RESUMO
Severe fever with thrombocytopenia syndrome (SFTS) is a widespread infectious disease with high mortality. Hence, identifying valuable biomarkers for detecting the early changes in SFTS is crucial. In this study, we investigated the relationship between the difference in hematocrit (HCT) and serum albumin (ALB) levels (HCT-ALB) and the prognosis of patients with SFTS virus infection. After excluding the patients who did not meet the SFTS diagnostic criteria, those with SFTS from the First Affiliated Hospital of Wannan Medical College were divided into a fatal and Nonfatal group based on their disease prognosis. A dynamic analysis of the daily laboratory data was conducted for 14 days following SFTS onset. A receiver operating characteristic (ROC) curve was used to evaluate the predictive value of HCT-ALB. Another sample of patients with SFTS admitted to the First Affiliated Hospital of Nanjing Medical University was utilized to verify the study conclusions. A total of 158 patients with SFTS were included. Among them, 126 patients were categorized in the Nonfatal group and 32 in the fatal group, leading to a mortality rate of 20.25% (32/158). Univariate analysis of the laboratory test findings and ROC curve analysis showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), HCT-ALB, and lactate dehydrogenase (LDH) had a relatively better ability to discriminate the disease condition of the patients with SFTS. Moreover, HCT-ALB served as a predictor of SFTS prognosis. Additionally, an area under the ROC curve (AUC) of 0.777 and a critical HCT-ALB value of 4.75 on day 7 were associated with a sensitivity of 83.3% and a specificity of 73.9%. On day 8 (AUC = 0.882), the critical value of HCT-ALB was 9.25, while the sensitivity was 100% and specificity was 76.5%. Further verification based on the data of 91 patients with SFTS admitted to the First Affiliated Hospital of Nanjing Medical University demonstrated a mortality rate of 51% (24/47) among those with HCT-ALB values >4.75 on day 7 of the disease course, highlighting the potential of the HCT-ALB value of >4.75 for predicting SFTS prognosis. High HCT-ALB values are closely related to the mortality of patients with SFTS. HCT-ALB is a sensitive and independent predictor of early disease in patients with SFTS.
Assuntos
Biomarcadores , Curva ROC , Albumina Sérica , Febre Grave com Síndrome de Trombocitopenia , Humanos , Masculino , Feminino , Prognóstico , Pessoa de Meia-Idade , Biomarcadores/sangue , Hematócrito , Idoso , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/sangue , Febre Grave com Síndrome de Trombocitopenia/mortalidade , Albumina Sérica/análise , Adulto , Phlebovirus , Índice de Gravidade de Doença , Idoso de 80 Anos ou mais , Aspartato Aminotransferases/sangueAssuntos
Astrócitos , Camundongos Knockout , Neurônios , Phlebovirus , Receptor de Interferon alfa e beta , Transdução de Sinais , Animais , Camundongos , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/deficiência , Neurônios/virologia , Neurônios/patologia , Astrócitos/virologia , Phlebovirus/genética , Morte Celular , Febre Grave com Síndrome de Trombocitopenia/virologia , Modelos Animais de DoençasRESUMO
Severe fever with thrombocytopenia syndrome (SFTS) represents an emerging infectious disease characterized by a substantial mortality risk. Early identification of patients is crucial for effective risk assessment and timely interventions. In the present study, least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was conducted to identify key risk factors associated with progression to critical illness at 7-day and 14-day. A nomogram was constructed and subsequently assessed for its predictive accuracy through evaluation and validation processes. The risk stratification of patients was performed using X-tile software. The performance of this risk stratification system was assessed using the Kaplan-Meier method. Additionally, a heat map was generated to visualize the results of these analyses. A total of 262 SFTS patients were included in this study, and four predictive factors were included in the nomogram, namely viral copies, aspartate aminotransferase (AST) level, C-reactive protein (CRP), and neurological symptoms. The AUCs for 7-day and 14-day were 0.802 [95% confidence interval (CI): 0.707-0.897] and 0.859 (95% CI: 0.794-0.925), respectively. The nomogram demonstrated good discrimination among low, moderate, and high-risk groups. The heat map effectively illustrated the relationships between risk groups and predictive factors, providing valuable insights with high predictive and practical significance.
