Lübeck, Germany
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Muller M.A.,University of Bonn | Meyer B.,University of Bonn | Corman V.M.,University of Bonn | Corman V.M.,German Center for Infection Research | And 20 more authors.
The Lancet Infectious Diseases | Year: 2015

Background: Scientific evidence suggests that dromedary camels are the intermediary host for the Middle East respiratory syndrome coronavirus (MERS-CoV). However, the actual number of infections in people who have had contact with camels is unknown and most index patients cannot recall any such contact. We aimed to do a nationwide serosurvey in Saudi Arabia to establish the prevalence of MERS-CoV antibodies, both in the general population and in populations of individuals who have maximum exposure to camels. Methods: In the cross-sectional serosurvey, we tested human serum samples obtained from healthy individuals older than 15 years who attended primary health-care centres or participated in a national burden-of-disease study in all 13 provinces of Saudi Arabia. Additionally, we tested serum samples from shepherds and abattoir workers with occupational exposure to camels. Samples were screened by recombinant ELISA and MERS-CoV seropositivity was confirmed by recombinant immunofluorescence and plaque reduction neutralisation tests. We used two-tailed Mann Whitney U exact tests, χ2, and Fisher's exact tests to analyse the data. Findings: Between Dec 1, 2012, and Dec 1, 2013, we obtained individual serum samples from 10 009 individuals. Anti-MERS-CoV antibodies were confirmed in 15 (0·15%; 95% CI 0·09-0·24) of 10 009 people in six of the 13 provinces. The mean age of seropositive individuals was significantly younger than that of patients with reported, laboratory-confirmed, primary Middle Eastern respiratory syndrome (43·5 years [SD 17·3] vs 53·8 years [17·5]; p=0·008). Men had a higher antibody prevalence than did women (11 [0·25%] of 4341 vs two [0·05%] of 4378; p=0·028) and antibody prevalence was significantly higher in central versus coastal provinces (14 [0·26%] of 5479 vs one [0·02%] of 4529; p=0·003). Compared with the general population, seroprevalence of MERS-CoV antibodies was significantly increased by 15 times in shepherds (two [2·3%] of 87, p=0·0004) and by 23 times in slaughterhouse workers (five [3·6%] of 140; p<0·0001). Interpretation: Seroprevalence of MERS-CoV antibodies was significantly higher in camel-exposed individuals than in the general population. By simple multiplication, a projected 44 951 (95% CI 26 971-71 922) individuals older than 15 years might be seropositive for MERS-CoV in Saudi Arabia. These individuals might be the source of infection for patients with confirmed MERS who had no previous exposure to camels. Funding: European Union, German Centre for Infection Research, Federal Ministry of Education and Research, German Research Council, and Ministry of Health of Saudi Arabia. © 2015 Elsevier Ltd.


Corman V.M.,University of Bonn | Jores J.,Kenya International Livestock Research Institute | Meyer B.,University of Bonn | Younan M.,Veterinaires Sans Frontieres | And 9 more authors.
Emerging Infectious Diseases | Year: 2014

Dromedary camels are a putative source for human infections with Middle East respiratory syndrome coronavirus. We showed that camels sampled in different regions in Kenya during 1992-2013 have antibodies against this virus. High densities of camel populations correlated with increased seropositivity and might be a factor in predicting long-term virus maintenance.


Muller M.A.,University of Bonn | Corman V.M.,University of Bonn | Corman V.M.,German Center for Infection Research | Jores J.,Kenya International Livestock Research Institute | And 9 more authors.
Emerging Infectious Diseases | Year: 2014

To analyze the distribution of Middle East respiratory syndrome coronavirus (MERS-CoV)–seropositive dromedary camels in eastern Africa, we tested 189 archived serum samples accumulated during the past 30 years. We identified MERS-CoV neutralizing antibodies in 81.0% of samples from the main camel-exporting countries, Sudan and Somalia, suggesting long-term virus circulation in these animals. © 2014, Centers for Disease Control and Prevention (CDC). All rights reserved.


Burkhardt C.,London School of Hygiene and Tropical Medicine | Burkhardt C.,Euroimmun AG | Sung P.-Y.,London School of Hygiene and Tropical Medicine | Celma C.C.,London School of Hygiene and Tropical Medicine | Roy P.,London School of Hygiene and Tropical Medicine
Journal of General Virology | Year: 2014

The mechanism used by bluetongue virus (BTV) to ensure the sorting and packaging of its 10 genomic segments is still poorly understood. In this study, we investigated the packaging constraints for two BTV genomic segments from two different serotypes. Segment 4 (S4) of BTV serotype 9 was mutated sequentially and packaging of mutant ssRNAs was investigated by two newly developed RNA packaging assay systems, one in vivo and the other in vitro. Modelling of the mutated ssRNA followed by biochemical data analysis suggested that a conformational motif formed by interaction of the 5′ and 3′ ends of the molecule was necessary and sufficient for packaging. A similar structural signal was also identified in S8 of BTV serotype 1. Furthermore, the same conformational analysis of secondary structures for positive-sense ssRNAs was used to generate a chimeric segment that maintained the putative packaging motif but contained unrelated internal sequences. This chimeric segment was packaged successfully, confirming that the motif identified directs the correct packaging of the segment. © 2014 The Authors.


