#Ribavirin and #Interferon #Therapy for Critically Ill Patients With #MERS: A Multicenter Observational Study (Clin Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Clin Infect Dis. 2019 Jun 25. pii: ciz544. doi: 10.1093/cid/ciz544. [Epub ahead of print]

Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study.

Arabi YM1, Shalhoub S2,3, Mandourah Y4, Al-Hameed F5, Al-Omari A6, Al Qasim E1, Jose J1, Alraddadi B7,8, Almotairi A9, Al Khatib K10, Abdulmomen A11, Qushmaq I7, Sindi AA12, Mady A13,14, Solaiman O15, Al-Raddadi R16, Maghrabi K15, Ragab A17, Al Mekhlafi GA18, Balkhy HH19, Al Harthy A13, Kharaba A20, Gramish JA21, Al-Aithan AM22, Al-Dawood A1, Merson L23, Hayden FG23,24, Fowler R25.

Author information: 1 Intensive Care Department, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia. 2 Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada. 3 King Fahad Armed Forces Hospital, Jeddah. 4 Military Medical Services, Ministry of Defense, Prince Sultan Military Medical City, Riyadh. 5 Department of Intensive Care, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Jeddah. 6 Department of Intensive Care, College of Medicine, Alfaisal University, Dr Sulaiman Al-Habib Group Hospitals, Riyadh. 7 Department of Medicine, King Faisal Specialist Hospital and Research Center, Jeddah. 8 Department of Medicine, University of Jeddah. 9 Department of Critical Care Medicine, King Fahad Medical City, Riyadh. 10 Intensive Care Department, Al-Noor Specialist Hospital, Makkah. 11 Department of Critical Care Medicine, King Saud University, Riyadh. 12 Department of Anesthesia and Critical Care, Faculty of Medicine, King Abdulaziz University, Jeddah. 13 Intensive Care Department, King Saud Medical City, Riyadh, Saudi Arabia. 14 Tanta University Hospitals, Egypt. 15 Intensive Care Department, King Faisal Specialist Hospital and Research Center, Riyadh. 16 Department of Community Medicine, Faculty of Medicine, King Abdulaziz University. 17 Intensive Care Department, King Fahd Hospital, Jeddah. 18 Department of Intensive Care Services, Prince Sultan Military Medical City. 19 Department of Infection Prevention and Control, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh. 20 Department of Critical Care, King Fahad Hospital, Ohoud Hospital, Al-Madinah. 21 Pharmaceutical Care Department, College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Riyadh. 22 Department of Medicine, Critical Care Division, King Abdulaziz Hospital, Al Ahsa, Saudi Arabia. 23 International Severe Acute Respiratory and Emerging Infection Consortium, Infectious Diseases Data Observatory, Oxford University, United Kingdom. 24 Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia School of Medicine, Charlottesville. 25 Institute of Health Policy Management and Evaluation, University of Toronto, Department of Critical Care Medicine and Department of Medicine, Sunnybrook Hospital, Ontario, Canada.

 

Abstract

BACKGROUND:

The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders.

METHODS:

This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders.

RESULTS:

Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73-1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30-1.44]; P = .29).

CONCLUSIONS:

In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

KEYWORDS: Middle East respiratory syndrome; coronavirus; interferon; pneumonia; ribavirin

PMID: 31925415 DOI: 10.1093/cid/ciz544

Keywords: Antivirals; Ribavirin; Interferons; MERS-CoV.

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#Antiviral activity of #ribavirin and #favipiravir against #human #astroviruses (J Clin Virol., abstract)

[Source: Journal of Clinical Virology, full page: (LINK). Abstract, edited.]

Journal of Clinical Virology / Available online 17 December 2019, 104247 / In Press, Journal Pre-proof / Short communication

Antiviral activity of ribavirin and favipiravir against human astroviruses

Andrew B Janowski a, Holly Dudley a, David Wang b,c

{a} Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA; {b} Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA; {c} Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA

Received 18 October 2019, Revised 9 December 2019, Accepted 16 December 2019, Available online 17 December 2019.

