Risk of Misinterpretation of Ebola Virus PCR Results After rVSV ZEBOV–GP Vaccination

Cnops, Lieselotte; Gerard, Michèle; Vandenberg, Olivier; Wijngaert, Sigi Van den; Heyndrickx, Leo; Willems, Elisabeth; Demeulemeester, Kathy; Clerck, Hilde De; Dediste, Anne; Callens, Steven; Munter, Paul De; Vlieghe, Erika; Bottieau, Emmanuel; Wuillaume, F; Esbroeck, Marjan Van; Ariën, Kevin K.

doi:10.1093/cid/civ131

Cited by 20 publications

(18 citation statements)

References 8 publications

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“…The individual survived with no evidence of overt clinical illness; however, whether the patient was actually exposed to EBOV remains uncertain. Subsequently, there were at least six cases of medical staff working in West Africa during the 2013-2016 epidemic who were treated with a single dose of the rVSV-EBOV vaccine at times ranging from approximately 24 to 43 hours after the potential exposure to EBOV 157,197,198 . All these individuals survived with mild vaccine-related clinical symptoms but no overt clinical illness, and it is again unknown whether any of these patients were actually exposed to EBOV.…”

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

106

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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

106

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“…Only a few EVD cases after needle sticks have been reported [46,53,[56][57][58][59][60][61][62][63][64][65]. However, parenteral inoculation is clearly established as a potent means of transmission and was associated with a shorter incubation period (6.3 days vs 9.5 days) and a higher overall mortality level (100% vs 88%) during the initial outbreak of EVD, in Yambuku during 1976 [66].…”

Section: Contact With Body Fluids and Cadaversmentioning

confidence: 99%

“…However, parenteral inoculation is clearly established as a potent means of transmission and was associated with a shorter incubation period (6.3 days vs 9.5 days) and a higher overall mortality level (100% vs 88%) during the initial outbreak of EVD, in Yambuku during 1976 [66]. Recently, some HCWs with sharps exposures have been treated with postexposure prophylactic administration of rVSV-ZEBOV vaccine [61,62,65], monoclonal antibodies and/or favipiravir [64], and TKM-100802 [65]; none of the reported cases developed EVD, and no sign of EBOV viremia was detectable, but it is not possible to know whether infection actually occurred.…”

Section: Contact With Body Fluids and Cadaversmentioning

confidence: 99%

Ebola Virus Shedding and Transmission: Review of Current Evidence

et al. 2016

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Background. The magnitude of the 2013-2016 Ebola virus disease outbreak in West Africa was unprecedented, with >28 500 reported cases and >11 000 deaths. Understanding the key elements of Ebola virus transmission is necessary to implement adequate infection prevention and control measures to protect healthcare workers and halt transmission in the community.Methods. We performed an extensive PubMed literature review encompassing the period from discovery of Ebola virus, in 1976, until 1 June 2016 to evaluate the evidence on modes of Ebola virus shedding and transmission.Findings. Ebola virus has been isolated by cell culture from blood, saliva, urine, aqueous humor, semen, and breast milk from infected or convalescent patients. Ebola virus RNA has been noted in the following body fluids days or months after onset of illness: saliva (22 days), conjunctiva/tears (28 days), stool (29 days), vaginal fluid (33 days), sweat (44 days), urine (64 days), amniotic fluid (38 days), aqueous humor (101 days), cerebrospinal fluid (9 months), breast milk (16 months [ preliminary data]), and semen (18 months). Nevertheless, the only documented cases of secondary transmission from recovered patients have been through sexual transmission. We did not find strong evidence supporting respiratory or fomite-associated transmission.

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“…Of note, one sample, obtained from a patient who was vaccinated with rVSV ZEBOV-GP as postexposure prophylaxis [17], that was weakly positive by the ITM GP RT-PCR kit but negative by the Altona RT-PCR kit was negative by the Idylla™ prototype Ebola virus test.…”

Section: Diagnostic Accuracymentioning

confidence: 99%

Development, Evaluation, and Integration of a Quantitative Reverse-Transcription Polymerase Chain Reaction Diagnostic Test for Ebola Virus on a Molecular Diagnostics Platform

Cnops¹,

Eede

Pettitt

et al. 2016

J Infect Dis.

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Background. The 2013-2016 Ebola epidemic in West Africa resulted in accelerated development of rapid diagnostic tests for emergency outbreak preparedness. We describe the development and evaluation of the Idylla™ prototype Ebola virus test, a fully automated sample-to-result molecular diagnostic test for rapid detection of Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV).Methods. The Idylla™ prototype Ebola virus test can simultaneously detect EBOV and SUDV in 200 µL of whole blood. The sample is directly added to a disposable cartridge containing all reagents for sample preparation, RNA extraction, and amplification by reverse-transcription polymerase chain reaction analysis. The performance was evaluated with a variety of sample types, including synthetic constructs and whole blood samples from healthy volunteers spiked with viral RNA, inactivated virus, and infectious virus.Results. The 95% limits of detection for EBOV and SUDV were 465 plaque-forming units (PFU)/mL (1010 copies/mL) and 324 PFU/mL (8204 copies/mL), respectively. In silico and in vitro analyses demonstrated 100% correct reactivity for EBOV and SUDV and no cross-reactivity with relevant pathogens. The diagnostic sensitivity was 97.4% (for EBOV) and 91.7% (for SUDV), the specificity was 100%, and the diagnostic accuracy was 95.9%.Conclusions. The Idylla™ prototype Ebola virus test is a fast, safe, easy-to-use, and near-patient test that meets the performance criteria to detect EBOV in patients with suspected Ebola.

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Risk of Misinterpretation of Ebola Virus PCR Results After rVSV ZEBOV–GP Vaccination

Cited by 20 publications

References 8 publications

Post-exposure treatments for Ebola and Marburg virus infections

Post-exposure treatments for Ebola and Marburg virus infections

Ebola Virus Shedding and Transmission: Review of Current Evidence

Development, Evaluation, and Integration of a Quantitative Reverse-Transcription Polymerase Chain Reaction Diagnostic Test for Ebola Virus on a Molecular Diagnostics Platform

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