Steroid pulse therapy in patients with encephalopathy associated with severe fever with thrombocytopenia syndrome

Nakamura, Shingen; Azuma, Momoyo; Maruhashi, Tomoko; Sogabe, Kimiko; Sumitani, Ryohei; Uemura, Munenori; Iwasa, Masami; Fujii, Shiro; Miki, Hirokazu; Kagawa, Keiichiro; Hiraga, Takashi; Kondo, Noriyasu; Fujita, Hiromi; Mahara, Fumihiko; Abe, Masahiro

doi:10.1016/j.jiac.2017.11.004

Cited by 31 publications

(24 citation statements)

References 13 publications

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“… 23 SFTSV infection-induced cytokine storm indirectly triggers consciousness disturbance. 24 More than half of patients suffered consciousness disturbance in our data. In clinical settings, steroid pulse therapy and plasma exchange are widely used to suppress excessive cytokine production, showing some visible effects.…”

Section: Discussionmentioning

confidence: 48%

Risk Factors and Clinical Characteristics of Severe Fever with Thrombocytopenia Syndrome

Wang¹,

Wu²,

Jiao³

et al. 2020

IJGM

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This study was to investigate the clinical characteristics and laboratory parameters of severe fever with thrombocytopenia syndrome (SFTS). Patients and Methods: A detailed retrospective analysis of clinical records for SFTS patients was conducted. Fifty-one cases confirmed SFTS virus infected were enrolled. The clinical characteristics and laboratory parameters between survivors and non-survivors were analyzed. Results: All patients aged between 30 and 80 years were farmers or residing in wooded and hilly areas. All patients occurred between April and October. The major clinical manifestations were fever, fatigue, diarrhea, myalgia, nausea and vomiting. Conscious disturbance, lymph node enlargement and hemorrhage were common. Fatal outcome occurred in 31.4% (16/51) of patients. Compared with survivors group, in non-survivors group, the proportion of consciousness disturbance, age, the levels of AST, LDH, Bun, Cr, PT and APTT were significantly increased, and PLT was significantly decreased. The age, PLT, AST, LDH, Cr, PT and APTT were the risk factors for fatal outcomes. Moreover, the age (OR, 1.245; 95% CI, 1.052-1.474) and APTT (OR, 1.095; 95% CI, 1.005-1.192) were the independent risk factors for fatal outcomes. Heteromorphic lymphocyte and hemophagocytosis could be found in SFTS patients, especially the proportion of finding hemophagocytosis was significantly higher in non-survivors group compared with survivors group. Conclusion:These results suggest SFTS is a systemic infection, the age and APTT can be used as potential predictors referring to severe SFTS cases.

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Section: Discussionmentioning

confidence: 48%

Risk Factors and Clinical Characteristics of Severe Fever with Thrombocytopenia Syndrome

Wang¹,

Wu²,

Jiao³

et al. 2020

IJGM

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“…Nevertheless, our study clearly indicates the potential therapeutic effect of nifedipine in treating SFTS patients and strongly supports the design of future clinical trials to evaluate the safety and efficacy of CCB therapy for SFTS patients, for both benidipine hydrochloride and nifedipine. Moreover, combination treatment with other supportive regimens, including the therapeutic plasma exchange or steroid pulse therapy, which has been suggested to be partially effective, [60][61][62] could be considered.…”

Section: Discussionmentioning

confidence: 99%

Calcium channel blockers reduce severe fever with thrombocytopenia syndrome virus (SFTSV) related fatality

Zhang

et al. 2019

Cell Res

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Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne infectious disease caused by a novel phlebovirus (SFTS virus, SFTSV), was listed among the top 10 priority infectious diseases by the World Health Organization due to its high fatality of 12%-50% and possibility of pandemic transmission. Currently, effective anti-SFTSV intervention remains unavailable. Here, by screening a library of FDA-approved drugs, we found that benidipine hydrochloride, a calcium channel blocker (CCB), inhibited SFTSV replication in vitro. Benidipine hydrochloride was revealed to inhibit virus infection through impairing virus internalization and genome replication. Further experiments showed that a broad panel of CCBs, including nifedipine, inhibited SFTSV infection. The anti-SFTSV effect of these two CCBs was further analyzed in a humanized mouse model in which CCB treatment resulted in reduced viral load and decreased fatality rate. Importantly, by performing a retrospective clinical investigation on a large cohort of 2087 SFTS patients, we revealed that nifedipine administration enhanced virus clearance, improved clinical recovery, and remarkably reduced the case fatality rate by >5-fold. These findings are highly valuable for developing potential host-oriented therapeutics for SFTS and other lethal acute viral infections known to be inhibited by CCBs in vitro.

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“…The development of specific treatment for SFTS is crucial because SFTSV infection is relatively rare and the affected patients are mainly elderly. Some proposed treatments for SFTS include steroid pulse therapy (Nakamura et al, 2018), plasma exchange (Oh et al, 2014;Yoo et al, 2019), and antiviral drugs (Saijo, 2018); however, their effectiveness remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Antiviral Drugs Against Severe Fever With Thrombocytopenia Syndrome Virus Infection

Takayama-Ito

Saijo

2020

Front. Microbiol.

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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by SFTS virus (SFTSV), which is a novel bunyavirus. SFTSV was first isolated from patients who presented with fever, thrombocytopenia, leukocytopenia, and multiorgan dysfunction in China. Subsequently, it was found to be widely distributed in Southeast Asia (Korea, Japan, and Vietnam). SFTSV can be transmitted not only from ticks but also from domestic animals, companion animals, and humans. Because the case fatality rate of SFTS is high (6-30%), development of specific and effective treatment for SFTS is required. Studies of potential antiviral drugs for SFTS-specific therapy have been conducted on existing or newly discovered agents in vitro and in vivo, with ribavirin and favipiravir being the most promising candidates. While animal experiments and retrospective studies have demonstrated the limited efficacy of ribavirin, it was also speculated that ribavirin would be effective in patients with a viral load <1 × 10 6 copies/mL. Favipiravir showed higher efficacy than ribavirin against SFTSV in in vitro assays and greater efficacy in animal models, even administrated 3 days after the virus inoculation. Although clinical trials evaluating the efficacy of favipiravir in SFTS patients in Japan are underway, this has yet to be confirmed. Other drugs, including hexachlorophene, calcium channel blockers, 2 ′ -fluoro-2 ′ -deoxycytidine, caffeic acid, amodiaquine, and interferons, have also been evaluated for their inhibitory efficacy against SFTSV. Among them, calcium channel blockers are promising because in addition to their efficacy in vitro and in vivo, retrospective clinical data have indicated that nifedipine, one of the calcium channel blockers, reduced the case fatality rate by >5-fold. Although further research is necessary to develop SFTS-specific therapy, considerable progress has been achieved in this area. Here we summarize and discuss recent advances in antiviral drugs against SFTSV.Keywords: severe fever with thrombocytopenia syndrome, severe fever with thrombocytopenia syndrome virus, antiviral, ribavirin, favipiravir Frontiers in Microbiology | www.frontiersin.org

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Steroid pulse therapy in patients with encephalopathy associated with severe fever with thrombocytopenia syndrome

Cited by 31 publications

References 13 publications

Risk Factors and Clinical Characteristics of Severe Fever with Thrombocytopenia Syndrome

Risk Factors and Clinical Characteristics of Severe Fever with Thrombocytopenia Syndrome

Calcium channel blockers reduce severe fever with thrombocytopenia syndrome virus (SFTSV) related fatality

Antiviral Drugs Against Severe Fever With Thrombocytopenia Syndrome Virus Infection

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