Assuntos
Estado Terminal , Nomogramas , Febre Grave com Síndrome de Trombocitopenia , Humanos , Febre Grave com Síndrome de Trombocitopenia/virologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Medição de Risco/métodos , Phlebovirus/genética , Proteína C-Reativa/análise , Adulto , Progressão da Doença , Aspartato Aminotransferases/sangueRESUMO
Severe fever with thrombocytopenia syndrome (SFTS) and hemorrhagic fever with renal syndrome (HFRS) usually have different infection routes, and coinfection is relatively rare. This study examines the clinical and etiological characteristics of coinfection by these two pathogens to provide important references for clinical diagnosis and treatment. Blood samples from 22 clinically diagnosed patients with HFRS were collected for molecular detection of HFRS and common tick and mouse borne diseases. Inoculate the blood of six severe and critically patients into cells to isolate and proliferate potential viruses, and retest the cell culture to determine the pathogen. In addition, complete data were collected from these 22 HFRS and concurrent SFTS patients, and white blood cells (WBCs), platelet (PLT), blood urea nitrogen (BUN), creatinine (Cr) and other data were compared and analyzed. A total of 31 febrile patients, including 22 HFRS patients and 9 SFTS patients, were collected from September 2021 to October 2022. Among these HFRS patients, 11 were severe or critical. Severe and critical HFRS patients were characterized by rodent exposure history, pharyngeal and conjunctival hyperemia, abnormal WBC and PLT counts, and elevated BUN and Cr values. Virus isolation and molecular detection on blood samples from 6 patients showed that three of the six severe patients were positive for hantaan virus (HTNV), and two of the three HTNV positives were also positive for SFTS bunyavirus (SFTSV). The two coinfected patients exhibited different clinical and laboratory characteristics compared to those infected by either virus alone. Coinfection of HTNV and SFTSV leads to severe and complex hemorrhagic fever. Laboratory characteristics, such as the indicators of WBC, PLT, BUN, and Cr, may differ between HFRS and SFTS. These findings have implications and provide references for the diagnosis and treatment of coinfected cases.
Assuntos
Coinfecção , Vírus Hantaan , Febre Hemorrágica com Síndrome Renal , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Humanos , Coinfecção/virologia , Vírus Hantaan/isolamento & purificação , Vírus Hantaan/genética , Vírus Hantaan/patogenicidade , Masculino , Feminino , Pessoa de Meia-Idade , Febre Grave com Síndrome de Trombocitopenia/virologia , Febre Grave com Síndrome de Trombocitopenia/sangue , Adulto , Phlebovirus/genética , Phlebovirus/isolamento & purificação , Febre Hemorrágica com Síndrome Renal/virologia , Febre Hemorrágica com Síndrome Renal/sangue , Febre Hemorrágica com Síndrome Renal/diagnóstico , Febre Hemorrágica com Síndrome Renal/complicações , Idoso , Animais , Adulto JovemRESUMO
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS), with a high mortality rate of up to 30%. The envelope glycoproteins of SFTSV, glycoprotein N (Gn) and glycoprotein C (Gc), facilitate the recognition of host receptors and the process of membrane fusion, allowing the virus to enter host cells. We previously reported a monoclonal antibody, mAb 40C10, capable of neutralizing different genotypes of SFTSV and SFTSV-related viruses. However, the specific neutralization mechanism is poorly understood. In this study, we elucidated the high-resolution structure of the SFTSV Gn head domain in complex with mAb 40C10, confirming that the binding epitope in the domain I region of SFTSV Gn, and it represented that a novel binding epitope of SFTSV Gn was identified. Through in-depth structural and sequence analyses, we found that the binding sites of mAb 40C10 are relatively conserved among different genotypes of SFTSV and SFTSV-related Heartland virus and Guertu virus, elucidating the molecular mechanism underlying the broad-spectrum neutralizing activity of mAb 40C10. Furthermore, we humanized of mAb 40C10, which is originally of murine origin, to reduce its immunogenicity. The resulting nine humanized antibodies maintained potent affinity and neutralizing activity. One of the humanized antibodies exhibited neutralizing activity at picomolar IC50 values and demonstrated effective therapeutic and protective effects in a mouse infection model. These findings provide a novel target for the future development of SFTSV vaccines or drugs and establish a foundation for the research and development of antibody therapeutics for clinical applications.