Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report

Schibler, Manuel; Vetter, Pauline; Cherpillod, Pascal; Petty, Tom J.; Cordey, Samuel; Vieille, Gaël; Yerly, Sabine; Siegrist, Claire‐Anne; Samii, Kaveh; Dayer, Julie-Anne; Docquier, Mylène; Zdobnov, Evgeny M.; Simpson, Andrew J. H.; Rees, Paul; Sarria, Felix Baez; Gasche, Yvan; Chappuis, François; Iten, Anne; Pittet, Didier; Pugin, Jérôme; Kaiser, Laurent

doi:10.1016/s1473-3099(15)00229-7

Cited by 50 publications

(43 citation statements)

References 30 publications

(38 reference statements)

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“…The importance of advanced supportive care, including electrolyte balance, ventilation and dialysis, was likely pivotal in the successful treatment of individuals infected with EBOV in developed countries during the recent EBOV epidemic 32,[125][126][127]148,149,188,217,218 . Only two of the twelve patients with EBOV (17%) treated in the USA during this epidemic (two imported cases, two infections identified in the USA and eight medically evacuated patients) died.…”

Section: Discussionmentioning

confidence: 99%

“…However, it was the only promising drug available at the time with a fairly well-known safety profile that could be repurposed and delivered orally, and it had been shown to have antiviral activity against EBOV in vitro and in mice 169,170 . Similar to ZMapp and TKM-100802, favipiravir was used to treat a number of patients evacuated from West Africa to Europe 126,146,149,171 , and the role of favipiravir in patient survival is impossible to discern given that all patients received advanced supportive care and most also received other experimental therapies.…”

Section: Small-molecule Antiviral Compoundsmentioning

confidence: 99%

“…In 1976, during the original EBOV (Mayinga strain) outbreak, a single patient was also treated with heparin but did not survive 202 . Heparin was used in two instances during the 2013-2016 EBOV epidemic 32,149 . Both patients in these reports survived, but they also received antiviral drugs and advanced supportive care; therefore, the role of heparin is unknown.…”

Section: Modulation Of the Coagulation Systemmentioning

confidence: 99%

“…ZMapp was subsequently used on at least four additional patients evacuated from West Africa to Europe and the USA [146][147][148] . ZMAb was also used in at least two cases 32,149 , as was MIL77 (REFS 32,150). The role of ZMapp, ZMAb or MIL77 in patient survival is impossible to discern as all the patients were repatriated to developed countries and received advanced supportive care; most also received other experimental therapies.…”

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Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

107

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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: 99%

Section: Small-molecule Antiviral Compoundsmentioning

confidence: 99%

Section: Modulation Of the Coagulation Systemmentioning

confidence: 99%

mentioning

confidence: 99%

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Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

107

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“…41 However, in general, data gathered over a long period from multiple sites-eg, within and between laboratories-cannot be compared, because each site used distinct and specifi c assays under variable conditions. 42 For instance, a 1-2 log 10 diff erence in Ebola virus viral load, which may be within the margin of error of RT-PCR testing within and between many laboratories and assays, might correlate with signifi cant diff erences in lethality. 10,[12][13][14] Standard curves, generated by assessing multiple samples with known quantities of fi loviral RNA, can be used to measure the variability of results and off er a better understanding of the meaning of results across laboratories and time points.…”

Section: Variability Of Fi Lovirus Load Determinationmentioning

confidence: 99%

Essentials of filoviral load quantification

Cnops

Griensven

Honko

et al. 2016

The Lancet Infectious Diseases

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Quantitative measurement of viral load is an important parameter in the management of fi lovirus disease outbreaks because viral load correlates with severity of disease, survival, and infectivity. During the ongoing Ebola virus disease outbreak in parts of Western Africa, most assays used in the detection of Ebola virus disease by more than 44 diagnostic laboratories yielded qualitative results. Regulatory hurdles involved in validating quantitative assays and the urgent need for a rapid Ebola virus disease diagnosis precluded development of validated quantitative assays during the outbreak. Because of sparse quantitative data obtained from these outbreaks, opportunities for study of correlations between patient outcome, changes in viral load during the course of an outbreak, disease course in asymptomatic individuals, and the potential for virus transmission between infected patients and contacts have been limited. We strongly urge the continued development of quantitative viral load assays to carefully evaluate these parameters in future outbreaks of fi lovirus disease.

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Perspectives towards antiviral drug discovery against Ebola virus

Mirza

Vanmeert

Ali

et al. 2019

Journal of Medical Virology

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Ebola virus disease (EVD), caused by Ebola viruses, resulted in more than 11 500 deaths according to a recent 2018 WHO report. With mortality rates up to 90%, it is nowadays one of the most deadly infectious diseases. However, no Food and Drug Administration‐approved Ebola drugs or vaccines are available yet with the mainstay of therapy being supportive care. The high fatality rate and absence of effective treatment or vaccination make Ebola virus a category‐A biothreat pathogen. Fortunately, a series of investigational countermeasures have been developed to control and prevent this global threat. This review summarizes the recent therapeutic advances and ongoing research progress from research and development to clinical trials in the development of small‐molecule antiviral drugs, small‐interference RNA molecules, phosphorodiamidate morpholino oligomers, full‐length monoclonal antibodies, and vaccines. Moreover, difficulties are highlighted in the search for effective countermeasures against EVD with additional focus on the interplay between available in silico prediction methods and their evidenced potential in antiviral drug discovery.

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Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report

Abstract: Geneva University Hospitals, Swiss Office of Public Health, Swiss Agency for Development and Cooperation, and Swiss National Science Foundation.

Cited by 50 publications

References 30 publications

Post-exposure treatments for Ebola and Marburg virus infections

Post-exposure treatments for Ebola and Marburg virus infections

Essentials of filoviral load quantification

Perspectives towards antiviral drug discovery against Ebola virus

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