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During the coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reliable diagnostics are absolutely indispensable. Molecular SARS-CoV-2 diagnostics based on nucleic acids (NA) derived from oro- or nasopharyngeal swabs constitute the current gold standard. Given the importance of test results, it is crucial to assess the quality of the underlying swab samples and NA extraction procedures. We determined NA concentrations in clinical samples used for SARS-CoV-2 testing applying an NA-specific dye. In comparison to cut-offs defined by SARS-CoV-2-positive samples, internal positive controls, and references from a federal laboratory, 90.85% (923 of 1016) of swabs contained NA concentrations enabling SARS-CoV-2 recognition. Swabs collected by local health authorities and the central emergency department either had significantly higher NA concentrations or were less likely to exhibit insufficient quality, arguing in favor of sampling centers with routined personnel. Interestingly, samples taken from females had significantly higher NA concentrations than those from males. Among eight longitudinal patient sample sets with intermitting negative quantitative reverse transcription polymerase chain reaction results, two showed reduced NA concentrations in negative specimens. The herein described fluorescence-based NA quantification approach is immediately applicable to evaluate swab qualities, optimize sampling strategies, identify patient-specific differences, and explain some peculiar test results including intermittent negative samples with low NA concentrations.

In February 2019, the fourth expert meeting on rapid diagnostic tests (RDTs) for sexually transmitted infections (STI) was held at the Robert Koch Institute (RKI) in Berlin. Novel technical developments and new aspects of RDT applications were discussed by representatives from the German STI Society (DSTIG); RKI; the Paul Ehrlich Institute; national reference centers for HIV, HBV, and HCV; and reference laboratories for Chlamydia, gonococci, and Treponema pallidum.As a result of this meeting, we present a revision of the joint statement on STI diagnostics with RDTs from 2017. The Regulation (EU) 2017/746 of the European Parliament and of the Council on in vitro diagnostic medical devices became effective in May 2017 and includes more stringent regulatory requirements for RDTs, mainly concerning conformity of manufacturing processes and performance characteristics of class D in vitro diagnostics (detection of HIV, HBV, HCV, and T. pallidum). Some RDTs for HIV, HCV, and T. pallidum have been evaluated in clinical studies and/or were WHO prequalified and may be used in low-threshold services. Among them are some HIV RDTs available and approved for self-testing. In addition, some HBV RDTs based on detection of HBs antigen (HBsAg) received WHO prequalification. However, false negative results may occur in samples with low HBsAg levels, as for instance in HIV-coinfected patients receiving antiretroviral therapy. For Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), antigen-based RDTs still do not allow reliable detection of infection. Only PCR-based CT/NG RDTs possess sufficient diagnostic accuracy to be used as point-of-care tests. Rapid PCR tests for NG, however, do not provide any information about antimicrobial resistance.

The COVID-19 pandemic poses enormous challenges to global healthcare sectors. To prevent the overburden of medical systems, it is crucial to distinguish individuals approaching the most infectious early phase from those in the declining non-infectious phase. However, a large fraction of transmission events occur during pre- or asymptomatic phases. Especially in the absence of symptoms, it is difficult to distinguish prodromal from late phases of infection just by RT-PCR since both phases are characterized by low viral loads and corresponding high Ct values (>30). We evaluated a new rapid test detecting IgG antibodies recognizing SARS-CoV-2 nucleocapsid protein using two commercial antibody assays and an in-house neutralization test before determining suitability for testing clinical swab material. Our analyses revealed the combination of the well-known RT-PCR and the new rapid antibody test using one single clinical nasopharyngeal swab specimen as a fast, cost-effective, and reliable way to discriminate prodromal from subsiding phases of COVID-19., Graphical abstract, Immunology; Virology