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Phlebovirus , Humanos , Animais , Anticorpos Antivirais/imunologia , Phlebovirus/imunologia , Camundongos , Anticorpos Neutralizantes/imunologia , Febre Grave com Síndrome de Trombocitopenia/imunologia , Proteínas do Envelope Viral/imunologia , Anticorpos Monoclonais/imunologia , Epitopos/imunologia , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Amplamente Neutralizantes/imunologiaRESUMO
Biting sandflies are known for transmitting leishmaniasis, but sandflies also transmit sandfly fever viruses that may disrupt military operations. Sandfly fever is caused by serotypes of the Phlebovirus genus (primarily the Naples, Sicilian, or Toscana serotypes). The illness is known colloquially as "three-day fever" and "papataci fever." The clinical course of the disease normally spans about 3 days, with patients exhibiting a prodromal phase consisting of fatigue, chills, abdominal pain, and possibly facial flushing and tachycardia. Disease onset is marked by hyperpyrexia, myalgia, and arthralgia. The incubation period is typically 3-5 days, with viremia in humans lasting typically less than 1 week. This manuscript describes sandfly appearance, behavior, and geographic distribution. It then lists comparable diseases for differential diagnosis. Finally, as no vaccine exists for the sandfly virus, it concludes with steps for preparation and prevention to prevent outbreaks from disrupting military operations.
Assuntos
Psychodidae , Humanos , Animais , Psychodidae/virologia , Febre por Flebótomos/diagnóstico , Insetos Vetores/virologia , Militares , Diagnóstico Diferencial , PhlebovirusRESUMO
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne illness with a notable morality risk that is becoming increasingly prevalent in East Asia (14-36%). Increasing evidence indicates a more direct role of the SFTS virus in renal impairment. However, few studies have explored the risk factors for and clinical outcomes of AKI in patients with SFTS. Therefore, in this study, we aimed to investigate risk factors and outcomes associated with AKI in patients with SFTS. In this retrospective cohort study, we included the data of 53 patients who were diagnosed with SFTS virus infection at Kangwon National University Hospital between 2016 and 2020. We incorporated laboratory data and medical information including comorbidities, complications, and mortality. Baseline characteristics, clinical features, laboratory parameters, and mortality rates of the non-AKI and AKI groups were compared. Patient survival of non-AKI and AKI groups were compared using the Kaplan-Meier method. To identify the population with poor prognosis, Cox regression analysis was used to identify the independent risk factors for in-hospital mortality in patients with SFTS. Of the 53 individuals, 29 (54.7%) were male, with an average age of 66.5 years. Nine patients (15.1%) died of SFTS. Twenty-seven (50.9%) patients exhibited AKI; the average time interval from fever onset to AKI occurrence was 3.6 days. Notably, 24 (88.9%) patients developed AKI within the first week of fever onset. Patients in the AKI group exhibited a significantly higher prevalence of diabetes and were older than those in the non-AKI group. The mortality rate was notably higher (29.6%) in the AKI group than in the non-AKI group (3.8%). Within the AKI cohort, advanced stages (stages 2 and 3) showed a 50% mortality rate, which was significantly higher than the 17.6% mortality rate in patients with stage 1 AKI. Additionally, Kaplan-Meier curves revealed lower survival rates among patients with AKI than among those without AKI (P = 0.017). Cox regression analysis identified leukopenia and elevated serum creatinine levels as significant risk factors for mortality. AKI is a common complication associated with SFTS. Moreover, the mortality rate was significantly higher in the patients who developed AKI than in those who did not. Our findings underscore the pivotal role of AKI as a prognostic marker of disease severity in patients with SFTS.
