Expert consensus on diagnosis and treatment of severe fever with thrombocytopenia syndrome / 中华临床感染病杂志

Since 2010, the incidence of severe fever with thrombocytopenia syndrome (SFTS) has been increased. Owing the progress in diagnosis and treatment, the overall mortality of SFTS in China has decreased, while the mortality in critical SFTS patients is still high. In order to provide guidance and working procedures for clinicians to diagnose and treat critical SFTS, the National Medical Center for Major Public Health Events invited experts to discuss and formulate this consensus based on their experience and up-to-date knowledge on SFTS.

Abnormal coagulation activity and the related clinical significance in patients with novel bunyavirus infection / 中华检验医学杂志

Objective:To explore the related indexes of coagulation and thrombosis and their clinical significance in patients with severe fever with thrombocytopenia symptoms (SFTS) during the onset and recovery period after novel bunyavirus infection.Methods:A total of 36 patients diagnosed with SFTS (SFTS onset group) and 18 convalescent SFTS patients, who were hospitalized in the First Affiliated Hospital of Anhui Medical University from April 12, 2020, to October 12, 2020 were recruited in this study. Thirty-six healthy controls were recruited from volunteers. Plasma was collected and prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time(TT), antithrombin-Ⅲ (AT-Ⅲ), fibrin degradation product (FDP) and D-dimer (D-D) were determined by automatic blood coagulation analyzer. Thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasminase-α2 plasminase inhibitor complex (PIC) and tissue plasminogen activator-plasminogen activator inhibitor 1 complex (t-PAIC) were determined by an automatic chemiluminescence analyzer.Results:Compared with the healthy control group, PT was significantly prolonged (12.5 [12.1, 13.6] s, vs 10.8 [10.5, 11.5] s, P<0.05) in SFTS onset group, but was still within the reference range (14.0-21.0 s), and APTT (49.1 [42.0, 58.2]s vs 28.5 [26.6, 30.4]s, P<0.05) was also significantly prolonged in SFTS onset group. Compared with healthy control group, FDP (6.07 [2.67, 8.64] μg/ml vs 1.00 [0.80, 1.87] μg/ml, P<0.001), D-D (2.27 [1.04, 2.98] μg/ml vs 0.30 [0.21, 0.47] μg/ml, P<0.001), TAT (16.05 [8.05, 26.58] ng/ml vs 3.55 [2.60, 4.85] ng/ml, P<0.001), PIC (4.44 [2.52, 5.54] μg/ml vs 0.84 [0.60, 1.35] μg/ml, P<0.001), TM ([19.41±8.29] TU/ml vs [9.33±1.89] TU/ml, P<0.001), and t-PAIC ([37.52±21.10] ng/ml vs [7.06±3.37] ng/ml, P<0.001) values were all significantly higher in the SFTS onset group (all P<0.001). The level of TAT in the SFTS recovery group (9.10 [3.95, 18.40] ng/ml) was still out of the reference range (<4 ng/ml), while the level of PIC in the SFTS recovery group was lower than in SFTS onset group (1.91 [1.45, 2.93] μg/ml vs 4.44 [2.52, 5.54] μg/ml, P<0.05). Compared with SFTS onset group, the levels of TM and t-PAIC were lower in the SFTS recovery group ( P<0.05). Conclusions:Coagulation system activation and vascular endothelial injury are evidenced in SFTS patients. In the convalescence period, the vascular endothelial injury is recovered, however, there is still a certain degree of coagulation dysfunction, therefore, it is necessary to monitor the coagulation indicator of discharged patients post SFTS.

