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1.
Emerg Infect Dis ; 30(5): 995-999, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38666641

RESUMEN

In a representative sample of female children and adolescents in Germany, Toxoplasma gondii seroprevalence was 6.3% (95% CI 4.7%-8.0%). With each year of life, the chance of being seropositive increased by 1.2, indicating a strong force of infection. Social status and municipality size were found to be associated with seropositivity.


Asunto(s)
Toxoplasma , Toxoplasmosis , Humanos , Femenino , Alemania/epidemiología , Toxoplasmosis/epidemiología , Toxoplasmosis/parasitología , Adolescente , Niño , Toxoplasma/inmunología , Estudios Seroepidemiológicos , Preescolar , Factores de Riesgo , Lactante , Anticuerpos Antiprotozoarios/sangre
2.
Epidemiol Infect ; 152: e16, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38220467

RESUMEN

During the COVID-19 pandemic in Germany, a variety of societal activities were restricted to minimize direct personal interactions and, consequently, reduce SARS-CoV-2 transmission. The aim of the CoViRiS study was to investigate whether certain behaviours and societal factors were associated with the risk of sporadic symptomatic SARS-CoV-2 infections. Adult COVID-19 cases and frequency-matched population controls were interviewed by telephone regarding activities that involved contact with other people during the 10 days before illness onset (cases) or before the interview (controls). Associations between activities and symptomatic SARS-CoV-2 infection were analysed using logistic regression models adjusted for potential confounding variables. Data of 859 cases and 1 971 controls were available for analysis. The risk of symptomatic SARS-CoV-2 infection was lower for individuals who worked from home (adjusted odds ratio (aOR) 0.5; 95% confidence interval (CI) 0.3-0.6). Working in a health care setting was associated with a higher risk (aOR: 1.5; 95% CI: 1.1-2.1) as were private indoor contacts, personal contacts that involved shaking hands or hugging, and overnight travelling within Germany. Our results are in line with some of the public health recommendations aimed at reducing interpersonal contacts during the COVID-19 pandemic.


Asunto(s)
COVID-19 , Adulto , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Estudios de Casos y Controles , Pandemias/prevención & control , Factores de Riesgo , Alemania/epidemiología
3.
Euro Surveill ; 29(5)2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38304949

RESUMEN

Dengue virus (DENV) infections after exposure in Egypt increased in Germany in 2023, with 36 cases vs zero to eight in 2017 to 2022. Over 90% of the patients had stayed on the Red Sea Coast (mostly Hurghada), almost 50% in private residences. Case numbers increased more strongly than traveller numbers. Mosquito control is more difficult in towns than hotel grounds, increasing the risk of infection at private residences. Physicians should consider dengue for unexplained fever after return from Egypt.


Asunto(s)
Aedes , Virus del Dengue , Dengue , Humanos , Animales , Dengue/diagnóstico , Dengue/epidemiología , Virus del Dengue/genética , Egipto/epidemiología , Viaje , Alemania/epidemiología , Mosquitos Vectores
4.
Euro Surveill ; 29(20)2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38757286

RESUMEN

BackgroundGiardia duodenalis is a major cause of gastroenteritis globally, and is the most common food- and waterborne parasitic infection in Europe.AimTo describe the epidemiology of reported acute giardiasis cases in Germany and compare demographic and clinical characteristics between imported and autochthonous cases.MethodsWe conducted a descriptive analysis of giardiasis cases that fulfilled the national case definition and were reported between January 2002 and December 2021. We defined an imported case as having at least one place of exposure abroad in the 3-25 days before symptom onset. We analysed case numbers and incidence by age, sex, month reported and geographic region, both overall and stratified by autochthonous and imported cases.ResultsFrom 2002 to 2021, 72,318 giardiasis cases were reported in Germany, corresponding to a mean annual incidence of 4.4 per 100,000 population. Annual incidence gradually decreased since 2013, declining sharply during the COVID-19 pandemic in 2020-21. Of 69,345 cases reported between 2002 and 2019, 35% were imported. Incidence of autochthonous cases (overall yearly mean: 3.1/100,000) was highest in males and young children (< 5 years); imported cases were predominantly adults aged 20-39 years. We identified seasonal patterns for imported and autochthonous cases.ConclusionsGiardiasis in Germany is typically assumed to be imported. Our data, however, underline the importance of autochthonous giardiasis. Travel advice might reduce imported infections, but prevention strategies for autochthonous infections are less clear. Dietary, behavioural and environmental risk factors need to be further investigated to enhance infection prevention measures for autochthonous giardiasis.