Assuntos
Injúria Renal Aguda , Febre Grave com Síndrome de Trombocitopenia , Humanos , Masculino , Feminino , Idoso , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Prognóstico , Febre Grave com Síndrome de Trombocitopenia/complicações , Estudos Retrospectivos , Pessoa de Meia-Idade , Fatores de Risco , Mortalidade Hospitalar , Biomarcadores/sangue , Idoso de 80 Anos ou mais , PhlebovirusRESUMO
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal infectious disease caused by the SFTS virus (SFTSV), posing a significant public health threat. This study aimed to construct a dynamic model for the early identification of SFTS patients at high risk of disease progression. METHODS: All eligible patients enrolled between April 2014 and July 2023 were divided into training and validation sets. Thirty-four clinical variables in the training set underwent analysis using least absolute shrinkage and selection operator (LASSO) logistic regression. Selected variables were then input into the multivariate logistic regression model to construct a dynamic nomogram. The model's performance was assessed using the area under the receiver operating characteristic curve (AUC-ROC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) in both training and validation sets. Kaplan-Meier survival analysis was utilized to evaluate prognostic performance. RESULTS: 299 SFTS patients entered the final investigation, with 208 patients in the training set and 90 patients in the validation set. LASSO and the multivariate logistic regression identified six significant prediction factors: age (OR, 1.060; 95% CI, 1.017-1.109; P = 0.007), CREA (OR, 1.017; 95% CI, 1.003-1.031; P = 0.019), PT (OR, 1.765; 95% CI, 1.175-2.752; P = 0.008), D-dimer (OR, 1.039; 95% CI, 1.005-1.078; P = 0.032), nervous system symptoms (OR, 8.244; 95% CI, 3.035-26.858; P < 0.001) and hemorrhage symptoms (OR, 3.414; 95% CI, 1.096-10.974; P = 0.035). The AUC-ROC, C-index, calibration plots, and DCA demonstrated the robust performance of the nomogram in predicting severity at admission, and Kaplan-Meier survival analysis indicated its utility in predicting 28-day mortality among SFTS patients. The dynamic nomogram is accessible at https://sfts.shinyapps.io/SFTS_severity_nomogram/ . CONCLUSION: This study provided a practical and readily applicable tool for the early identification of high-risk SFTS patients, enabling the timely initiation of intensified treatments and protocol adjustments to mitigate disease progression.
Assuntos
Nomogramas , Febre Grave com Síndrome de Trombocitopenia , Humanos , Masculino , Febre Grave com Síndrome de Trombocitopenia/virologia , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/mortalidade , Feminino , Pessoa de Meia-Idade , Idoso , Modelos Logísticos , Prognóstico , Índice de Gravidade de Doença , Curva ROC , Phlebovirus , Estimativa de Kaplan-Meier , Estudos Retrospectivos , AdultoRESUMO
Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is prevalent in East Asia. However, the use of glucocorticoids (GCs) in the treatment of SFTS remains controversial. Methods: In this retrospective cohort study, we collected the data from patients with SFTS at Wuhan Union Hospital to evaluate the effect of GC therapy. Mortality and secondary infections were compared as outcomes. After searching public databases, we also included articles that examined GC use in patients with SFTS for meta-analysis. Results: Patients treated with GC had higher fatality rates (21.1% vs. 11.9%, respectively; P=0.006) and a longer length of stay (10.6 ± 5.1 vs. 9.5 ± 4.2, respectively; P=0.033). In cohorts adjusted using propensity score matching and inverse probability of treatment weighting, no significant differences in fatality rates and length of stay were observed. A meta-analysis of 4243 SFTS patient revealed that those treated with GCs had significantly higher mortality (OR=3.46, 95% CI =2.12-5.64, P<0.00001) and secondary infection rate (OR=1.97, 95% CI=1.45-2.67, P<0.0001). Discussion: GC should be used cautiously when treating SFTS. No significant differences were identified in terms of mortality and secondary infection rates between patients with SFTS treated with or without GC.