A clustering analysis based on clinical laboratory indications of patients with bunyavirus infection / 中国基层医药

Objective@#To execute a hierarchical cluster of clinical laboratory indicators in patients with bunyavirus infection.@*Methods@#From July 2015 to July 2017, 14 patients with bunyavirus infection in Zhoushan Hospital were selected.The blood routine, coagulation function and biochemical indicators were detected.Cluster analysis and grouping were carried out by hierarchical clustering method.@*Results@#Hierarchical clustering classification was eventually divided into 2 cases of A category[with TT high and BNP high as the main characteristics(TThighBNPhigh)] and 12 cases of B category[with TT low and BNP low as the main characteristics (TTlowBNPlow)]. The days of hormone drugs and dosage of hormone drugs in A category were (7.43±3.53)d, (489.19±173.02)mg, respectively, which were higher than those in B category[(5.20±1.03)d and (115.11±46.58)mg], the differences were statistically significant(t=2.76, 55.56, all P<0.05).@*Conclusion@#It needs probably to pay more days and dose of hormonal drugs for patients with TThighBNPhigh.

A clustering analysis based on clinical laboratory indications of patients with bunyavirus infection / 中国基层医药

Objective To execute a hierarchical cluster of clinical laboratory indicators in patients with bunyavirus infection.Methods From July 2015 to July 2017,14 patients with bunyavirus infection in Zhoushan Hospital were selected.The blood routine, coagulation function and biochemical indicators were detected.Cluster analysis and grouping were carried out by hierarchical clustering method.Results Hierarchical clustering classifica-tion was eventually divided into 2 cases of A category[with TT high and BNP high as the main characteristics (TThigh-BNPhigh)] and 12 cases of B category[with TT low and BNP low as the main characteristics (TTlowBNPlow)].The days of hormone drugs and dosage of hormone drugs in A category were (7.43 ±3.53)d,(489.19 ±173.02) mg, respectively,which were higher than those in B category [(5.20 ±1.03)d and (115.11 ±46.58)mg],the differences were statistically significant (t＝2.76,55.56,all P＜0.05).Conclusion It needs probably to pay more days and dose of hormonal drugs for patients with TThighBNPhigh.

Prevalence of severe fever with thrombocytopenia syndrome virus infection in Zhoushan island and duration of serum positive IgG antibody in infected patients / 中华临床感染病杂志

Objective@#To analyze the prevalence of severe fever with thrombocytopenia syndrome virus(SFTSV)infection in Zhoushan island of Zhejiang province and the duration of serum positive IgG antibody in patients infected with SFTSV.@*Methods@#One thousand one hundred and twenty-two healthy people from Zhoushan island of Zhejiang province were recruited for cross-sectional study in August 2019, including 641 from non-epidemic areas and 481 from epidemic areas. The serum SFTSV-IgG antibody was detected by enzyme-linked immunosorbent assay (ELISA), and the positive rates of SFTSV-IgG antibody were compared between people from the epidemic areas and non epidemic areas. Meanwhile, the antibody titer of SFTSV-IgG in 19 patients confirmed between July 2011 and June 2018 was detected by indirect ELISA. SPSS 17.0 software was used to analyze data.@*Results@#The positive rate of SFTSV-IgG antibody was 1.5% (7/481) in the epidemic area, which was higher than that in the non-epidemic area (0/641) (χ2=7.187, P<0.01). The positive rates of SFTSV-IgG antibody in 2019 were lower than those in the epidemic area (11.7%) and non-epidemic area (2.5%) in 2013 (χ2=22.556 and 10.352, both P<0.01). The serum SFTSV-IgG antibody of 18 patients with previous infection was still positive, and the longest one lasted for 8 years.@*Conclusions@#There is a SFTSV latent infection in population from epidemic area of Zhoushan island. The SFTSV-IgG antibody can last for a long time in patients with SFTS and it may have certain protective effect.

Epidemiological and Clinical Characteristics of Confirmed Cases of Severe Fever With Thrombocytopenia Syndrome in Jeju Province, Korea, 2014-2018 / 예방의학회지