Background In Germany, risk of hepatitis C virus (HCV) infection is highest among people who inject drugs (PWID). New injectors (NI) are particularly vulnerable for HCV-acquisition, but little is known about health seeking behaviour and opportunities for intervention in this group. We describe characteristics, HCV prevalence, estimated HCV incidence and awareness of HCV-status among NIs and missed opportunities for hepatitis C testing. Methods People who had injected drugs in the last 12 months were recruited into a cross-sectional serobehavioural study using respondent-driven sampling in 8 German cities, 2011–2014. Data on sociodemographic characteristics, previous HCV testing and access to care were collected through questionnaire-based interviews. Capillary blood was tested for HCV. People injecting drugs Results Of 2059 participants with available information on duration of injection drug use, 232 (11% were NI. Estimated HCV incidence among NI was 19.6 infections/100 person years at risk (95% CI 16–24). Thirty-six percent of NI were HCV-positive (thereof 76% with detectable RNA) and 41% of those HCV-positive were unaware of their HCV-status. Overall, 27% of NI reported never having been HCV-tested. Of NI with available information, more than 80% had attended low-threshold drug services in the last 30 days, 24% were released from prison in the last 12 months and medical care was most commonly accessed in hospitals, opioid substitution therapy (OST)-practices, practices without OST and prison hospitals. Conclusion We found high HCV-positivity and low HCV-status awareness among NI, often with missed opportunities for HCV-testing. To increase early diagnosis and facilitate treatment, HCV-testing should be offered in all facilities, where NI can be reached, especially low-threshold drug services and addiction therapy, but also prisons, hospitals and practices without OST.

Patenschaftsmodelle als besonderer Typus freiwilligen Engagements haben Konjunktur. In einer kritischen Reflexion dieses Booms wird zum einen nach den Motiven und Interessen der verschiedenen beteiligten Akteure (engagierte Burger*innen, frei-gemeinnutzige oder offentliche Organisationen) gefragt, zum anderen nach Wirkungen und Nebenwirkungen von Patenmodellen. Hierbei werden Widerspruche, Chancen und Risiken deutlich. Vor diesem Hintergrund pladiert der Beitrag dafur, Patenschaftsprojekte konsequent in einen zivilgesellschaftlichen Rahmen zu stellen und somit primar nicht als private Aktivitaten, sondern als gesellschaftspolitisches Projekt zu verstehen. Eine solche Einordnung hat eine Reihe konzeptioneller und praktischer Konsequenzen.

Der Beitrag verdeutlicht Herausforderungen und Gelingensfaktoren des Programms „Aktion Neue Nachbarn“. Neben den besonderen Qualitaten personlicher Patenbezuge wird insbesondere die organisationale Wirkung von Patenansatzen im Bereich des freiwilligen Engagements (hier fur die Zielgruppe gefluchteter Menschen) beleuchtet. Dabei werden Patenmodelle als Ko-Produktionsansatze innerhalb einer hierarchischen professionellen Organisation und Patenstrukturen als Innovationsmotoren zur Offnung von Organisationen fur freiwilliges Engagement und Partizipation gesehen.

Auch wenn von Reisen wahrend der COVID-19-Pandemie gegenwartig noch weitgehend abzusehen ist, bleibt Tollwut ein wichtiges Thema, dem Sie sich spatestens dann wieder widmen mussen, wenn die ersten Kurzentschlossenen zur Reiseberatung in Ihrer Praxis erscheinen werden. Dieser Beitrag frischt Ihr vorhandenes Wissen auf und informiert Sie insbesondere uber das von der WHO propagierte verkurzte praexpositionelle Impfschema.

Die Kinder- und Jugendhilfe (KJH) ist nicht nur ein quantitativ groses, sondern auch ein traditionell dynamisches und innovationsfreudiges Arbeitsfeld der Sozialen Arbeit. Nicht wenige Fachkonzepte wurden zuerst in der KJH diskutiert und umgesetzt, bevor sie spater auch in anderen Hilfebereichen rezipiert wurden: Bspw. Lebensweltorientierung, Empowerment, Sozialraumorientierung oder partizipative Planung. Einen in vielerlei Hinsicht wichtigen Meilenstein markierte die Einfuhrung des SGB VIII in 1990.

