[Postexposure prophylaxis after bite of a broad-winged bat with evidence of European bat lyssavirus 1 (EBLV-1)]. / Postexpositionsprophylaxe nach Biss einer Breitflügelfledermaus mit Nachweis des Europäischen Fledermaus-Lyssavirus 1 (EBLV-1).

Germany has been considered free of terrestrial rabies since 2008 as a result of intensive vaccination and surveillance efforts but reservoirs of the lyssaviruses EBLV­1 and EBLV­2 persist in bat colonies and thus pose a potential risk of infection. We report on a patient who suffered a bat bite in an urban setting in which European bat lyssavirus 1 (EBLV-1) was detected in the euthanized bat. We performed active and passive postexposure prophylaxis (PEP). This case study illustrates the ongoing risk of rabies infection due to close bat contacts in Germany and is intended to sensitize primary care physicians to take such exposure events seriously and to perform a regular PEP including administration of rabies immunoglobulin.

Chylothorax due to hepatic alveolar echinococcosis with infiltration of diaphragm and left pleura: a case report.

BACKGROUND: Alveolar echinococcosis (AE) is an endemic parasitic zoonosis in Germany. In most cases, the liver is the primary organ affected. CASE PRESENTATION: A 59-year old female patient presented with increasing exertional dyspnea and unintentional weight loss. A computed tomography (CT) scan showed a left-sided chylous pleural effusion and multiple intrahepatic masses with infiltration of the diaphragm and the pleura. The findings were initially misinterpreted as hepatocellular carcinoma (HCC) with infiltrating growth. Liver biopsy of one of the masses showed no evidence of malignancy, but an amorphous necrosis of unclear origin. HCC was further ruled out by magnetic resonance imaging (MRI). However, MRI findings were highly suspicious for hepatothoracic dissemination and complications due to AE. Typical histologic findings in a repeated and more specific examination of the liver tissue and a positive serology for echinococcosis confirmed the diagnosis of AE. As the hepatic and pulmonary manifestations were considered inoperable in a curative matter, an anti-parasitic treatment with albendazole was initiated. A video-assisted thoracoscopic surgery (VATS) with removal of the chylous effusion as well as a talc pleurodesis was performed to relieve the patient from dyspnea. Two months later, the patient was asymptomatic and a positron emission tomography (PET)-CT-scan with [18 F] fluoro-2-deoxy-d-glucose (FDG) showed a remarkable diminution of the hepatic manifestation. CONCLUSIONS: This case demonstrates a rare presentation of alveolar echinococcosis with a focus on pulmonary symptoms, emphasizing the importance of evaluation for pulmonary involvement in patients with AE and respiratory symptoms.

Fever in the Returning Traveler.

BACKGROUND: It is predicted that approximately two billion tourist trips to foreign countries will be taken worldwide each year by 2030. Germany has long been among the most active countries in tourism. The frequency of illness among persons returning from developing and newly industrialized countries is 43-79%. The appropriate diagnosis of fever in returning travelers is a clinically important matter, as it can be a sign of a life-threatening illness. METHODS: This review is based on publications (2001-2022) retrieved by a selective search in PubMed for studies on the epidemiology, diagnosis, and treatment of febrile illnesses in returning travelers, or on specific tropical diseases. RESULTS: Diarrhea, fever, and skin changes are the most common manifestations of disease after travel to tropical and sub - tropical areas. The diagnostic evaluation should be performed in a series of steps, beginning with a precise travel history and the identification of specific risk factors. Among travelers returning from sub-Saharan Africa, Plasmodium falciparum malaria is the most common cause of fever on presentation to centers for infectious diseases and tropical medicine, affecting approximately 50 per 1000 travelers. Among persons returning from travel to Southeast Asia, dengue fever is the most common infectious disease, affecting 50-160 per 1000 travelers. Further potentially dangerous diseases include chikungunya and zika fever, typhoid and paratyphoid fever, amoebic liver abscess, visceral leishmaniasis (kala-azar), leptospirosis, and, very rarely, imported cases of viral hemorrhagic fever. COVID-19 and influenza are important differential diagnoses. CONCLUSION: The differential diagnosis can be narrowed by thorough history-taking with particular attention to the patient's travel route, combined with a good knowledge of the geographic spread and incubation times of the main tropical diseases. Algorithms help clinicians to focus the diagnostic work-up and select the appropriate further laboratory tests and diagnostic procedures.

