographic scenarios, namely the projected population for Germany, the projected population additionally accounting for increased immigration as observed in 2015/2016, and a stationary population. RESULTS: Projected demographic changes alone result in an increase of annual HZ cases by 18.3% and a decrease of varicella cases by 45.7% between 1990 and 2060. Independently of the demographic scenario, varicella vaccination reduces the cumulative number of varicella cases until 2060 by approximately 70%, but also increases HZ cases by 10%. Unlike the currently licensed live attenuated HZ vaccine, the new subunit vaccine candidate might completely counteract this effect. Relative vaccine effects were consistent across all demographic scenarios. CONCLUSION: Demographic dynamics will be a major determinant of HZ epidemiology in the next 50 years. While stationary population models are appropriate for assessing vaccination impact, models incorporating realistic population structures allow a direct comparison to surveillance data and can thus provide additional input for immunization decision-making and resource planning.
Assuntos
Vacina contra Varicela/uso terapêutico , Varicela/prevenção & controle , Demografia , Vacina contra Herpes Zoster/uso terapêutico , Herpes Zoster/prevenção & controle , Modelos Teóricos , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Varicela/epidemiologia , Criança , Emigração e Imigração/estatística & dados numéricos , Alemanha/epidemiologia , Herpes Zoster/epidemiologia , Humanos , Programas de Imunização/métodos , Programas de Imunização/estatística & dados numéricos , Incidência , Masculino , Pessoa de Meia-Idade , Dinâmica Populacional/estatística & dados numéricos , Vacinação/métodos , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to assess the cost-effectiveness of human papillomavirus (HPV) vaccination in addition to the current cervical cancer screening programme in Germany using a dynamic transmission model. METHODS: Based on a mathematical model simulating the transmission dynamics and the natural history of HPV infection and associated diseases (cervical intraepithelial neoplasia, cervical cancer, and genital warts), we estimated the epidemiological and economic consequences of HPV vaccination with both the quadrivalent and bivalent vaccines. In our base case analysis, we assessed the cost-effectiveness of vaccinating 12-year-old girls with a 3-dose schedule. In sensitivity analysis, we also evaluated the use of a 2-dose schedule and assessed the impact of vaccinating boys. RESULTS: From a health care payer perspective, incremental cost-effectiveness ratios (ICERs) of a 3-dose schedule were 34,249 per quality-adjusted life year (QALY) for the bivalent and 14,711 per QALY for the quadrivalent vaccine. Inclusion of indirect costs decreased ICERs by up to 40%. When adopting a health care payer perspective, ICERs of a 2-dose approach decreased to 19,450 per QALY for the bivalent and to 3645 per QALY for the quadrivalent vaccine. From a societal perspective, a 2-dose approach using the quadrivalent vaccine was a cost-saving strategy while using the bivalent vaccine resulted in an ICER of 13,248 per QALY. Irrespective of the perspective adopted, additional vaccination of boys resulted in ICERs exceeding 50,000 per QALY, except for scenarios with low coverage (20%) in girls. CONCLUSIONS: Our model results suggest that routine HPV vaccination of 12-year-old girls with three doses is likely to be cost-effective in Germany. Due to the additional impact on genital warts, the quadrivalent vaccine appeared to be more cost-effective than the bivalent vaccine. A 2-dose schedule of the quadrivalent vaccine might even lead to cost savings when adopting a societal perspective. The cost-effectiveness of additional vaccination of boys was highly dependent on the coverage in girls.
RESUMO
The Sertoli cell (SC)-specific knockout (KO) of connexin43 (Cx43) results in spermatogenic arrest at the level of spermatogonia and/or SC-only syndrome. Histology of the interstitial compartment suggests Leydig cell (LC) hyperplasia. Our aim has been to investigate possible effects of the SC-specific KO of Cx43 (SCCx43KO) on interstitial LC. We therefore counted LC via the optical dissector method (per microliter of testicular tissue and per testis) and found LC to be significantly increased in SCCx43KO(-/-) compared with wild-type mice. Semiquantitative western blot together with Cx43 and 3ß-hydroxysteroid dehydrogenase immunohistochemistry showed that Cx43 protein was significantly reduced and barely detectable in LC in adult SCCx43KO(-/-) mice. This reduction of Cx43 protein was accompanied by a reduction of Cx43 mRNA as analyzed by laser-assisted microdissection of interstitial cells and subsequent quantitative real-time polymerase chain reaction (PCR). Interestingly, Cx45, another recently detected connexin in LC, was also downregulated. Preliminary qualitative data of LC differentiation markers (Thb2, Hsd3b6) and a steroidogenic marker (Hsd17b3) obtained by reverse transcription plus PCR revealed no obvious differences. Thus, the loss of Cx43 in SC also provokes the downregulation of connexins in interstitial LC at the transcriptional and translational levels. Moreover, SCCx43KO leads to alterations in LC numbers. Despite these alterations, steroidogenesis seems not to be impaired. Further studies, including ultrastructural analysis of the tissue as well as quantitative examination of additional LC markers and testosterone, and functional in vitro experiments, should provide more information about LC differentiation and function in SCCx43KO(-/-) mice.