OBJECTIVES: Jeju Province is well known as the region showing the highest incidence of severe fever with thrombocytopenia syndrome (SFTS) in South Korea. The aim of this study was to evaluate the epidemiological and clinical characteristics of SFTS patients in Jeju Province. METHODS: The primary data for this study were obtained from the Integrated Diseases and Health Control System of the Korea Centers for Disease Control and Prevention (KCDCIS). The selection criteria were confirmed cases of SFTS with a residence listed in Jeju Province at the time of diagnosis, reported to the KCDCIS between July 16, 2014 and November 30, 2018. RESULTS: Of 55 confirmed cases of SFTS, the case fatality rate was 10.9% (95% confidence interval [CI], 4.1 to 22.2). The most common presenting symptoms at diagnosis of severe fever, myalgia, and diarrhea had incidences of 83.6% (95% Cl, 71.2 to 92.2), 45.5% (95% Cl, 32.0 to 59.5), and 40.0% (95% CI, 27.0 to 54.1), respectively. CONCLUSIONS: Compared to SFTS patients nationwide in 2013-2015, the subjects of this study exhibited a lower case fatality rate and had a lower incidence of severe fever, myalgia, and confusion.

A case of severe fever with thrombocytopenia syndrome virus related encephalitis / 中华神经科杂志

The severe fever with thrombocytopenia syndrome virus (SFTSV),a new RNA virus,was discovered in recent years,which can lead to fever,thrombocytopenia and multiple organ dysfunction.Picks is the main media A case of a SFTSV-related encephalitis diagnosed by second-generation gene sequencing was reported here.The patient had fever,disturbance of consciousness,convulsions,with thrombocytopenia and enzymatic indicators increased significantly.After active anti-virus and supportive treatment,the prognosis was good.It is our aim to suggest that,in the epidemic season,when you meet thesimilar patients like this,you should consider the possibility of SFTSV-related encephalitis.Virus nucleic acid detection and second-generation gene sequencing technology are helpful for timely diagnosis and treatment and reducing mortality of the disease.

Hantavirus pulmonary syndrome in Tucumán province associated to an unexpected viral genotype

We describe the characterization of the viral genotype involved in the first case of hantavirus pulmonary syndrome reported in Tucumán, a Northwestern province of Argentina. A 23-year-old woman, with no record of travel history and previously diagnosed with an antiphospholipid syndrome, died after 11 days of severe cardiopulmonary insufficiency. Among the four endemic regions of hantavirus pulmonary syndrome in Argentina, the Northwest Region has the highest incidence, exceeding 50% of all reported cases in the country. Until now, only Salta and Jujuy (2 out of the 6 provinces composing the Northwest Region), reported cases of hantavirus pulmonary syndrome, all of which occurred in the Yungas Forest area. Remarkably, the viral genotype characterized in this case showed higher nucleotide identity with the Andes-BsAs genotype most prevalent in Buenos Aires province, located 1400 km apart from Tucumán, than with any of the commonly found genotypes in the Northwest Region. The Andes-BsAs genotype has been associated with 30% lethality and interhuman transmission in Buenos Aires province. Interhuman transmission cannot be ruled out in the present case.

Se describe la caracterización del genotipo viral del primer caso de síndrome pulmonar por hantavirus reportado en la Provincia de Tucumán. Una mujer de 23 años, con diagnóstico previo de síndrome antifosfolipídico y sin antecedente de viaje reciente, falleció tras 11 días de enfermedad. De las cuatro regiones endémicas para este síndrome, la región Noroeste es la de mayor incidencia del país, concentrando más del 50% de los casos informados en Argentina. Hasta el momento, solamente dos de las seis provincias que componen la región Noroeste, Salta y Jujuy, habían registrado síndrome pulmonar por hantavirus con casos en áreas pertenecientes a la Selva de las Yungas. Desde ahora, se suma a dicha región la provincia de Tucumán. Llamativamente, el genotipo viral caracterizado en este caso mostró mayor identidad con el genotipo más prevalente en la provincia de Buenos Aires llamado Andes-BsAs, y no como se esperaba, con los genotipos comúnmente encontrados en la región Noroeste. El genotipo Andes-BsAs se ha asociado a letalidad próxima al 30% y también a transmisión interhumana en la provincia de Buenos Aires. No se puede descartar transmisión interhumana en el presente caso.

