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To investigate 2,017 cases of hantavirus disease in Germany, we compared 38 new patient-derived Puumala virus RNA sequences identified in 2010 with bank vole-derived small segment RNA sequences. The epidemic process was driven by outbreaks of 6 Puumala virus clades comprising strains of human and vole origin. Each clade corresponded to a different outbreak region. [ABSTRACT FROM AUTHOR]

We identified Dobrava-Belgrade virus infection in Turkey (from a strain related to hantavirus strains from nearby countries) in a patient who had severe symptoms leading to panhypopituitarism, but no known risk for hantavirus. Our findings emphasize the need for increased awareness of hantaviruses in the region and assessment of symptomatic persons without known risk factors for infection. [ABSTRACT FROM AUTHOR]

We present the molecular identification of Apodemus agrarius (striped field mouse) as reservoir host of the Dobrava-Belgrade virus (DOBV) lineage DOBV-Aa in 3 federal states of Germany. Phylogenetic analyses provided evidence for multiple spillover of DOBV-Aa to A. flavicollis, a crucial prerequisite for host switch and genetic reassortment. [ABSTRACT FROM AUTHOR]

Dobrava-Belgrade virus (DOBV) is a European hantavirus that causes hemorrhagic fever with renal syndrome (HFRS); case-fatality rates in Balkan countries are as high as 12%. To determine causative agents, we examined 126 cases of DOBV-associated HFRS in central and southern European Russia. In central Russia (Lipetsk, Voronezh, Orel regions), outbreaks were caused by a DOBV variant (DOBV-Aa) carried by Apodemus agrarius. In southern Russia (Sochi district), where HFRS is endemic, HFRS cases were caused by a new DOBV variant (DOBV-Ap), found in A. ponticus, a novel hantavirus natural host. Both viruses, DOBV-Aa/Lipetsk and DOBV-Ap/Sochi, were isolated through Vero E6 cells, genetically characterized, and used for serotyping of the HFRS patients' serum. The clinical severity of HFRS caused by DOBV-Aa resembles that of HFRS caused by Puumala virus (mild to moderate); clinical severity of disease caused by DOBV-Ap infections is more often moderate to severe. [ABSTRACT FROM AUTHOR]

Background: The etiology of fever of unknown origin (FUO) in sub-Saharan Africa often remains unexplained., Methods: We performed a retrospective laboratory-based observational study of 550 Guinean patients with FUO testing negative for Ebola virus from March to December 2014. Blood-borne pathogens were diagnosed by polymerase chain reaction (PCR) or reverse transcription-PCR (RT-PCR), serologic tests, and targeted and unbiased high-throughput sequencing (HTS)., Results: In 275 of 550 individuals, we found evidence of ≥1 pathogen by molecular methods. We identified Plasmodium in 35.6% of patients via PCR, with P falciparum constituting 96.4% of these cases. Pathogenic bacteria, including Salmonella and Klebsiella, were detected in 18.4% of patients through PCR and HTS. Resistance determinants against first-line antibiotics were found in 26.9% of pooled sera by HTS. Yellow fever, Lassa, and Ebola viruses were detected in 5.8% of patients by RT-PCR; HTS-guided RT-PCR confirmed Orungo virus infection in 1 patient. Phylogenetic analyses revealed that the viral genomes matched the available genomic data in terms of location and time. Indirect immunofluorescence assays revealed immunoglobulin M antibodies against yellow fever, Ebola, dengue, West Nile, and Crimean Congo hemorrhagic fever viruses in 11 of 100 patients who were PCR or RT-PCR negative. One in 5 patients who were infected presented coinfections, predominantly malaria associated with sepsis-causing bacteria, in adults (12.1%) and children (12.5%), whereas viral coinfections were rare. Patients presented fever (74.7%), asthenia (67.7%), emesis (38.2%), diarrhea (28.3%), and hemorrhage (11.8%), without clear etiology associations., Conclusions: An exhaustive laboratory investigation elucidated infectious causes of FUO in 52.3% of patients. Quality control and strengthening laboratory capacities in sub-Saharan Africa are essential for patient care, outbreak response, and regionally appropriate diagnostics., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Outside Asia, Seoul virus (SEOV) is an underestimated pathogen. In Germany, autochthonous SEOV-associated hantavirus disease has not been unequivocally diagnosed. We found clinical and molecular evidence for SEOV infection in a young woman; her pet rat was the source of infection.