Assuntos
Conexina 43/genética , Técnicas de Inativação de Genes , Células Intersticiais do Testículo/citologia , Células de Sertoli/metabolismo , 3-Hidroxiesteroide Desidrogenases/análise , 3-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Contagem de Células , Conexina 43/análise , Conexinas/análise , Conexinas/genética , Regulação da Expressão Gênica , Células Intersticiais do Testículo/metabolismo , Masculino , Camundongos , Camundongos Knockout , RNA Mensageiro/análise , RNA Mensageiro/genética , Células de Sertoli/citologia , Esteroides/metabolismoRESUMO
BACKGROUND: A systematic review was conducted to assess the cost-effectiveness of routine varicella and herpes zoster (HZ) vaccination in high-income countries estimated by modelling studies. METHODS: A PubMed search was performed to identify relevant studies published before October 2013. Studies were included in the review if they (i) evaluated the cost-effectiveness of routine childhood or adolescent varicella vaccination and/or HZ vaccination targeting the elderly, and if they (ii) reported results for high-income countries. RESULTS: A total of 38 model-based studies were identified that fulfilled the inclusion criteria. Routine childhood or adolescent varicella vaccination was cost-effective or cost-saving from a payer perspective and always cost-saving from a societal perspective when ignoring its potential impact on HZ incidence due to reduced or absent exogenous boosting. The inclusion of the potential impact of childhood varicella vaccination on HZ led to net quality-adjusted life-year (QALY) losses or incremental cost-effectiveness ratios exceeding commonly accepted thresholds. Additional HZ vaccination could partially mitigate this effect. Studies focusing only on the evaluation of HZ vaccination reported a wide range of results depending on the selected target age-group and the vaccine price, but most found HZ vaccination to be a cost-effective or marginally cost-effective intervention. Cost-effectiveness of HZ vaccination was strongly dependent on the age at vaccination, the price of the vaccine, the assumed duration of protection and the applied cost per QALY threshold. CONCLUSIONS: While HZ vaccination is mostly considered cost-effective, cost-effectiveness of varicella vaccination primarily depends on the in- or exclusion of exogenous boosting in the model. As a consequence, clarification on the role of exogenous boosting is crucial for decision-making regarding varicella vaccination.
Assuntos
Vacina contra Varicela/administração & dosagem , Vacina contra Varicela/economia , Varicela/prevenção & controle , Países Desenvolvidos/estatística & dados numéricos , Herpes Zoster/prevenção & controle , Fatores Etários , Varicela/epidemiologia , Comércio , Análise Custo-Benefício , Herpes Zoster/epidemiologia , Vacina contra Herpes Zoster/administração & dosagem , Vacina contra Herpes Zoster/economia , Humanos , Incidência , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Klinefelter's syndrome is a male sex-chromosomal disorder (47,XXY), causing hypogonadism, cognitive and metabolic deficits. The majority of patients are infertile due to complete germ cell loss after puberty. As the depletion occurs during development, the possibilities to study the underlying causes in humans are limited. In this study, we used the 41,XX(Y*) mouse model to characterise the germ line postnatally. We examined marker expression of testicular cells focusing on the spermatogonial stem cells (SSCs) and found that the number of germ cells was approximately reduced fivefold at day 1pp in the 41,XX(Y*) mice, indicating the loss to start prenatally. Concurrently, immunohistochemical SSC markers LIN28A and PGP9.5 also showed decreased expression on day 1pp in the 41,XX(Y*) mice (48.5 and 38.9% of all germ cells were positive), which dropped to 7.8 and 7.3% on 3dpp, and were no longer detectable on days 5 and 10pp respectively. The differences in PCNA-positive proliferating cells in XY* and XX(Y*) mice dramatically increased towards day 10pp. The mRNA expression of the germ cell markers Lin28a (Lin28), Pou5f1 (Oct4), Utf1, Ddx4 (Vasa), Dazl, and Fapb1 (Sycp3) was reduced and the Lin28a regulating miRNAs were deregulated in the 41,XX(Y*) mice. We suggest a model for the course of germ cell loss starting during the intrauterine period. Neonatally, SSC marker expression by the already lowered number of spermatogonia is reduced and continues fading during the first postnatal week, indicating the surviving cells of the SSC population to be disturbed in their stem cell characteristics. Subsequently, the entire germ line is then generally lost when entering meiosis.
