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Biomedical subjects

E Schreier

Publications and source records attributed to E Schreier.

At least 19 recordsLinked to original sources

Outbreak of hepatitis A in two federal states of Germany: bakery products as vehicle of infection.

In April 2004, increased numbers of hepatitis A were noted in six neighbouring districts in Germany. Exploratory interviews showed that patients had consumed bakery products from company X where two employees had been diagnosed with hepatitis A in February. A case-control study of consumption of products of company X was carried out through telephone interviews. Altogether, 64 cases were identified. Fifty-two cases and 112 controls aged >or=16 years were included in the case-control study. In total, 46/52 cases and 37/112 controls had consumed company X products [odds ratio (OR) 15.5, 95% confidence interval (CI) 6.1-39.7]. Of these, 36/46 cases and 16/37 controls had consumed pastries (OR 4.7, 95% CI 1.8-12.3), 25/46 cases and 12/37 controls had consumed filled doughnuts (OR 2.5, 95% CI 1.0-6.1). Sequence analysis of the VP1-2A junction region indicated 100% strain homology between cases and an infected employee of company X. We recommended reinforcement of hygiene precautions, and consideration of a prolongation of compulsory work absence after post-exposure vaccination.

Case-Control Studies↗

Molecular characterization of human astroviruses isolated in Brazil, including the complete sequences of astrovirus genotypes 4 and 5.

Human astroviruses (HAstV) are recognized as an important cause of gastroenteritis in young children worldwide. This study describes the molecular characteristics of astroviruses isolated in Brazil, using RT-PCR and molecular sequencing of segments of all three viral ORFs. Genetic analysis of a 348-nucleotide segment from ORF 2 demonstrated that the Brazilian isolates belong to HAstV genotypes 1 to 5 and 8. ORF 1b sequences displayed a high degree of nucleotide identity even between different genotypes, which disfavours HAstV genotyping in this region. ORF 1a sequence analysis classified all Brazilian samples as genogroup A. The complete sequences of HAstV genotype 4 (putative serotype 4) and genotype 5 (putative serotype 5) were determined for the first time.

Astroviridae Infections↗

Molecular characterization of the first Aichi viruses isolated in Europe and in South America.

The occurrence of Aichi virus, a picornavirus associated with acute gastroenteritis, has so far only been described in Asian countries. This study reports the first finding of Aichi virus in clinical specimens from Germany and Brazil. The nucleotide sequences of both a German and a Brazilian isolate were determined, analyzed, and compared to known Aichi sequences. The German strain turned out to be a member of genogroup A, while the Brazilian belonged to genogroup B. For a primary assessment of the epidemiological importance of Aichi virus in Germany, a panel of 485 German serum samples was screened for antibody to Aichi virus, and a seroprevalence of 76% was found.

Antibodies, Viral↗

[Norovirus infections in Germany].

Noroviruses are responsible for the majority of acute viral gastroenteritis infections worldwide. Transmission may be faecal-oral or through contaminated food and water or airborne by virus-containing aerosols. Characteristics of noroviruses that facilitate their spread are their high concentration in stool and vomitus, their extreme environmental stability, their low infectious dose as well as the lack of long-lasting immunity. The majority of norovirus infections occur in large outbreaks among persons living in institutional settings, such as hospitals and nursing homes, although sporadic cases also occur. Children and elderly persons are most often affected. Illness is characterized by acute onset of projectile vomiting. For prevention and control of norovirus outbreaks strict control management is necessary. Based on the high genomic variability new variant noroviruses with different pathogenic factors can arise. Depending on the circulating variant the extent of the usual winter peak can vary enormously. Available diagnostic methods include RT-PCR assays for detection of viral RNA, electron microscopy and enzyme immunoassays (EIA) for detection of viral antigens. The implicated virus can be subtyped through nucleotide sequencing and linked to a specific outbreak. With the enactment of the Protection against Infection Act in January 2001 a mandatory reporting system of norovirus infections was established. Analysis of surveillance data from this system permits a detailed overview of the nationwide epidemiology of this disease in Germany.

