Clinical and Virological Characteristics of Ebola Virus Disease Patients Treated With Favipiravir (T-705)—Sierra Leone, 2014

Bai, Chunmei; Mu, Jinsong; Kargbo, David; Song, Yi; Niu, Wenkai; Nie, Weimin; Kanu, Alex; Liu, Weiwei; Wang, Yaoping; Dafae, Foday; Yan, Tao; Hu, Yi; Deng, Yong-Qiang; Lu, Huijun; Yang, Fan; Zhang, Xiaoguang; Sun, Yang; Cao, Yanghui; Su, Haoxiang; Sun, Yu; Liu, Wensen; Wang, Chengyu; Qian, Jun; Liu, Liu; Wang, Hong; Tong, Yigang; Liu, Zeyuan; Chen, Yunsong; Wang, Hongquan; Kargbo, Brima; Gao, George F.; Jiang, Jia-Fu

doi:10.1093/cid/ciw571

Cited by 145 publications

(116 citation statements)

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“…A retrospective analysis of favipiravir therapy suggested some benefit in long-term survival, although the difference was not statistically significant 174 .…”

Section: Small-molecule Antiviral Compoundsmentioning

confidence: 96%

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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“…A retrospective analysis of favipiravir therapy suggested some benefit in long-term survival, although the difference was not statistically significant 174 .…”

Section: Small-molecule Antiviral Compoundsmentioning

confidence: 96%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

107

View full text Add to dashboard Cite

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“…In mid-November 2014, favipiravir was given to 39 patients with severe EVD admitted to the Sierra Leone-China Friendship Hospital [29]. Patients (17–39 years old) received oral favipiravir at doses of 800 mg bid on day 1, and 600 mg bid on day 2, based on recommendations for use in influenza infections [29].…”

Section: Small Molecule Inhibitors: Direct Intracellular Inhibition Omentioning

confidence: 99%

“…Patients (17–39 years old) received oral favipiravir at doses of 800 mg bid on day 1, and 600 mg bid on day 2, based on recommendations for use in influenza infections [29]. Patients also received supportive treatments in the following days until recovery, hospital transfer or death.…”

Section: Small Molecule Inhibitors: Direct Intracellular Inhibition Omentioning

confidence: 99%

“…Survival rate and viremia in the favipiravir cohort were compared to control patients who were admitted to the same center earlier and treated with only supportive treatments. Results from the subsets with all endpoint observations available from the 2 groups (n=17 for the favipiravir group, n=18 for the control group) showed a higher survival rate in the favipiravir group (64.8% vs. 27.8%) [29]. Improvement of disease symptoms was observable in the favipiravir group, combined with a significant reduction in viral RNA load (>100 fold) determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR).…”

Section: Small Molecule Inhibitors: Direct Intracellular Inhibition Omentioning

confidence: 99%

“…Improvement of disease symptoms was observable in the favipiravir group, combined with a significant reduction in viral RNA load (>100 fold) determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). These results indicated that favipiravir might be able to confer a survival benefit to EVD in humans [29]. …”

Section: Small Molecule Inhibitors: Direct Intracellular Inhibition Omentioning

confidence: 99%

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Clinical Evaluation of Ebola Virus Disease Therapeutics

Liu

Wong

et al. 2017

Trends in Molecular Medicine

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Ebola virus disease (EVD) was first described over 40 years ago, but no treatment has been approved for humans. The 2013–2016 EVD outbreak in West Africa has expedited the clinical evaluation of several candidate therapeutics that act through different mechanisms, but with mixed results. Nevertheless, these studies are important because the accumulation of clinical data and valuable experience in conducting efficacy trials under emergency circumstances will lead to better implementation of similar studies in the future. Here, we summarize the results of EVD clinical trials, focus on the discussion of factors that may have potentially impeded the effectiveness of existing candidate therapeutics, and highlight considerations that may help meet the challenges ahead in the quest to develop clinically-approved drug(s).

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