Assuntos
Células Germinativas/patologia , Síndrome de Klinefelter/patologia , Proteínas de Ligação a RNA/metabolismo , Animais , Biomarcadores/metabolismo , Contagem de Células , Modelos Animais de Doenças , Regulação da Expressão Gênica no Desenvolvimento , Síndrome de Klinefelter/genética , Síndrome de Klinefelter/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas de Ligação a RNA/genética , Maturidade Sexual/genética , Espermatogônias/patologia , Testículo/metabolismo , Testículo/patologia , Cromossomo Y/genéticaRESUMO
BACKGROUND: Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany. METHODS: A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion. RESULTS: In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children. CONCLUSIONS: Our results demonstrate that vaccinating children 2-17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany.
Assuntos
Programas de Imunização , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Modelos Teóricos , Vacinas Atenuadas/administração & dosagem , Adolescente , Criança , Pré-Escolar , Simulação por Computador , Feminino , Alemanha , Humanos , Lactente , Masculino , VacinaçãoRESUMO
INTRODUCTION: Invasive meningococcal disease (IMD) causes significant mortality and long-term sequelae. This study assesses the potential public health impact of adolescent vaccination strategies employing MenACWY and MenC vaccines in Germany, where the existing meningococcal immunisation programme predominantly involves MenC administration in toddlers. METHODS: A dynamic transmission model was developed to simulate the carriage of five meningococcal serogroup compartments (AY/B/C/W/Other) from 2019 until 2060 within 1-year age groups from 0 to 99 years of age. IMD cases were estimated based on case-carrier ratios. The model considered vaccine effectiveness against carriage acquisition and IMD. RESULTS: The model predicts that introducing MenACWY adolescent vaccination could lead to a considerable reduction in IMD incidence, with the potential to prevent up to 65 cases per year and a cumulative total of 1467 cases by 2060. This decrease, mainly driven by herd effects, would result in a reduction of IMD incidence across all age groups, regardless of vaccination age. Furthermore, implementing MenACWY vaccination in adolescents is projected to decrease annual MenACWY-related IMD mortality by up to 64%, equating to an overall prevention of 156 IMD deaths by 2060. These protective outcomes are expected to culminate in approximately 2250 life years gained (LYG) throughout the model's projected time horizon. In contrast, the adoption of MenC vaccination in adolescents is predicted to have minimal influence on both IMD incidence and mortality, as well as on LYG. CONCLUSION: The results of this study demonstrate that implementing MenACWY vaccination for adolescents in Germany is likely to notably reduce IMD incidence and mortality across age groups. However, the introduction of MenC adolescent vaccination shows only limited impact. Considering the extensive healthcare resources typically required for IMD management, these findings suggest the potential for economic benefits associated with the adoption of MenACWY adolescent vaccination, warranting further cost-effectiveness analysis.
RESUMO
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
Marmosets are used as preclinical model in reproductive research. In contrast to other primates, they display short gestation times rendering this species valid for exploration of effects on fertility. However, their peculiar endocrine regulation differs from a those of macaques and humans. We subjected male marmosets to previously clinically tested hormonal regimens that are known to effectively suppress spermatogenesis. Beside a control group, seven groups (each n=6) were investigated for different periods of up to 42 months: regimen I, (four groups) received testosterone undecanoate (TU) and norethisterone enanthate (NETE); regimen II, (two groups) received TU and NETE followed by NETE only; and regimen III, (one group) received NETE only. Testicular volume, cell ploidy and histology, endocrine changes and fertility were monitored weekly. TU and NETE and initial TU and NETE treatment followed by NETE failed to suppress spermatogenesis and fertility. Testicular volumes dropped, although spermatogenesis was only mildly affected; however, testicular cellular composition remained stable. Serum testosterone dropped when NETE was given alone but the animals remained fertile. Compared with controls, no significant changes were observed in sperm motility and fertility. Administration of TU and NETE affected testicular function only mildly, indicating that the regulatory role of chorionic gonadotrophin and testosterone on spermatogenesis is obviously limited and testicular function is maintained, although the endocrine axis is affected by the treatment. In conclusion, marmosets showed a different response to regimens of male contraception from macaques or men and have to be considered as a problematic model for preclinical trials of male hormonal contraception.