Hombach A.,Bernhard Nocht Institute for Tropical Medicine | Ommen G.,Bernhard Nocht Institute for Tropical Medicine | Ommen G.,EUROIMMUN AG | MacDonald A.,Bernhard Nocht Institute for Tropical Medicine | Clos J.,Bernhard Nocht Institute for Tropical Medicine
Journal of Cell Science | Year: 2014

Leishmania parasites must survive and proliferate in two vastly different environments - the guts of poikilothermic sandflies and the antigen-presenting cells of homeothermic mammals. The change of temperature during the transmission from sandflies to mammals is both a key trigger for the progression of their life cycle and for elevated synthesis of heat shock proteins, which have been implicated in their survival at higher temperatures. Although the functions of the main heat shock protein families in the Leishmania life cycle have been studied, nothing is known about the roles played by small heat shock proteins. Here, we present the first evidence for the pivotal role played by the Leishmania donovani 23-kDa heat shock protein (which we called HSP23), which is expressed preferentially during the mammalian stage where it assumes a perinuclear localisation. Loss of HSP23 causes increased sensitivity to chemical stressors and renders L. donovani non-viable at 37°C. Consequently, HSP23-null mutants are non-infectious to primary macrophages in vitro. All phenotypic effects could be abrogated by the introduction of a functional HSP23 transgene into the null mutant, confirming the specificity of the mutant phenotype. Thus, HSP23 expression is a prerequisite for L. donovani survival at mammalian host temperatures and a crucial virulence factor. © 2014. Published by The Company of Biologists Ltd.


Hombach A.,Bernhard Nocht Institute for Tropical Medicine | Ommen G.,Bernhard Nocht Institute for Tropical Medicine | Ommen G.,EUROIMMUN AG | Chrobak M.,Bernhard Nocht Institute for Tropical Medicine | Clos J.,Bernhard Nocht Institute for Tropical Medicine
Cellular Microbiology | Year: 2013

The heat shock protein 90 plays a pivotal role in the life cycle control of Leishmania donovani promoting the fast-growing insect stage of this parasite. Equally important for insect stage growth is the co-chaperone Sti1. We show that replacement of Sti1 is only feasible in the presence of additional Sti1 transgenes indicating an essential role. To better understand the impact of Sti1 and its interaction with Hsp90, we performed a mutational analysis of Hsp90. We established that a single amino acid exchange in the LeishmaniaHsp90 renders that protein resistant to the inhibitor radicicol (RAD), yet does not interfere with its functionality. Based on this RAD-resistant Hsp90, we established a combined chemical knockout/gene complementation (CKC) approach. We can show that Hsp90 function is required in both insect and mammalian life stages and that the Sti1-binding motif of Hsp90 is crucial for proliferation of insect and mammalian stages of the parasite. The Sti1-binding motif in LeishmaniaHsp90 is suboptimal - optimizing the motif increased initial intracellular proliferation underscoring the importance of the Hsp90-Sti1 interaction for this important parasitic protozoan. The CKC strategy we developed will allow the future analysis of more Hsp90 domains and motifs in parasite viability and infectivity. © 2012 Blackwell Publishing Ltd.


Komorowski L.,Euroimmun AG | Teegen B.,Euroimmun AG | Probst C.,Euroimmun AG | Aulinger-Stocker K.,University of Lübeck | And 3 more authors.
Journal of Crohn's and Colitis | Year: 2013

Background: Autoantibodies against exocrine pancreas (PAb) have been reported to be pathognomonic markers of Crohn's disease (CD). Recently, the glycoprotein GP2 has been proposed as the exclusive target for PAb but two equally prevalent binding patterns can be observed in the indirect immunofluorescence test (IIFT) using cryosections of human pancreas: a reticulogranular and a droplet pattern. Aim: To identify autoantigens corresponding to the staining patterns. Methods: Different lectins were screened for their ability to immobilize PAb-reactive glycoproteins from cell free human pancreas. The glycoproteins were then purified via UEA-I affinity chromatography and identified by mass spectrometry. The two candidate autoantigens were separately expressed in HEK293 cells, and the recombinant cells applied as substrates in IIFT to analyze sera from 96 patients with CD, 89 controls and hybridoma supernatants during the generation of murine monoclonal antibodies. Results: The UEA-I eluate was able to neutralize PAb reactivity of both patterns in IIFT. It contained two major constituents which were identified as the glycoproteins CUZD1 and GP2. With the recombinant cells, 35.4% of the CD patients exhibited positive reactions (CUZD1 alone 19.8%, GP2 alone 9.4%, and both antigens 6.2%). The reaction with the CUZD1 expressing cells was strictly correlated to the reticulogranular pattern, whereas the antibodies causing the droplet pattern stained the GP2 expressing cells. Antigen-capture ELISA using the newly generated monoclonal antibodies against CUZD1 and GP2 verified this relationship. Conclusions: The concordant reactivities of the different platforms can be regarded as a proof for the authenticity of the two identified autoantigens. © 2012 European Crohn's and Colitis Organisation.