The emerging occurrence of antibiotic-resistant bacterial pathogens leads to a recollection of bacteriophage as antimicrobial therapeutics. This article presents a short overview of the clinical phage application including their use in military medicine and discusses the genotypic and phenotypic properties of a potential "ideal" therapeutic phage. We describe current efforts to engineer phage for their improved usability in pathogen treatment. In addition, phage can be applied for pathogen detection, selective drug delivery, vaccine development, or food and surface decontamination. Instead of viable phage, (engineered) phage-derived enzymes, such as polysaccharide depolymerases or peptidoglycan-degrading enzymes, are considered as promising therapeutic candidates. Finally, we briefly summarize the use of phage for the detection and treatment of "Category A priority pathogens".

To screen diagnostic specimens for the presence of hantavirus genomes or to identify new hantaviruses in nature, the pan-hanta L-PCR assay, a broadly reactive nested reverse transcription polymerase chain reaction (RT-PCR) assay targeting the L segment, is highly preferred over other assays because of its universality and high sensitivity. In contrast, the geographic allocation of Puumala virus strains to defined outbreak regions in Germany was previously done based on S segment sequences. We show that the routinely generated partial L segment sequences resulting from the pan-hanta L-PCR assay provide sufficient phylogenetic signal to inform the molecular epidemiology of the Puumala virus. Consequently, an additional S segment analysis seems no longer necessary for the identification of the spatial origin of a virus strain., Competing Interests: The authors declare no conflict of interest.

Seoul hantavirus-associated hemorrhagic fever with renal syndrome cases are rare outside Asia and have not yet been found in Germany. We report clinical and molecular evidence for a Seoul virus infection in a patient in Germany. The infection was most likely acquired during a stay in Sulawesi, Indonesia.

As early as 1943, the German physician Helmut Ruska visualized the virus of varicella and zoster (at that time, he was not completely certain whether the virus was the same) by the newly developed electron microscope; he is regarded as the discoverer of this virus. Here, we present a translation of his classical paper into the English language. In our introduction and commentary to his paper, we discuss the significance of Helmut Ruska's work for the development of virology, his distinction between the varicella, zoster, and herpes virus group on one hand and poxviruses on the other, as well as the development of imaging techniques which have refined or substituted for electron microscopy of viruses and virus-infected cells., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background: Very recently, a novel European hantavirus, Sochi virus, has been discovered which causes severe courses of hantavirus disease with a case fatality rate of about 15 percent., Objectives: We aimed to study to which extent and with which clinical severity children were affected by Sochi virus infection., Study Design: Sochi virus infection of patients was confirmed by molecular, serological, and epizoonotic studies. Clinical and laboratory parameters were analyzed for the age group of up to 15 years (n = 6) in comparison to all older patients (n = 56)., Results: 9.7 percent of patients with hantavirus disease studied (6/62) were up to 15 years old. The children showed moderate to severe clinical courses similarly to the situation in adults., Conclusions: While children are in general considered to be less affected by hantavirus infections than adults, in case of highly pathogenic hantaviruses, such as Sochi virus, frequency of clinical cases as well as their clinical course are comparable between children and adults. Therefore, hantavirus disease, particularly in regions endemic to highly pathogenic hantaviruses, should be considered in cases of unclear fever and kidney/pulmonary failure in children., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Various hantaviruses have been discovered in unconventional hosts (shrews and bats) in Africa. Up to now, it was unknown whether these viruses pose a threat for human health. In this study, using newly established serological assays, we demonstrated evidence of shrew-borne hantavirus infections in humans from Côte d'Ivoire and Gabon., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Sochi virus was recently identified as a new hantavirus genotype carried by the Black Sea field mouse, Apodemus ponticus. We evaluated 62 patients in Russia with Sochi virus infection. Most clinical cases were severe, and the case-fatality rate was as high as 14.5%.

