Bradycardia Related to Ribavirin in Four Pediatric Patients with Crimean-Congo Hemorrhagic Fever

Abstract

Crimean-Congo hemorrhagic fever (CCHF) is a potentially fatal fever due to infection with the CCHF virus, which belongs to the genus Nairovirus in the Bunyaviridae family and causes severe disease in humans, with reported mortality rates of 15–70% (Centers for Disease Control and Prevention 1983). Humans become infected through the bites of ticks, by contact with blood or tissue from viremic livestock, or by contact with a patient with CCHF during the acute phase of infection (Khan et al. 1997). Uysal et al. (2012) reported bradycardia in a patient with CCHF related to ribavirin treatment. We have observed the same side effect in four pediatric patients that also resolved with discontinuation of ribavirin.

Case Reports

Four children aged between 11 and 15 years old (mean 13.8±1.9 years) were admitted to hospital with fever and tick bite history within a week. Physical examination of the patients was normal. Laboratory studies of the patients showed thrombocytopenia (mean 92±38×10⁹/L), leukopenia (mean 2.5±1.7×10⁹/L), and elevated creatinine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase levels (ALT) (mean 432 U/L, 1007 U/L, 172 U/L, and 81 U/L, respectively). Ribavirin was initiated to these four patients, and bradycardia developed within 3–5 days (mean 3.8±0.9 days) (admission/postribavirin heart rates were 88/48 min, 92/46 min, 76/52 min, and 68/44 min). Sinus bradycardia was present at electrocardiography of the patients, whereas echocardiographic assessments were normal. The 24-h ambulatory rhythm Holter records also revealed sinus bradycardia. Discontinuation of ribavirin led to normal heart rhythm within a day in all of the patients. None of the cases were severe CCHF cases, and they all recovered completely when discharged.

Conclusions

Although cardiac involvement other than rhythm abnormalities has been reported in patients with CCHF (Engin et al. 2009, Gul et al. 2011, Yilmaz et al. 2011), Uysal et al. (2012) first reported bradycardia related to ribavirin in an adult patient. Our observation with four pediatric patients might prove that bradycardia could be another adverse effect of ribavirin that was underestimated. Bradycardia was also detected in 19–73% of individuals with hemorrhagic fever with renal syndrome (HFRS) who were under ribavirin therapy. Although bradycardia might be due to the course of CCHF itself, normal cardiac rhythm after discontinuation of ribavirin suggests that bradycardia might be due to ribavirin. Cardiac involvement in HFRS could explain the etiology of bradycardia, yet randomized controlled studies are needed to evaluate adverse effects of ribavirin. The source population of future studies should be patients receiving ribavirin for treatment of CCHF and other viral diseases. Also observation in patients receiving ribavirin by means of bradycardia is suggested.

Footnotes

Author Disclosure Statement

The authors have no conflict of interest to disclose.

References

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