Assuntos
Glucocorticoides , Febre Grave com Síndrome de Trombocitopenia , Humanos , Estudos Retrospectivos , Febre Grave com Síndrome de Trombocitopenia/tratamento farmacológico , Febre Grave com Síndrome de Trombocitopenia/mortalidade , Glucocorticoides/uso terapêutico , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Phlebovirus/efeitos dos fármacos , Resultado do Tratamento , Tempo de Internação , Adulto , China/epidemiologiaRESUMO
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe viral hemorrhagic fever and thrombocytopenia syndrome with a fatality rate of up to 30%. No licensed vaccines or therapeutics are currently available for humans. Here, we develop seven monoclonal antibodies (mAbs) against SFTSV surface glycoprotein Gn. Mechanistic studies show that three neutralizing mAbs (S2A5, S1G3, and S1H7) block multiple steps during SFTSV infection, including viral attachment and membrane fusion, whereas another neutralizing mAb (B1G11) primarily inhibits the viral attachment step. Epitope binning and X-ray crystallographic analyses reveal four distinct antigenic sites on Gn, three of which have not previously been reported, corresponding to domain I, domain II, and spanning domain I and domain II. One of the most potent neutralizing mAbs, S2A5, binds to a conserved epitope on Gn domain I and broadly neutralizes infection of six SFTSV strains corresponding to genotypes A to F. A single dose treatment of S2A5 affords both pre- and post-exposure protection of mice against lethal SFTSV challenge without apparent weight loss. Our results support the importance of glycoprotein Gn for eliciting a robust humoral response and pave a path for developing prophylactic and therapeutic antibodies against SFTSV infection.
Assuntos
Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Antivirais , Epitopos , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Phlebovirus/imunologia , Camundongos , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Febre Grave com Síndrome de Trombocitopenia/imunologia , Febre Grave com Síndrome de Trombocitopenia/virologia , Febre Grave com Síndrome de Trombocitopenia/prevenção & controle , Humanos , Epitopos/imunologia , Feminino , Camundongos Endogâmicos BALB C , Proteínas do Envelope Viral/imunologia , Cristalografia por Raios X , Chlorocebus aethiops , Glicoproteínas/imunologia , Células VeroRESUMO
Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1-/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1-/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach.
Assuntos
Astrócitos , Infecções por Bunyaviridae , Camundongos Knockout , Phlebovirus , Receptor de Interferon alfa e beta , Animais , Astrócitos/virologia , Astrócitos/patologia , Camundongos , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/deficiência , Phlebovirus/genética , Phlebovirus/fisiologia , Phlebovirus/patogenicidade , Infecções por Bunyaviridae/virologia , Infecções por Bunyaviridae/patologia , Infecções por Bunyaviridae/imunologia , Encéfalo/virologia , Encéfalo/patologia , Encéfalo/imunologia , Medula Espinal/virologia , Medula Espinal/patologia , Modelos Animais de Doenças , Neurônios/virologia , Neurônios/patologia , Camundongos Endogâmicos C57BL , Tronco Encefálico/virologia , Tronco Encefálico/patologia , Morte CelularRESUMO
Severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie Banda virus, is an emerging tick-borne Bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS). Currently, symptomatic treatment and antiviral therapy with ribavirin and favipiravir are used in clinical management. However, their therapeutical efficacy is hardly satisfactory in patients with high viral load. In this study, we explored the antiviral effects of selective estrogen receptor modulators (SERMs) on SFTSV infection and the antiviral mechanisms of a representative SERM, bazedoxifene acetate (BZA). Our data show that SERMs potently inhibited SFTSV-induced cytopathic effect (CPE), the proliferation of infectious viral particles, and viral RNA replication and that BZA effectively protected mice from lethal viral challenge. The mode of action analysis reveals that BZA exerts antiviral effects during the post-entry stage of SFTSV infection. The transcriptome analysis reveals that GRASLND and CYP1A1 were upregulated, while TMEM45B and TXNIP were downregulated. Our findings suggest that SERMs have the potential to be used in the treatment of SFTSV infection.