Hantavirus infections in Germany appear periodically with peak numbers every 2-3 years. The reported cases in the years 2007, 2010 and 2012 exceeded many times over those in the years in-between. In order to reveal faults of certain in vitro diagnostic assays (IVDs), to harmonize the performances of the individual assays and to improve the users' competence in interpreting the results, the National Consiliary Laboratory for Hantaviruses and INSTAND e.V. (Society for Promoting Quality Assurance in Medical Laboratories e.V.) established an external quality assessment (EQA) scheme for proficiency testing of hantavirus serodiagnostics. The first EQA scheme (pilot study) started in March 2009 with 58 participating laboratories from Germany and neighboring countries. Twice a year four serum samples were sent out to the participants to investigate whether the sample reflects an acute or past infection and to distinguish between infections with the hantavirus types Puumala virus (PUUV) and Dobrava-Belgrade virus (DOBV), both endemic in Central Europe. In addition, samples negative for anti-hantavirus antibodies were tested in order to examine the specificity of the IVDs applied in the participating laboratories. An increasing number of laboratories participated, with a maximum of 92 in March 2014. When summarizing in total 2592 test results, the laboratories reached an overall specificity of 96.7% and a sensitivity of 95% in their detection of a hantavirus infection. A correct distinction between acute and past infections was forwarded in 90-96% of replies of laboratories. Exact serotyping (PUUV vs. DOBV) of the infection was reported in 81-96% of replies with the lowest accuracy for past DOBV infections; cross-reactivities between diagnostic antigens of the two viruses as well as persistent IgM titers in humans may interfere with exact testing. The EQAs revealed acceptable results for the serodiagnostic of hantavirus infection including serotyping but further improvement is still needed., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Arenaviruses are feared as agents that cause viral hemorrhagic fevers. We report the identification, isolation, and genetic characterization of 2 novel arenaviruses from Namaqua rock mice in Namibia. These findings extend knowledge of the distribution and diversity of arenaviruses in Africa.

Hantaviruses are emerging zoonotic viruses which cause human disease in Africa, America, Asia, and Europe. This review summarizes the progress in hantavirus epidemiology and diagnostics during the previous decade. Moreover, we discuss the influence of ecological factors on the worldwide virus distribution and give an outlook on research perspectives for the next years., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Members of the Dobrava-Belgrade virus (DOBV) species are hantaviruses carried by different Apodemus mice as reservoir hosts and causing haemorrhagic fever with renal syndrome (HFRS) in humans. In Central Europe, the Kurkino genotype of DOBV, associated with the striped field mouse, Apodemus agrarius, is prevalent. This paper presents the first extensive study of the serological and molecular diagnostics, epidemiology and clinics of DOBV-Kurkino infections in Central Europe. Serum samples from 570 German patients living in the habitat of A. agrarius (north and northeast Germany) and exhibiting febrile disease, were analysed. All samples were tested by ELISA, subsets of samples were also analysed by immunoblot, neutralization assay, and RT-PCR. A group of 86 individuals was confirmed as DOBV-infected. The virus neutralization assay allowed a reliable identification of DOBV antibodies during both acute and convalescent phases of infection. However, differentiation of relevant DOBV genotypes was not possible by neutralization test but required molecular analysis. Whereas DOBV IgM antibodies tend to persist in the infected organism, RNAaemia seems to be short. Nucleotide sequences were amplified from four patients, and their analysis demonstrated infection by DOBV-Kurkino. With respect to the initial results, the high degree of identity of local patient-derived and A. agrarius-derived virus sequences may allow a closer allocation of the geographical place where the human infection occurred. In contrast to moderate/severe HFRS caused by the DOBV genotypes Dobrava or Sochi, all available data showed a mild clinical course of HFRS caused by DOBV-Kurkino infection without lethal outcomes., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

This paper summarizes the progress in the search for hantaviruses and hantavirus infections in Africa. After having collected molecular evidence of an indigenous African hantavirus in 2006, an intensive investigation for new hantaviruses has been started in small mammals. Various novel hantaviruses have been molecularly identified not only in rodents but also in shrews and bats. In addition, the first African hantavirus, Sangassou virus, has been isolated and functionally characterized in cell culture. Less is known about the ability of these hantaviruses to infect humans and to cause diseases. To date, no hantavirus genetic material could be amplified from patients' specimens collected in Africa. Serological studies in West Africa, based on a battery of screening and confirmatory assays, led to the detection of hantavirus antibodies in the human population and in patients with putative hantavirus disease. In addition to this overview, we present original data from seroepidemiological and field studies conducted in the Southern part of Africa. A human seroprevalence rate of 1.0% (n=1442) was detected in the South African Cape Region whereas no molecular evidence for the presence of hantavirus was found in 2500 small animals trapped in South Africa and Namibia., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Dobrava-Belgrade virus (DOBV) is a human pathogen that has evolved in, and is hosted by, mice of several species of the genus Apodemus. We propose a subdivision of the species Dobrava-Belgrade virus into four related genotypes - Dobrava, Kurkino, Saaremaa, and Sochi - that show characteristic differences in their phylogeny, specific host reservoirs, geographical distribution, and pathogenicity for humans.