Caliciviridae Infections↗

Nosocomial transmission of hepatitis C virus from an anesthesiologist to three patients--epidemiologic and molecular evidence.

Acute hepatitis C occurred in three patients who had undergone gynecologic surgery in an outpatient clinic on a single day. Epidemiologic and virologic investigations revealed virus transmission from an anesthesiologist with chronic hepatitis C. HCV sequencing demonstrated that all four persons were infected by the same strain. The precise mode of transmission could not be elucidated but hygienic standards had been severely neglected.

Adult↗

Generation of recombinant norovirus-like particles (VLP) in the human endothelial kidney cell line 293T.

Noroviruses (NVs) are the major cause of non-bacterial outbreaks of gastroenteritis. Here we report a new alternative system to generate recombinant NV virus-like particles (rNV-VLP) in a human endothelial kidney cell line (HEK). Transfecting HEK-293T cells with an expression vector coding for the ORF-2 gene lead to the expression of the viral structural protein VP1 which spontaneously assembled into virus-like particles (VLP), as shown by electron microscopy. The transfected cells did not show a cytopathic effect and released rNV-VLP into the culture medium. The HEK-293T cell derived particles were morphologically indistinguishable to the rNV-VLP produced from baculovirus and the Venezuelan equine encephalitis virus (VEE)-replicon. The produced particles were stable for at least 2.5 months at 4 degrees C.

Cell Line↗

Detection of enteric viruses and bacterial indicators in German environmental waters.

A German mining lake and the supplying surface waters, which are located downstream of a sewage plant, were examined regarding their microbiological and virological quality. Between October 2002 and September 2003, specific PCR methods were used to determine the occurrence of enteric viruses in 123 water specimens drawn at different sites downstream of the waste water treatment plant and in 9 samples from the sewage plant influent. Detection rates in sewage plant effluents and surface water samples depended on sampling sites and were: 29-76% for enterovirus (EntV), 24-42% (astrovirus, AstV), 15-53% (norovirus, NV), 3-24% (rotavirus, RoV), 5-20% (hepatitis A virus, HAV) and 20% (adenovirus, AdV). AstV genome load of selected samples was between 3.7 x 10(3) to 1.2 x 10(8) genome equivalents per liter (gen.equ./l), depending on sampling location; NV average genome load ranged from 1.8 x 10(4) to 9.7 x 10(5) gen.equ./l. Cell culture methods showed that three out of 18 PCR positive samples contained infectious EntV. Even though microbiological parameters such as Escherichia coli, enterococci and coliphages indicated acceptable microbiological water quality, the virological data of this study suggest the possibility that surface waters may be a source for enteric viral infections.

Adenoviruses, Human↗

An outbreak of viral meningitis associated with a public swimming pond.

From July to October 2001, 215 cases of aseptic meningitis occurred among the inhabitants of the German city of Kassel and neighbouring counties. A matched case-control study identified bathing in a public, nature-like pond during the beginning of the outbreak as a risk factor for disease [matched odds ratio (mOR) 44.8, 95% confidence interval (CI) 3.9-515.6]. Among bathers, patients with meningitis spent more time in the water (mOR 18.8, 95% CI 2.0-174.1) and swallowed water more frequently (mOR = 7.3, 95% CI 0.7-81.8). Of 30 cerebrospinal fluid samples tested, echovirus 30 was cultured from 16, and echovirus 13 from seven. An echovirus 30 sequence obtained from one pond water sample showed a 99% nucleotide and 100% amino-acid homology with patient isolates. This outbreak demonstrates the potential of nature-like swimming ponds to cause widespread community infection with substantial public health impact.

Adolescent↗

Detection and characterization of norovirus outbreaks in Germany: application of a one-tube RT-PCR using a fluorogenic real-time detection system.