Assuntos
Antiespermatogênicos/administração & dosagem , Callithrix/sangue , Fertilidade/efeitos dos fármacos , Noretindrona/análogos & derivados , Testosterona/análogos & derivados , Animais , Peso Corporal/efeitos dos fármacos , Gonadotropina Coriônica/metabolismo , Epididimo/efeitos dos fármacos , Masculino , Modelos Animais , Noretindrona/administração & dosagem , Tamanho do Órgão , Hipófise/metabolismo , Ploidias , Motilidade dos Espermatozoides , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testosterona/administração & dosagem , Testosterona/sangueRESUMO
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
The outcome of sperm competition (i.e. competition for fertilization between ejaculates from different males) is primarily determined by the relative number and quality of rival sperm. Therefore, the testes are under strong selection to maximize both sperm number and quality, which are likely to result in trade-offs in the process of spermatogenesis (e.g. between the rate of spermatogenesis and sperm length or sperm energetics). Comparative studies have shown positive associations between the level of sperm competition and both relative testis size and the proportion of seminiferous (sperm-producing) tissue within the testes. However, it is unknown how the seminiferous tissue itself or the process of spermatogenesis might evolve in response to sperm competition. Therefore, we quantified the different germ cell types and Sertoli cells (SC) in testes to assess the efficiency of sperm production and its associations with sperm length and mating system across 10 species of New World Blackbirds (Icteridae) that show marked variation in sperm length and sperm competition level. We found that species under strong sperm competition generate more round spermatids (RS)/spermatogonium and have SC that support a greater number of germ cells, both of which are likely to increase the maximum sperm output. However, fewer of the RS appeared to elongate to mature spermatozoa in these species, which might be the result of selection for discarding spermatids with undesirable characteristics as they develop. Our results suggest that, in addition to overall size and gross morphology, testes have also evolved functional adaptations to maximize sperm quantity and quality.
Assuntos
Fertilização , Passeriformes/fisiologia , Espermatogênese , Espermatozoides/fisiologia , Testículo/fisiologia , Adaptação Fisiológica , Animais , Forma Celular , Tamanho Celular , Masculino , Especificidade da Espécie , Contagem de Espermatozoides , Testículo/citologiaRESUMO
Hypergonadotropic hypogonadism is a major feature of Klinefelter syndrome (KS), assumed to be caused by testicular hormone resistance. It was previously shown that intratesticular testosterone levels in vivo and Leydig cell function in vitro seem to be normal indicating other functional constraints. We hypothesized that impaired testicular vascularization/blood flow could be a co-factor to the observed hypergonadotropic hypogonadism. We evaluated the testicular vascular system by measuring blood vessel sizes during postnatal development and testis blood flow in adult 41,XXY* mice. Proportional distribution and size of blood vessels were analyzed during testicular development (1, 3, 5, 7, 10, 21 dpp, 15 wpp). While ratios of the vessel/testis area were different at 15 wpp only, a lower number of smaller and mid-sized blood vessels were detected in adult KS mice. For testicular blood flow determination we applied contrast enhanced ultrasound. Floating and reperfusion time for testicular blood flow was increased in 41,XXY* mice (floating: XY* 28.8 ± 1.69 s vs XXY* 44.6 ± 5.6 s, p = 0.0192; reperfusion XY* 19.7 ± 2.8 s vs XXY*: 29.9 ± 6.2 s, p = 0.0134), indicating a diminished blood supply. Our data strengthen the concept that an impaired vascularization either in conjunction or as a result of altered KS testicular architecture contributes to hormone resistance.
Assuntos
Síndrome de Klinefelter/fisiopatologia , Testículo/irrigação sanguínea , Testículo/crescimento & desenvolvimento , Animais , Circulação Sanguínea , Vasos Sanguíneos/diagnóstico por imagem , Modelos Animais de Doenças , Hipogonadismo/fisiopatologia , Síndrome de Klinefelter/sangue , Células Intersticiais do Testículo , Masculino , Camundongos , Camundongos Transgênicos , Espermatogênese/genética , Testosterona/sangue , Ultrassonografia/métodosRESUMO
In 2018, a panel of health economics and meningococcal disease experts convened to review methodologies, frameworks, and decision-making processes for economic evaluations of vaccines, with a focus on evaluation of vaccines targeting invasive meningococcal disease (IMD). The panel discussed vaccine evaluation methods across countries; IMD prevention benefits that are well quantified using current methods, not well quantified, or missing in current cost-effectiveness methodologies; and development of recommendations for future evaluation methods. Consensus was reached on a number of points and further consideration was deemed necessary for some topics. Experts agreed that the unpredictability of IMD complicates an accurate evaluation of meningococcal vaccine benefits and that vaccine cost-effectiveness evaluations should encompass indirect benefits, both for meningococcal vaccines and vaccines in general. In addition, the panel agreed that transparency in the vaccine decision-making process is beneficial and should be implemented when possible. Further discussion is required to ascertain: how enhancing consistency of frameworks for evaluating outcomes of vaccine introduction can be improved; reviews of existing tools used to capture quality of life; how indirect costs are considered within models; and whether and how the weighting of quality-adjusted life-years (QALY), application of QALY adjustment factors, or use of altered cost-effectiveness thresholds should be used in the economic evaluation of vaccines.