Monitoring recency of infection helps to identify current transmission in vulnerable populations for effective disease control. We have established an in-house avidity based hepatitis C virus (HCV) recency assay based on the Monolisa Anti-HCV PLUS Version 3 ELISA kit for use of dried serum/plasma spots (DS/PS) in order to distinguish recent and long-term infections. A first panel of DS/PS (n = 218; genotype 1 n = 170 and non-genotype 1 n = 48) consisting of primary and at least one follow up sample was used to analyze the temporal changes of the Avidity Index (AI) over time. Sub-panels of longitudinal DS/PS (n = 66) and acute cases (26 weeks; n = 34) were taken to calculate the Mean Duration of Recent Infection (MDRI) and the False Long-term Rate (FLTR), respectively. A second panel of DS/PS104 weeks (n = 132) and a third panel of DS/PS prepared from resolved infections (≥180 days since last positive; n = 32) were used to calculate the False Recent Rate (FRR). For all genotypes, the optimal AI cut-off was determined to be 40% resulting in an MDRI of 364 days (95% CI: 223-485). FLTR was 5.9% (95% CI: 0.7-19.7), 8.3% (95% CI: 1-27), and 0% (-) and FRR was 13.6% (95% CI: 8.3-20.7), 11.7% (95% CI: 6.6-19), and 30.6% (95% CI: 9.1-61.4) for all genotypes, genotype 1, and non-genotype 1 infections, respectively. For resolved infections, the FRR was 53.1% (95% CI: 35.8-70.4). Thus, this assay performs particularly well for genotype 1 reaching a high rate of correct discriminations between infections acquired less than a year before diagnosis and those acquired earlier by applying an AI cut-off of 40%. Due to a rapid decline in avidity post resolution of an HCV infection this assay is not recommended to be used in HCV RNA negative patients.

Am 5.2.16 fand am Robert-Koch-Institut in Berlin ein Expertentreffen zum Thema „Schnelltests in der Diagnostik sexuell ubertragbarer Infektionen“ statt. Das Ziel dieser Tagung war, die in einem vorangegangenen Treffen im Januar 2012 erarbeitete Bewertung der Schnelltests fur den Einsatz in der Infektionsdiagnostik von HIV, HBV, HCV, T. pallidum, C. trachomatis und N. gonorrhoeae in „niedrigschwelligen Einrichtungen“ unter Berucksichtigung neuer Erkenntnisse und Entwicklungen dem aktuellen Stand anzupassen. Die von der Bundesregierung kurzlich beschlossene Strategie zur Eindammung von HIV, Hepatitis B und C und anderen sexuell ubertragbaren Infektionen beschreibt einen Mangel an Testmoglichkeiten und verfolgt eine Steigerung der Testangebote und einen besseren Zugang. Eine wichtige Option um Testbarrieren zu senken, reprasentiert der Einsatz von Schnelltests, die als niedrigschwelliges Testangebot in Beratungsstellen angeboten werden und auch als Heimtests durchgefuhrt werden konnen. Basierend auf den in klinischen Studien evaluierten Leistungsmerkmalen sind einige HIV-, HCV- und Syphilis-Schnelltests durchaus als point-of-care Test (POCT) geeignet. Fur C. trachomatis und N. gonorrhoeae erreichen nur PCR-basierte POCTs eine ausreichende diagnostische Genauigkeit. Der Einsatz von Schnelltest ist in Deutschland an bestimmte Vorgaben des IfSG und MPG gebunden. Die Abgabe von HIV-Diagnostika an Privatpersonen (zwecks Heimtestung) ist in Deutschland untersagt (§ 11, MPG). Die Feststellung und Ubermittlung einer Infektionskrankheit ist einem Arzt vorbehalten und darf auch nicht als Ferndiagnose erfolgen (§ 24, IfSG). Daruber hinaus unterliegen Schnelltests, wie alle labormedizinischen Analysen einer Qualitatssicherung entsprechend den Richtlinien der Bundesarztekammer.

