A rapid test recognizing mucosal SARS-CoV-2-specific antibodies distinguishes prodromal from convalescent COVID-19.

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.

Over 90% of clinical swabs used for SARS-CoV-2 diagnostics contain sufficient nucleic acid concentrations.

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.

[Rapid diagnosis of sexually transmitted infections : Joint statement of DSTIG, RKI, and PEI, as well as the reference centers for HIV, HBV, and HCV and consulting laboratories for Chlamydia, gonococci, and Treponema pallidum]. / Schnelltestdiagnostik sexuell übertragbarer Infektionen : Gemeinsame Stellungnahme von DSTIG, RKI, PEI sowie den Referenzzentren für HIV, HBV und HCV und Konsiliarlaboren für Chlamydien, Gonokokken und Treponema pallidum.

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.

History of detention and the risk of hepatitis C among people who inject drugs in Germany.

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.

Schnelltest-Diagnostik sexuell übertragbarer Infektionen in niedrigschwelligen Einrichtungen : Gemeinsame Stellungnahme des RKI, PEI und der DSTIG.

On February 5th, 2016 an expert meeting on rapid diagnostic tests (RDT) for sexually transmitted infections (STI) was held in Berlin at the Robert-Koch-Institute. The aim of the conference was to update a former evaluation of RDTs for diagnosis of HIV, HBV, HCV, T. pallidum, C. trachomatis and N. gonorrhoeae in low-threshold counseling services for STI that had been published after the previous meeting in 2012. According to the strategy to control HIV, hepatitis B and C and other STI, recently adopted by the German Government, there is a lack of test capabilities and a demand for more testing services as well as improved access to testing. Using RDTs as low-threshold test services in counseling centers or even for testing at home may provide an important option to lower the barrier of testing. Based on performance data evaluated in clinical trials some RDTs for HIV, HCV and syphilis are quite well suited as a point-of-care Test (POCT). In contrast, sufficient diagnostic accuracy for detection of C. trachomatis and N. gonorrhoeae can only be achieved by PCR-based POCTs. In Germany the use of POCTs is subjected to legal stipulations of IfSG and MPG. Of importance, it is not allowed to deliver HIV tests to private persons for home testing (§ 11, MPG). Furthermore, both assessment and communication of infectious diseases are reserved to the physician and must not happen as remote diagnostics (§ 24, IfSG). In addition, like all laboratory tests, RDTs are subject to quality assessment according to guidelines of the German Medical Association.

High variability of HIV and HCV seroprevalence and risk behaviours among people who inject drugs: results from a cross-sectional study using respondent-driven sampling in eight German cities (2011-14).

BACKGROUND: People who inject drugs (PWID) are at increased risk of acquiring and transmitting HIV and Hepatitis C (HCV) due to sharing injection paraphernalia and unprotected sex. To generate seroprevalence data on HIV and HCV among PWID and related data on risk behaviour, a multicentre sero- and behavioural survey using respondent driven sampling (RDS) was conducted in eight German cities between 2011 and 2014. We also evaluated the feasibility and effectiveness of RDS for recruiting PWID in the study cities. METHODS: Eligible for participation were people who had injected drugs within the last 12 months, were 16 years or older, and who consumed in one of the study cities. Participants were recruited, using low-threshold drop-in facilities as study sites. Initial seeds were selected to represent various sub-groups of people who inject drugs (PWID). Participants completed a face-to-face interview with a structured questionnaire about socio-demographics, sexual and injecting risk behaviours, as well as the utilisation of health services. Capillary blood samples were collected as dried blood spots and were anonymously tested for serological and molecular markers of HIV and HCV. The results are shown as range of proportions (min. and max. values (%)) in the respective study cities. For evaluation of the sampling method we applied criteria from the STROBE guidelines. RESULTS: Overall, 2,077 PWID were recruited. The range of age medians was 29-41 years, 18.5-35.3 % of participants were female, and 9.2-30.6 % were foreign born. Median time span since first injection were 10-18 years. Injecting during the last 30 days was reported by 76.0-88.4 % of participants. Sharing needle/syringes (last 30 days) ranged between 4.7 and 22.3 %, while sharing unsterile paraphernalia (spoon, filter, water, last 30 days) was reported by 33.0-43.8 %. A majority of participants (72.8-85.8 %) reported incarceration at least once, and 17.8-39.8 % had injected while incarcerated. Between 30.8 and 66.2 % were currently in opioid substitution therapy. Unweighted HIV seroprevalence ranged from 0-9.1 %, HCV from 42.3-75.0 %, and HCV-RNA from 23.1-54.0 %. The implementation of RDS as a recruiting method in cooperation with low-threshold drop in facilities was well accepted by both staff and PWID. We reached our targeted sample size in seven of eight cities. CONCLUSIONS: In the recruited sample of mostly current injectors with a long duration of injecting drug use, seroprevalence for HIV and HCV varied greatly between the city samples. HCV was endemic among participants in all city samples. Our results demonstrate the necessity of intensified prevention strategies for blood-borne infections among PWID in Germany.