Outbreaks of gastroenteritis caused by Norovirus are an increasing public health problem worldwide. The virus is transmitted by contaminated food and by person-to-person. In Germany, a new health reporting system including Norovirus infections has been introduced in 2001. Norovirus outbreaks (73%) diagnosed in our lab occurred in the first half of the year. Phylogenetic analysis shows that 90% belonged to genogroup II (GGII) with the majority related to prototypes Lordsdale/93 and Tarragona/2001. To date, PCR is the most sensitive and specific method for the detection but several procedures are needed to evaluate the amplification product. To minimize the risk of product carryover, a fast and simple procedure with a minimal number of steps are required. A one-tube RT-PCR method is described using the real-time TaqMan-PCR system. Primer sets and probes for both genogroup I (GGI) and genogroup II (GGII) sequences were developed. The specificity and sensitivity of this method was evaluated on 70 Norovirus positive stool samples of 70 outbreaks in Germany and 34 European samples by comparing the detection rate to those of an in-house RT-nested PCR. Overall, 93% of the PCR positive samples have been detected by the TaqMan-PCR including isolates of four different GGI and seven different GGII genotypes. Using plasmid standards for quantitation, virus loads between 10(2) and 10(10) genomic equivalents/ml stool suspension were found. The advantages of the one-step RT/TaqMan-PCR system for detection and quantitation of Norovirus are the high throughput of clinical samples and a decrease of the risk of contamination.

Caliciviridae Infections↗

[The norovirus-epidemic in Berlin - clinic, epidemiology, and prevention].

INTRODUCTION: During the winter 2002/2003, an increased number of outbreaks of acute gastroenteritis caused by norovirus was reported from Germany, some other European countries and the USA. In this study, the epidemiological and clinical features of the Berlin norovirus outbreak were investigated in order to identify the reasons for the spread of norovirus gastroenteritis and possible control measures. METHODS: Cases and spread of norovirus infection in eleven long-term care facilities and a university hospital in Berlin were monitored from October 2002 to February 2003. To investigate the symptomatology and routes of transmission, a retrospective and interview-based study of infected staff members was performed. RESULTS: Norovirus outbreaks in eleven long-term care facilities affected 314 patients (attack rate: 28.3 %, rate of hospitalisation: 20.7 %). 219 persons were affected in the hospital, during a period of four months. Sequence analysis revealed the circulation of Norovirus genogroup II (Grimsby-like viruses). The mean duration of symptoms was 69 hours. The duration of outbreaks on specific wards was negatively correlated with the time of returning to work (mean: 1.8 days) of the staff members after the disease. DISCUSSION: This report demonstrates the potential of norovirus to cause large outbreaks by person to person transmission. Spread by aerosols generated by vomiting and environmental contamination seem to be particular important in institutional settings. The duration of symptoms was longer than reported previously, reflecting a possible increased virulence. Besides this, the outbreak was facilitated by insufficient preventive measures.

Adult↗

Sustained virological response in hepatitis C virus type 1b infected patients is predicted by the number of mutations within the NS5A-ISDR: a meta-analysis focused on geographical differences.