Antibody Course and Memory B-Cell Response in the First Year After Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: The possibility of repeat infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raises questions regarding quality and longevity of the virus-induced immune response. METHODS: The antibody course and memory B-cell (MBC) response against SARS-CoV-2 proteins, influenza virus nucleoprotein (NP), and tetanus toxin were examined in adults with mild to moderate SARS-CoV-2 infection in the first year after infection. RESULTS: The concentration of SARS-CoV-2 receptor binding domain (RBD)-specific antibodies was low compared with the concentration of influenza virus NP-specific antibodies. The SARS-CoV-2 RBD antibody half-life increased from 95 days in the first 6 months to 781 days after 9-12 months. The SARS-CoV-2 NP antibody half-life increased from 88 to 248 days. Two thirds of the subjects had SARS-CoV-2-specific MBC responses 12 months after infection. The SARS-CoV-2 antibody levels correlated with the MBC frequency at 12 months. CONCLUSIONS: The low concentration of SARS-CoV-2 spike protein antibodies indicates that re-exposure to the virus or vaccination are required to use the B-cell immunity to full capacity. The existence of a robust SARS-CoV-2 MBC response at 12 months in most subjects and the substantially increasing antibody half-life provide evidence that the immune response is developing into long-term immunity. The early antibody reaction and the ensuing MBC response are interdependent.

Diagnostic Specificity of Two Dengue Virus IgG ELISAs after Yellow Fever and Japanese Encephalitis Virus Vaccination.

Dengue virus (DENV) antibody assays frequently cross-react with sera from individuals who have been infected with or vaccinated against related flaviviruses. The goal of this study was to determine the specificity of two DENV ELISAs with sera from individuals vaccinated against yellow fever virus (YFV) and Japanese encephalitis virus (JEV). The Panbio and the Novatec Dengue IgG ELISAs were tested with sera obtained 3-4 weeks or 0.5-6 years after YFV or JEV vaccination and the diagnostic specificity of the assays was determined. As controls, the sera were tested using DENV, YFV, JEV, Zika and West Nile virus neutralization assays. The diagnostic specificity of the Panbio and the Novatec ELISA with sera from YFV-vaccinated subjects was 98.2% and 88.2%, respectively. Cross-reactions were rare in the first 4 weeks despite high YFV-neutralizing antibody titers and were mostly found later. The specificity of the Panbio and Novatec assays with sera from JEV-vaccinated individuals was 100% and 92.9%. Cross-reactions occurred in the early time period after vaccination. The measurement values of the two ELISAs correlated strongly. Thus, the Panbio ELISA showed higher diagnostic specificity and may be suitable for seroprevalence studies in areas with high disease prevalence.

[Vaccinations]. / Impfungen.

Vaccination is considered one of the most important achievements of modern medicine and has saved millions of lives. As a result, the age-old fear of severe or fatal infectious diseases has largely been forgotten in society; however, the pandemic triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shows how quickly this fear can return. Also, many people have reservations about medical measures, especially if they are directed against vague dangers. Paradoxically, the success of vaccinations jeopardizes the acceptance. To counteract this development, this article provides information on basic vaccination principles, legal frameworks and components of vaccines. It explains the most important categories, goals, core elements of vaccination programs and the most important recommendations of the Standing Committee on Vaccination at the Robert Koch Institute (STIKO). It explains the current state of knowledge with respect to required resources, assessment of vaccine reactions, complication management and possible vaccine damage.

Current pharmacotherapy of cryptosporidiosis: an update of the state-of-the-art.

Introduction: Cryptosporidiosis has emerged as a major cause of diarrheal disease worldwide. It has especially serious health consequences for young, malnourished children living in endemic areas and for individuals with highly impaired T-cell function, such as HIV-positive individuals with low CD4 counts or immunosuppressed solid-organ transplant recipients.Areas covered: A selective literature search using PubMed was performed to review the available therapeutics to treat cryptosporidiosis, as well as related advances in drug development.Expert opinion: The only FDA-approved antiparasitic treatment in immunocompetent patients is nitazoxanide; however, it has failed to demonstrate convincing effectiveness among HIV-positive patients, immunosuppressed individuals and malnourished children. Thus, restoring HIV-positive patients' cellular immune response through effective antiretroviral therapy (ART), or reducing or changing immunosuppressive drugs, is important. Several new targets have been identified for chemotherapy, and the development of drugs for these targets has progressed, including parasite kinases, nucleic acid synthesis and processing, proteases and lipid metabolism. Candidate drugs that have been shown to be effective and safe in a neonatal calf model will most likely constitute the next advance for clinical trials in humans. However, developing an effective and inexpensive vaccination, as well as complementing structural preventive measures, would most decisively reduce the global cryptosporidiosis burden.

Performance of a SARS CoV-2 antibody ELISA based on simultaneous measurement of antibodies against the viral nucleoprotein and receptor-binding domain.

SARS CoV-2 antibody assays measure antibodies against the viral nucleoprotein (NP) or spike protein. The study examined if testing of antibodies against both antigens increases the diagnostic sensitivity. Sera (N=98) from infected individuals were tested with ELISAs based on the NP, receptor-binding domain (RBD), or both proteins. The AUROCs were 0.958 (NP), 0.991 (RBD), and 0.992 (NP/RBD). The RBD- and NP/RBD-based ELISAs showed better performance than the NP-based assay. Simultaneous testing for antibodies against NP and RBD increased the number of true and false positives. If maximum diagnostic sensitivity is required, the NP/RBD-based ELISA is preferable. Otherwise, the RBD-based ELISA is sufficient.

