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1.
BMC Vet Res ; 20(1): 190, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734647

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a fatal zoonosis caused by ticks in East Asia. As SFTS virus (SFTSV) is maintained between wildlife and ticks, seroepidemiological studies in wildlife are important to understand the behavior of SFTSV in the environment. Miyazaki Prefecture, Japan, is an SFTS-endemic area, and approximately 100 feral horses, called Misaki horses (Equus caballus), inhabit Cape Toi in Miyazaki Prefecture. While these animals are managed in a wild-like manner, their ages are ascertainable due to individual identification. In the present study, we conducted a seroepidemiological survey of SFTSV in Misaki horses between 2015 and 2023. This study aimed to understand SFTSV infection in horses and its transmission to wildlife. A total of 707 samples from 180 feral horses were used to determine the seroprevalence of SFTSV using enzyme-linked immunosorbent assay (ELISA). Neutralization testing was performed on 118 samples. In addition, SFTS viral RNA was detected in ticks from Cape Toi and feral horses. The overall seroprevalence between 2015 and 2023 was 78.5% (555/707). The lowest seroprevalence was 55% (44/80) in 2016 and the highest was 92% (76/83) in 2018. Seroprevalence was significantly affected by age, with 11% (8/71) in those less than one year of age and 96.7% (435/450) in those four years of age and older (p < 0.0001). The concordance between ELISA and neutralization test results was 88.9% (105/118). SFTS viral RNA was not detected in ticks (n = 516) or feral horses. This study demonstrated that horses can be infected with SFTSV and that age is a significant factor in seroprevalence in wildlife. This study provides insights into SFTSV infection not only in horses but also in wildlife in SFTS-endemic areas.


Assuntos
Doenças dos Cavalos , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Cavalos , Estudos Soroepidemiológicos , Japão/epidemiologia , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/virologia , Doenças dos Cavalos/sangue , Phlebovirus/isolamento & purificação , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , Febre Grave com Síndrome de Trombocitopenia/veterinária , Febre Grave com Síndrome de Trombocitopenia/virologia , Feminino , Masculino , Anticorpos Antivirais/sangue , Carrapatos/virologia , Ensaio de Imunoadsorção Enzimática/veterinária , Animais Selvagens/virologia
2.
BMC Neurol ; 24(1): 158, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730325

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a natural focal disease transmitted mainly by tick bites, and the causative agent is SFTS virus (SFTSV). SFTS can rapidly progress to severe disease, with multiple-organ failure (MOF) manifestations such as shock, respiratory failure, disseminated intravascular coagulation (DIC) and death, but cases of SFTS patients with central nervous system (CNS) symptoms onset and marked persistent involuntary shaking of the perioral area and limbs have rarely been reported. CASE PRESENTATION: A 69-year-old woman with fever and persistent involuntary shaking of the perioral area and limbs was diagnosed with SFTS with CNS symptom onset after metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) and peripheral blood identified SFTSV. The patient developed a cytokine storm and MOF during the course of the disease, and after aggressive antiviral, glucocorticoid, and gamma globulin treatments, her clinical symptoms improved, her laboratory indices returned to normal, and she had a good prognosis. CONCLUSION: This case gives us great insight that when patients with CNS symptoms similar to those of viral encephalitis combined with thrombocytopenia and leukopenia are encountered in the clinic, it is necessary to consider the possibility of SFTS involving the CNS. Testing for SFTSV nucleic acid in CSF and blood (mNGS or polymerase chain reaction (PCR)) should be carried out, especially in critically ill patients, and treatment should be given accordingly.


Assuntos
Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Humanos , Feminino , Idoso , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Phlebovirus/genética , Phlebovirus/isolamento & purificação , Insuficiência de Múltiplos Órgãos/virologia , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia
3.
J Med Virol ; 96(5): e29647, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38708790