BACKGROUND AND AIMS: There is growing evidence that the response of hepatitis C virus (HCV) genotype 1b infected patients towards interferon (IFN) therapy is influenced by the number of mutations within the carboxy terminal region of the NS5A gene, the interferon sensitivity determining region (ISDR). PATIENTS AND METHODS: In order to attain better insight into this correlation, a file comprising published data on ISDR strains from 1230 HCV genotype 1b infected patients, mainly from Japan and Europe, was constructed and analysed by logistic regression. Sustained virological response (SVR) was defined as negative HCV RNA six months after treatment. RESULTS: The distribution of wild-, intermediate-, and mutant-type ISDR sequences differed significantly between Japanese (n = 655) (44.1%, 37.6%, and 18.3%) and European patients (n = 525) (24.8%, 63.4%, and 11.8%; p<0.001). There was a significant positive correlation between the number of ISDR mutations and SVR rate, irrespective of geographical region. The likelihood of SVR with each additional mutation within the ISDR was considerably more pronounced in Japanese compared with European patients (odds ratios 1.82 v 1.39; p<0.001). Pretreatment viraemia of <6.6 log copies/ml and ISDR mutant-type infection was associated with an SVR rate of 97.1% in Japanese patients but only 52.5% in European patients. Pretreatment viraemia was a stronger predictor of SVR than ISDR mutation number in Japanese patients whereas in European patients both parameters had similar predictive power. CONCLUSION: These data support the concept that mutant-type ISDR strains may represent a subtype within genotype 1b with a more favourable response towards IFN therapy.

Antiviral Agents↗

Molecular typing of echovirus serotype 4 isolates.

We report on clinical samples Stuttgart/97, Berlin/99 and Jasi/99 associated with aseptic meningitis. All three samples contained echovirus 4 (E4) but Stuttgart/97 was simultaneous infected with echovirus 30 (E30). The genetic relationship of the E4 strains was assessed using RT-PCR and direct sequencing of amplicons derived from the genomic region encoding the capsid protein VP1. The sequences have been compared with each other and with sequences of further E4 strains obtained from GenBank. The analysis confirms that sequences of recent isolates have drifted away from elderly strains over a longer period of time. Several amino acid changes in assumed antigenic sites of the VP1 gene may be sufficient to cause changes in antigenic specificity and therefore they may be a reason for failure of serological typing of some new antigenic E4 variants.

Amino Acid Sequence↗

[Worldwide eradication of poliomyelitis].

Poliomyelitis, an infectious disease with acute and persistent flaccid paralysis is caused by poliovirus (types 1, 2 or 3), an enterovirus. The infection is asymptomatic in 95% of infected subjects. Most of the paralytic cases occur in adolescents or adults in the course of polio type 1 infection. In the prevaccination era, in countries with poor hygienic conditions, infection in early childhood was common, mostly asymptomatic, and immunity in the population prevailed. In developed countries polio often struck adolescents and adults taking its toll in paralytic disease. The introduction of vaccination with the Salk vaccine (IPV Inactivated Polio Vaccine) in the USA and in Europe in 1956 and with the Oral Polio Vaccine (OPV) developed by Sabin worldwide in the early sixties made it possible to control the epidemic in large geographic areas, but it could not eliminate the disease worldwide. Poliomyelitis is still endemic in Central Africa and in the Indian sub-continent. Acts of war led to the reduction in the vaccination rate in different geographic areas, and smaller epidemics with wild virus but also with reverted vaccine strains occurred. In some parts of the world the rate of vaccination also declined due to elimination of poliomyelitis, and it came to small epidemics of paralytic polio mainly caused by reverted vaccine strains circulating in the population. Reverted vaccine strains also remain a central problem in the eradication of poliomyelitis projected for 2005 by the World Health Organisation. A high vaccination rate, preferably with 3 doses of OPV in infancy or early childhood, and exact worldwide monitoring of cases is indispensable for the eradication. For the complete eradication of poliovirus the live vaccine OPV would have to be changed to an inactivated vaccine IPV worldwide. However, this is presently unachieveable, because of logistic problems and high costs.

Adolescent↗

Aseptic meningitis in Germany associated with echovirus type 13.