DOI: https://doi.org/10.1016/j.jcv.2019.104247

 

Highlights

  • Ribavirin inhibits replication of astrovirus VA1 and classic human astrovirus 4.
  • Replication of astrovirus VA1 is reduced by favipiravir.
  • No significant cytotoxicity was detected for favipiravir or ribavirin.

 

Abstract

Background

Recent recognition of invasive astrovirus infections, including encephalitis and viremia in humans, have highlighted the need for effective anti-astrovirus therapeutics. However, there is a paucity of data regarding the in vitro activity of broad-spectrum RNA antivirals against astroviruses, including ribavirin and favipiravir.

Objectives

We quantified the EC50 values for ribavirin and favipiravir against two human astrovirus strains, astrovirus VA1 (VA1) and human astrovirus 4 (HAstV4).

Study Design

Caco-2 cells were infected with VA1 or HAstV4 in the presence of ribavirin or favipiravir (dose range 0.1-1000 μM), and the cells were maintained in media containing the drugs for 72 hours. Viral RNA was extracted and quantified by qRT-PCR. As a surrogate for cytotoxicity, cellular adenosine triphosphate (ATP) from each drug treatment was also measured.

Results

VA1 replication was inhibited 10-100-fold by both ribavirin (EC50 = 154μM) and favipiravir (EC50 = 246 μM). In contrast, ribavirin inhibited HAstV4 replication (EC50 = 268 μM) but favipiravir only reduced replication by 44% at the highest dose. Mild reductions in ATP (17-31%) was only observed at the highest concentration of ribavirin (1000 μM) and no significant decrease in ATP was detected for any concentration of favipiravir.

Conclusions

Ribavirin inhibited both human astrovirus species and favipiravir was only active against VA1. In the future, the in vivo efficacy of these drugs could be tested with development of an animal model of human astrovirus infection

Keywords: Astroviruses – astrovirus VA1 – classic human astrovirus – ribavirin – favipiravir – antiviral

© 2019 Elsevier B.V. All rights reserved.

Keywords: Antivirals; Ribavirin; Favipiravir; Astrovirus.

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A cell-based, infectious-free, #platform to identify #inhibitors of #lassa virus #ribonucleoprotein (vRNP) activity (Antiviral Res., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Antiviral Res. 2019 Nov 28:104667. doi: 10.1016/j.antiviral.2019.104667. [Epub ahead of print]

A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.

Cubitt B1, Ortiz-Riano E2, Cheng BY2, Kim YJ1, Yeh CD3, Chen CZ3, Southall NOE3, Zheng W3, Martinez-Sobrido L2, de la Torre JC4.

Author information: 1 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA. 2 Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY, 14642, USA. 3 National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, 20892, USA. 4 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, 92037, USA. Electronic address: juanct@scripps.edu.

 

Abstract

The mammarenavirus Lassa (LASV) is highly prevalent in West Africa where it infects several hundred thousand individuals annually resulting in a high number of Lassa fever (LF) cases, a febrile disease associated with high morbidity and significant mortality. Mounting evidence indicates that the worldwide-distributed prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. There are not Food and Drug Administration (FDA) licensed vaccines and current anti-mammarenavirus therapy is limited to an off-label use of ribavirin that is only partially effective and can cause significant side effects. Therefore, there is an unmet need for novel antiviral drugs to combat LASV. This task would be facilitated by the implementation of high throughput screens (HTS) to identify inhibitors of the activity of the virus ribonucleoprotein (vRNP) responsible for directing virus RNA genome replication and gene transcription. The use of live LASV for this purpose is jeopardized by the requirement of biosafety level 4 (BSL4) containment. We have developed a virus-free cell platform, where expression levels of reporter genes serve as accurate surrogates of vRNP activity, to develop cell-based assays compatible with HTS to identify inhibitors of LASV and LCMV mammarenavirus vRNP activities.

Copyright © 2019. Published by Elsevier B.V.

PMID: 31786250 DOI: 10.1016/j.antiviral.2019.104667

Keywords: Mammarenavirus; Lassa fever; Ribavirin.

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#Jamestown Canyon Virus #Encephalitis in a #Heart #Transplant Patient (Transpl Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Transpl Infect Dis. 2019 Nov 12:e13210. doi: 10.1111/tid.13210. [Epub ahead of print]

Jamestown Canyon Virus Encephalitis in a Heart Transplant Patient.