Objectives: The aim of this study was to investigate the association between detention experience and hepatitis C virus (HCV) status, the role of duration and frequency of detention, and whether risk behaviours practiced in detention could explain an observed increase in risk. Methods: Current drug injectors (injecting in the last 12 months) were recruited to participate in a sero-behavioural, cross-sectional survey using respondent-driven sampling in eight German cities during the years 2011–2014. Using multivariable logistic regression, the association between HCV status and reported detention experience was investigated. Results: A total of 1998 participants were included in the analysis. Of these, 19.9% reported no detention experience, 28.6% short and rare experience (≤3.5 years in total, ≤3 times), 12.1% short but frequent experience, 7.1% long but rare experience, and 32.4% long and frequent experience. After correcting for HCV risk factors, the association between detention experience and HCV status remained statistically significant. By adjusting the model for intramural risk behaviours, the odds ratios of detention experience were reduced but remained significant. Conclusions: The proportion of people who inject drugs positive for HCV increased with both frequency and duration of their detention experience. As intramural risk behaviours could not fully explain this increase, it appears that transfers between community and custody may confer additional risks. Keywords: HCV, PWID, Prison, Incarceration, Detention, Germany

Im Projekt „Soziale Integration und Teilhabe im landlichen Raum“ wurde fur ein Stadtviertel einer mittelgrosen Kreisstadt eine Sozialraumanalyse zur sozialen Teilhabe durchgefuhrt. Das Stadtviertel umfasst als Wohngebiet rund 5.500 Einwohner/-innen. Kennzeichnend fur das Gebiet sind die Mischbebauung sowie eine Bevolkerungsstruktur, die sich durch viele Familien mit Migrationshintergrund, sozial benachteiligte Familien sowie einem leicht erhohten Anteil an Senior/-innen auszeichnet.

HCV RNA assays are of central importance for virological diagnostics and for clinical planning and monitoring of an antiviral combination treatment of chronic HCV infections. The objective of the pre-market evaluation of the VERSANT HCV RNA 1.0 Assay (kPCR) was to collect analytical performance data for this new method of HCV RNA quantification and to compare them with the high standards that exist in this context. The assay exhibited a specificity of 100%. The mean intra- and inter-assay imprecision was 14.1% and 14.6%, respectively. The detection limit was determined to be 16IU/ml (95% confidence interval: 11.9-30.6IU/ml) and consequently corresponded to the manufacturer's claims (i.e. 15IU/ml). The test exhibited linearity for all HCV genotypes in a broad range from 15 to 10(8)IU HCV RNA/ml. Hence, the kPCR assay in general is well suitable for HCV RNA determinations in clinical practice. However, in a methodological comparison, a considerable under-quantification of the concentrations of HCV genotype 2 and 3 isolates was detected. Provided that the assay's manufacturer will quickly remedy this shortcoming, the VERSANT HCV RNA 1.0 (kPCR) can be called a completely reliable technique for HCV RNA quantification in routine virological diagnostics.

Soziale Dienstleistungen werden immer starker in einem Welfare Mix erbracht. Im Zentrum des Beitrags stehen sozialwirtschaftliche Unternehmen als ‚hybride Organisationen‘, die mit verschiedenen gesellschaftlichen Sektoren verknupft und durch sie gepragt sind. Sozialmanagement kann verstanden werden als Steuerung hybrider sozialwirtschaftlicher Organisationen. In diesem Kontext entfaltet das Konzept des Dilemmatamanagements seine Produktivitat als Ansatz des Managements hybrider Organisationen.

