Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study

Hunt, Luke; Gupta-Wright, Ankur; Simms, Victoria; Tamba, Fayia; Knott, Victoria; Tamba, Kongoneh; Heisenberg-Mansaray, Saidu; Tamba, Emmanuel; Sheriff, Alpha Karim; Conteh, Sorie; Smith, Thomas J.; Tobin, Shelagh; Brooks, Tim; Houlihan, Catherine; Cummings, Rachael; Fletcher, Tom

doi:10.1016/s1473-3099(15)00144-9

Cited by 174 publications

(223 citation statements)

References 18 publications

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“…From published articles and news reports, there were also likely 15 patients infected with EBOV in Europe during the epidemic (two imported cases, one infection identified in Spain and twelve medically evacuated patients), of whom three died (20%). By comparison, mortality for EBOV reported in treatment centres in West Africa was 37-74% 211,[219][220][221][222] . Advanced supportive care clearly improved patient survival.…”

Section: Discussionmentioning

confidence: 93%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

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: Discussionmentioning

confidence: 93%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

111

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“…Data for Sudan virus-infected (SUDV-infected) patients demonstrated liver and tissue injury, together with renal failure and possible acute pancreatitis (3). More recent reports of biological follow-up for isolated patients or cohorts have confirmed these results and suggested that rhabdomyolysis is a common features in EVD (4)(5)(6)(7)(8). We report here the clinical, virological, and biological parameters recorded for a cohort of EBOV-infected patients hospitalized in the Macenta and Nzerekore ETCs between December 2014 and January 2015 who did not receive any experimental EBOV-specific therapy.…”

Section: Introductionmentioning

confidence: 93%

Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea

Vernet¹,

Reynard²,

Fizet³

et al. 2017

JCI Insight

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“…E bola virus (EBOV) contains a single-stranded negative-sense RNA genome and constitutes, together with Marburg virus and Cueva virus, the family of Filoviridae, order Mononegavirales. Filoviruses cause a severe fever accompanied by gastrointestinal symptoms, vascular leakage, multiorgan failure, and shock (1,2). The reported case fatality rates can reach 90%.…”

Section: Importancementioning

confidence: 99%

Dynamic Phosphorylation of VP30 Is Essential for Ebola Virus Life Cycle

Biedenkopf

Lier

Becker

2016

J Virol

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Ebola virus is the causative agent of a severe fever with high fatality rates in humans and nonhuman primates. The regulation of Ebola virus transcription and replication currently is not well understood. An important factor regulating viral transcription is VP30, an Ebola virus-specific transcription factor associated with the viral nucleocapsid. Previous studies revealed that the phosphorylation status of VP30 impacts viral transcription. Together with NP, L, and the polymerase cofactor VP35, nonphosphorylated VP30 supports viral transcription. Upon VP30 phosphorylation, viral transcription ceases. Phosphorylation weakens the interaction between VP30 and the polymerase cofactor VP35 and/or the viral RNA. VP30 thereby is excluded from the viral transcription complex, simultaneously leading to increased viral replication which is supported by NP, L, and VP35 alone. Here, we use an infectious virus-like particle assay and recombinant viruses to show that the dynamic phosphorylation of VP30 is critical for the cotransport of VP30 with nucleocapsids to the sites of viral RNA synthesis, where VP30 is required to initiate primary viral transcription. We further demonstrate that a single serine residue at amino acid position 29 was sufficient to render VP30 active in primary transcription and to generate a recombinant virus with characteristics comparable to those of wild-type virus. In contrast, the rescue of a recombinant virus with a single serine at position 30 in VP30 was unsuccessful. Our results indicate critical roles for phosphorylated and dephosphorylated VP30 during the viral life cycle. IMPORTANCEThe current Ebola virus outbreak in West Africa has caused more than 28,000 cases and 11,000 fatalities. Very little is known regarding the molecular mechanisms of how the Ebola virus transcribes and replicates its genome. Previous investigations showed that the transcriptional support activity of VP30 is activated upon VP30 dephosphorylation. The current study reveals that the situation is more complex and that primary transcription as well as the rescue of recombinant Ebola virus also requires the transient phosphorylation of VP30. VP30 encodes six N-proximal serine residues that serve as phosphorylation acceptor sites. The present study shows that the dynamic phosphorylation of serine at position 29 alone is sufficient to activate primary viral transcription. Our results indicate a series of phosphorylation/dephosphorylation events that trigger binding to and release from the nucleocapsid and transcription complex to be essential for the full activity of VP30.

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Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study

Abstract: None.

Cited by 174 publications

References 18 publications

Post-exposure treatments for Ebola and Marburg virus infections

Post-exposure treatments for Ebola and Marburg virus infections

Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea

Dynamic Phosphorylation of VP30 Is Essential for Ebola Virus Life Cycle

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