Medical Advice for Travelers.

BACKGROUND: In 2019, 1.5 billion international tourist trips were counted worldwide. Germany, with 70.8 million vacations lasting ≥ 5 days, was one of the populations most willing to travel. These days, even elderly and multimorbid persons regularly travel long-distance, which can be associated with significant health risks. By advising travelers and implementing preventive measures, the risk of illness can be reduced significantly. METHODS: A selective survey of PubMed was performed to identify publications on medical advice for travelers between 2000 and 2020. We included guidelines, studies, and recommendations that mainly deal with the preventive aspects of travel medicine and have a high level of practical relevance and the highest possible level of evidence. Previously published guidelines (based on the GRADE criteria) were adopted, and recommendations not based on the results of scientific studies were characterized as Good Clinical Practice (GCP). RESULTS: Many medical recommendations for travelers still rely on individualized, experience-based, or consensus-based assessments. Apart from a review of medical history and vaccination status, a risk analysis is performed, travel fitness is evaluated individually, and a prevention plan is designed. Particular attention is devoted to malaria prophylaxis, vector protection, and traveler's diarrhea. Medical advice before travel is especially important for the elderly, children, pregnant women, the chronically ill, long-term and adventure travelers as well as migrants from malaria-endemic areas who are returning home. CONCLUSION: The health risks associated with travel can be minimized by specialist medical advice. Many recommendations are empirical in nature and require further research.

Sensitivity of SARS-CoV-2 antibody tests with late convalescent sera.

SARS-CoV-2-specific IgM antibodies wane during the first three months after infection and IgG antibody levels decline. This may limit the ability of antibody tests to identify previous SARS-CoV-2 infection at later time points. To examine if the diagnostic sensitivity of antibody tests falls off, we compared the sensitivity of two nucleoprotein-based antibody tests, the Roche Elecsis II Anti-SARS-CoV-2 and the Abbott SARS-CoV-2 IgG assay and three glycoprotein-based tests, the Abbott SARS-CoV-2 IgG II Quant, Siemens Atellica IM COV2T and Euroimmun SARS-CoV-2 assay with 53 sera obtained 6 months after SARS-CoV-2 infection. The sensitivity of the Roche, Abbott SARS-CoV-2 IgG II Quant and Siemens antibody assays was 94.3% (95% confidence interval (CI) 84.3-98.8%), 98.1 % (95% CI: 89.9-100%) and 100 % (95% CI: 93.3-100%). The sensitivity of the N-based Abbott SARS-CoV-2 IgG and the glycoprotein-based Euroimmun ELISA was 45.3 % (95% CI: 31.6-59.6%) and 83.3% (95% CI: 70.2-91.9%). The nucleoprotein-based Roche and the glycoprotein-based Abbott receptor binding domain (RBD) and Siemens tests were more sensitive than the N-based Abbott and the Euroimmun antibody tests (p = 0.0001 to p = 0.039). The N-based Abbott antibody test was less sensitive 6 months than 4-10 weeks after SARS-CoV-2 infection (p = 0.0001). The findings show that most SARS-CoV-2 antibody assays correctly identified previous infection 6 months after infection. The sensitivity of pan-Ig antibody tests was not reduced at 6 months when IgM antibodies have usually disappeared. However, one of the nucleoprotein-based antibody tests significantly lost diagnostic sensitivity over time.

Autochthonous West Nile virus infection outbreak in humans, Leipzig, Germany, August to September 2020.

Following a distinct summer heat wave, nine autochthonous cases of West Nile fever and West Nile neuroinvasive disease, including one fatality, were observed in Leipzig, Germany, in August and September 2020. Phylogenetic analysis demonstrated close relationships in viruses from humans, animals and mosquitos in eastern Germany, obtained during the preceding 2 years. The described large cluster of autochthonous West Nile virus infections in Germany indicates endemic seasonal circulation of lineage 2 viruses in the area.

Comparison of the diagnostic sensitivity of SARS-CoV-2 nucleoprotein and glycoprotein-based antibody tests.