Askar W1, Menaria P2, Thohan V3, Brummitt CF4.

Author information: 1 Department of Internal Medicine Residency, Aurora Healthcare, Milwaukee, WI. 2 Department of Hospital Medicine, Aurora St. Luke’s Medical Center, Aurora Healthcare, Milwaukee, WI. 3 Department of Advanced Heart Failure Therapies, Mission Health System, Asheville, NC. 4 Department of Infectious Diseases, Aurora Healthcare, Milwaukee, WI.

 

Abstract

Jamestown Canyon virus (JtCV) is an arbovirus and a member of the California serogroup. To our knowledge, all the cases of JtCV have been reported in immunocompetent patients since it was first detected in 1997. We report a case of JtCV encephalitis in a solid organ transplant patient. A 48-year-old female from Wisconsin had multiple hospital admissions for symptoms of progressive confusion, visual hallucinations, and inability to perform self-care. Initial evaluation was significant for lymphocytes in cerebrospinal fluid (CSF), and multiple infectious and metabolic causes were excluded. Further investigation found JtCV IgM in serum, and CSF. The patient’s clinical course was compatible with JtCV encephalitis and she was treated with ribavirin in addition to reduction of her immunosuppressive medications. She showed gradual and significant improvement in her mental and functional status. JtCV can cause a variety of symptoms that range from a flu-like syndrome to encephalitis. There have been an increased number of reported cases in recent years which is attributed to increased physician awareness and the availability of laboratory testing. Optimal treatment is still not known.

© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PMID: 31713971 DOI: 10.1111/tid.13210

Keywords: Jamestown Canyon Virus; Arbovirus; Encephalitis; USA; Wisconsin; Organ transplantation.

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#Clinical #outcomes among #hospital #patients with Middle East respiratory syndrome #coronavirus (#MERS-CoV) #infection (BMC Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMC Infect Dis. 2019 Oct 22;19(1):870. doi: 10.1186/s12879-019-4555-5.

Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection.

Habib AMG1, Ali MAE1, Zouaoui BR1, Taha MAH1, Mohammed BS2, Saquib N3.

Author information: 1 College of Medicine, Sulaiman Al Rajhi Colleges, P.O. Box 777, Bukayriah, Al-Qassim, Zip code 51941, Saudi Arabia. 2 Buraidah Central Hospital, Buraidah, Saudi Arabia. 3 College of Medicine, Sulaiman Al Rajhi Colleges, P.O. Box 777, Bukayriah, Al-Qassim, Zip code 51941, Saudi Arabia. a.saquib@sr.edu.sa.

 

Abstract

BACKGROUND:

Mortality is high among patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. We aimed to determine hospital mortality and the factors associated with it in a cohort of MERS-CoV patients.

METHODS:

We reviewed hospital records of confirmed cases (detection of virus by polymerase chain reaction from respiratory tract samples) of MERS-CoV patients (n = 63) admitted to Buraidah Central Hospital in Al-Qassim, Saudi Arabia between 2014 and 2017. We abstracted data on demography, vital signs, associated conditions presented on admission, pre-existing chronic diseases, treatment, and vital status. Bi-variate comparisons and multiple logistic regressions were the choice of data analyses.

RESULTS:

The mean age was 60 years (SD = 18.2); most patients were male (74.6%) and Saudi citizens (81%). All but two patients were treated with Ribavirin plus Interferon. Hospital mortality was 25.4%. Patients who were admitted with septic shock and/or organ failure were significantly more likely to die than patients who were admitted with pneumonia and/or acute respiratory distress syndrome (OR = 47.9, 95% CI = 3.9, 585.5, p-value 0.002). Age, sex, and presence of chronic conditions were not significantly associated with mortality.

CONCLUSION:

Hospital mortality was 25%; septic shock/organ failure at admittance was a significant predictor of mortality.

KEYWORDS: Interferon alpha; MERS-CoV; Mortality; Ribavirin

PMID: 31640578 DOI: 10.1186/s12879-019-4555-5

Keywords: MERS-CoV; Saudi Arabia; ARDS; Septic shock; Ribavirin; Interferon.