Assuntos
Antivirais , Phlebovirus , Moduladores Seletivos de Receptor Estrogênico , Febre Grave com Síndrome de Trombocitopenia , Replicação Viral , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Phlebovirus/efeitos dos fármacos , Camundongos , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Febre Grave com Síndrome de Trombocitopenia/tratamento farmacológico , Febre Grave com Síndrome de Trombocitopenia/virologia , Replicação Viral/efeitos dos fármacos , Humanos , Chlorocebus aethiops , Feminino , Linhagem Celular , Células Vero , Modelos Animais de DoençasRESUMO
RATIONALE: The geographic spread of Japanese spotted fever (JSF) in China is gradually expanding, particularly in regions where severe fever with thrombocytopenia syndrome (SFTS) is highly prevalent, with both diseases sharing similarities in epidemiology and clinical presentation. The microbiological diagnosis of JSF is challenging, compounded by low awareness among healthcare professionals in newly affected areas. Moreover, primary healthcare facilities without polymerase chain reaction (PCR) testing capabilities for SFTS often misdiagnose JSF as SFTS. PATIENT CONCERNS: All 3 patients had a history of working in the fields, with cold like symptoms in the early fever stages, but the fever did not improve after a few days. The accompanying symptoms were also very different. Physical examination revealed enlarged lymph nodes, different forms of rash, with or without eschar. Laboratory tests showed thrombocytopenia, eosinophilia, elevated lactate dehydrogenase, and transaminase, with 1 patient experiencing renal damage. It is worth noting that these 3 patients reside in an area where SFTS is endemic, and there have been no prior reports of JSF. They exhibited clinical symptoms and laboratory test results closely resembling those of SFTS. Therefore, they were initially misdiagnosed with SFTS in their local hospitals. DIAGNOSES: The 3 patients who arrived at our hospital 7 days after symptom onset and were subsequently diagnosed with JSF by metagenomic next-generation sequencing (mNGS). INTERVENTIONS: Doxycycline treatment for 1 week. OUTCOMES: The patients' symptoms quickly improved with no side effects, and the results of laboratory tests went back to normal. LESSONS: By comparing the clinical characteristics of JSF patients and SFTS patients comprehensively, we found that APTT and procalcitonin levels may be valuable in assisting in the identification of SFTS and JSF. In all areas where tick-borne diseases are endemic, include SFTS-epidemic areas, we recommend using the Weil-Felix test to screen for potential rickettsiosis in patients presenting with fever and thrombocytopenia with or without rash in primary healthcare settings, as well as simultaneous testing for the SFTS virus and spotted fever group rickettsioses sequence. Additionally, mNGS sequencing should be used to confirm the diagnosis and provide information for epidemiological investigations in patients who are suspected of having spotted fever group rickettsiosis.
Assuntos
Phlebovirus , Humanos , Masculino , Phlebovirus/isolamento & purificação , Pessoa de Meia-Idade , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , China/epidemiologia , Rickettsiose do Grupo da Febre Maculosa/diagnóstico , Rickettsiose do Grupo da Febre Maculosa/epidemiologia , Feminino , Adulto , Doxiciclina/uso terapêutico , Doenças Endêmicas , Erros de Diagnóstico , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: Since its discovery, severe fever with thrombocytopenia syndrome (SFTS) has been characterized by rapid progression and poor prognosis, and no specific treatment is available. The aim of this study was to investigate the early warning indicators of mortality in SFTS patients. METHODS: This is a retrospective cross-sectional study. The study subjects were patients who were admitted to the hospital with a confirmed diagnosis of SFTS from January 2023 to October 2023, and their clinical symptoms and signs at the time of admission, as well as the laboratory indexes of the first blood collection after admission were collected, grouped according to the prognosis, and statistically analyzed. RESULTS: A total of 141 patients were collected, of which 27 patients died and 114 patients were in the survival group. Through statistical analysis, patients with combined hemorrhagic manifestations, disturbance of consciousness, lymphopenia, elevated lipase, and prolonged thrombin time on admission were independent risk factors for patients' death. By plotting the working characteristic curve of the subjects, as well as calculating the area under the curve, the results showed that the AUC of lymphopenia count was 0.670, 95% CI (0.563-0.776), P = 0.006; the AUC of elevated serum lipase index was 0.789, 95% CI (0.699-0.878), p < 0.001; the AUC of prolonged thrombin time was 0.749, 95% CI (0.645-0.854), p < 0.001. CONCLUSION: Patients with hemorrhagic manifestations, disturbance of consciousness, lymphocyte reduction, elevated serum lipase, and prolonged thrombin time on admission are more worthy of the clinician's attention, and require early and effective interventions to avoid further disease progression.