Asunto(s)
Giardiasis , Humanos , Giardiasis/epidemiología , Alemania/epidemiología , Adulto , Masculino , Femenino , Incidencia , Persona de Mediana Edad , Adolescente , Niño , Adulto Joven , Anciano , Preescolar , Lactante , Viaje , COVID-19/epidemiología , Vigilancia de la Población , SARS-CoV-2 , Distribución por Edad , Gastroenteritis/epidemiología , Gastroenteritis/parasitología , Enfermedades Transmisibles Importadas/epidemiología , Distribución por Sexo , Estaciones del Año , Anciano de 80 o más Años
5.
BMC Bioinformatics ; 24(1): 355, 2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37735349

RESUMEN

BACKGROUND: Genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with kidney function. By combining these findings with post-GWAS information (e.g., statistical fine-mapping to identify independent association signals and to narrow down signals to causal variants; or different sources of annotation data), new hypotheses regarding physiology and disease aetiology can be obtained. These hypotheses need to be tested in laboratory experiments, for example, to identify new therapeutic targets. For this purpose, the evidence obtained from GWAS and post-GWAS analyses must be processed and presented in a way that they are easily accessible to kidney researchers without specific GWAS expertise. MAIN: Here we present KidneyGPS, a user-friendly web-application that combines genetic variant association for estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics consortium with annotation of (i) genetic variants with functional or regulatory effects ("SNP-to-gene" mapping), (ii) genes with kidney phenotypes in mice or human ("gene-to-phenotype"), and (iii) drugability of genes (to support re-purposing). KidneyGPS adopts a comprehensive approach summarizing evidence for all 5906 genes in the 424 GWAS loci for eGFR identified previously and the 35,885 variants in the 99% credible sets of 594 independent signals. KidneyGPS enables user-friendly access to the abundance of information by search functions for genes, variants, and regions. KidneyGPS also provides a function ("GPS tab") to generate lists of genes with specific characteristics thus enabling customizable Gene Prioritisation (GPS). These specific characteristics can be as broad as any gene in the 424 loci with a known kidney phenotype in mice or human; or they can be highly focussed on genes mapping to genetic variants or signals with particularly with high statistical support. KidneyGPS is implemented with RShiny in a modularized fashion to facilitate update of input data ( https://kidneygps.ur.de/gps/ ). CONCLUSION: With the focus on kidney function related evidence, KidneyGPS fills a gap between large general platforms for accessing GWAS and post-GWAS results and the specific needs of the kidney research community. This makes KidneyGPS an important platform for kidney researchers to help translate in silico research results into in vitro or in vivo research.


Asunto(s)
Estudio de Asociación del Genoma Completo , Insuficiencia Renal Crónica , Humanos , Animales , Ratones , Fenotipo , Riñón , Mapeo Cromosómico
6.
Epidemiol Infect ; 151: e61, 2023 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-37057860

RESUMEN

Healthcare-associated foodborne outbreaks (HA-FBOs) can cause significant morbidity and mortality, affecting particularly vulnerable hospital populations. Electronic records of food served in healthcare facilities (HCFs) could be useful for timely investigations of HA-FBOs. We explored the availability and usability of electronic food menu data to support investigations of HA-FBOs through a survey among 35 HCFs in Germany (n = 13) and in Italy (n = 22). Large variability was reported in the storage time of menu data (from no storage up to 10 years) and their formats, including paper, electronic (PDF, Word, Excel), or fully searchable databases (15/22 in Italian HCFs, 3/13 in German HCFs). Food products that may present a risk to vulnerable persons - including deli salads, raw/fermented sausage products, soft cheese, smoked fish or frozen berries - were offered on the menu of all HCFs in Germany, and one-third of the Italian HCFs. The usability of electronic food menu data for the prevention or investigation of HA-FBOs may be suboptimal in a large number of HCFs in Germany, as well as in some HCFs in Italy. Standardised collection for use of electronic food menu data might help discover the association between illnesses and food eaten during outbreak investigations. Hospital hygienists, food safety and public health authorities should collaborate to increase implementation of food safety guidelines.