SINGAPORE--(Marketwired - Nov 21, 2016) - EUROIMMUN (SEA) and Angsana Molecular & Diagnostics today build a strategic partnership on the allergy diagnostics and testing to support clinicians, hospitals and private laboratories in South East Asia. This collaboration helps to bring the diagnostics and patient care synergies toward a better clinical management of patients with suspected allergies. Under the strategic collaboration, Angsana Molecular & Diagnostics would offer the comprehensive analysis of sensitizations against inhalation, food and other allergens to provide the precise determination of allergen. EUROIMMUN is committed with the customized two Allergy profiles to be well suited and cater to the region. "There is a need for greater understanding on the risk of true poly-sensitizations for better patient management. With the simultaneous multi-parameter screening, the cooperation with EUROIMMUN gives us perfect position to take lead in allergy diagnostics and testing in the SEA region," says Dr Chris Tan, Chief Executive Officer and founder of Angsana Molecular & Diagnostics. Dr Chris Tan added that, "This partnership enables us to combine cost effective and accurate health screening providing an expanded, high-quality diagnostics service under the CAP-accredited environment." The significance of this cooperation and contribution from both partners is recognized by Li Chuan, President of APAC Group and Managing Director of EUROIMMUN (SEA) Pte Ltd. "Our collaboration with Angsana Diagnostics will provide a precise determination for Allergy diagnostics to benefit the patients with suspected allergies. Furthermore, EUROIMMUN is committed to promote and focus on the use of allergy testing via EUROIMMUN Academy as continuous medical education to the clinicians and others." As a leading company in medical diagnostics, the cooperation between EUROIMMUN and Angsana Molecular & Diagnostics will play an important role in promoting the importance of diagnostics in the Asia Pacific region. Chief Executive Officer and Founder of EUROIMMUN Medizinische Labordiagnostika AG, Prof. Dr. Winfried Stöcker emphasized that the "Asia Pacific region has been one of the important markets for EUROIMMUN and we will continue to support the diagnostics market growth and development in Asia and EUROIMMUN, will and strive to enhance our collaboration with clinicians, medical providers to improve health outcomes and provide precise patient management." EUROIMMUN was founded in 1987 and has its headquarters in Lübeck, Germany. It is committed to develop, produce and sell test systems for the diagnosis of diseases, and software and automation solutions for the performance and evaluation of these assays. So far laboratories in about 200 countries use EUROIMMUN products for the diagnosis of autoimmune, infectious diseases and allergies, and to perform genetic analyses. The company is based on worldwide-patented state-of-the-art production methods and microanalysis techniques and is one of the world's leading manufacturers of medical laboratory diagnostics. The company's reference laboratory is unequalled in the whole field of autoimmune diagnostics. With their quality and standardization, EUROIMMUN products are conquering the leading position in medical diagnostics worldwide. For more information, visit http://www.euroimmun.com.


Gutierrez C.,University of Las Palmas de Gran Canaria | Tejedor-Junco M.T.,University of Las Palmas de Gran Canaria | Gonzalez M.,University of Las Palmas de Gran Canaria | Lattwein E.,EUROIMMUN AG | Renneker S.,EUROIMMUN AG
Eurosurveillance | Year: 2015

In 2012, a new betacoronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), was identified in humans. Several studies confirmed dromedary camels to be a potential reservoir and a source for human infection. Camels located on the Canary Islands were included in those studies and ca 10% of them were positive for MERS-CoV-specific antibodies. However, these findings could not be correctly interpreted because epidemiological information was not provided. Thus, further investigations were necessary to clarify these results. A total of 170 camels were investigated in this survey, of which seven (4.1%) were seropositive by ELISA. Epidemiological information revealed that all seropositive camels had been imported from Africa 20 or more years prior. We conclude that seropositive camels had contact with MERS-CoV in Africa and that there is no shedding of the virus among camels or people around the farms on the Canary Islands. However, the presence of antibodies in the camel herds should be monitored. © 2015, European Centre for Disease Prevention and Control (ECDC). All rights reserved.


Probst C.,Euroimmun AG | Saschenbrecker S.,Euroimmun AG | Stoecker W.,Euroimmun AG | Komorowski L.,Euroimmun AG
Multiple Sclerosis and Related Disorders | Year: 2014

The spectrum of neurological autoimmune diseases has expanded substantially in the last 15 years due to the discovery of new anti-neuronal antibodies. There are at present numerous technical challenges for developing and improving standardized serological test systems for the detection of these autoantibodies, some of which occur very rarely. In particular, the determination of autoantibodies against complex cell surface structures generally requires authentically presented target antigens. Finally, research into syndrome associations benefits from multiplex analyses and accelerates the understanding of the complex autoimmune processes, forming an important basis for the development of novel therapy concepts.

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