RESUMO

Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in patients with severe fever with thrombocytopenia syndrome (SFTS), yet SFTS-associated IPA (SAPA)'s risk factors remain undefined. A multicenter retrospective cohort study across Hubei and Anhui provinces (May 2013-September 2022) utilized least absolute shrinkage and selection operator (LASSO) regression for variable selection. Multivariable logistic regression identified independent predictors of SAPA, Cox regression highlighted mortality-related risk factors. Of the 1775 screened SFTS patients, 1650 were included, with 169 developing IPA, leading to a 42-day mortality rate of 26.6% among SAPA patients. Multivariable logistic regression revealed SAPA risk factors including advanced age, petechia, hemoptysis, tremor, low albumin levels, elongated activated partial thromboplastin time (APTT), intensive care unit (ICU) admission, glucocorticoid usage, intravenous immunoglobulin (IVIG) and prolonged hospital stays. Cox regression identified predictors of 42-day mortality, including ecchymosis at venipuncture sites, absence of ICU admission, elongated prothrombin time (PT), vasopressor and glucocorticoid use, non-antifungals. Nomograms constructed on these predictors registered concordance indexes of 0.855 (95% CI: 0.826-0.884) and 0.778 (95% CI: 0.702-0.854) for SAPA onset and 42-day mortality, respectively. Lower survival rates for SAPA patients treated with glucocorticoids (p < 0.001) and improved 14-day survival with antifungal therapy (p = 0.036). Improving IPA management in SFTS-endemic areas is crucial, with effective predictive tool.


Assuntos
Aspergilose Pulmonar Invasiva , Febre Grave com Síndrome de Trombocitopenia , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Aspergilose Pulmonar Invasiva/mortalidade , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Febre Grave com Síndrome de Trombocitopenia/complicações , Idoso , China/epidemiologia , Adulto
4.
Sci Rep ; 14(1): 10627, 2024 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724615

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by a novel Bunyavirus infection with low population immunity and high mortality rate. Lacking specific therapies, the treatment measures vary with the severity of the disease, therefore, a case control study involved 394 SFTS patients was taken to determine risk factors for mortality. Comparative clinical data from the first 24 h after admission was collected through the electronic medical record system. Independent risk factors for death of SFTS were identified through univariate and multivariate binary logistic regression analyses. The results of the logistic regression were visualized using a nomogram which was created by downloading RMS package in the R program. In our study, four independent mortality risk factors were identified: advanced age(mean 70.45 ± 7.76 years), MODS, elevated APTT, and D-dimer. The AUC of the nomogram was 0.873 (0.832, 0.915), and the model passes the calibration test namely Unreliability test with P = 0.958, showing that the model's predictive ability is excellent. The nomogram to determine the risk of death in SFTS efficiently provide a basis for clinical decision-making for treatment.


Assuntos
Nomogramas , Febre Grave com Síndrome de Trombocitopenia , Humanos , Febre Grave com Síndrome de Trombocitopenia/mortalidade , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Estudos de Casos e Controles , Idoso de 80 Anos ou mais , Prognóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo
5.
BMC Med ; 22(1): 204, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764059

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease, and its morbidity and mortality are increasing. At present, there is no specific therapy available. An exacerbated IFN-I response and cytokine storm are related to the mortality of patients with SFTS. Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor that can block proinflammatory cytokines and inhibit the type I IFN pathway. We aimed to explore the use of ruxolitinib plus standard of care for severe SFTS. METHODS: We conducted a prospective, single-arm study of severe SFTS. We recruited participants aged 18 years or older who were admitted to the hospital with laboratory-confirmed severe SFTS and whose clinical score exceeded 8 points within 6 days of symptom onset. Participants received oral ruxolitinib (10 mg twice a day) for up to 10 days. The primary endpoint was 28-day overall survival. The secondary endpoints included the proportion of participants who needed intensive care unit (ICU) admission, total cost, changes in neurologic symptoms and clinical laboratory parameters, and adverse events (AEs) within 28 days. A historical control group (HC group, n = 26) who met the upper criteria for inclusion and hospitalized from April 1, 2021, to September 16, 2022, was selected and 1:1 matched for baseline characteristics by propensity score matching. RESULTS: Between Sep 16, 2022, and Sep 16, 2023, 26 participants were recruited into the ruxolitinib treatment group (RUX group). The 28-day overall mortality was 7.7% in the RUX group and 46.2% in the HC group (P = 0.0017). There was a significantly lower proportion of ICU admissions (15.4% vs 65.4%, p < 0.001) and total hospitalization cost in the RUX group. Substantial improvements in neurologic symptoms, platelet counts, hyperferritinemia, and an absolute decrease in the serum SFTS viral load were observed in all surviving participants. Treatment-related adverse events were developed in 6 patients (23.2%) and worsened in 8 patients (30.8%), and no treatment-related serious adverse events were reported. CONCLUSIONS: Our findings indicate that ruxolitinib has the potential to increase the likelihood of survival as well as reduce the proportion of ICU hospitalization and being tolerated in severe SFTS. Further trials are needed. TRAIL REGISTRATION: ChiCTR2200063759, September 16, 2022.


