Infect Chemother.  2017 Mar;49(1):72-77. 10.3947/ic.2017.49.1.72.

Two Treatment Cases of Severe Fever and Thrombocytopenia Syndrome with Oral Ribavirin and Plasma Exchange

• Park I
• Kim HI
• Kwon KT

• KMID: 2375103
• DOI: http://doi.org/10.3947/ic.2017.49.1.72

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease. The primary symptoms associated with SFTS are fever, thrombocytopenia, leukopenia, nausea, and vomiting. Disease progression shows high mortality rate accompanied with multiple organ failure, bleeding tendency, and altered mentality. However, only supportive care has been the basis for the treatment of SFTS. We are reporting two patients who showed central nervous system manifestation, but cured them with ribavirin together with plasma exchange in an early state. The first case is a 60-year-old male, who was admitted to the hospital with a 7-day history of fever, chills, and thrombocytopenia. He was treated with empirical antibiotics; however, he experienced persistent high fever and an altered mentality has occurred. On hospital day 6, the SFTS virus (SFTSV) result from a real-time reverse transcription-polymerase chain reaction (RT-PCR) was confirmed positive. Therefore, ribavirin (30 mg/kg as initial loading dose, 15 mg/kg qid for 4 days and then 7.5 mg/kg qid as maintenance dose) was administered orally for 11 days and plasma exchange was performed for 5 days. The clinical outcome has improved. The second case is a 48-year-old male, who was admitted to the hospital with a 10-day history of fever, chills, myalgia, diarrhea, and thrombocytopenia. He was treated with empirical antibiotics. On hospital day 3, ribavirin (30 mg/kg as initial loading dose, 15 mg/kg qid as maintenance dose) was administered orally for 4 days and plasma exchange was performed for 4 days due to his high fever and altered mentality after a positive SFTSV result from a real-time RT-PCR. The patient had a successful recovery.

Keyword

Severe fever with thrombocytopenia syndrome; Bunyavirus; Ribavirin; Plasma exchange

MeSH Terms

Anti-Bacterial Agents
Central Nervous System
Chills
Diarrhea
Disease Progression
Fever*
Hemorrhage
Humans
Leukopenia
Male
Middle Aged
Mortality
Multiple Organ Failure
Myalgia
Nausea
Orthobunyavirus
Plasma Exchange*
Plasma*
Ribavirin*
Thrombocytopenia*
Tick-Borne Diseases
Vomiting
Anti-Bacterial Agents
Ribavirin

Figure

• 

  Figure 1 Laboratory findings and fever of two patients with severe fever with thrombocytopenia syndrome. CPK, creatinine phosphokinase; LDH, lactate dehydrogenase; HD, hospital day.

Reference

1. Yu XJ, Liang MF, Zhang SY, Liu Y, Li JD, Sun YL, Zhang L, Zhang QF, Popov VL, Li C, Qu J, Li Q, Zhang YP, Hai R, Wu W, Wang Q, Zhan FX, Wang XJ, Kan B, Wang SW, Wan KL, Jing HQ, Lu JX, Yin WW, Zhou H, Guan XH, Liu JF, Bi ZQ, Liu GH, Ren J, Wang H, Zhao Z, Song JD, He JR, Wan T, Zhang JS, Fu XP, Sun LN, Dong XP, Feng ZJ, Yang WZ, Hong T, Zhang Y, Walker DH, Wang Y, Li DX. Fever with thrombocytopenia associated with a novel bunyavirus in China. N Engl J Med. 2011; 364:1523–1532.

2. Shin JS, Park JH, Kwon DH. Epidemiologic and clinical characteristics of severe fever with thrombocytopenia syndrome in the Republic of Korea. Public Health Weekly Report. 2014; 7:493–498.

3. Gai ZT, Zhang Y, Liang MF, Jin C, Zhang S, Zhu CB, Li C, Li XY, Zhang QF, Bian PF, Zhang LH, Wang B, Zhou N, Liu JX, Song XG, Xu A, Bi ZQ, Chen SJ, Li DX. Clinical progress and risk factors for death in severe fever with thrombocytopenia syndrome patients. J Infect Dis. 2012; 206:1095–1102.

4. Ding F, Zhang W, Wang L, Hu W, Soares Magalhaes RJ, Sun H, Zhou H, Sha S, Li S, Liu Q, Li Q, Yang W, Huang L, Li C, Yin W. Epidemiologic features of severe fever with thrombocytopenia syndrome in China, 2011-2012. Clin Infect Dis. 2013; 56:1682–1683.