Background High prevalence of drug use and injection-related risk behaviours have been reported among former Soviet Union (FSU)-migrants. To investigate hepatitis C (HCV) and HIV seroprevalence and related risk behaviours in this subgroup in Germany, we compared first generation FSU-migrants and native Germans using data from a sero-behavioural survey of people who inject drugs (PWID). Methods Current injectors were recruited using respondent-driven sampling in eight German cities in 2011–2014. Questionnaire-based interviews were conducted and dried blood spots collected and tested for anti-HCV, HCV-RNA, and anti-HIV1/2. Descriptive and multivariable analyses (MVA) were performed. Results A total of 208 FSU-born and 1318 native German PWID were included in the analysis. FSU-migrants were younger than Germans (median age: 33 vs. 39 years), and more often male (83.1% vs. 75.9%, p = 0.022). HCV seroprevalence was 74.5% in FSU-migrants vs. 64.6% in Germans (p = 0.006), HIV seroprevalence was 5.8% and 4.6%, respectively (p = 0.443). The proportion of FSU-migrants reporting injecting-related risk behaviours was higher than among Germans: injecting daily (39.4% vs. 30.2%, p = 0.015), with friends (39.2% vs. 31.2%, p = 0.038), cocaine (32.7% vs. 23.8%, p = 0.044), more than one drug (18.2% vs. 9.6%, p = 0.006), and sharing filters/cookers (35.5% vs. 28.0%, p = 0.045). No statistically significant differences were observed in HIV/HCV testing rates (range: 50.7%–65.6%), opioid substitution treatment (43.9% vs. 50.5%), and access to clean needles/syringes (89.8% vs. 90.3%). In MVA, risk for HCV-infection was increased in male FSU-migrants compared to German males (OR 3.32, p = 0.006), no difference was identified between female FSU-migrants and German females (OR: 0.83, p = 0.633). Conclusion Male FSU-migrants were at highest risk of being HCV infected. Therefore, targeted actions are needed to ensure access and acceptance of harm reduction measures, including HCV-testing and -treatment for this subpopulation of PWID.

Background People who inject drugs (PWID) are the most important risk group for incident Hepatitis C virus (HCV) infection. In PWID in Europe HCV genotype 3a is highly prevalent. Unfortunately, many of the recently developed directly acting antiviral drugs against HCV (DAAs) are suboptimal for treatment of this genotype. Detection of resistance-associated variants (RAV) in genotype 3a may help to optimize treatment decisions, however, robust protocols for amplification and sequencing of HCV NS5A as an important target for treatment of genotype 3a are currently lacking. Objectives The aim of this study was to establish a protocol for sequencing of HCV NS5A in genotype 3a and to determine the frequency of RAVs in treatment-naive PWID living in Germany. Study design The full NS5A region was amplified and sequenced from 110 HCV genotype 3a infected PWID using an in-house PCR protocol. Results With the established protocol the complete NS5A region was successfully amplified and sequenced from 110 out of 112 (98.2%) genotype 3a infected PWID. Phylogenetic analysis of sequences from PWID together with unrelated genotype 3a sequences from a public database showed a scattered distribution without geographic clustering. Viral polymorphisms A30K and Y93H known to confer resistance in a GT3a replication model were present in 8 subjects (7.2%). Conclusions A protocol for amplification of nearly all GT3a samples was successfully established. Substitutions conferring resistance to NS5A inhibitors were detected in a few treatment-naive PWID.

Dieser Beitrag entwickelt unter Bezugnahme auf politologische und soziologische Diskurse ein spezifisches Verstandnis von Sozialmanagement, genauer als Steuerung hybrider sozialwirtschaftlicher Organisationen. Ausgehend von der breiten Diskussion um (Sozial-)Managementkonzepte „fur und in der Sozialwirtschaft“ pladieren wir fur einen Zugang, der die vielfaltigen Spannungsfelder, in denen sich sozialwirtschaftliche Einrichtungen bewegen (und bewahren mussen), aufnimmt und mit einem spezifischen Organisations- und Managementverstandnis verknupft.

A preventive effect of early human cytomegalovirus (HCMV) replication was evaluated in 136 non-Hodgkin lymphoma (NHL) patients with mature B-cell NHLs (n = 94), and mature T- and NK-cell NHLs (n = 42) after allogeneic stem cell transplantation (alloSCT). Most study-patients (85%) had received at least 2 cycles of chemotherapy and 60% had also received an autograft prior to alloSCT. First detection of CMV-replication by HCMV antigenemia/viremia was found at a median of day +33 after alloSCT. The cumulative incidence of relapse at 5 years after alloSCT was 38% (95% confidence interval [95%CI]: 26–49) in 82 patients without compared to 22% (95%CI: 8–37) in 54 patients with HCMV antigenemia/viremia (p = .013). A decreased relapse risk of HCMV replication was confirmed by multivariate analysis for HCMV antigenemia/viremia (Hazard ratio [HR]: 0.29, 95%CI: 0.11–0.76, p

„Demografischer Wandel“, „Differenzierung“, „Individualisierung“ und „Selbstbestimmungswille“ - mit diesen Stichworten wurde einleitend die aktuelle gesellschaftliche Entwicklung skizziert. Vor diesem Hintergrund erweist sich die Gewahrleistung von Versorgung alterer Menschen als zunehmend komplexe Herausforderung. Dabei geht es auch, aber keineswegs allein um gesundheitliche Versorgung. Hinzu kommen die Bereiche Wohnen, Freizeitgestaltung usw.