Asunto(s)
Queso , Enfermedades Transmitidas por los Alimentos , Animales , Enfermedades Transmitidas por los Alimentos/epidemiología , Enfermedades Transmitidas por los Alimentos/etiología , Microbiología de Alimentos , Brotes de Enfermedades , Alemania/epidemiología
7.
Euro Surveill ; 28(34)2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37616114

RESUMEN

BackgroundLyme borreliosis (LB), caused by Borrelia burgdorferi (Bb), is the most common tick-borne infection in Germany. Antibodies against Bb are prevalent in the general population but information on temporal changes of prevalence and estimates of seroconversion (seroincidence) and seroreversion are lacking, especially for children and adolescents.AimWe aimed at assessing antibodies against Bb and factors associated with seropositivity in children and adolescents in Germany.MethodsWe estimated seroprevalence via two consecutive cross-sectional surveys (2003-2006 and 2014-2017). Based on a longitudinal survey component, we estimated annual seroconversion/seroreversion rates.ResultsSeroprevalence was 4.4% (95% confidence interval (CI): 3.9-4.9%) from 2003 to 2006 and 4.1% (95% CI: 3.2-5.1%) from 2014 to 2017. Seroprevalence increased with age, was higher in male children, the south-eastern regions of Germany and among those with a high socioeconomic status. The annual seroconversion rate was 0.3% and the annual seroreversion rate 3.9%. Males were more likely to seroconvert compared with females. Low antibody levels were the main predictor of seroreversion.ConclusionWe did not detect a change in seroprevalence in children and adolescents in Germany over a period of 11 years. Potential long-term changes, for example due to climatic changes, need to be assessed in consecutive serosurveys. Seroconversion was more likely among children and adolescents than among adults, representing a target group for preventive measures. Seroreversion rates are over twice as high in children and adolescents compared with previous studies among adults. Thus, seroprevalence estimates and seroconversion rates in children are likely underestimated.


Asunto(s)
Borrelia burgdorferi , Enfermedad de Lyme , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Anticuerpos Antibacterianos , Estudios Transversales , Alemania/epidemiología , Inmunoglobulina G , Seroconversión , Estudios Seroepidemiológicos , Enfermedad de Lyme/epidemiología
8.
Euro Surveill ; 28(23)2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37289431

RESUMEN

In March 2023, 34 associated cases of iatrogenic botulism were detected in Germany (30 cases), Switzerland (two cases), Austria (one case), and France (one case). An alert was rapidly disseminated via European Union networks and communication platforms (Food- and Waterborne Diseases and Zoonoses Network, EpiPulse, Early Warning and Response System) and the International Health Regulation mechanism; the outbreak was investigated in a European collaboration. We traced sources of the botulism outbreak to treatment of weight loss in Türkiye, involving intragastric injections of botulinum neurotoxin. Cases were traced using a list of patients who had received this treatment. Laboratory investigations of the first 12 German cases confirmed nine cases. The application of innovative and highly sensitive endopeptidase assays was necessary to detect minute traces of botulinum neurotoxin in patient sera. The botulism notification requirement for physicians was essential to detect this outbreak in Germany. The surveillance case definition of botulism should be revisited and inclusion of cases of iatrogenic botulism should be considered as these cases might lack standard laboratory confirmation yet warrant public health action. Any potential risks associated with the use of botulinum neurotoxins in medical procedures need to be carefully balanced with the expected benefits of the procedure.


Asunto(s)
Toxinas Botulínicas , Botulismo , Clostridium botulinum , Animales , Humanos , Toxinas Botulínicas/efectos adversos , Botulismo/diagnóstico , Botulismo/epidemiología , Botulismo/etiología , Neurotoxinas , Viaje , Brotes de Enfermedades , Pérdida de Peso , Enfermedad Iatrogénica/epidemiología
9.
Int J Mol Sci ; 24(22)2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-38003595