BACKGROUND: Echoviruses are the commonest cause of aseptic meningitis. Echovirus type 13 which has not been isolated in Germany over a long period of time was the predominant enterovirus serotype associated with different local outbreaks of aseptic meningitis in Germany in 2000. METHODS: Virus isolation was performed from cerebrospinal fluid and stools. In order to study the genetic relationship of echovirus type 13 isolates, sequence analysis of a part of VP1 (~300 nt) was carried out. Isolates from different geographic regions were compared to each other as well as to elder viruses (prototype strain from 1953, four isolates from 1965-1986). RESULTS: Overall, 55 isolates of echovirus type 13 were obtained from different parts of Germany. It was shown that the new isolated strains have a very high degree of homology on the nucleotide level (> 98%)) but differ significantly from the old strains (76-85%). CONCLUSIONS: a) Rare enterovirus serotypes can cause serious illness.b) The molecular drift has also been shown for other enterovirus serotypes.

Adolescent↗

Molecular characterization of human astroviruses in Germany.

The molecular epidemiology of human astroviruses (HAstV) was studied using fecal specimens from different regions in Germany during 1998/99 by RT-PCR and sequencing of ORF2 amplicons. HAstV of genotypes 1-4 were found to cocirculate in Germany. The complete sequence of one isolate representing genogroup 3 (putative serotype 3) was determined.

Amino Acid Sequence↗

Prevalence of markers for hepatitis A, B and C in the German population. Results of the German National Health Interview and Examination Survey 1998.

The prevalence of serological parameters indicative of infection with hepatitis A, B and C was determined using sera collected from representative population samples in the former East German (new) federal states and the West German (old) federal states during the German National Health and Examination Survey in 1998. Sera were tested for antibodies to hepatitis A virus (HAV), to hepatitis B core antigen (HBc) and to hepatitis B surface antigen (HBsAg), hepatitis C Virus (HCV), as well as for the presence of HBsAg and HCV-RNA. The mean weighted prevalence of anti-HAV was 46.5% (95% CI: 45.3-47.7) and increased markedly with age. The mean weighted prevalence of past infection with hepatitis B was 7.7% (95% CI: 7.0-8.4) in the old federal states and 4.3% (95% CI: 3.2-5.3) in the new federal states, corresponding to an overall prevalence of 7.0% (95% CI: 6.4-7.6). The mean weighted prevalence of HBsAg carriage was 0.6% (95% CI: 0.4-0.8), while the prevalence of HCV antibodies was 0.4% (95% CI: 0.2-0.5).

Cross-Sectional Studies↗

An outbreak of viral gastroenteritis in a mother-and-child health clinic.

An outbreak of diarrhoeal disease in a modern mother-and-child health clinic prompted the health authorities to initiate a retrospective cohort study in order to assess the scope of the outbreak and to identify possible risk factors. The management of the clinic had been rather concerned because four similar outbreaks had occurred during the last two years. A total of 151 guests, i.e. mothers with their children, who had arrived some days before the peak of the outbreak for a three-week-stay and another 15 guests who had arrived earlier and had extended their stay were enrolled in the study which mainly focused on the possible role of treatment measures as risk factors. In addition, a total of 49 staff members were requested to provide information about symptoms, working area and attendance at work. Relevant data were available from 164 of 166 guests and 47 of 49 staff members (response rates 98.8% and 96.0%, respectively). The attack rate among guests was 44.0% (adults 27.0%, children 54.0%) and among staff 23.4%. The mean age of affected children (3.5 years) was significantly lower than that of those not affected (6.3 years). The main symptoms were diarrhoea and vomiting. The sudden start of the outbreak suggested a single source of infection which, however, remained unknown. Person-to-person transmission was supposed to be the cause of the following spread. No association between distinct treatment measures and the disease was proven by the cohort study. Norwalk-like viruses as well as astroviruses were detected by polymerase chain reaction in specimens taken from seven patients. No other enteropathogenic agents were found. Regarding the special conditions in a mother-and-child health clinic where social contacts among guests are much more frequent and intensive than among patients in a "normal" hospital, measures to prevent the spread of gastrointestinal infections should concentrate on early recognition and isolation of symptomatic individuals. Guests and staff members should be instructed to keep to the rules of personal hygiene, especially handwashing. If disinfection is required, it should be virucidal.

Adolescent↗