—–

#Ribavirin for the #Treatment of #Lassa Fever: A Systematic Review and Meta-Analysis (Int J Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Int J Infect Dis. 2019 Jul 26. pii: S1201-9712(19)30300-5. doi: 10.1016/j.ijid.2019.07.015. [Epub ahead of print]

Ribavirin for the Treatment of Lassa Fever: A Systematic Review and Meta-Analysis.

Eberhardt KA1, Mischlinger J1, Jordan S1, Groger M1, Günther S2, Ramharter M3.

Author information: 1 Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine and I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 2 Department of Virology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. 3 Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine and I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: ramharter@bnitm.de.

 

Abstract

OBJECTIVES:

Lassa fever (LF) causes annual outbreaks in endemic regions with high mortality of symptomatic patients. Ribavirin is recommended as standard treatment for LF in national and international guidelines but the evidence base for this recommendation has been questioned recently.

METHODS:

We conducted a systematic review and included 6 studies providing efficacy data of ribavirin treatment for LF (PROSPERO protocol CRD42018103994).

RESULTS:

Besides retrospective case series, the evidence mostly relies on a single prospective clinical trial with critical risk of bias. In this trial, LF associated mortality is reduced for patients with elevated aspartate aminotransferase (AST) when treated with ribavirin (OR 0.41, 95% CI 0.23-0.73), while mortality is higher for patients without elevated AST (OR 2.37, 95% CI 1.07-5.25).

CONCLUSIONS:

Based on the available data, current treatment guidelines may therefore put patients with mild LF at increased risk of death. The role of ribavirin in the treatment of LF requires urgent reassessment.

Copyright © 2019. Published by Elsevier Ltd.

KEYWORDS: Haemorrhagic Fever; LASV; Lassa Fever; Ribavirin

PMID: 31357056 DOI: 10.1016/j.ijid.2019.07.015

Keywors: Lassa fever; Antivirals; Ribavirin; Drugs safety.

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#Repurposing of #ribavirin as an adjunct #therapy against invasive #Candida strains: In vitro study (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Repurposing of ribavirin as an adjunct therapy against invasive Candidastrains: In vitro study

Hanane Yousfi, Carole Cassagne, Stéphane Ranque, Jean-marc Rolain, Fadi Bittar

DOI: 10.1128/AAC.00263-19

 

ABSTRACT

The use of antifungal agents in clinical settings is limited by the appearance of drug resistance and adverse side effects. There is, therefore, an urgent need to develop new drugs to strengthen the treatment of invasive fungal diseases. The aim of this study is to describe the potential repurposing of ribavirin as an adjunct therapy against Candida spp.

Primary screening of Prestwick chemical library against Candida albicans ATCC 90028 and fluconazole-resistant Candida albicans was performed. Subsequently, we evaluated the response of 100 Candida spp strains to ribavirin, an antiviral agent, using the broth microdilution method as recommended by CLSI. We checked the involvement of efflux pump activity in the development of ribavirin-resistance. We studied time-kill curves and performed a checkerboard assay for ribavirin-antifungals combinations study.

Twenty-one nonstandard antifungal compounds were identified, including ribavirin. Ribavirin had, in vitro, an antifungal activity against 63 Candida strains including C. albicans, C. parapsilosis and C. tropicalis, with a minimum inhibitory concentrations (MICs) ranging from 0.37 to 3.02 μg/ml, while MICs for C. krusei, C. glabrata, C. lusitaniae and some C. albicans remain high (≥ 24.16 μg/ml). No relation was observed between efflux pump activity and ribavirin-resistance. Ribavirin exhibited a fungistatic activity against multidrug-resistant (MDR) C. albicans and a fungicidal activity against C. parapsilosis strain. In addition, ribavirin acted synergistically with azoles against Candida strains for which ribavirin MICs were < 24.4 μg/ml.

This study highlights the potential clinical application of ribavirin, alone or in association with other antifungal agents, as an adjunct anti-Candida drug.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antibiotics; Drugs Resistance; Candida spp.; Ribavirin.

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