Management of Accidental Exposure to Ebola Virus in the Biosafety Level 4 Laboratory, Hamburg, Germany

Günther, Stephan; Feldmann, Heinz; Geisbert, Thomas W.; Hensley, Lisa E.; Rollin, Pierre E.; Nichol, Stuart T.; Ströher, Ute; Artsob, Harvey; Peters, C. J.; Ksiazek, Thomas G.; Becker, Stephan; Meulen, Jan ter; Ölschläger, Stephan; Schmidt‐Chanasit, Jonas; Sudeck, Hinrich; Burchard, Gerd; Schmiedel, Stefan

doi:10.1093/infdis/jir298

Cited by 139 publications

(86 citation statements)

References 31 publications

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“…The rVSV-EBOV vaccine was used to treat accidental laboratory exposures and repatriated patients during the 2013-2016 epidemic. The initial use in humans was to treat a laboratory exposure to EBOV about 40 hours after the incident 196 . The individual survived with no evidence of overt clinical illness; however, whether the patient was actually exposed to EBOV remains uncertain.…”

Section: Vaccine Vectors As Post-exposure Treatmentsmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

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111

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| The filoviruses -Ebola virus and Marburg virus -cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively. R E V I E W SNATURE REVIEWS | DRUG DISCOVERY VOLUME 17 | JUNE 2018 | 413 © 2 0 1 8 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . AstheniaMuscular weakness. MyalgiaMuscular pain. ArthralgiaJoint pain. LeukopeniaA condition of having a low number of circulating leukocytes, including neutrophils, eosinophils, basophils, lymphocytes and monocytes. LymphocytopeniaA condition of having a low number of circulating leukocytes, including natural killer cells, T cells and B cells. ThrombocytopeniaA condition of having a low number of circulating thrombocytes, also known as platelets.and Ebolavirus. The Marburgvirus genus contains a single species, Marburg marburgvirus, which contains two members, Marburg virus (MARV) and Ravn virus (RAVV). The Ebolavirus genus consists of five distinct species: Bundibugyo ebolavirus (BDBV), Reston ebolavirus (RESTV), Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV; previously termed 'Côte d'Ivoire ebolavirus' but more commonly known as 'Ivory Coast ebolavirus') and Zaire ebolavirus (EBOV). MARV, RAVV, BDBV, SUDV and EBOV are important human pathogens, with case fatality rates often up to 90% for MARV, RAVV and EBOV, and around 55% for SUDV 8,10 . On the basis of two small outbreaks in 2007 and 2012, BDBV seems to be the least pathogenic, with a case fatality rate of about 40-48% 11,12 . In 1994, TAFV was associated with a number of deaths in chimpanzees and a single symptomatic but non-lethal human infection in the Republic of Côte d'Ivoire 13,14 . RESTV is lethal for macaques but is not thought to cause disease in humans 15 . An outbreak of RESTV was reported in pigs in the Philippines in 2008; however, it remains uncertain whether the disease observed in the pigs was caused by RESTV or other agents reported to have co-infected the animals 16 . Clinical manifestationsClinical and laboratory signs of disease caused by filovirus infection are nonspecific and usually associated with an incubation period of 2-21 days (mean 4-10 days) 8,17 . Illness begins with an abrupt onset of fever, astheni...

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Section: Vaccine Vectors As Post-exposure Treatmentsmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

Self Cite

111

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“…Although a small handful of infections with viral hemorrhagic fever viruses have occurred in research settings (5)(6)(7), it is reassuring that imported clinical cases in the US have not led to known laboratory-acquired infections (8 -11 ). Nevertheless, patients with EVD treated in the US and Europe have frequently been managed in high containment facilities-often using point-of-care testing and/or satellite laboratories (10,(12)(13)(14).…”

confidence: 99%

Bloodborne Viral Pathogen Contamination in the Era of Laboratory Automation

Bryan¹,

Cook²,

Atienza³

et al. 2016

Clinical Chemistry

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BACKGROUND The CDC states that laboratory testing for persons under investigation for Ebola virus disease can be safely performed using automated laboratory instruments by adhering to bloodborne pathogen practices. We therefore sought to investigate the levels of viral contamination of a total laboratory automation (TLA) system to guide risk mitigation strategies for handling infectious agents. METHODS Environmental swabs followed by PCR for hepatitis B (HBV) and hepatitis C (HCV) viruses were taken from a chemistry TLA system during routine clinical use and after running a small number of high-titer HCV samples. Control experiments were performed to ensure the recovery of DNA and RNA viruses by swabs from a representative nonporous surface. RESULTS Of 79 baseline swabs for nucleic acids performed on the TLA system, 10 were positive for HBV and 8 for HCV. Viral nucleic acid was consistently detected from swabs taken from the distal inside surface of the decapper discharge chute, with areas adjacent to the decapper instrument and the centrifuge rotor also positive for HBV or HCV nucleic acid. Contamination was occasionally detected on exposed surfaces in areas without protective barriers between samples and personnel. After running known HCV-positive samples, at least one additional site of contamination was detected on an exposed area of the line. CONCLUSIONS A low level of viral contamination of automated clinical laboratory equipment occurs in clinical use. Given the risks associated with highly infectious agents, there is a need for risk-mitigation procedures when handling all samples.

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“…The post-exposure treatment properties of the VSV-EBOV vaccine have been used on several occasions in laboratory and healthcare workers exposed to and potentially infected with EBOV. 47 , 48 The use of the VSV-EBOV vaccine in thousands of people during phase 2/3 clinical trials also showed that it is feasible to manufacture large-scale vaccine batches for deployment in outbreak situations.…”

Section: Resultsmentioning

confidence: 99%

The vesicular stomatitis virus-based Ebola virus vaccine: From concept to clinical trials

Suder

Furuyama

Feldmann

et al. 2018

Human Vaccines & Immunotherapeutics

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The devastating Ebola virus (EBOV) epidemic in West Africa in 2013–2016 accelerated the progress of several vaccines and antivirals through clinical trials, including the replication-competent vesicular stomatitis virus-based vaccine expressing the EBOV glycoprotein (VSV-EBOV). Extensive preclinical testing in animal models demonstrated the prophylactic and post-exposure efficacy of this vaccine, identified the mechanism of protection, and suggested it was safe for human use. Based on these data, VSV-EBOV was extensively tested in phase 1–3 clinical trials in North America, Europe and Africa. Although some side effects of vaccination were observed, these clinical trials showed that the VSV-EBOV was safe and immunogenic in humans. Moreover, the data supported the use of VSV-EBOV as an emergency vaccine in individuals at risk for Ebola virus disease. In this review, we summarize the results of the extensive preclinical and clinical testing of the VSV-EBOV vaccine.

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Management of Accidental Exposure to Ebola Virus in the Biosafety Level 4 Laboratory, Hamburg, Germany

Cited by 139 publications

References 31 publications

Post-exposure treatments for Ebola and Marburg virus infections

Post-exposure treatments for Ebola and Marburg virus infections

Bloodborne Viral Pathogen Contamination in the Era of Laboratory Automation

The vesicular stomatitis virus-based Ebola virus vaccine: From concept to clinical trials

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