RESUMEN

Mitochondrial dysfunction is a common occurrence in the aging process and is observed in diseases such as age-related macular degeneration (AMD). Increased levels of reactive oxygen species lead to damaged mitochondrial DNA (mtDNA), resulting in dysfunctional mitochondria, and, consequently, mtDNA causes further harm in the retinal tissue. However, it is unclear whether the effects are locally restricted to the high-energy-demanding retinal pigment epithelium or are also systematically present. Therefore, we measured mtDNA copy number (mtDNA-CN) in peripheral blood using a qPCR approach with plasmid normalization in elderly participants with and without AMD from the AugUR study (n = 2262). We found significantly lower mtDNA-CN in the blood of participants with early (n = 453) and late (n = 170) AMD compared to AMD-free participants (n = 1630). In regression analyses, we found lower mtDNA-CN to be associated with late AMD when compared with AMD-free participants. Each reduction of mtDNA-CN by one standard deviation increased the risk for late AMD by 24%. This association was most pronounced in geographic atrophy (OR = 1.76, 95% CI 1.19-2.60, p = 0.004), which has limited treatment options. These findings provide new insights into the relationship between mtDNA-CN in blood and AMD, suggesting that it may serve as a more accessible biomarker than mtDNA-CN in the retina.


Asunto(s)
ADN Mitocondrial , Degeneración Macular , Humanos , Anciano , ADN Mitocondrial/genética , Variaciones en el Número de Copia de ADN , Mitocondrias/genética , Degeneración Macular/genética , Retina
10.
Kidney Int ; 102(2): 405-420, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35643372

RESUMEN

Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD) is caused by mutations in one of at least five genes and leads to kidney failure usually in mid adulthood. Throughout the literature, variable numbers of families have been reported, where no mutation can be found and therefore termed ADTKD-not otherwise specified. Here, we aim to clarify the genetic cause of their diseases in our ADTKD registry. Sequencing for all known ADTKD genes was performed, followed by SNaPshot minisequencing for the dupC (an additional cytosine within a stretch of seven cytosines) mutation of MUC1. A virtual panel containing 560 genes reported in the context of kidney disease (nephrome) and exome sequencing were then analyzed sequentially. Variants were validated and tested for segregation. In 29 of the 45 registry families, mutations in known ADTKD genes were found, mostly in MUC1. Sixteen families could then be termed ADTKD-not otherwise specified, of which nine showed diagnostic variants in the nephrome (four in COL4A5, two in INF2 and one each in COL4A4, PAX2, SALL1 and PKD2). In the other seven families, exome sequencing analysis yielded potential disease associated variants in novel candidate genes for ADTKD; evaluated by database analyses and genome-wide association studies. For the great majority of our ADTKD registry we were able to reach a molecular genetic diagnosis. However, a small number of families are indeed affected by diseases classically described as a glomerular entity. Thus, incomplete clinical phenotyping and atypical clinical presentation may have led to the classification of ADTKD. The identified novel candidate genes by exome sequencing will require further functional validation.


Asunto(s)
Enfermedades Renales Poliquísticas , Riñón Poliquístico Autosómico Dominante , Adulto , Pruebas Genéticas , Estudio de Asociación del Genoma Completo , Humanos , Mutación , Enfermedades Renales Poliquísticas/genética , Riñón Poliquístico Autosómico Dominante/genética
11.
Kidney Int ; 102(3): 624-639, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35716955

RESUMEN

Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.


Asunto(s)
N-Acetilgalactosaminiltransferasas , Insuficiencia Renal Crónica , Insuficiencia Renal , Estudios Transversales , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Tasa de Filtración Glomerular/genética , Humanos , Riñón , Estudios Longitudinales , N-Acetilgalactosaminiltransferasas/genética , Insuficiencia Renal/genética
12.
Basic Res Cardiol ; 117(1): 45, 2022 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-36068416