Assuntos
Nitrilas , Pirazóis , Pirimidinas , Febre Grave com Síndrome de Trombocitopenia , Humanos , Pirazóis/uso terapêutico , Nitrilas/uso terapêutico , Masculino , Feminino , Pirimidinas/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Febre Grave com Síndrome de Trombocitopenia/tratamento farmacológico , Padrão de Cuidado , Adulto , Hospitalização , Resultado do Tratamento
6.
Virol J ; 21(1): 113, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760812

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS virus (SFTSV) is transmitted by tick bites and contact with the blood or body fluids of SFTS patients. Animal-to-human transmission of SFTS has been reported in Japan, but not in China. In this study, the possible transmission route of two patients who fed and cared for farm-raised fur animals in a mink farm was explored. METHOD: An epidemiological investigation and a genetic analysis of patients, animals and working environment were carried out. RESULTS: It was found that two patients had not been bitten by ticks and had no contact with patients infected with SFTS virus, but both of them had skinned the dying animals. 54.55% (12/22) of the farm workers were positive for SFTS virus antibody. By analyzing the large, medium and small segments sequences, the viral sequences from the two patients, animals and environments showed 99.9% homology. CONCLUSION: It is suspected that the two patients may be directly infected by farm-raised animals, and that the virus may have been transmitted by aerosols when skinning dying animals. Transmission by direct blood contacts or animal bites cannot be ignored.


Assuntos
Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Phlebovirus/genética , Phlebovirus/isolamento & purificação , Phlebovirus/classificação , China/epidemiologia , Febre Grave com Síndrome de Trombocitopenia/transmissão , Febre Grave com Síndrome de Trombocitopenia/virologia , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , Humanos , Masculino , Anticorpos Antivirais/sangue , Filogenia , Feminino , Pessoa de Meia-Idade , Vison/virologia , Fazendas , Adulto , Fazendeiros , RNA Viral/genética
7.
BMC Infect Dis ; 24(1): 476, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714948

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (Dabie bandavirus), which has become a substantial risk to public health. No specific treatment is available now, that calls for an effective vaccine. Given this, we aimed to develop a multi-epitope DNA vaccine through the help of bioinformatics. The final DNA vaccine was inserted into a special plasmid vector pVAX1, consisting of CD8+ T cell epitopes, CD4+ T cell epitopes and B cell epitopes (six epitopes each) screened from four genome-encoded proteins--nuclear protein (NP), glycoprotein (GP), RNA-dependent RNA polymerase (RdRp), as well as nonstructural protein (NSs). To ascertain if the predicted structure would be stable and successful in preventing infection, an immunological simulation was run on it. In conclusion, we designed a multi-epitope DNA vaccine that is expected to be effective against Dabie bandavirus, but in vivo trials are needed to verify this claim.


Assuntos
Epitopos de Linfócito T , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Vacinas de DNA , Vacinas Virais , Vacinas de DNA/imunologia , Vacinas de DNA/genética , Phlebovirus/imunologia , Phlebovirus/genética , Febre Grave com Síndrome de Trombocitopenia/prevenção & controle , Febre Grave com Síndrome de Trombocitopenia/imunologia , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Vacinas Virais/imunologia , Vacinas Virais/genética , Humanos , Desenho Assistido por Computador , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/genética , Animais , Biologia Computacional
8.
J Med Virol ; 96(4): e29612, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639291

