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CME / ABIM MOC

Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies

  • Authors: Hung-Yuan Cheng, DPhil; Clare E. French, PhD; Alex P. Salam, DPhil; Sarah Dawson, MSc; Alexandra McAleenan, PhD; Luke A. McGuinness, PhD; Jelena Savović, PhD; Peter W. Horby, MD, PhD; Jonathan A. C. Sterne, PhD
  • CME / ABIM MOC Released: 7/25/2022
  • Valid for credit through: 7/25/2023
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  • Credits Available

    Physicians - maximum of 1.00 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 1.00 ABIM MOC points

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for infectious disease clinicians, internists and other clinicians caring for patients with Lassa fever.

The goal of this activity is for learners to be better able to describe the effectiveness of ribavirin for treatment of Lassa fever, according to a systematic review of published literature and unpublished study results, appraised using ROBINS-I, a state-of-the-art risk for bias tool.

Upon completion of this activity, participants will:

  • Describe the overall effectiveness of ribavirin for treatment of Lassa fever, according to a systematic review of published literature and unpublished study results
  • Determine the effectiveness of ribavirin for treatment of Lassa fever in subgroups, according to a systematic review of published literature and unpublished study results
  • Identify clinical impli the effectiveness of ribavirin for treatment of Lassa fever, according to a systematic review of published literature and unpublished study results


Disclosures

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All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated according to Medscape policies. Others involved in the planning of this activity have no relevant financial relationships.


Faculty

  • Hung-Yuan Cheng, DPhil

    Population Health Sciences
    University of Bristol
    Bristol, United Kingdom

  • Clare E. French, PhD

    Population Health Sciences
    University of Bristol
    National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Behavioural Science and Evaluation 
    University of Bristol
    Bristol, United Kingdom

  • Alex P. Salam, DPhil

    Pandemic Sciences Centre
    University of Oxford
    Oxford, United Kingdom
    United Kingdom Public Health Rapid Support Team
    London, United Kingdom

  • Sarah Dawson, MSc

    Population Health Sciences
    University of Bristol
    Bristol, United Kingdom

  • Alexandra McAleenan, PhD

    Population Health Sciences
    University of Bristol
    Bristol, United Kingdom

  • Luke A. McGuinness, PhD

    Population Health Sciences
    University of Bristol
    Bristol, United Kingdom

  • Jelena Savović, PhD

    Population Health Sciences
    University of Bristol
    National Institute for Health and Care Research (NIHR)
    Applied Research Collaboration West (ARC West)
    Bristol, United Kingdom

  • Peter W. Horby, MD, PhD

    Pandemic Sciences Centre
    University of Oxford
    International Severe Acute Respiratory and emerging Infections Consortium (ISARIC)
    Oxford, United Kingdom

  • Jonathan A. C. Sterne, PhD

    Population Health Sciences
    University of Bristol, Bristol
    National Institute for Health and Care Research (NIHR)
    Bristol Biomedical Research Centre
    Bristol, United Kingdom

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has the following relevant financial relationships:
    Formerly owned stocks in: AbbVie Inc.

Editor

  • Jude Rutledge, BA

    Copyeditor 
    Emerging Infectious Diseases

Compliance Reviewer

  • Leigh Schmidt, MSN, RN, CMSRN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Leigh Schmidt, MSN, RN, CMSRN, CNE, CHCP, has no relevant financial relationships.


Accreditation Statements



In support of improving patient care, this activity has been planned and implemented by Medscape, LLC and Emerging Infectious Diseases. Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

    For Physicians

  • Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.

    Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

    Contact This Provider

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]


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CME / ABIM MOC

Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies

Authors: Hung-Yuan Cheng, DPhil; Clare E. French, PhD; Alex P. Salam, DPhil; Sarah Dawson, MSc; Alexandra McAleenan, PhD; Luke A. McGuinness, PhD; Jelena Savović, PhD; Peter W. Horby, MD, PhD; Jonathan A. C. Sterne, PhDFaculty and Disclosures

CME / ABIM MOC Released: 7/25/2022

Valid for credit through: 7/25/2023

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Abstract and Introduction

Abstract

Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.

Introduction

Lassa virus infection, first described in 1962, is a viral hemorrhagic fever[1]. It is a substantial public health burden, causing an estimated 100,000–200,000 cases each year, mainly in West Africa[2,3]. Many cases are mild or asymptomatic and are not formally diagnosed[4]. The nonspecific clinical manifestation makes Lassa fever difficult to recognize on clinical grounds alone, especially in the early phases. The case-fatality rate is estimated to be 10%–20% in hospitalized patients[5,6] but increases sharply during outbreaks[7]. No vaccine is available, but studies examining recombinant vaccinia virus in animals have entered the preclinical phase, and a DNA vaccine has entered a phase I trial in humans[8–10]. Lassa virus is part of the US Centers for Disease Control and Prevention’s list of category A Select Agents and is considered a priority pathogen by the World Health Organization (WHO) because of its epidemic potential, its severity, lack of available vaccines, and, most important, limited therapeutic options.

The most influential study of the efficacy of ribavirin in treatment of Lassa fever, published in 1986, reported that administration of intravenous ribavirin within the first 6 days of illness decreased mortality rates from severe Lassa fever from 55% to 5%[11]. These findings have underpinned the widespread use of, and unequivocal recommendations for, ribavirin for treatment of Lassa fever. Several retrospective observational studies document the use of ribavirin and describe lower case-fatality rates in patients treated with ribavirin[12–17]. However, potential biases in those results make it difficult to evaluate the effectiveness of ribavirin in clinical practice. Recent unpublished results obtained through the US Freedom of Information Act, and secondary analysis of these results, weaken the case for use of ribavirin[18]. Therefore, we undertook a systematic review of published and unpublished study results, which we appraised by using a state-of-the-art risk for bias tool[19], to evaluate ribavirin for treating Lassa fever.