Concordance between self-reported and measured HIV and hepatitis C virus infection status among people who inject drugs in Germany.

BACKGROUND: People who inject drugs (PWID) are disproportionately affected by both HIV and hepatitis C infection (HCV). Awareness of infection status is essential to ensure linkage to appropriate healthcare for those infected, who need treatment and regular follow-up, as well as for uninfected individuals, who need access to targeted testing and counselling services. In this paper we compare self-reported HIV and HCV status with serological markers of infection among PWID recruited through respondent driven sampling. METHODS: From 2011 through 2014, biological and behavioural data was collected from 2,077 PWID in Germany. Dried blood spots from capillary blood samples were collected and screened for HCV antibodies, HCV RNA and HIV-1/-2 antibodies. HIV reactive samples were confirmed by Western blot. RESULTS: Laboratory testing revealed that 5 % were infected with HIV and 81 % were aware of being infected. Chronic HCV infection was detected in 41 % of the participants, 2 % had an acute HCV infection, 22 % had a cleared infection, and 34 % were unexposed to HCV. The concordance between self-reported and measured HCV status was lower than for HIV, with 73 % of those with chronic HCV infection being aware of their infection. CONCLUSIONS: We found a relatively high awareness of HIV and HCV infection status among PWID. Nevertheless, access to appropriate testing, counselling and care services targeted to the needs of PWID should be further improved, particularly concerning HCV. TRIAL REGISTRATION: Ethical approval was received from the ethics committee at the medical university of Charité, Berlin, Germany in May 2011 and with an amendment approved retrospectively on 19/11/2012 (No EA4/036/11). The German Federal Commissioner for Data Protection and Freedom of Information approved the study protocol retrospectively on 29/11/2012 (III-401/008#0035).

Instructive even after a decade: Complete results of initial virological diagnostics and re-evaluation of molecular data in the German rabies virus "outbreak" caused by transplantations.

In 2005, six patients in Germany received solid organs and both corneas from a donor with an unrecognized rabies infection. Initial virological diagnostics with the machinery available at the two national reference laboratories could quickly clarify the situation. Rabies virus antigen was detected in the organ donor's brain. In two of the three recipients with neurological alterations, intra vitam diagnosis was achieved by conventional RT-PCRs. Comparison of the phylogenetic relatedness of the different viral isolates proved transmission from the donor and, consequently, also established the diagnosis for the third patient. As indicated by the titre of neutralizing antibodies, the liver transplant recipient was protected from the lethal infection due to a vaccination against rabies virus, which he had received more than 15 years ago. All samples from the recipients of the corneas were invariably negative. Re-evaluation of the molecular data by real-time PCR did not lead to an improvement of intra vitam diagnosis but provided intriguing insights regarding the relative amounts of rabies virus RNA in different body fluids and peripheral organs. In saliva and skin, they were 250-200,000 times lower than in the infected patient's brains. Furthermore, in saliva samples taken serially from the same patient fluctuations by a factor of 160-500 were recorded. These findings highlight the problems of intra vitam diagnosis of rabies virus infections and make understandable why the virus can escape from all diagnostic attempts. Finally, in this context one should recall an almost trivial fact: Simple and appropriate postexposure prophylaxis could not only have saved the young organ donor's life but would also have prevented the whole transplantation-associated rabies "outbreak" in Germany.

Performance characteristics of the VERSANT hepatitis C virus RNA 1.0 (kPCR) assay.

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.

Natural prevalence of resistance-associated variants in hepatitis C virus NS5A in genotype 3a-infected people who inject drugs in Germany.