RESUMO

To explore the association and impact between viral myocarditis and mortality in patients with severe fever with thrombocytopenia syndrome. A dynamic analysis was conducted between fatal group and nonfatal group regarding the daily epidemiology data, clinical symptoms, and electrocardiogram (ECG), echocardiogram, and laboratory findings. Outcomes of patients with and without viral myocarditis were compared. The association between viral myocarditis and mortality was analyzed. Among 183 severe fever with thrombocytopenia syndrome patients, 32 were in the fatal group and 151 in the nonfatal group; there were 26 (81.25%) with viral myocarditis in the fatal group, 66 (43.70%) with viral myocarditis in the nonfatal group (p < 0.001), 79.35% of patients had abnormal ECG results. The abnormal rate of ECG in the fatal group was 100%, and in the nonfatal group was 74.83%. Univariate analysis found that the number of risk factors gradually increased on Day 7 of the disease course and reached the peak on Day 10. Combined with the dynamic analysis of the disease course, alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase fraction, lactate dehydrogenase, hydroxybutyrate dehydrogenase, neutrophil count, serum creatinine, Na, Ca, carbon dioxide combining power, amylase, lipase, activated partial thromboplastin time and thrombin time had statistically significant impact on prognosis. The incidence of fever with thrombocytopenia syndrome combined with viral myocarditis is high, especially in the fatal group of patients. Viral myocarditis is closely related to prognosis and is an early risk factor. The time point for changes in myocarditis is Day 7 of the course of the disease.


Assuntos
Miocardite , Febre Grave com Síndrome de Trombocitopenia , Viroses , Humanos , Miocardite/complicações , Miocardite/epidemiologia , Prevalência , Viroses/complicações , Viroses/epidemiologia , Febre/epidemiologia , Progressão da Doença
9.
PLoS Negl Trop Dis ; 18(4): e0012125, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38626191

RESUMO

Hyperglycemia is correlated with worse in-hospital outcomes in acute infectious diseases such as coronavirus disease 2019 (COVID-19) and severe fever with thrombocytopenia syndrome (SFTS). This study assessed the relationship between fasting plasma glucose (FPG) levels and in-hospital mortality, disease type, and secondary infections among individuals with SFTS without preexisting diabetes. The clinical data and laboratory results upon admission of 560 patients with SFTS without preexisting diabetes meeting the inclusion criteria at Wuhan Union Hospital were collected. FPG levels in surviving patients with SFTS subjects were significantly lower than those in patients with SFTS who had died (P<0.0001). In multivariate Cox regression, high FPG level (≥11.1 mmol/L) was a risk factor independently associated with the in-hospital death of patients with SFTS without preexisting diabetes. Similarly, the FPG levels in general patients with SFTS were significantly lower than those in patients with severe SFTS (P<0.0001). Multivariate logistic regression identified high FPG level (7.0-11.1 mmol/L) as a risk factor independently associated with SFTS severity. While FPG levels were comparable between patients with SFTS with and without secondary infection (P = 0.5521), logistic regression analysis revealed that high FPG levels were not a risk factor for secondary infection in patients with SFTS without preexisting diabetes. High FPG level on admission was an independent predictor of in-hospital death and severe disease in individuals with SFTS without preexisting diabetes. FPG screening upon admission and glycemic control are effective methods for improving the prognosis of patients with SFTS.


Assuntos
Glicemia , COVID-19 , Jejum , Febre Grave com Síndrome de Trombocitopenia , Humanos , Masculino , Feminino , Glicemia/análise , Pessoa de Meia-Idade , Idoso , Febre Grave com Síndrome de Trombocitopenia/sangue , Febre Grave com Síndrome de Trombocitopenia/virologia , Jejum/sangue , COVID-19/sangue , COVID-19/mortalidade , COVID-19/complicações , Fatores de Risco , Mortalidade Hospitalar , SARS-CoV-2 , Hiperglicemia/complicações , Adulto , China/epidemiologia , Estudos Retrospectivos , Idoso de 80 Anos ou mais
10.
PLoS Negl Trop Dis ; 18(4): e0012068, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38626222

RESUMO

OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) is an epidemic emerging infectious disease with high mortality rate. We investigated the association between liver injury and clinical outcomes in patients with SFTS. METHODS: A total of 291 hospitalized SFTS patients were retrospectively included. Cox proportional hazards model was adopted to identify risk factors of fatal outcome and Kaplan-Meier curves were used to estimate cumulative risks. RESULTS: 60.1% of patients had liver injury at admission, and the median alanine transaminase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) levels were 76.4 U/L, 152.3 U/L, 69.8 U/L and 9.9 µmol/L, respectively. Compared to survivors, non-survivors had higher levels of AST (253.0 U/L vs. 131.1 U/L, P < 0.001) and ALP (86.2 U/L vs. 67.9 U/L, P = 0.006), higher proportion of elevated ALP (20.0% vs. 4.4%, P < 0.001) and liver injury (78.5% vs. 54.9%, P = 0.001) at admission. The presence of liver injury (HR 2.049, P = 0.033) at admission was an independent risk factor of fatal outcome. CONCLUSIONS: Liver injury was a common complication and was strongly associated with poor prognosis in SFTS patients. Liver function indicators should be closely monitored for SFTS patients.