Hantaviruses are considered to be emerging viruses due to their increasing significance as human pathogens and their cyclic reappearance during outbreaks. Central Europe is an important endemic region for hantavirus infections. Reflecting the presence of all relevant small mammals serving as reservoir hosts, close to all recognized European hantaviruses occur also in Central Europe. Important human pathogens, Puumala and Dobrava-Belgrade viruses, are present and cause hemorrhagic fever with renal syndrome of various severities. Moreover, several of the newly recognized shrew- and mole-borne hantaviruses are present. In this review, we summarize current data on molecular detection of hantaviruses in reservoir hosts as well as on molecular epidemiology of human hantavirus infections in Central Europe.

Sochi virus, a novel genetic variant of Dobrava-Belgrade virus, was isolated in cell culture from a fulminant lethal case of hantavirus disease presenting with shock and combined kidney and lung failure. Sochi virus is transmitted to humans from host reservoir Apodemus ponticus and must be considered a life-threatening emerging agent.

The tri-segmented RNA genome of hantaviruses facilitates genetic reassortment by segment swapping when cells are co-infected with different virus strains. We found efficient in vitro reassortment between members of two different genetic lineages of the Dobrava-Belgrade virus species, the weakly virulent DOBV-Aa and highly virulent DOBV-Af. In all reassortants, S and L segments originated from the same parental strain, and only the M segment was exchanged. To identify functional differences between the parental strains DOBV-Aa and DOBV-Af in cell culture and to compare them with the reassortants, we studied elements of the innate immunity in virus-infected cells. The contrasting phenotypes of the parental viruses were maintained by the reassortants carrying the respective S and L segments of the parental virus and were not influenced by the origin of the M segment.

A large outbreak of hemorrhagic fever with renal syndrome (HFRS) occurred in the winter of 2006-2007 in a region southeast of Moscow in Central European Russia. Of the 422 patients with HFRS investigated in this study, 58 patients were found to be infected by Puumala virus, whereas as many as 364 were infected by Dobrava-Belgrade virus (DOBV). Early serum samples from 10 DOBV-infected patients were used for nucleic acid amplification, which was successful for 5 patients. Molecular analyses demonstrated that the causative hantavirus belongs to the DOBV-Aa genetic lineage, which is carried by the striped field mouse (Apodemus agrarius) as the natural reservoir host. Neutralization assays with convalescent-phase sera from these patients confirmed infection by DOBV-Aa; related viruses, such as the Dobrava-Slovenia virus (DOBV-Af) and the Dobrava-Sochi virus (DOBV-Ap), were neutralized at lower efficiencies. The clinical courses of the 205 patients enrolled in the study were found to be mostly mild to moderate; however, an unexpectedly high fraction (27%) of patients exhibited severe illness. One patient died from kidney failure and showed symptoms of generalized subcutaneous hemorrhage. The results provide molecular, serodiagnostic, and clinical evidence that DOBV-Aa is a common pathogen in East Europe that causes large outbreaks of HFRS.

Objectives: The potential risk of accidental infection by hantaviruses in a clinical or research laboratory necessitates special precautionary measures. A biosafety program must address handling and disposal of infectious materials as well as appropriate virus inactivation or depletion procedures to permit necessary further processing of specimens outside the biosafety level 3 laboratory., Methods: To study the elimination of hantavirus infectivity, the effects of different chemical and physical inactivation and depletion procedures were investigated on Hantaan virus-containing materials. An infectivity assay for hantaviruses was utilised to verify these procedures which are commonly preceding investigations such as ELISA, flow cytometry analysis, Western blot or immunofluorescence assay., Results: Chemical inactivation with methanol, paraformaldehyde, acetone/methanol and detergent-containing lysis buffer as well as physical forces such as UV irradiation and filtration efficiently reduced viral infectivity in infected cells and their supernatants below the detection limit., Conclusion: The virus inactivation and depletion methods described herein are suitable to prepare non-infectious samples for further use in immunological, virological and cell-biological assays., (Copyright (c) 2005 S. Karger AG, Basel.)