5. Zhang YZ, He YW, Dai YA, Xiong Y, Zheng H, Zhou DJ, Li J, Sun Q, Luo XL, Cheng YL, Qin XC, Tian JH, Chen XP, Yu B, Jin D, Guo WP, Li W, Wang W, Peng JS, Zhang GB, Zhang S, Chen XM, Wang Y, Li MH, Li Z, Lu S, Ye C, de Jong MD, Xu J. Hemorrhagic fever caused by a novel Bunyavirus in China: pathogenesis and correlates of fatal outcome. Clin Infect Dis. 2012; 54:527–533.

6. Yoo SJ, Heo ST, Lee KH. Severe fever with thrombocytopenia syndrome. Korean J Crit Care Med. 2014; 29:59–63.

7. Heo ST, Cheon M, Kim JW. Four cases of severe fever with thrombocytopenia syndrome occurring in Jeju. Korean J Dermatol. 2014; 52:173–177.

8. Liu W, Lu QB, Cui N, Li H, Wang LY, Liu K, Yang ZD, Wang BJ, Wang HY, Zhang YY, Zhuang L, Hu CY, Yuan C, Fan XJ, Wang Z, Zhang L, Zhang XA, Walker DH, Cao WC. Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in china who had severe fever with thrombocytopenia syndrome. Clin Infect Dis. 2013; 57:1292–1299.

9. Oh WS, Heo ST, Kim SH, Choi WJ, Han MG, Kim JY. Plasma exchange and ribavirin for rapidly progressive severe fever with thrombocytopenia syndrome. Int J Infect Dis. 2014; 18:84–86.

10. Kim KH, Yi J, Kim G, Choi SJ, Jun KI, Kim NH, Choe PG, Kim NJ, Lee JK, Oh MD. Severe fever with thrombocytopenia syndrome, South Korea, 2012. Emerg Infect Dis. 2013; 19:1892–1894.

11. Kim SH, Kim KP, Heo ST, Kim YR, Kang SH. Experience of therapeutic plasma exchange in patients with severe fever with thrombocytopenia syndrome. Korean J Blood Transfus. 2014; 25:211–217.

12. Kurnaz F, Metan G, Coskun R, Kaynar L, Eser B, Doğanay M. A case of Crimean-Congo haemorrhagic fever successfully treated with therapeutic plasma exchange and ribavirin. Trop Doct. 2011; 41:181–182.

13. Shimojima M, Fukushi S, Tani H, Yoshikawa T, Fukuma A, Taniguchi S, Suda Y, Maeda K, Takahashi T, Morikawa S, Saijo M. Effects of ribavirin on severe fever with thrombocytopenia syndrome virus in vitro. Jpn J Infect Dis. 2013; 67:423–427.

14. Ohagi Y, Tamura S, Nakamoto C, Nakamoto H, Saijo M, Shimojima M, Nakano Y, Fujimoto T. Mild clinical course of severe fever with thrombocytopenia syndrome virus infection in an elderly Japanese patient. Case Rep Infect Dis. 2014; 2014:918135.

15. Burrows FS, Carlos LM, Marriott D, Havryk A, Plit M, Glanville AR. Oral ribavirin is a cost-effective alternative to intravenous ribavirin for respiratory syncytial virus (RSV) infection after lung transplantation (LTx). J Heart Lung Transplant. 2013; 32:S109.

16. Mardani M, Jahromi MK, Naieni KH, Zeinali M. The efficacy of oral ribavirin in the treatment of crimean-congo hemorrhagic fever in Iran. Clin Infect Dis. 2003; 36:1613–1618.

17. Lee MJ, Kim KH, Yi J, Choi SJ, Choe PG, Park WB, Kim NJ, Oh MD. In vitro antiviral activity of ribavirin against severe fever with thrombocytopenia syndrome virus. [Epub ahead of print]. Korean J Intern Med. 2016.

18. Mokrzycki MH, Kaplan AA. Therapeutic plasma exchange: complications and management. Am J Kidney Dis. 1994; 23:817–827.

19. Russmann S, Grattagliano I, Portincasa P, Palmieri VO, Palasciano G. Ribavirin-induced anemia: mechanisms, risk factors and related targets for future research. Curr Med Chem. 2006; 13:3351–3357.

20. Deng B, Zhou B, Zhang S, Zhu Y, Han L, Geng Y, Jin Z, Liu H, Wang D, Zhao Y, Wen Y, Cui W, Zhou Y, Gu Q, Sun C, Lu X, Wang W, Wang Y, Li C, Wang Y, Yao W, Liu P. Clinical features and factors associated with severity and fatality among patients with severe fever with thrombocytopenia syndrome Bunyavirus infection in Northeast China. PLoS One. 2013; 8:e80802.