Assuntos
Febre Grave com Síndrome de Trombocitopenia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Febre Grave com Síndrome de Trombocitopenia/mortalidade , Febre Grave com Síndrome de Trombocitopenia/virologia , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , Estudos Retrospectivos , Idoso , Fígado/patologia , Fosfatase Alcalina/sangue , Fatores de Risco , Testes de Função Hepática , Aspartato Aminotransferases/sangue , Adulto , Phlebovirus , Alanina Transaminase/sangue , Idoso de 80 Anos ou mais , Modelos de Riscos Proporcionais , Bilirrubina/sangue
11.
J Med Virol ; 96(5): e29626, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38654664

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high mortality rate. Differentiating between SFTS and hemorrhagic fever with renal syndrome (HFRS) is difficult and inefficient. Retrospective analysis of the medical records of individuals with SFTS and HFRS was performed. Clinical and laboratory data were compared, and a diagnostic model was developed based on multivariate logistic regression analyzes. Receiver operating characteristic curve analysis was used to evaluate the diagnostic model. Among the 189 patients, 113 with SFTS and 76 with HFRS were enrolled. Univariate analysis revealed that more than 20 variables were significantly associated with SFTS. Multivariate logistic regression analysis revealed that gender, especially female gender (odds ratio [OR]: 4.299; 95% confidence interval [CI]: 1.163-15.887; p = 0.029), age ≥65 years (OR: 16.386; 95% CI: 3.043-88.245; p = 0.001), neurological symptoms (OR: 12.312; 95% CI: 1.638-92.530; p = 0.015), leukopenia (<4.0 × 109/L) (OR: 17.355; 95% CI: 3.920-76.839; p < 0.001), and normal Cr (OR: 97.678; 95% CI: 15.483-616.226; p < 0.001) were significantly associated with SFTS but not with HFRS. The area under the curve of the differential diagnostic model was 0.960 (95% CI: 0.936-0.984), which was significantly better than that of each single factor. In addition, the model exhibited very excellent sensitivity and specificity (92.9% and 85.5%, respectively). In cases where HFRS and SFTS are endemic, a diagnostic model based on five parameters, such as gender, age ≥65 years, neurological symptoms, leukopenia and normal Cr, will facilitate the differential diagnosis of SFTS and HFRS in medical institutions, especially in primary care settings.


Assuntos
Febre Hemorrágica com Síndrome Renal , Curva ROC , Febre Grave com Síndrome de Trombocitopenia , Humanos , Feminino , Masculino , Febre Hemorrágica com Síndrome Renal/diagnóstico , Febre Hemorrágica com Síndrome Renal/virologia , Pessoa de Meia-Idade , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/virologia , Estudos Retrospectivos , Idoso , Diagnóstico Diferencial , Adulto , Diagnóstico Precoce , Idoso de 80 Anos ou mais , Sensibilidade e Especificidade
12.
Front Immunol ; 15: 1348836, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646523

RESUMO

Dabie Banda virus (DBV), a tick-borne pathogen, was first identified in China in 2009 and causes profound symptoms including fever, leukopenia, thrombocytopenia and multi-organ dysfunction, which is known as severe fever with thrombocytopenia syndrome (SFTS). In the last decade, global incidence and mortality of SFTS increased significantly, especially in East Asia. Though previous studies provide understandings of clinical and immunological characteristics of SFTS development, comprehensive insight of antiviral immunity response is still lacking. Here, we intensively discuss the antiviral immune response after DBV infection by integrating previous ex- and in-vivo studies, including innate and adaptive immune responses, anti-viral immune responses and long-term immune characters. A comprehensive overview of potential immune targets for clinical trials is provided as well. However, development of novel strategies for improving the prognosis of the disease remains on challenge. The current review may shed light on the establishment of immunological interventions for the critical disease SFTS.