RESUMEN

Tachycardiomyopathy is characterised by reversible left ventricular dysfunction, provoked by rapid ventricular rate. While the knowledge of mitochondria advanced in most cardiomyopathies, mitochondrial functions await elucidation in tachycardiomyopathy. Pacemakers were implanted in 61 rabbits. Tachypacing was performed with 330 bpm for 10 days (n = 11, early left ventricular dysfunction) or with up to 380 bpm over 30 days (n = 24, tachycardiomyopathy, TCM). In n = 26, pacemakers remained inactive (SHAM). Left ventricular tissue was subjected to respirometry, metabolomics and acetylomics. Results were assessed for translational relevance using a human-based model: induced pluripotent stem cell derived cardiomyocytes underwent field stimulation for 7 days (TACH-iPSC-CM). TCM animals showed systolic dysfunction compared to SHAM (fractional shortening 37.8 ± 1.0% vs. 21.9 ± 1.2%, SHAM vs. TCM, p < 0.0001). Histology revealed cardiomyocyte hypertrophy (cross-sectional area 393.2 ± 14.5 µm2 vs. 538.9 ± 23.8 µm2, p < 0.001) without fibrosis. Mitochondria were shifted to the intercalated discs and enlarged. Mitochondrial membrane potential remained stable in TCM. The metabolite profiles of ELVD and TCM were characterised by profound depletion of tricarboxylic acid cycle intermediates. Redox balance was shifted towards a more oxidised state (ratio of reduced to oxidised nicotinamide adenine dinucleotide 10.5 ± 2.1 vs. 4.0 ± 0.8, p < 0.01). The mitochondrial acetylome remained largely unchanged. Neither TCM nor TACH-iPSC-CM showed relevantly increased levels of reactive oxygen species. Oxidative phosphorylation capacity of TCM decreased modestly in skinned fibres (168.9 ± 11.2 vs. 124.6 ± 11.45 pmol·O2·s-1·mg-1 tissue, p < 0.05), but it did not in isolated mitochondria. The pattern of mitochondrial dysfunctions detected in two models of tachycardiomyopathy diverges from previously published characteristic signs of other heart failure aetiologies.


Asunto(s)
Cardiomiopatías , Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Animales , Cardiomiopatías/etiología , Humanos , Mitocondrias/metabolismo , Miocardio/metabolismo , Conejos
13.
BMC Geriatr ; 22(1): 34, 2022 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-34998375

RESUMEN

BACKGROUND: Containment measures in the COVID-19 pandemic protected individuals at high risk, particularly individuals at old age, but little is known about how these measures affected health-related behavior of old aged individuals. We aimed to investigate the impact of the spring 2020 lockdown in Germany on healthcare-seeking and health-related lifestyle in the old aged and to identify susceptible subgroups. METHODS: We conducted a follow-up survey among the pre-pandemically well-characterized participants of our AugUR cohort study, residents in/around Regensburg aged 70+ years and relatively mobile. A self-completion questionnaire on current behavior, perceived changes, and SARS-Cov-2 infection was mailed in May 2020, shortly before contact restrictions ended. Pre-pandemic lifestyle and medical conditions were derived from previous study center visits. RESULTS: Among 1850 survey participants (73-98 years; net-response 89%), 74% were at increased risk for severe COVID-19 according to medical conditions; four participants reported SARS-CoV-2 infection (0.2%). Participants reported changes in behavior: 29% refrained from medical appointments, 14% increased TV consumption, 26% reported less physical activity, but no systematic increase of smoking or alcohol consumption. When comparing during- and pre-lockdown reports of lifestyle within participant, we found the same pattern as for the reported perceived changes. Women and the more educated were more susceptible to changes. Worse QOL was perceived by 38%. CONCLUSIONS: Our data suggest that the spring 2020 lockdown did not affect the lifestyle of a majority of the mobile old aged individuals, but the substantial proportions with decreased physical activity and healthcare-seeking are markers of collateral damage.


Asunto(s)
COVID-19 , Anciano , Estudios de Cohortes , Control de Enfermedades Transmisibles , Atención a la Salud , Femenino , Alemania/epidemiología , Humanos , Estilo de Vida , Persona de Mediana Edad , Pandemias , Calidad de Vida , SARS-CoV-2
14.
Euro Surveill ; 27(27)2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35801518

RESUMEN

By 22 June 2022, 521 cases of monkeypox were notified in Germany. The median age was 38 years (IQR: 32-44); all cases were men. In Berlin, where 69% of all cases occurred, almost all were men who have sex with men. Monkeypox virus likely circulated unrecognised in Berlin before early May. Since mid-May, we observed a shift from travel-associated infections to mainly autochthonous transmission that predominantly took place in Berlin, often in association with visits to clubs and parties.