Assuntos
Febre Grave com Síndrome de Trombocitopenia , Humanos , Masculino , Feminino , Febre Grave com Síndrome de Trombocitopenia/mortalidade , Febre Grave com Síndrome de Trombocitopenia/sangue , Febre Grave com Síndrome de Trombocitopenia/virologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Prognóstico , Fatores de Risco , Phlebovirus , Adulto , Idoso de 80 Anos ou maisRESUMO
Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified tick-borne viral hemorrhagic fever caused by Dabie Banda virus (DBV). The virus was first discovered in eastern China in 2009 and is now considered an infectious disease with a mortality rate ranging from 6.3% to 30%. The best strategy for controlling SFTS is to develop effective vaccines. However, no approved vaccines are currently available to prevent this disease, despite the number of extensive and in-depth studies conducted on DBV in the past few years. This review focuses on the structure of DBV and the induced host immune responses which are the fundamental factors in vaccine development, and thoroughly summarizes the current research progress on DBV vaccines. The developing DBV vaccines include protein subunit vaccines, live attenuated vaccines, recombinant virus vector vaccines, and DNA vaccines. At present, almost all candidate vaccines for DBV are in the laboratory development or preclinical stages. There remain challenges in successfully developing clinically approved DBV vaccines.
Assuntos
Vacinas Virais , Humanos , Vacinas Virais/imunologia , Animais , Vacinas Atenuadas/imunologia , Desenvolvimento de Vacinas , Febre Grave com Síndrome de Trombocitopenia/prevenção & controle , Febre Grave com Síndrome de Trombocitopenia/imunologia , Phlebovirus/imunologia , Phlebovirus/genética , Vacinas de DNA/imunologia , Vacinas de Subunidades Antigênicas/imunologiaRESUMO
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus recognized by the World Health Organization as an emerging infectious disease of growing concern. Utilizing phylodynamic and phylogeographic methods, we have reconstructed the origin and transmission patterns of SFTSV lineages and the roles demographic, ecological, and climatic factors have played in shaping its emergence and spread throughout Asia. Environmental changes and fluctuations in tick populations, exacerbated by the widespread use of pesticides, have contributed significantly to its geographic expansion. The increased adaptability of Lineage L2 strains to the Haemaphysalis longicornis vector has facilitated the dispersal of SFTSV through Southeast Asia. Increased surveillance and proactive measures are needed to prevent further spread to Australia, Indonesia, and North America.
Assuntos
Phlebovirus , Filogeografia , Febre Grave com Síndrome de Trombocitopenia , Phlebovirus/genética , Animais , Sudeste Asiático , Febre Grave com Síndrome de Trombocitopenia/virologia , Febre Grave com Síndrome de Trombocitopenia/transmissão , Humanos , Filogenia , Vetores Aracnídeos/virologia , Carrapatos/virologia , Ixodidae/virologia , Espécies IntroduzidasRESUMO
Central China has been reported to be one of the most important endemic areas of zoonotic infection by spotted fever group rickettsiae (SFGR), severe fever with thrombocytopenia syndrome virus (SFTSV) and hantaan virus (HTNV). Due to similar clinical symptoms, it is challenging to make a definite diagnosis rapidly and accurately in the absence of microbiological tests. In the present study, an all-in-one real-time PCR assay was developed for the simultaneous detection of nucleic acids from SFGR, SFTSV and HTNV. Three linear standard curves for determining SFGR-ompA, SFTSV-L and HTNV-L were obtained within the range of 101-106 copies/µL, with the PCR amplification efficiencies ranging from 93.46% to 96.88% and the regression coefficients R2 of >0.99. The detection limit was 1.108 copies/µL for SFGR-ompA, 1.075 copies/µL for SFTSV-L and 1.006 copies/µL for HTNV-L, respectively. Both the within-run and within-laboratory coefficients of variation on the cycle threshold (Ct) values were within the range of 0.53%-2.15%. It was also found there was no statistical difference in the Ct values between single template and multiple templates (PSFGR-ompA = 0.186, PSFTSV-L = 0.612, PHTNV-L = 0.298). The sensitivity, specificity, positive and negative predictive value were all 100% for determining SFGR-ompA and SFTSV-L, 97%, 100%, 100% and 99.6% for HTNV-L, respectively. Therefore, the all-in-one real-time PCR assay appears to be a reliable, sensitive, rapid, high-throughput and low cost-effective method to diagnose the zoonotic infection by SFGR, SFTSV and HTNV.