In vitro antiviral activity of ribavirin against severe fever with thrombocytopenia syndrome virus

BACKGROUND/AIMS: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV), a novel bunyavirus. As yet, there is no effective antiviral therapy for SFTS. Ribavirin is a broad-spectrum antiviral agent, which has been tried for treatment of SFTS. In this study, antiviral activity of ribavirin against SFTSV has been investigated. METHODS: Vero cell-grown SFTSV strain Gangwon/Korea/2012 was treated with ribavirin at various concentrations. Antiviral activity of ribavirin was evaluated by inhibition of the SFTSV cytopathic effect in Vero cells and quantification of viral RNA load in culture supernatant using one-step real-time reverse transcription polymerase chain reaction. Cytotoxicity of ribavirin was determined by a tetrazolium-based colorimetric method. RESULTS: Ribavirin reduced SFTSV titers in a dose-dependent manner, with a half-maximal inhibitory concentration ranged from 3.69 to 8.72 μg/mL. Cytopathic effects were reduced as ribavirin concentration increased. No significant cytotoxicity was detected at ribavirin concentrations of ≤ 31.3 μg/mL. CONCLUSIONS: Ribavirin exhibited inhibitory activity against SFTSV replication in vitro, which suggests that ribavirin can be used as a potential antiviral agent for SFTS.

Seroprevalence of Severe Fever with Thrombocytopenia Syndrome in Southeastern Korea, 2015

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease characterized by fever, thrombocytopenia and diarrhea. SFTS was firstly reported in Korea in 2013 but its seroprevalence in the country has yet to be investigated. Here, we investigate the seroprevalence of SFTS in a Korean population. A cross-sectional study was conducted on patients who had their sera tested for various reasons at a tertiary university hospital on particular days in May 2015. This study was conducted in a tertiary hospital in southeastern Korea. Total antibodies including immunoglobulin G (IgG) and immunoglobulin M (IgM), specific to SFTS virus (SFTSV) in serum samples were detected by a double-antigen sandwich enzyme-linked immunosorbent assay (ELISA). A total of 1,069 serum samples were tested. Median age was 59 years (range 12–96 years), and 51.5% were male. Overall, 22 patients (2.1%) were tested positive for anti-SFTSV antibodies. The SFTS seroprevalence increased significantly with age (P = 0.034). The seropositive rate of rural area was higher than that of urban area (7.7% vs. 1.9%, P = 0.040). Seropositive rates were not significantly different among underlying diseases. None of the antibody-positive patients showed typical symptoms or laboratory findings of SFTS at the time of sample collection. Results of real-time reverse transcription polymerase chain reaction (RT-PCR) were negative for all the seropositive patients. Our study shows 2.1% SFTS seroprevalence among the patients visiting a tertiary hospital in Korea. Seroprevalence is higher in older and rural population.

Morphological characteristics of bone marrow in severe fever with thrombocytopenia syndrome:analysis of 28 cases / 中华临床感染病杂志

Objective To assess the morphological characteristics of bone marrow in patients of severe fever with thrombocytopenia syndrome ( SFTS) and its value in diagnosis.Methods The bone marrow morphology was retrospectively reviewed in 28 laboratory confirmed patients with SFTS from Zhoushan Hospital during January 2012 and December 2015.The correlation between bone marrow -derived macrophage and peripheral blood cells was analyzed with t test.Results All patients presented leukocytopenia and thrombocytopenia.Poor bone marrow hematopoietic function was observed in 23 patients (82%) showing granulocyte, erythrocyte and megakaryocyte hypoplasia , but no pathological hematopoietic disorder was observed.Eighteen patients (64%) had various degrees of increased amount of macrophage in the bone marrow; peripheral white blood cell count and platelets in patients with macrophage ≥0.5% were lower than those with macrophage <0.5%, and the difference was of statistical significance (t =3.836 and 4.499, P<0.01).Conclusion SFTS patients have characteristic bone marrow morphology , and bone marrow examination is beneficial for differentiation of SFTS from blood lymphatic system diseases and other virus infection.