Assuntos
Análise Custo-Benefício , Infecções Meningocócicas , Vacinas Meningocócicas , Humanos , Modelos Econômicos , Qualidade de Vida , VacinaçãoRESUMO
Several aberrant chromosomal constellations are known in men. Of these the karyotype XXY (Klinefelter syndrome, KS) is the most common chromosomal disorder with a prevalence of about one in 800 live-born boys. KS is associated with hypogonadism and is suspected to cause variable physical, physiological and cognitive abnormalities. As a supernumerary X chromosome is also associated with infertility, sound animal models for KS are difficult to obtain. In this study, male mice with two X chromosomes (XX(Y*)) were derived from fathers carrying a structurally rearranged Y chromosome (Y*) that resulted in physical attachment of a part of the Y chromosome to one X. These animals display certain physiological features that resemble closely those of human KS and can also be utilized to study X chromosomal imbalance and cognition. Therefore 15 XX(Y*) males and 15 XY* controls were subjected to a battery of behavioral tests, including a general health check, analysis of spontaneous exploration and locomotor activity, measures for anxiety-related behavior and the "novel object task" to test memory performance. Physiologically, XY* males did not differ from C57Bl/6 wild type mice carrying a normal Y chromosome, which provided a valid control group. All mice appeared healthy. XX(Y*) mice did not differ from their wild type littermates with respect to locomotion, exploration and anxiety-related behavior. XX(Y*) male mice, however, exhibited no significant recognition memory performance in contrast with wild type XY* males that readily fulfilled a given task. These findings support the hypothesis that the presence of a supernumerary X in male mice influences cognitive abilities. We suggest that the altered endocrine state and/or changes in the dosage of X-linked genes in the XX(Y*) mouse model affect brain function, in particular those regions responsible for cognition and learning behavior.
Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos/complicações , Transtornos da Memória/etiologia , Reconhecimento Psicológico/fisiologia , Cromossomo X , Análise de Variância , Animais , Ansiedade/etiologia , Ansiedade/genética , Comportamento Animal/fisiologia , Peso Corporal/genética , Comportamento Exploratório/fisiologia , Hormônio Foliculoestimulante/metabolismo , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Cariotipagem , Hormônio Luteinizante/metabolismo , Masculino , Transtornos da Memória/genética , Camundongos , Camundongos Endogâmicos C57BL , Radioimunoensaio , Cromossomo YRESUMO
BACKGROUND: In the absence of detailed information about the population size and behaviour data of men-who-have-sex-with-men (MSM), the estimation of prevalence rates of sexually transmitted infections (STIs) and the design of public health interventions become difficult. The aim of the present study is to estimate the lower boundary of age-specific population sizes and retrieve self-reported information from this population. METHODS: We used publicly accessible data from a large online dating and social network website for MSM in Germany to retrieve data on the age and regional distribution of profiles. The profiles were also stratified by their information on the preferred position during anal intercourse, safer sex, and sexual identity. RESULTS: A total of 464,873 user profiles correspond to an average 15.2 profiles per 1,000 male inhabitants in Germany, varying between 7.6 and 45.6 across federal states. Although the information on the absolute numbers for different age groups is limited by the search engine, age-specific relative frequencies were found to increase from 12.9 in the age group of 18 to 20 year olds to 24.6 profiles per 1,000 male inhabitants in the 28 to 30 year olds. The data shows age-specific trends for safer sex with an increasing easiness of reporting "never" engaging in safer sex or stating that safer sex "needs discussion" with increasing age. Around one third of profile owners stated to be versatile with respect to the preferred position in anal intercourse. All other options ("only bottom", "more bottom", "only top", "more top") were preferred equally likely by roughly 10% of profile owners, respectively. CONCLUSIONS: Online social network or dating sites can provide some information about specific populations in the absence of other data sources. The presented results are the first to report age-specific rates of MSM per 1,000 male inhabitants in Germany and may be useful to estimate age-specific prevalence or incidence rates as well as to inform health promotion activities and modelling studies for MSM in Germany.