Assuntos
Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Humanos , Imunidade Adaptativa , Imunidade Inata , Phlebovirus/imunologia , Febre Grave com Síndrome de Trombocitopenia/imunologia , Febre Grave com Síndrome de Trombocitopenia/terapia
13.
Appl Microbiol Biotechnol ; 108(1): 303, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639795

RESUMO

Severe fever with thrombocytopenia syndrome virus (SFTSV) causes the highly fatal disease in humans. To facilitate diagnosis, the native form of subunit glycoprotein (Gn), a prime target for potential vaccines and therapies, was produced in Nicotiana benthamiana using a Bamboo mosaic virus-based vector system. By fusion with secretory signal tags, SSExt, derived from the extension protein, and the (SP)10 motif, the yield of the recombinant Gn (rGn) was remarkably increased to approximately 7 mg/kg infiltrated leaves. Ultimately, an rGn-based ELISA was successfully established for the detection of SFTSV-specific antibodies in serum samples from naturally infected monkeys. As validated with the reference method, the specificity and sensitivity of rGn-ELISA were 94% and 96%, respectively. In conclusion, utilizing well-suited fusion tags facilitates rGn production and purification in substantial quantities while preserving its antigenic properties. The rGn-ELISA, characterized by its commendable sensitivity and specificity could serve as a viable alternative diagnostic method for assessing SFTSV seroprevalence. KEY POINTS: • SFTSV Gn, fused with secretory signal tags, was expressed by the BaMV-based vector. • The plant fusion tags increased expression levels and eased the purification of rGn. • The rGn-ELISA was established and validated; its specificity and sensitivity > 94%.


Assuntos
Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Humanos , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Phlebovirus/genética , Phlebovirus/metabolismo , Estudos Soroepidemiológicos , Glicoproteínas/metabolismo , Anticorpos
14.
Parasit Vectors ; 17(1): 107, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38444018

RESUMO

BACKGROUND: Ticks serve as vectors for a diverse array of pathogens, including viruses responsible for both human and livestock diseases. Symbiotic bacteria hold significant potential for controlling tick-borne disease. However, the alteration of tick gut bacterial community in response to pathogen infection has not been analyzed for any tick-borne viruses. Here, the impact of severe fever with thrombocytopenia syndrome virus (SFTSV) infection on bacterial diversity in the gut of Haemaphysalis longicornis is investigated. METHODS: Unfed tick females were artificially infected with SFTSV. The gut samples were collected and the genomic DNA was extracted. We then investigated alterations in gut bacterial composition in response to SFTSV infection through 16S rRNA gene sequencing. RESULTS: The study found that a reduction in the number of operational taxonomic units (OTUs) in the tick gut following SFTSV infection. However, there were no significant changes in alpha diversity indices upon infection. Four genera, including Corynebacterium, Arthrobacter, Sphingomonas, and Escherichia, were identified as biomarkers for the tick gut without SFTSV infection. Notably, the predicted correlation network indicated that the biomarkers Sphingomonas and Escherichia exhibited positive correlations within the same subcommunity, which was altered upon viral infection. CONCLUSIONS: These findings revealed that the change in tick gut bacterial composition upon SFTSV infection and could facilitate the discovery new target for tick-borne viral disease control.


Assuntos
Microbioma Gastrointestinal , Febre Grave com Síndrome de Trombocitopenia , Feminino , Humanos , Animais , Haemaphysalis longicornis , RNA Ribossômico 16S/genética , Biomarcadores
15.
Br J Haematol ; 204(5): 1999-2006, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38438264

RESUMO

Prolonged coagulation times, such as activated partial thromboplastin time (APTT) and thrombin time (TT), are common in patients infected with severe fever with thrombocytopenia syndrome virus (SFTSV) and have been confirmed to be related to patient's poor outcome by previous studies. To find out the reason for prolonged coagulation time in patients with SFTSV infection, and whether it predicts haemorrhagic risk or not. Seventy-eight consecutive patients with confirmed SFTSV infection were enrolled in this prospective, single-centre, observational study. Several global and specific coagulation parameters of these patients on admission were detected, and the haemorrhagic events during hospitalization and their outcomes were recorded. Most of the enrolled patients had prolonged APTT (82.1%) and TT (80.8%), normal prothrombin time (83.3%) and intrinsic coagulation factors above haemostatic levels (97.4%). The heparin-like effect was confirmed by a protamine neutralization test and anti-Xa activity detection in most patients. Interestingly, the APTT and TT results were significantly positively correlated with the levels of endothelial markers and viral load, respectively. The APTT was independently associated with the haemorrhage of patients. The prolonged APTT and TT of SFTS patients may mainly be attributed to endogenous heparinoids and are associated with increased haemorrhagic risk.