Pulmonary imaging and clinical features of severe fever with thrombocytopenia syndrome bunyavirus infection / 中华临床感染病杂志

Objective To review pulmonary CT imaging features and their correlations with the changes on clinical indexes in patients infected with severe fever with thrombocytopenia syndrome bunyavirus (novel bunyavirus).Methods Clinical data and pulmonary CT findings of 19 patients infected with the novel bunyavirus in Zhoushan Hospital and Daishan Hospital of Zhejiang Province during May 2011 and August 2012 were collected.Infection of the novel bunyavirus was confirmed by Zhejiang Provincial Center for Disease Control and Prevention (CDC).All patients received high resolution CT scanning at initial period,critical period and recovery period.And the changes on WBC,platelet (PLT) and lymphocytes (mainly CD4 + T lymphocytes) were observed.Repeated measures analysis of variance and least significant difference (LSD) were performed,and correlation between the changes on clinical parameters and pulmonary imaging was studied.Results In pulmonary CT images,13 out of 19 cases presented groundglass shadow,5 cases presented consolidation shadow,3 cases presented retisculation,5 cases presented pleural thickening and adhesion,and 3 cases presented mediastinal lymphadenopathy.Sixteen patients presented the involvement of bilateral lungs and 3 patients unilateral.Pleural effusion was observed in 11 cases.There were significant differences in WBC,PLT and CD4+T count among initial,critical and recovery periods in 15 patients with obvious lung lesions (F =20.21,28.37 and 32.92,P ＜0.01).And the above indexes dropped to the lowest points during critical period,which were (1.6 ± 0.6) x 109/L,(26.0 ±9.1) x 109/L and (100.0 ± 66.2) x 106/L,respectively.After treatment,pulmonary CT scan showed that the foci were completely absorbed and no sequelae were observed.Conclusion The changes on pulmonary CT imaging are correlated with those of clinical indexes in novel bunyavirus infection,and the prognosis is good if patients receive the appropriate treatment in the early stage.

Dynamic changes of peripheral blood lymphocyte subsets in fever with thrombocytopenia syndrome patients / 中华检验医学杂志

Objective The aim of this study is to dynamically investigate peripheral blood lymphocyte subsets in fever with thrombocytopenia syndrome (SFTS) patients at different stages,to evaluate the influence of these changes in the infection process.Methods Case-control study was used in the research.Twelveconfirmedthrombocytopeniasyndromevirus ( SFTSV ) infectedpatientswere enrolled.According to SFTS prevention guide issued by Chinese Ministry of Health,these patients were divided into two groups,recovery group and death group.For each group,dynamic profiles of the CD3 + T cells,CD4 + helper T cells,CD8 + cytotoxic T cell and CD3 - CD16 + CD56 + natural killer cells were tested by flow cytometry.Meanwhile, the relationshipsbetween these dynamicchanges and liver function,leukocytes,and platelets were analyzed respectively.Two independent-samples t test was used to compare the difference of the peripheral blood lymphocyte subsets count between the SFTS patients and healthy control.Small sample was analyzed by Mann-Whitney U test.Results In the early stage of infection,Th cells in peripheral blood of recovery group were significantly reduced and Th/Tc ratio was reversed.On day 5,7,9 of post infection,Th cell counts in peripheral blood were (740.9 ± 6.4),(836.2 ± 272.3 ) and ( 1083.6 ± 319.7 ) cells/μl respectively,which were significantly lower than health control ( 1351.4 ± 295.1 ) cells/μl ( t value was -2.883,-4.235,-2.145 respectively,all P ＜0.05).Tc cell counts were significantly more than healthy controls (690.1 ± 194.8) cells/μl through the course,which were ( 1006.3 ±356.5),(1166.4±242.4),(1102.4±245.9),(991.3±205.1) and (886.5±154.5) cells/μl on day 7,9,11,13,15 of the course (t value was 3.312,5.661,4.574,3.874,2.382,all P＜0.05).NK cells were decreased significantly from the ninth day of the course.Associated with abnormal changes of cell subsets,WBC and PLT decreased significantly,and serum ALT,AST,LDH and CK etc.were higher than normal level.With the disease recovery,the abnormality above was gradually improved.In contrast,death cases showed significant decrease in T and Th cells compared with health control (P ＜ 0.05).On day 7,8,9 of the course,the counts of total T cell were (735.9 ± 359.9),(724.9 ± 125.9),(845.3 ± 389.3) cells/μl and the counts of Th cell were ( 533.2 ± 246.9 ),( 532.1 ± 105.7 ),( 551.7 ± 86.9 ) cells/μl,significantly lower than healthy control ( 1727.9 ± 230.2 ) cells/μl and ( 1351.4 ± 295.1 ) cells/μl,with statistically differences (z value was - 2.828, - 2.342,- 2.342 and - 2.828, - 2.342, - 2.342,all P ＜ 0.05 ).On day 7,8,9 of the course,the numbers of NK cell in death group were ( 1141.8 ± 415.5),( 1047.2 ±68.4),( 1276.3 ±545.3) cells/μl,which were significantly more than health group (470.7 ± 242.2) cells/μl,with statistically differences (z value was - 2.180,- 2.335,- 2.258,all P ＜0.05).Conclusions SFTSV infection can induce cell immunity damage.The changes of lymphocyte subsets are associated with clinical classification and prognosis.Significant reduction of T cell and CD4 +cell in peripheral blood are accompanied with significant increase of NK cell,which may be a pivotal indicator of poor prognosis and play an important role in making appropriate strategy in clinical treatment.( Chin J Lab Med,2012,35:826-831 )