Background/Aims While the adaptive immune response is crucial for spontaneous resolution of acute hepatitis C virus (HCV) infection, it also constitutes the driving force for viral escape. For acutely HCV-infected dialysis patients, little is known about the host response and its impact on viral evolution. Methods Four haemodialysis patients accidentally infected with the same HCV strain were prospectively investigated with respect to the clinical course, CD4+ and CD8+ T-cell responses, neutralizing antibodies, viral kinetics and sequence variability. Results In one patient, a robust CD4+ T-cell response was associated with transient control of infection, while in the other patients, weak responses correlated with persistently high viremia. Despite the presence of CD8+ T-cell effectors in the first patient, no sequence differences were detected in targeted regions of the viral genome in any of the patients when viral persistence was established. Genetic stability in the envelope genes, including the hypervariable regions, correlated with low-level or absent neutralizing antibodies in all of the patients. Conclusions The establishment of viral persistence in the special patient group of dialysis patients is due to a failure of the adaptive immune system, as shown by the absence of significant T-cell and antibody responses, as well as viral variability.

OA hybrid The idea of collecting blood on a paper card and subsequently using the dried blood spots (DBS) for diagnostic purposes originated a century ago. Since then, DBS testing for decades has remained predominantly focused on the diagnosis of infectious diseases especially in resourcelimited settings or the systematic screening of newborns for inherited metabolic disorders and only recently have a variety of new and innovative DBS applications begun to emerge. For many years, pre-analytical variables were only inappropriately considered in the field of DBS testing and even today, with the exception of newborn screening, the entire pre-analytical phase, which comprises the preparation and processing of DBS for their final analysis has not been standardized. Given this background, a comprehensive step-by-step protocol, which covers al the essential phases, is proposed, i.e., collection of blood; preparation of blood spots; drying of blood spots; storage and transportation of DBS; elution of DBS, and finally analyses of DBS eluates. The effectiveness of this protocol was first evaluated with 1,762 coupled serum/DBS pairs for detecting markers of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infections on an automated analytical platform. In a second step, the protocol was utilized during a pilot study, which was conducted on active drug users in the German cities of Berlin and Essen.

The major aim of the project was the development of virus-like particles (VLP) displaying B- and T-cell epitopes of hepatitis C virus (HCV) proteins. To this end, hepatitis B virus core (HBc) particles were used as a carrier of HCV epitopes. Fragments of HCV genes encoding core (aa 98) and NS3 (aa 155) proteins were fused to the 3' terminus of the truncated HBV core gene. All recombinant plasmids led to relatively high levels of expression of chimeric proteins in E. coli, which resulted in the formation of complete "mature" VLP. Chimeric HBc/HCV VLPs were purified by combination of gel filtration and sucrose gradient centrifugation, and used for immunogenicity studies in mice. All variants of hybrid particles induced high humoral and cellular responses to HBcAg. Immunization with the HBc/HCV core particles led to relatively low antibody and T-cell proliferative responses to HCV core epitopes. The HBc/HCV NS3 particles were able to induce high levels of anti-NS3 antibodies in the absence of proliferative responses to HCV epitopes. Thus, the results of the current study have demonstrated the principal possibility of using VLP on the basis of HBcAg for creation of a new type of HCV-specific immunogen.