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) has been followed by the rapid development of antibody tests. To assess the utility of the tests for clinical use and seroepidemiologic studies, we examined the sensitivity of commercial antibody tests from Roche, Abbott, Novatec, Virotech Siemens, Euroimmun, and Mediagnost in a prospective diagnostic study. The tests were evaluated with 73 sera from SARS CoV-2 RNA positive individuals with mild to moderate disease or asymptomatic infection. Sera were obtained at 2-3 weeks (N = 25) or > 4 weeks (N = 48) after symptom onset and viral RNA test. The overall sensitivity of the tests ranged from 64.4-93.2%. The most sensitive assays recognized 95.8-100 % of the sera obtained after 4 weeks or later. Sera drawn at 2-3 weeks were recognized with lower sensitivity indicating that the optimal time point for serologic testing is later than 3 weeks after onset of the disease. Nucleoprotein- and glycoproteinbased assays had similar sensitivity indicating that tests with both antigens are suitable for serological diagnostics. Breakdown of the test results showed that nucleoprotein- and glycoprotein-based tests of comparable sensitivity reacted with different sets of sera. The observation indicates that a combination of nucleoprotein- and glycoprotein-based tests would increase the percentage of positive results.

A young woman from an Echinococcus-endemic area with progressive abdominal distension: a case report.

BACKGROUND: Cystic echinococcosis is a zoonotic infection caused by Echinococcus granulosus. This case report shows the difficulty in differential diagnosis in a patient with highly suspected hydatid disease. CASE PRESENTATION: A 29-year-old Chinese woman presented with progressive abdominal distension. Imaging results revealed a large multicystic tumor with typical features of hydatid disease. There was no clear relationship between the cystic tumor and the liver, which led to the assumption of primary extrahepatic cystic echinococcosis. After albendazole therapy was initiated, a laparotomy was performed and a huge ovarian cystadenoma was diagnosed. CONCLUSIONS: This case highlights the possible challenges of differential diagnosis in patients with suspicion of hydatid cysts.

[Typhoid and paratyphoid fever]. / Typhus abdominalis und Paratyphus.

Typhoid fever and paratyphoid fever are systemic infectious diseases of global significance caused by Salmonella enterica subspecies enterica Serovar Typhi (short name: Salmonella Typhi) or Serovar Paratyphi (short name: Salmonella Paratyphi). The course of these fecal-orally transmitted diseases is mainly characterized by a high fever. Left untreated, the course of typhoid fever can be severe and lethal. The infection is almost always acquired outside of Europe (mainly in India) and is notifiable in Germany, Austria and Switzerland. Paratyphoid is an attenuated disease of typhoid fever caused by Salmonella Paratyphi. Available vaccines only protect against Salmonella Typhi. Antibiotic resistance reflects the situation in endemic countries and shows a worrying increase of multi-drug resistant isolates. Currently, third-generation cephalosporins such as ceftriaxone are recommended as first-line therapy; if sensitive to quinolones, fluoroquinolones such as ciprofloxacin may continue to be administered. Crucial preventive measures for travelers to endemic regions include consistent water and food hygiene as well as vaccination, whereby only protection rates of 50-70 % are achieved by currently available vaccines. In the light of increasing multi-drug resistance, a more effective conjugate vaccine against Salmonella Typhi with cross-reactivity against Salmonella Paratyphi is needed more than ever.

Hospital-wide ELectronic medical record evaluated computerised decision support system to improve outcomes of Patients with staphylococcal bloodstream infection (HELP): study protocol for a multicentre stepped-wedge cluster randomised trial.

INTRODUCTION: Staphylococci are the most commonly identified pathogens in bloodstream infections. Identification of Staphylococcus aureus in blood culture (SAB) requires a prompt and adequate clinical management. The detection of coagulase-negative staphylococci (CoNS), however, corresponds to contamination in about 75% of the cases. Nevertheless, antibiotic therapy is often initiated, which contributes to the risk of drug-related side effects. We developed a computerised clinical decision support system (HELP-CDSS) that assists physicians with an appropriate management of patients with Staphylococcus bacteraemia. The CDSS is evaluated using data of the Data Integration Centers (DIC) established at each clinic. DICs transform heterogeneous primary clinical data into an interoperable format, and the HELP-CDSS displays information according to current best evidence in bacteraemia treatment. The overall aim of the HELP-CDSS is a safe but more efficient allocation of infectious diseases specialists and an improved adherence to established guidelines in the treatment of SAB. METHODS AND ANALYSIS: The study is conducted at five German university hospitals and is designed as a stepped-wedge cluster randomised trial. Over the duration of 18 months, 135 wards will change from a control period to the intervention period in a randomised stepwise sequence. The coprimary outcomes are hospital mortality for all patients to establish safety, the 90-day disease reoccurrence-free survival for patients with SAB and the cumulative vancomycin use for patients with CoNS bacteraemia. We will use a closed, hierarchical testing procedure and generalised linear mixed modelling to test for non-inferiority of the CDSS regarding hospital mortality and 90-day disease reoccurrence-free survival and for superiority of the HELP-CDSS regarding cumulative vancomycin use. ETHICS AND DISSEMINATION: The study is approved by the ethics committee of Jena University Hospital and will start at each centre after local approval. Results will be published in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: DRKS00014320.