Asunto(s)
Brotes de Enfermedades , Mpox/epidemiología , Mpox/transmisión , Minorías Sexuales y de Género , Adulto , Berlin/epidemiología , Transmisión de Enfermedad Infecciosa/estadística & datos numéricos , Alemania/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Mpox/diagnóstico , Mpox/etiología , Viaje
15.
Eur Heart J ; 42(20): 2000-2011, 2021 05 21.
Artículo en Inglés | MEDLINE | ID: mdl-33677556

RESUMEN

AIMS: Our objective was to better understand the genetic bases of dilated cardiomyopathy (DCM), a leading cause of systolic heart failure. METHODS AND RESULTS: We conducted the largest genome-wide association study performed so far in DCM, with 2719 cases and 4440 controls in the discovery population. We identified and replicated two new DCM-associated loci on chromosome 3p25.1 [lead single-nucleotide polymorphism (SNP) rs62232870, P = 8.7 × 10-11 and 7.7 × 10-4 in the discovery and replication steps, respectively] and chromosome 22q11.23 (lead SNP rs7284877, P = 3.3 × 10-8 and 1.4 × 10-3 in the discovery and replication steps, respectively), while confirming two previously identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A genetic risk score constructed from the number of risk alleles at these four DCM loci revealed a 3-fold increased risk of DCM for individuals with 8 risk alleles compared to individuals with 5 risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analyses on iPSC-derived cardiomyocytes identify SLC6A6 as the most likely DCM gene at the 3p25.1 locus. This gene encodes a taurine transporter whose involvement in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggest SMARCB1 as the candidate culprit gene. CONCLUSION: This study provides a better understanding of the genetic architecture of DCM and sheds light on novel biological pathways underlying heart failure.


Asunto(s)
Cardiomiopatía Dilatada , Insuficiencia Cardíaca Sistólica , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Proteínas Reguladoras de la Apoptosis , Cardiomiopatía Dilatada/genética , Cromosomas , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Insuficiencia Cardíaca Sistólica/genética , Humanos , Polimorfismo de Nucleótido Simple/genética
16.
Genet Epidemiol ; 44(7): 759-777, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32741009

RESUMEN

Imaging technology and machine learning algorithms for disease classification set the stage for high-throughput phenotyping and promising new avenues for genome-wide association studies (GWAS). Despite emerging algorithms, there has been no successful application in GWAS so far. We establish machine learning-based phenotyping in genetic association analysis as misclassification problem. To evaluate chances and challenges, we performed a GWAS based on automatically classified age-related macular degeneration (AMD) in UK Biobank (images from 135,500 eyes; 68,400 persons). We quantified misclassification of automatically derived AMD in internal validation data (4,001 eyes; 2,013 persons) and developed a maximum likelihood approach (MLA) to account for it when estimating genetic association. We demonstrate that our MLA guards against bias and artifacts in simulation studies. By combining a GWAS on automatically derived AMD and our MLA in UK Biobank data, we were able to dissect true association (ARMS2/HTRA1, CFH) from artifacts (near HERC2) and identified eye color as associated with the misclassification. On this example, we provide a proof-of-concept that a GWAS using machine learning-derived disease classification yields relevant results and that misclassification needs to be considered in analysis. These findings generalize to other phenotypes and emphasize the utility of genetic data for understanding misclassification structure of machine learning algorithms.


Asunto(s)
Errores Diagnósticos/estadística & datos numéricos , Serina Peptidasa A1 que Requiere Temperaturas Altas/genética , Aprendizaje Automático , Degeneración Macular/genética , Proteínas/genética , Algoritmos , Estudio de Asociación del Genoma Completo , Humanos , Funciones de Verosimilitud , Modelos Genéticos , Fenotipo , Reino Unido
17.
Emerg Infect Dis ; 27(9): 2485-2488, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34424172

RESUMEN

We used 10 years of surveillance data to describe listeriosis frequency in Germany. Altogether, 5,576 cases were reported, 91% not pregnancy associated; case counts increased over time. Case-fatality rate was 13% in non-pregnancy-associated cases, most in adults ≥65 years of age. Detecting, investigating, and ending outbreaks might have the greatest effect on incidence.


Asunto(s)
Listeriosis , Brotes de Enfermedades , Femenino , Alemania/epidemiología , Humanos , Incidencia , Listeriosis/epidemiología , Embarazo
18.
Emerg Infect Dis ; 27(8): 2097-2106, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34286687

RESUMEN

Toxoplasmosis is a zoonotic infection contracted through Toxoplasma gondii-contaminated food, soil, or water. Seroprevalence in Germany is high, but estimates of disease incidence are scarce. We investigated incidences for various toxoplasmosis manifestations using anonymized healthcare claims data from Germany for 2011-2016. Patients with a toxoplasmosis diagnosis during the annual observational period were considered incident. The estimated incidence was adjusted to the general population age/sex distribution. We estimated an annual average of 8,047 toxoplasmosis patients in Germany. The average incidence of non-pregnancy-associated toxoplasmosis patients was 9.6/100,000 population. The incidence was highest in 2011, at 10.6 (95% CI 9.4-12.6)/100,000 population, and lowest in 2016, at 8.0 (95% CI 7.0-9.4)/100,000 population. The average incidence of toxoplasmosis during pregnancy was 40.3/100,000 pregnancies. We demonstrate a substantial toxoplasmosis disease burden in Germany. Public health and food safety authorities should implement toxoplasmosis-specific prevention programs.