Assuntos
Hemorragia , Febre Grave com Síndrome de Trombocitopenia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Tempo de Tromboplastina Parcial , Hemorragia/sangue , Hemorragia/etiologia , Estudos Prospectivos , Febre Grave com Síndrome de Trombocitopenia/sangue , Heparina/uso terapêutico , Adulto , Tempo de Trombina , Phlebovirus , Coagulação Sanguínea , Fatores de Risco , Idoso de 80 Anos ou mais
16.
Viruses ; 16(3)2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38543766

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne zoonotic disease, is caused by infection with SFTS virus (SFTSV). A previous study reported that human-to-human direct transmission of SFTSV can occur. However, potential animal-to-animal transmission of SFTSV without ticks has not been fully clarified. Thus, the objective of this study was to investigate potential mice-to-mice transmission of SFTSV by co-housing three groups of mice [i.e., wild-type mice (WT), mice injected with an anti-type I interferon-α receptor-blocking antibody (IFNAR Ab), and mice with knockout of type I interferon-α receptor (IFNAR KO)] as spreaders or recipients with different immune competence. As a result, co-housed IFNAR Ab and IFNAR KO mice showed body weight loss with SFTS viral antigens detected in their sera, extracorporeal secretions, and various organs. Based on histopathology, white pulp atrophy in the spleen was observed in all co-housed mice except WT mice. These results obviously show that IFNAR Ab and IFNAR KO mice, as spreaders, exhibited higher transmissibility to co-housed mice than WT mice. Moreover, IFNAR KO mice, as recipients, were more susceptible to SFTSV infection than WT mice. These findings suggest that type I interferon signaling is a pivotal factor in mice intraspecies transmissibility of SFTSV in the absence of vectors such as ticks.


Assuntos
Infecções por Bunyaviridae , Interferon Tipo I , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Doenças Transmitidas por Carrapatos , Humanos , Animais , Camundongos
17.
Immun Inflamm Dis ; 12(2): e1184, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38376000

RESUMO

BACKGROUND: This study aimed to identify a novel inflammatory index and construct a nomogram for predicting in-hospital mortality due to severe fever with thrombocytopenia syndrome (SFTS). METHODS: This cohort included 610 patients with SFTS hospitalized in Wuhan Union Hospital between March 2017 and November 2022. The ratio of C-reactive protein (CRP) to the prognostic nutritional index (PNI) was calculated and used to reflect patients' inflammatory status. Propensity score matching (PSM) was utilized to balance confounding factors between the low- and high-CRP/PNI groups. SFTS individuals from Jinyinhu Hospital were used as the validation cohort. RESULTS: Patients with SFTS and high CRP/PNI were significantly correlated with a higher percentage of severe and critical SFTS types and higher in-hospital mortality rates than those with low CRP/PNI. CRP/PNI was the potent risk indicator for in-hospital mortality in individuals with SFTS. The CRP/PNI nomogram showed a good predictive value for in-hospital mortality in patients with SFTS. After PSM, the predictive performance of CRP/PNI for 28-day mortality was excellent. Finally, the CRP/PNI could still assess patients with SFTS at different risks based on SFTS data from another medical center. CONCLUSION: The CPR/PNI ratio exhibited a strong positive correlation with the SFTS disease type and could predict in-hospital mortality in the early stages of SFTS. The CPR/PNI ratio could substantially help clinicians facilitate the early identification of patients with high-risk SFTS and the timely initiation of intensive therapy.