GBV-B, a member of the Flaviviridae family of viruses, is the virus most closely related to HCV, and GBV-B infection in tamarin monkeys might represent a valuable surrogate animal model of HCV infection. In the current study, GBV-B was successfully transmitted to two marmosets (Callithrix jaccus). The infection resulted in viremia of 14- and 17-week duration, respectively, and was accompanied by elevation of isocitrate dehydrogenase activity. These data confirm that marmosets might represent an attractive model for GBV-B infection. The sequence of GBV-B NS5A, which was previously reported to have one of the highest mutation rates during infection in tamarins, was determined for viruses recovered from the inoculum and from marmoset blood samples obtained at weeks 1, 8, and 14 post inoculation in one marmoset and at weeks 2, 8, and 17 post inoculation in the other marmoset. In both animals, we detected four substitutions (R1945K, K2052G, F2196L, and G2268E), in the virus recovered immediately before viral clearance. Interestingly, two of these mutations (F2196L and G2268E) were described recently for viruses recovered from persistently infected tamarins. Appearance of these mutations presumably reflects a mechanism of immune escape rather than adaptation of the virus to a new host.

Hospital-acquired hepatitis B (HBV) and C virus (HCV) infections continue to occur despite increased awareness of this problem among the medical community. One hundred six patients were infected in a haematology oncology ward for children, over the time period 1996 to 2000. Serum samples from 45 such patients and 3 from infected medical personnel were used for nucleic acid amplification. HBV core, as well as HCV core and hypervariable region 1 (HVR1) nucleotide sequences, were analysed by phylogenetic tree analysis, in order to characterise the epidemiological pattern of viral transmission on the ward. Samples from 32 patients were positive for HBV-DNA or HCV-RNA by PCR. Ten patients were positive for both markers. Seventeen out of twenty-three HCV core gene sequences were found to be evolutionarily related and clustered separately from other local sequences in the phylogenetic tree, indicating nosocomial transmission. This was confirmed by analysis of HVR1 gene sequences. One nurse and one physician from the ward were HCV RNA positive, but their HCV sequences were not related evolutionarily to those of the patient cluster. Fifteen out of nineteen HBV core gene sequences were also clustered together and were positioned separately in the relevant tree. Epidemiological investigation excluded a common source infection and indicated that spread of infection was most likely due to inappropriate infection control measures on the ward. No obvious risk factors for transmission were identified during the retrospective survey in patients with related sequences, except use of multidose vials for saline and poor staff compliance with routine hand hygiene procedures. The preventive measures that were introduced reduced the incidence of infection significantly. No new cases of HBV infection and only three anti-HCV seroconversions occurred over a period of 19 months. The introduction and maintenance of strict prevention measures over a 2 year period, combined with HBV vaccination, reduced significantly the incidence of new HCV and HBV infections.

Background: In 1997 a new human virus, TTV, was identified. The clinical significance of the TTV infection, however, remains unknown. Objective: Establishment of the prevalence of TTV DNA in different population groups in Germany and the assessment of the possible clinical significance of TTV infection. Study design: Detection of the TTV DNA by PCR in blood donors, patients with end-stage liver disease, and multiple transfused patients with haemotological disorders. Results: TTV DNA was detected in 16 of 122 (13.1%) volunteer blood donors, in 34 of 77 (44.2%) patients with end-stage liver disease, and in 21 of 38 (55.3%) multiple transfused patients. There was no difference in the prevalence of the TTV DNA in end-stage liver disease patients with regard to sex, age, presence of HCV and HBV infection markers, and etiology of liver disease. Phylogenetic analysis of the amplified DNA fragments from 12 randomly selected TTV infected subjects demonstrated that in Germany at least two putative TTV genotypes and four subtypes are circulating. Conclusions: (i) TTV is widely spread in German population; (ii) one of the possible ways of its transmission is blood transfusion; (iii) TTV infection most probably does not generally lead to the development of the end-stage liver disease.