Asunto(s)
Toxoplasma , Toxoplasmosis , Anticuerpos Antiprotozoarios , Atención a la Salud , Femenino , Alemania/epidemiología , Humanos , Incidencia , Embarazo , Factores de Riesgo , Estudios Seroepidemiológicos , Toxoplasmosis/epidemiología
19.
Contact Dermatitis ; 85(5): 489-493, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34161620

RESUMEN

BACKGROUND: Hand eczema (HE) is a chronic inflammatory skin disease caused by a genetic predisposition and environmental exposures. There is a lack of population-based studies on skin diseases in the elderly. OBJECTIVES: Our aim was to estimate the frequency of HE in the elderly to determine its burden of disease in this particular population. METHODS: We analyzed data from the research platform AugUR, a study on chronic diseases in the elderly (n = 1133, ages 70-95 years, mean age 77.6, 45.1% women). Raw frequencies were estimated using self-reports on physician-diagnosed HE from a standardized personal interview. Frequencies were standardized to the Bavarian population weighted by gender and 5-year age-groups. RESULTS: In our sample 2.7% (95% confidence interval [CI] 1.6-4.3) of the paticipants reported to ever have been diagnosed with HE. Among those 57% were male. After standardization, the frequency was estimated at 2.8% (95% CI 1.9-3.9). There were no differences between male and female participants. CONCLUSIONS: Compared to other studies on lifetime frequency of HE, our estimates seem to be remarkably lower. More in-depth studies with validated diagnoses are warranted to precisely estimate the burden of HE in the elderly.


Asunto(s)
Eccema/epidemiología , Evaluación Geriátrica/métodos , Dermatosis de la Mano/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica/epidemiología , Estudios Transversales , Dermatitis Alérgica por Contacto/epidemiología , Femenino , Alemania/epidemiología , Humanos , Masculino , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios
20.
Euro Surveill ; 26(41)2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34651575

RESUMEN

BackgroundHealthcare-associated foodborne outbreaks (HA-FBO) may have severe consequences, especially in vulnerable groups.AimThe aim was to describe the current state of HA-FBO and propose public health recommendations for prevention.MethodsWe searched PubMed, the Outbreak Database (Charité, University Medicine Berlin), and hand-searched reference lists for HA-FBO with outbreak onset between 2001 and 2018 from Organisation for Economic Co-operation and Development (OECD) countries and HA-FBO (2012-2018) from the German surveillance system. Additionally, data from the European Food Safety Authority were analysed.ResultsThe literature search retrieved 57 HA-FBO from 16 OECD countries, primarily in the US (n = 11), Germany (n = 11) and the United Kingdom (n = 9). In addition, 28 HA-FBO were retrieved from the German surveillance system. Based on the number of outbreaks, the top three pathogens associated with the overall 85 HA-FBO were Salmonella (n = 24), norovirus (n = 22) and Listeria monocytogenes (n = 19). Based on the number of deaths, L. monocytogenes was the main pathogen causing HA-FBO. Frequently reported implicated foods were 'mixed foods' (n = 16), 'vegetables and fruits' (n = 15) and 'meat and meat products' (n = 10). Consumption of high-risk food by vulnerable patients, inadequate time-temperature control, insufficient kitchen hygiene and food hygiene and carriers of pathogens among food handlers were reported as reasons for HA-FBO.ConclusionTo prevent HA-FBO, the supply of high-risk food to vulnerable people should be avoided. Well working outbreak surveillance facilitates early detection and requires close interdisciplinary collaboration and exchange of information between hospitals, food safety and public health authorities.


Asunto(s)
Enfermedades Transmitidas por los Alimentos , Atención a la Salud , Países Desarrollados , Brotes de Enfermedades , Contaminación de Alimentos , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/epidemiología , Humanos , Vigilancia de la Población
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