Assuntos
Avaliação Nutricional , Febre Grave com Síndrome de Trombocitopenia , Humanos , Pontuação de Propensão , Prognóstico , Nomogramas
18.
Pathol Res Pract ; 254: 155143, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38301364

RESUMO

Solitary fibrous tumors (SFTs) are known for their heterogeneous morphology, characterized by a variety of cell shapes and different growth patterns. They can also arise in various anatomical locations, most commonly in extremities and deep soft tissues. Despite this diversity in morphology and location, all SFTs share a common molecular signature involving the NAB2::STAT6 gene fusion. Due to their unpredictable clinical behavior, establishing prognostic factors is crucial. This study aims to evaluate an orbital risk stratification system (RSS) proposed by Huang et al. for use in extraorbital SFTs using a database of 97 cases. The Huang model takes into consideration tumor size, mitotic figures, Ki-67 index, and dominant constituent cell (DCC) as key variables. Survival analysis confirmed the model's predictive value, with higher-risk scores being associated with poorer outcomes. However, in contrast to the orbital SFTs studied by Huang et al., our study did not find a correlation between tumor size and recurrence in extraorbital cases. While the Huang model performs slightly better than other RSS, it falls short on achieving statistical significance in distinguishing recurrence risk groups in extraorbital locations. In conclusion, this study validates the Huang RSS for use in extraorbital SFTs and underscores the importance of considering DCC, mitotic count, and Ki-67 together. However, we found that including tumor size in this model did not improve prognostic significance in extraorbital SFTs. Despite the benefits of this additional RSS, vigilant monitoring remains essential, even in cases classified as low-risk due to the inherent unpredictability of SFT clinical outcomes.


Assuntos
Hemangiopericitoma , Neoplasias Orbitárias , Febre Grave com Síndrome de Trombocitopenia , Tumores Fibrosos Solitários , Humanos , Neoplasias Orbitárias/genética , Prognóstico , Antígeno Ki-67 , Proteínas Repressoras/genética , Tumores Fibrosos Solitários/diagnóstico , Tumores Fibrosos Solitários/genética , Fator de Transcrição STAT6/genética , Medição de Risco , Biomarcadores Tumorais/genética
19.
BMC Infect Dis ; 24(1): 240, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389047

RESUMO

OBJECTIVE: This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors. METHODS: Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM. RESULTS: SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P < 0.05). Multivariate analysis identified elevated LDH upon admission (OR = 1.004, 95% CI: 1-1.008, P = 0.050), elevated NT-proBNP (OR = 1.005, 95% CI: 1.001-1.008, P = 0.007), and consciousness disorders (OR = 112.852, 95% CI: 3.676 ~ 3464.292, P = 0.007) as independent risk factors for SFTS-SVM. LDH and NT-proBNP had AUCs of 0.728 and 0.744, respectively, in predicting SFTS-SVM. Critical values of LDH (> 978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM. CONCLUSION: Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds.


Assuntos
Miocardite , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Trombocitopenia , Viroses , Humanos , Estudos Retrospectivos , Trombocitopenia/complicações , Trombocitopenia/diagnóstico , Miocardite/complicações , Miocardite/diagnóstico , Transtornos da Consciência/complicações , Febre/complicações
20.
Pathol Res Pract ; 255: 155207, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38394808

RESUMO

Solitary fibrous tumor (SFT) is a relatively rare mesenchymal fibroblastic tumor occurring most commonly in adults with no gender predilection. Although the pathological diagnosis of SFT is usually straightforward, some difficulties may occasionally arise mainly due to the wide morphological spectrum exhibited by this tumor. In the present paper we aimed to evaluate the unusual clinicopathological features in a series of 31 SFTs arising from parenchymal organs, superficial soft tissues and deep soft tissues. Our results emphasize that SFTs may occur anywhere, including unusual sites such as periosteum of the thoracic spine, mesorectal tissue, hepatic hilum, paravescial space, kidney and breast. Moreover, a wide morphological spectrum was observed in tumors included in our series. The most striking morphological features observed included: extensive lipomatous component, myxoid stromal changes, epithelioid cell component, metaplastic mature bone, neurofibroma-like, myxofibrosarcoma-like and pseudoalveolar-like areas. Additionally, multinucleated giant cells and sarcomatous dedifferentiation were also identified. Our paper emphasizes that SFT may occur in unusual anatomical locations and exhibits a wide morphological spectrum. Pathologists must be aware of these features to avoid confusion with other benign and malignant neoplasms that may show overlapping morphological features.


Assuntos
Hemangiopericitoma , Sarcoma , Febre Grave com Síndrome de Trombocitopenia , Tumores Fibrosos Solitários , Humanos , Adulto , Biomarcadores Tumorais , Tumores Fibrosos Solitários/patologia , Hemangiopericitoma/patologia
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