In order to assess the human medical significance of the rabies zoonosis in Germany, the data of the relevant surveillance and of the registration systems as well as prescriptions submitted to the statutory health insurance (SHI) were assessed. In all, 2441 of the 81 280 total examinations for rabies conducted on animals were performed subsequent to contact with humans. In this context 54% of exposures were attributed to wild animals and 46%, to domestic animals. In 2006 and 2007 there were still 0.42 and 0.34 veterinary medical analyses per 100 000 inhabitants, respectively, subsequent to human contact. After the proclamation that Germany was free of terrestrial rabies, these indices dropped to 0.2 in 2009 and 2010. During the survey period, 21 700 doses of rabies vaccine were issued annually for SHI prescriptions on average; they would have been adequate for approximately 7230 complete courses of rabies pre-exposure prophylaxis or 4340 complete post-exposure treatments. For which of these two principal indications the vaccines were actually used cannot be determined from the SHI prescriptions. Taken together, the officially available data from rabies surveillance or registration systems even in combination with a nearly complete record of SHI prescription numbers did not allow an even nearly adequate reconstruction of the human medical significance of the rabies zoonosis in Germany. If one desired to achieve this, one would have to use, for example, an approach that is known from other European countries such as France, Finland, or The Netherlands.

To examine the tissue samples of 2 corneal recipients from a rabies-infected donor for the presence of rabies to explain their survival.Interventional case series with a review of the literature. The explanted corneal donor buttons were examined via nested reverse transcriptase polymerase chain reaction. The patients were followed up ophthalmologically and neurologically. Antirabies antibodies were measured in blood samples, and skin biopsies were examined by direct fluorescent antibody staining.Two patients received corneas from the same multiorgan donor. Six weeks after transplantation, 3 of the donor's organ recipients became symptomatic and rabies virus was confirmed in tissue from the donor's central nervous system. Immediately, both the corneal recipients underwent active and passive postexposure treatment. The corneal buttons were replaced. Examination of the explanted donor corneas, skin biopsies, and serum and saliva samples showed no signs of rabies infection. The 2 corneal recipients were followed up at our hospital and, to date, are without symptoms of infection.Transmission of the potentially deadly rabies virus by corneal transplantation has been described previously. To our knowledge, this is the first report in which no rabies virus transmission occurred without immediate postexposure treatment.

Hepatitis D virus (HDV) infection is an important etiologic agent of fulminant hepatitis and may aggravate the clinical course of chronic hepatitis B infection resulting in cirrhosis and liver failure. This report describes the establishment of a real-time reverse transcriptase polymerase chain reaction method that allows the quantitative detection of HDV-1 and HDV-3 with a sensitivity in a linear range of 2 x 10(3) to 10(8) copies/mL. Additionally, the new assay provides the opportunity to distinguish HDV-1 from HDV-3 by a subsequent melting curve analysis, an important option because these HDV types are highly associated with severe clinical outcome. The results of the melting curve analysis of 42 HDV sequences obtained in this study and the phylogenetic analysis based on 139 full-length sequences from GenBank were consistent and showed that all sequences described here cluster within the HDV-1 clade. Therefore, this assay is useful for monitoring of antiviral treatment and molecular epidemiologic studies of HDV distribution.

BACKGROUND: Blood donors with indeterminate hepatitis C virus antibody (anti-HCV) reactivity are rejected from blood donation. As they are mostly nonviremic, the source of these reactions remains unclear. Reasons for such findings can be resolved HCV infections as well as unspecific antibody reactions. The aim of this study was to investigate HCV-specific T-cell response in blood donors to determine the reason for the weak antibody detection. STUDY DESIGN AND METHODS: Anti-HCV reactivity was tested in 72 blood donors initially diagnosed with an indeterminate HCV result by enzyme-linked immunosorbent assay and immunoblot. Cellular immune response was measured by proliferation assay and enzyme-linked immunosorbent spot analysis after stimulation with viral proteins core, NS3, and NS4. RESULTS: In 56% of donors anti-HCV reactivity was detectable in the screening assay whereas 72% had a reaction in the confirmation immunoblot. Forty-six percent of donors had a cellular immune response against HCV proteins. The response was most frequent to NS3 protein. CONCLUSION: In almost half of donors the indeterminate result in serologic testings could be explained by a previous resolved HCV infection as the pattern of T-cell response was similar to these patients. These findings indicate that HCV-specific antibodies disappear more rapidly after resolved infection than HCV-specific T cells. These results are important for counseling blood donors and patients with indeterminate serologic results.