Experience with Ribavirin for Treatment and Postexposure Prophylaxis of Hemorrhagic Fever Viruses: Crimean Congo Hemorrhagic Fever, Lassa Fever, and Hantaviruses

Rusnak, Janice M.

doi:10.1177/153567601101600203

Cited by 17 publications

(27 citation statements)

References 154 publications

(196 reference statements)

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“…This was associated with a Ͼ1,000-fold decrease in the production of infectious virus. The decrease in infectious virus production was also dose dependent, and the IC 50 was 27 M; this is similar to or lower than the IC 50 s observed for other RNA viruses that are susceptible to in vivo ribavirin treatment (39)(40)(41). Based on the mechanism of action against other RNA viruses (39), the decreased infectivity may be a result of error catastrophe from the increased mutation frequency.…”

Section: Effect Of Prophylactic Ribavirin On Ebola Virus Infection Inmentioning

confidence: 84%

Determination and Therapeutic Exploitation of Ebola Virus Spontaneous Mutation Frequency

Alfson

Worwa

Carrión

et al. 2016

J Virol

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Ebola virus (EBOV) is an RNA virus that can cause hemorrhagic fever with high fatality rates, and there are no approved vaccines or therapies. Typically, RNA viruses have high spontaneous mutation rates, which permit rapid adaptation to selection pressures and have other important biological consequences. However, it is unknown if filoviruses exhibit high mutation frequencies. Ultradeep sequencing and a recombinant EBOV that carries the gene encoding green fluorescent protein were used to determine the spontaneous mutation frequency of EBOV. The effects of the guanosine analogue ribavirin during EBOV infections were also assessed. Ultradeep sequencing revealed that the mutation frequency for EBOV was high and similar to those of other RNA viruses. Interestingly, significant genetic diversity was not observed in viable viruses, implying that changes were not well tolerated. We hypothesized that this could be exploited therapeutically. In vitro, the presence of ribavirin increased the error rate, and the 50% inhibitory concentration (IC 50 ) was 27 M. In a mouse model of ribavirin therapy given pre-EBOV exposure, ribavirin treatment corresponded with a significant delay in time to death and up to 75% survival. In mouse and monkey models of therapy given post-EBOV exposure, ribavirin treatment also delayed the time to death and increased survival. These results demonstrate that EBOV has a spontaneous mutation frequency similar to those of other RNA viruses. These data also suggest a potential for therapeutic use of ribavirin for human EBOV infections. IMPORTANCEEbola virus (EBOV) causes a severe hemorrhagic disease with high case fatality rates; there are no approved vaccines or therapies. We determined the spontaneous mutation frequency of EBOV, which is relevant to understanding the potential for the virus to adapt. The frequency was similar to those of other RNA viruses. Significant genetic diversity was not observed in viable viruses, implying that changes were not well tolerated. We hypothesized that this could be exploited therapeutically. Ribavirin is a viral mutagen approved for treatment of several virus infections; it is also cheap and readily available. In cell culture, we showed that ribavirin was effective at reducing production of infectious EBOV. In mouse and monkey models of therapy given post-EBOV exposure, ribavirin treatment delayed the time to death and increased survival. These data provide a better understanding of EBOV spontaneous mutation and suggest that ribavirin may have great value in the context of human disease.

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Section: Effect Of Prophylactic Ribavirin On Ebola Virus Infection Inmentioning

confidence: 84%

Determination and Therapeutic Exploitation of Ebola Virus Spontaneous Mutation Frequency

Alfson

Worwa

Carrión

et al. 2016

J Virol

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“…95,96 Use of intravenous ribavirin has been recommended for treatment of CCHF, and oral ribavirin has also been used for postexposure prophylaxis. 76,97,98 …”

Section: Molecular Assaysmentioning

confidence: 98%

Crimean-Congo Hemorrhagic Fever

Shayan

Bokaean

Shahrivar

et al. 2015

Lab Med

103

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Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the Bunyaviridae family and Nairovirus genus. The viral genome consists of 3 RNA segments of 12 kb (L), 6.8 kb (M), and 3 kb (S). Crimean-Congo hemorrhagic fever (CCHF) is the most widespread tickborne viral infection worldwide: it has been reported in many regions of Africa, the Middle East, and Asia. The geographical distribution of CCHFV corresponds most closely with the distribution of members of the tick genera, and Hyalomma ticks are the principal source of human infection. In contrast to human infection, CCHFV infection is asymptomatic in all species. Treatment options for CCHF are limited; immunotherapy and ribavirin are effective in the treatment of CCHF; the efficacy of ribavirin in the treatment of CCHF has not yet been proven. This article reviews the history, epidemiology, clinical symptoms, pathogenesis, diagnosis, and treatment of CCHFV, as well as the development of a vaccine against it.

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“…Intravenous (IV) ribavirin can be used for therapy, and oral ribavirin can be used as post-exposure prophylaxis (PEP) for Crimean-Congo hemorrhagic fever and hemorrhagic fever with renal syndrome, though efficacy is not clearly established [19]. For HFRS, early initiation of IV therapy may reduce morbidity and mortality [8].…”

Section: Pharmacologic Treatmentmentioning

confidence: 99%

Viral Hemorrhagic Fever: Bunyaviridae

Kahlon

2015

Curr Treat Options Infect Dis

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Experience with Ribavirin for Treatment and Postexposure Prophylaxis of Hemorrhagic Fever Viruses: Crimean Congo Hemorrhagic Fever, Lassa Fever, and Hantaviruses

Cited by 17 publications

References 154 publications

Determination and Therapeutic Exploitation of Ebola Virus Spontaneous Mutation Frequency

Determination and Therapeutic Exploitation of Ebola Virus Spontaneous Mutation Frequency

Crimean-Congo Hemorrhagic Fever

Viral Hemorrhagic Fever: Bunyaviridae

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