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-naïve 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.

Dried blood spots--preparing and processing for use in immunoassays and in molecular techniques.

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 resource-limited 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.

A multicentre sero-behavioural survey for hepatitis B and C, HIV and HTLV among people who inject drugs in Germany using respondent driven sampling.

BACKGROUND: People who inject drugs are at high risk for hepatitis B, hepatitis C and HIV. HTLV was reported by neighboring countries to be prevalent in this population, but the situation for Germany is unclear. To generate seroprevalence and related behavioural data and to enhance prevention efforts against these infections for drug users in Germany, a multicentre sero- and behavioural survey was initiated. People who inject drugs are not well reached by services for testing and counselling for blood-borne infections in Germany. An interventional part of the study is intended to prove feasibility and acceptance of testing and counselling in low-threshold drop-in settings. METHODS/DESIGN: Between May 2011 and March 2015, eligible participants (persons having injected drugs within the last 12 months, aged 16 years+, and living in the study city) are recruited by respondent driven sampling, using low-threshold drop-in facilities as study-sites in eight German cities with large drug scenes. Calculated sample size is 2,033 participants. Capillary blood samples collected as dried blood spots are anonymously tested for serological and molecular markers of hepatitis B and C, HIV, and HTLV I and II. A detailed face-to-face-interview about hepatitis- and HIV-related knowledge, former testing, imprisonment, sexual and injecting risk behaviour is conducted with participants. Staff is trained to offer pre- and post-test-counselling of blood-borne infections and HIV rapid testing to participants. DISCUSSION: We chose respondent driven sampling for recruitment of participants to improve representativeness of results. Persons, who are not reached by the facility where the study is conducted, are aimed to be included by recruitment through their personal social network of injecting drug users. To reduce differential biases in the questions on knowledge of transmission and prevention of infections, we present true statements on hepatitis B, C and HIV, their possible routes of transmission and measures of prevention to participants. Participants are told that the statements are true and are asked to answer if they knew this fact already or if it is new to them. In case of knowledge gaps they are offered free targeted counselling as well as free HIV rapid testing and post-test counselling of HIV and hepatitis test results.

Detection of infections with hepatitis B virus, hepatitis C virus, and human immunodeficiency virus by analyses of dried blood spots--performance characteristics of the ARCHITECT system and two commercial assays for nucleic acid amplification.

BACKGROUND: Nowadays, dried blood spots (DBS) are primarily used to obtain diagnostic access to risk collectives such as intravenous drug users, who are prone to infections with hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Before DBS analyses can be used in this diagnostic context, however, a comprehensive evaluation of its performance characteristics must be conducted. To the best of our knowledge, the current study presents for the first time such essential data for the Abbott ARCHITECT system, which is currently the worldwide leading platform in this field of infection diagnostics. METHODS: The investigation comprised 1,762 paired serum/DBS samples and a total of 3,524 determinations with the Abbott ARCHITECT HBsAg, anti-HBc, anti-HBs, anti-HCV and HIV-1-p24-antigen/anti-HIV 1/2 assays as well as with the artus HBV LC PCR and VERSANT HCV RNA qualitative (TMA) tests. RESULTS: In the context of DBS testing, a specificity of 100% was recorded for the seven serological and molecular biological assays. The analytical sensitivity of HBsAg, anti-HBc, anti-HBs, anti-HCV, HIV-1-p24-antigen/anti-HIV 1/2, HBV DNA, and HCV RNA detections in DBS eluates was 98.6%, 97.1%, 97.5%, 97.8%, 100%, 93%, and 100%, respectively. DISCUSSION/CONCLUSIONS: The results obtained indicate that it is today possible to reliably detect HBsAg, anti-HBc, anti-HBs, anti-HCV and HIV-1-p24 antigen/anti-HIV 1/2 with state-of-the-art analytical systems such as the Abbott ARCHITECT in DBS eluates even when a comparatively high elution volume of 1,000 µl is used. They also provide evidence for the inherent analytical limits of DBS testing, which primarily concern the anti-HBc/anti-HBs system for individuals with HIV infections and nucleic acid tests with relatively low analytical sensitivity.

Assessment of the human medical significance of the rabies zoonosis in Germany--analysis of available data and desiderata.

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.

Survival after transplantation of corneas from a rabies-infected donor.