The type III restriction endonuclease EcoP15I was used in isolating fragments of 26 bp from defined positions of cDNAs. We call this substantially improved variant to the conventional serial analysis of gene expression (SAGE) procedure "SuperSAGE." By applying SuperSAGE to Magnaporthe grisea (blast)-infected rice leaves, gene expression profiles of both the rice host and blast fungus were simultaneously monitored by making use of the fully sequenced genomes of both organisms, revealing that the hydrophobin gene is the most actively transcribed M. grisea gene in blast-infected rice leaves. Moreover, SuperSAGE was applied to study gene expression changes before the so-called hypersensitive response in INF1 elicitor-treated Nicotiana benthamiana, a "nonmodel" organism for which no DNA database is available. Again, SuperSAGE allowed rapid identification of genes up- or down-regulated by the elicitor. Surprisingly, many of the down-regulated genes coded for proteins involved in photosynthesis. SuperSAGE will be especially useful for transcriptome profiling of two or more interacting organisms like hosts and pathogens, and of organisms, for which no DNA database is available.

Orthodox Type IIP restriction endonucleases, which are commonly used in molecular biological work, recognize a single palindromic DNA recognition sequence and cleave within or near this sequence. Several new studies have reported on structural and biochemical peculiarities of restriction endonucleases that differ from the orthodox in that they require two copies of a particular DNA recognition sequence to cleave the DNA. These two sites requiring restriction endonucleases belong to different subtypes of Type II restriction endonucleases, namely Types IIE, IIF and IIS. We compare enzymes of these three types with regard to their DNA recognition and cleavage properties. The simultaneous recognition of two identical DNA sites by these restriction endonucleases ensures that single unmethylated recognition sites do not lead to chromosomal DNA cleavage, and might reflect evolutionary connections to other DNA processing proteins that specifically function with two sites.

OKT3 monoclonal antibody (MoAb) therapy is well established in the prevention and therapy of acute rejection in transplant patients. Unfortunately, this therapy is associated with several short-term (cytokine release syndrome) and long-term (infections, EBV-related lymphoma) side effects. Recently, we were able to demonstrate an association between the TNF alpha release following the first OKT3 MoAb infusions and the appearance of human cytomegalovirus (HCMV) reactivation several days later. In order to prevent this TNF alpha associated HCMV reactivation patients were additionally treated with pentoxifylline (PTX), a methylxanthine derivative that has been shown to suppress TNF alpha induction. Although the TNF alpha peak plasma level following OKT3 MoAb treatment was markedly reduced, the incidence of HCMV reactivation and HCMV disease was not influenced. In transient transfection experiments using HCMV immediate early enhancer/promoter CAT reporter gene constructs PTX enhanced the promoter activity independently from TNF alpha in premonocytic cells. Furthermore, PTX acted synergistically with TNF alpha. In virus-infected human embryonal lung fibroblasts HCMV replication was triggered in the presence of both PTX and TNF alpha, while either substance alone had only marginal effects. The stimulatory effect of PTX on the immediate early (IE) enhancer/promoter was mediated via CREB/ ATF, a eukaryotic transcription factor that binds to the 19 bp sequence motif in the enhancer region, while TNF alpha stimulation was mediated by activation of the transcription factor NF-kappaB and its binding to the 18 bp sequence motif in the enhancer. These data suggest a potential side effect of cAMP-elevating drugs such as PTX.

Using New York City's 1975 financial crisis as an example, this article argues that the classic inelastic theory of wage demand for public sector employment (higher wages do not lead to reductions in employment) has been supplanted in the mid-1970s by a kinked demand relationship (the idea that higher wages can and do lead to reductions in employment), wherein unions can improve wages for their respective memberships only by implementing strategies that lend themselves to facilitating an increase in overall demand for government services.