Clinical features and genetic sequences of severe fever with thrombocytopenia syndrome bunyavirus in a new-epidemic region of Zhejiang Province, China / 中华传染病杂志

ObjectiveTo investigate the clinical characteristics,epidemiology of patients with severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) infection and genetic sequences of SFTSV.MethodsClinical data of five cases of severe fever with thrombocytopenia syndrome (SFTS)from Zhoushan Hospital during May 2011 to July 2011 were retrospectively analyzed.SFTSV gene was amplified by polymerase chain reaction (PCR).CD3+ CD4+ and CD3+ CD8+T lymphocytes were detected by flow cytometry (FCM).The sequences of isolated SFTSV strains were compared with those in GenBank. ResultsThe symptoms of continuous high fever,sore muscles,enlarged superficial lymph nodes,abdominal pain,diarrhea with gastrointestinal hemorrhage were observed.The white blood cells,platelets and CD3+ CD4+ T lymphocytes were progressive decreased in acute phase with the minimum of (0.97-2.00) × 109/L,(12-42) × 109/L and 7.52％-20.39％,respectively.The SFTSV was isolated from the sera of two patients.The sequences were compared with SFTSV sequences in GenBank.The homology of RNA-dependent RNA polymerase gene was 96％ compared with BX-2010,L-WWG,LN3,JS4,SD4,HN6 and AH12; the glycoprotein gene was 94％ ; N protein gene was 95％ compared with JS4,SD4 and LN4.The homology of the above three genes between two isolates was 99％.ConclusionsOur results suggest that SFTSV is sporadic in Zhejiang Province which is probably from native epidemic focus.SFTS is progressive and severe with acute onset.Multiple organ dysfunction is common in severe eases.

Clinical features and epidemiological analysis of severe fever with thrombocytopenia syndrome associated with Bunyavirus infection in Zhejiang province / 中华临床感染病杂志

ObjectiveTo review the epidemiology,clinical characteristics,pathological changes and treatment of severe fever with thrombocytopenia syndrome (SFTS) associated with the novel Bunyavirus infection.MethodsClinical data of five cases of SFTS from Zhoushan Hospital during May,2011 and July,2011 were retrospectively analyzed,and related literatures were also reviewed.ResultsPersistent high fever,sore muscles,enlarged superficial lymph nodes,abdominal pain,diarrhea with gastrointestinal hemorrhage,progressive decrease of phtelets and white blood cells were observed.The platelets deceased to 30 × 109/L during d9 and d19 after the onset,and recovered in about one week later.The white cells deceased to 1.0 x 109/L.CD4+ T and CD8+ T lymphocytes decreased remarkably during d7 and d10 after the onset.ConclusionsSFTS usually occurs in middle and old aged people from hilly region.It is severe and has abrupt onset.Damages on heart,liver and kidney may occur.In addition to tick bite,there may be other transmission ways.