PURPOSE: To examine the tissue samples of 2 corneal recipients from a rabies-infected donor for the presence of rabies to explain their survival. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparative evaluation of the immunogenicity of combined hepatitis A and B vaccine by a prospective and retrospective trial.

In the past, immunogenicity of hepatitis A and B vaccines needed to be questioned in persons of advanced age, especially in those of 40 years and older. We performed a comparative multicenter prospective and retrospective study with the combined hepatitis A and B vaccine Twinrix to identify factors influencing the results of the vaccination in a population of all age groups. Out of 489 subjects enrolled, 241 were vaccinated in a prospective study (group 1) and 248 subjects in a retrospective study (group 2) in 17 German centers with median age of 40.1 (14-79) years. Following three applications of the combined hepatitis A/B vaccine we found 96.2% with protective antibodies against HAV and 88.7% were protected against HBV. With increasing age the subjects developed decreasing anti-HBs antibody levels whereas the seroprotection rate was significantly reduced by age (p < 0.05) in the retrospective study group only. Subjects with arterial hypertension and thyroid disease showed significantly decreased protection rates. The timing of the HBV antibody control seems to be important especially in low-responders because protective antibodies may drop below the detection limit within some month. The combined hepatitis A and B vaccine Twinrix proved to be highly effective against HBV, although antibody concentrations and seroprotection rates decreased with increasing age.

Awareness of rabies risks and knowledge about preventive measures among experienced German travel health advisors.

BACKGROUND: Every year, millions of people travel to countries where rabies is enzootic. However, the quality of rabies-specific information provided by travel health advisors and the extent of their knowledge about pre- and postexposure prophylaxis have not been examined on a large-scale basis up to now. METHODS: 5,780 German physicians and pharmacists, who identified themselves as active travel health advisors, were chosen from a database. The selected providers were asked to complete an Internet-based questionnaire. The form requested both demographic information and the assessment of different concrete scenarios, each of which featured individuals seeking pre-travel advice on rabies or appropriate postexposure treatment after returning from abroad. RESULTS: Overall, 496 physicians and pharmacists completed the questionnaire. Almost all respondents indicated that they would mention the risk of rabies and appropriate preventive measures to long-term travelers and tourists planning to visit rural areas. However, only 35% to 60% of the advisors would provide this information to individuals on business trips, package tours, or travelers in urban centers as well. The assessment of the scenarios yielded 51% to 98% of adequate advice. Potentially harmful decisions included, for instance, the failure to recommend further prophylactic measures after exposure of already vaccinated people or the fact that the necessary postexposure prophylaxis was inappropriately withheld in cases where treatment had been initially delayed. CONCLUSIONS: Although the participants of this study were well aware of the travel-associated rabies risks and provided adequate information about this health hazard to most of their clients, evident flaws exist regarding the correct assessment of specific situations in pre- and postexposure rabies prophylaxis. Our findings therefore provide important cues on topics that should be more intensely covered during future postgraduate training in travel medicine and also underline the need for more practically orientated, readily available information on specific prophylactic treatment against rabies.

Cyclosporine versus tacrolimus in patients with HCV infection after liver transplantation: effects on virus replication and recurrent hepatitis.

AIM: To determine the effects of the calcineurin inhibitors, cyclosporine and tacrolimus, on hepatitis C virus (HCV) replication and activity of recurrent hepatitis C in patients post liver transplantation. METHODS: The data of a cohort of 107 patients who received liver transplantation for HCV-associated liver cirrhosis between 1999 and 2003 in our center were retrospectively analyzed. The level of serum HCV-RNA and the activity of recurrent hepatitis were compared between 47 patients who received either cyclosporine or tacrolimus as the primary immunosuppressive agent and an otherwise similar immunosuppressive regimen which did not lead to biliary complications within the first 12 mo after transplantation. RESULTS: HCV-RNA increased within 3 mo after transplantation but the differences between the cyclosporine group and the tacrolimus group were insignificant (P=0.49 at 12 mo). In addition, recurrent hepatitis as determined by serum transaminases and histological grading of portal inflammation and fibrosis showed no significant difference after 12 mo (P=0.34). CONCLUSION: Cyclosporine or tacrolimus as a primary immunosuppressive agent does not influence the induction or severity of recurrent hepatitis in HCV-infected patients after liver transplantation.