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Bradycardia in a patient with Crimean-Congo hemorrhagic fever related to ribavirin treatment.

Key words Bradycardia; Crimean-Congo hemorrhagic fever; ribavirin

Crimean-Congo hemorrhagic fever (CCHF) has been reported from more than 30 countries around the world. Ribavirin is the only drug which has in vitro effect on CCHF virus. Although there is a debate on the clinical benefit of ribavirin, some experts from the endemic areas strongly recommend ribavirin in patients with CCHF based on in vitro activity and rare adverse events with shortterm use (1). Here, we report bradycardia in a patient with CCHF related to high dose ribavirin administration.

Case history

A 57-yr old man was admitted to hospital with fever, fatigue and epistaxis. He was living in an endemic area of CCHF and had history of tick bite four days previously. The physical examination was unremarkable except fever of 38.2[degrees]C. Laboratory tests were as follows: White blood cells (WBC) 1.9 x [10.sup.9]/l (neutrophils 90%); hemoglobin was 11.3 g/l; thrombocyte count was 128 x [10.sup.9]/l. The level of aspartate aminotransferase (AST) was 97 U/l; alanine aminotransferase (ALT) was 55 U/l; lactate dehydrogenase (LDH) was 510 U/l; Gama-glutamyl transferase (GGT) was 20 U/l; total bilirubin was 0.7 mg/dl; prothrombin time was 13 sec; activated partial thromboplastin time was 35 sec; and International Normalized Ratio (INR) was 1.18. The renal function tests and serum electrolytes were in normal range. On third day of followup thrombocytes decreased to 43 x [10.sup.9]/l and then 18 x [10.sup.9]/l. AST and ALT increased to 431 and 189 U/l. Fever continued to spike and ribavirin (2 g loading then 4 g/day maintenance) was started with thrombocyte replacement. After three days of ribavirin treatment bradycardia (heart rate of 30-40/min) developed. Electrocardiograpy was normal except sinusoidal bradycardia. Echocardiography and ambulatuar holter record for 24 h did not reveal any pathologic finding. Serum electrolytes were in normal range. Ribavirin was stopped on fourth day and the heart rate became normal one day later. Clinical diagnosis of CCHF was confirmed by ELISA test that was performed at Refik Saydam National Public Health Agency (RSHM), the reference laboratory for CCHF. On the sixth day of admission fever was resolved and laboratory findings improved as WBC 3.7 x 109/l; hemoglobin 13.3 g/l; thrombocytes 166 x [10.sup.9]/l; AST: 127 U/l; ALT: 131 U/l; ALP: 89 U/l; GGT: 78 U/l; and LDH: 387 U/l. He was discharged in good condition on the 10th day of hospitalization.


Cardiac involvement was reported in patients with CCHF based on echocardiography findings (2). Two recent studies evaluated the electrocardiography of 49 adult and 23 pediatric patients with CCHF. Although T-wave negativity or bundle branch block was detected in adult patients, rhythm abnormality was not detected in any patient (3,4). In our patient, cardiac involvement was ruled out with completely normal echocardiography. The main adverse events related to high dose ribavirin were reversible hemolytic anemia and hypomagnesemia in patients with hemorrhagic fever with renal syndrome (HFRS). Bradycardia was reported in three of 34 patients who received high dose ribavirin. However, bradycardia was also detected as the manifestation of the disease in 19-73% of individuals with HFRS, and in this setting it is very difficult to make a differential diagnosis either bradycardia developed because of the cardiac involvement of HFRS or related to ribavirin treatment (5). Rhythm abnormality was not detected as an adverse effect in the studies which evaluated the role of oral or intravenous ribavirin in the treatment of CCHF (1,6,7). To the best of our knowladge, this is the first case reporting bradycardia related to ribavirin treatment in a patient with CCHF. It can be concluded that physicians who use ribavirin in the treatment of CCHF should be careful about the rare adverse events related to this drug.

Conflicts of interest: None related to this study for all authors.

Funding source: None

Received: 5 March 2012 Accepted in revised form: 18 July 2012


(1.) Ergonul O. Treatment of Crimean-Congo hemorrhagic fever. Antiviral Res 2008; 78: 125-31.

(2.) Engin A, Yilmaz MB, Elaldi N, Erdem A, Yalta K, Tandogan I, et al. Crimean-Congo hemorrhagic fever: Does it involve the heart? Int J Infect Dis 2009; 13: 369-73.

(3.) Yilmaz MB, Engin A, Bektasoglu G, Zorlu A, Ege MR, Bakir M, et al. Does electrocardiography at admission predict outcome in Crimean-Congo hemorrhagic fever? J Vector Borne Dis 2011; 48: 150-k

(4.) Gul I, Kaya A, Giiven AS, Karapinar H, Kiiciikdurmaz Z, Yilmaz A, et al. Cardiac findings in children with Crimean-Congo hemorrhagic fever. Med Sci Monit 2011;17: CR457-60.

(5.) Rusnak J, Byrne WR, Chung KN, Gibbs PH, Kim TT, Boudreau EF, et al. Experience with intravenous ribavirin in the treatment of hemorrhagic fever with renal syndrome in Korea. Antiviral Res 2009; 81: 68-76.

(6.) Koksal Y, Yimaz G, Aksoy F, Aydin H, Yavuz I, Iskender S, et al. The efficacy of ribavirin in the treatment of CrimeanCongo hemorrhagic fever in Eastern Black Sea region in Turkey. J Clin Virol 2010; 47: 65-8.

(7.) Bodur H, Erbay A, Akinci E, Onguru P, Bayazit N, Eren S, Kubar A. Effect of oral ribavirin treatment on the viral load and disease progression in Crimean-Congo hemorrhagic fever. Int J Infect Dis 2011; 15: 44-7.

Correspondence to: Dr Gokhan Metan, Associate Professor in Infectious Diseases, Erciyes Universitesi Tip Fakiiltesi, Gevher Nesibe Hastanesi, Enfeksiyon Hastaliklari Klinigi Kat:10, Melikgazi, Kayseri, Turkey 38039 E-mail:;

Burcu Uysal & Gokhan Metan

Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
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Article Details
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Title Annotation:Case Report
Author:Uysal, Burcu; Metan, Gokhan
Publication:Journal of Vector Borne Diseases
Article Type:Case study
Geographic Code:6ZAIR
Date:Sep 1, 2012
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