Elsevier

Journal of Infection

Volume 58, Issue 3, March 2009, Pages 238-244
Journal of Infection

Efficacy of oral ribavirin treatment in Crimean-Congo haemorrhagic fever: A quasi-experimental study from Turkey

https://doi.org/10.1016/j.jinf.2009.01.014Get rights and content

Summary

Objective

The aim of this study was to evaluate the efficacy of oral ribavirin treatment in patients with Crimean-Congo haemorrhagic fever (CCHF).

Methods

In 2004, all patients diagnosed with CCHF were treated with oral ribavirin, however in 2003 none of the CCHF patients had been given treatment due to lack of confirmatory diagnostic information at that time in Turkey. In this study, patients treated with ribavirin in 2004 (n = 126) were compared with ribavirin-untreated CCHF patients (n = 92) in 2003. Patients only with a definitive diagnosis of CCHF (clinical symptoms plus the presence of specific IgM antibodies against CCHF virus and presence of viral antigen) were included in this study.

Results

There was no difference in the case-fatality rate between treated and untreated patients (7.1% vs. 11.9%; P > 0.05). A Cox Proportional Hazards regression analysis revealed that altered sensorium and prolonged international normalized ratio were independent predictors of mortality.

Conclusion

Our results showed that oral ribavirin treatment did not improve the survival rate in CCHF patients. Ribavirin and supportive care are the only available choices for treatment of CCHF patients, but to ascertain the efficacy of ribavirin, more laboratory and observational studies are necessary and ultimately, to elucidate these conflicting results and evaluate the efficacy undoubtedly, a multicenter randomised controlled trial will be needed.

Introduction

Crimean-Congo haemorrhagic fever (CCHF) is a potentially fatal, acute infection caused by CCHF virus belonging to the Nairovirus genus of the family Bunyaviridae.1 Ribavirin, an antiviral compound, has been shown to be effective against several haemorrhagic fever viruses such as Rift Valley Fever virus, Hantaan virus, and Lassa virus.2, 3, 4, 5 Furthermore, it inhibits the replication of CCHF virus in Vero cells and in animal models of CCHF.6, 7 Previously published case-series8, 9, 10 and a comparative study using historical controls11 suggested that oral ribavirin may be beneficial in the treatment of CCHF. Although not approved by Food and Drug Administration (FDA), oral ribavirin has been recommended by the World Health Organization (WHO) as a potential therapeutic agent for CCHF.9

The incidence of CCHF has dramatically increased in recent years in several countries in Africa, Middle East, and Central Asia.12 Likewise, dramatically increased numbers of patients with a haemorrhagic fever of unknown aetiology have been admitted to tertiary care hospitals from rural parts of North East Anatolia and Southern Black Sea region in Turkey starting from 2001. The disease was later confirmed to be CCHF in late 2003. Since the diagnosis was not known at the time of hospitalisation, none of the patients received ribavirin until 2004, clinical characteristics of those patients have been published previously.13 In 2004, all the hospitals in Turkey started to treat the patients diagnosed with CCHF by oral ribavirin. This naturally occurring condition was in accordance with a quasi-experimental study design and gave us the opportunity to evaluate the effectiveness of oral ribavirin treatment by comparing patients who were admitted in 2004 with patients who were admitted in 2003.14

Section snippets

Study design, patient population and participating centres

This was a multicenter, quasi-experimental (pre–post) intervention study. All patients diagnosed in 2004 were treated with ribavirin administered orally; the recovery and disease progression in these patients were compared with patients who were diagnosed in 2003 and did not receive ribavirin. Patients with a definitive diagnosis of CCHF which required typical clinical presentation plus the presence of specific IgM antibody or isolation of viral antigen were included in this study.13 Four large

Demographics, clinical and laboratory characteristics of the treated and untreated cohorts

In 2003, 92 patients were diagnosed with CCHF. None of these patients were treated with oral ribavirin at that time. In 2004, a total of 166 patients were admitted to participating centres with suspected CCHF. Five patients could not be treated with oral ribavirin due to pregnancy and problems in obtaining the medication. Of the 161 ribavirin-treated patients, 126 of them had a definitive diagnosis of CCHF and were included in the present study. Of the total 218 patients included (both treated

Discussion

The present study is the largest comparative study in the literature on the effect of oral ribavirin treatment in confirmed CCHF patients. Our results showed that, ribavirin treatment did not improve survival rate in CCHF patients. In our study, there was a clear time point when the treatment strategy changed for all the patients, therefore it is more appropriate to call this study quasi-experimental rather than a historical control study.14 This design helps to avoid selection bias which is

Acknowledgements

We would like to thank our colleagues from the Turkish Ministry of Health for their contributions.

References (22)

  • S.P. Fisher-Hoch et al.

    Crimean Congo-haemorrhagic fever treated with oral ribavirin

    Lancet

    (1995)
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