Assuntos
Vírus Hantaan , Phlebovirus , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Febre Grave com Síndrome de Trombocitopenia , China/epidemiologia , Vírus Hantaan/genética , Vírus Hantaan/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Phlebovirus/genética , Phlebovirus/isolamento & purificação , Humanos , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Rickettsia/isolamento & purificação , Rickettsia/genética , Rickettsiose do Grupo da Febre Maculosa/diagnóstico , AnimaisRESUMO
BACKGROUND: Rodents are recognized as major reservoirs of numerous zoonotic pathogens and are involved in the transmission and maintenance of infectious diseases. Furthermore, despite their importance, diseases transmitted by rodents have been neglected. To date, there have been limited epidemiological studies on rodents, and information regarding their involvement in infectious diseases in the Republic of Korea (ROK) is still scarce. METHODOLOGY/PRINCIPAL FINDINGS: We investigated rodent-borne pathogens using nested PCR/RT-PCR from 156 rodents including 151 Apodemus agrarius and 5 Rattus norvegicus from 27 regions in eight provinces across the ROK between March 2019 and November 2020. Spleen, kidney, and blood samples were used to detect Anaplasma phagocytophilum, Bartonella spp., Borrelia burgdorferi sensu lato group, Coxiella burnetii, Leptospira interrogans, and severe fever with thrombocytopenia syndrome virus (SFTSV). Of the 156 rodents, 73 (46.8%) were infected with Bartonella spp., 25 (16.0%) with C. burnetii, 24 (15.4%) with L. interrogans, 21 (13.5%) with A. phagocytophilum, 9 (5.8%) with SFTSV, and 5 (3.2%) with Borrelia afzelii. Co-infections with two and three pathogens were detected in 33 (21.1%) and 11 rodents (7.1%), respectively. A. phagocytophilum was detected in all regions, showing a widespread occurrence in the ROK. The infection rates of Bartonella spp. were 83.3% for B. grahamii and 16.7% for B. taylorii. CONCLUSIONS/SIGNIFICANCE: To the best of our knowledge, this is the first report of C. burnetii and SFTSV infections in rodents in the ROK. This study also provides the first description of various rodent-borne pathogens through an extensive epidemiological survey in the ROK. These results suggest that rodents harbor various pathogens that pose a potential threat to public health in the ROK. Our findings provide useful information on the occurrence and distribution of zoonotic pathogens disseminated among rodents and emphasize the urgent need for rapid diagnosis, prevention, and control strategies for these zoonotic diseases.
Assuntos
Anaplasma phagocytophilum , Bartonella , Coxiella burnetii , Zoonoses , Animais , República da Coreia/epidemiologia , Zoonoses/epidemiologia , Zoonoses/microbiologia , Ratos , Coxiella burnetii/isolamento & purificação , Coxiella burnetii/genética , Bartonella/isolamento & purificação , Bartonella/genética , Anaplasma phagocytophilum/isolamento & purificação , Anaplasma phagocytophilum/genética , Roedores/microbiologia , Murinae/microbiologia , Animais Selvagens/microbiologia , Animais Selvagens/virologia , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/microbiologia , Doenças dos Roedores/virologia , Phlebovirus/genética , Phlebovirus/isolamento & purificação , Reservatórios de Doenças/microbiologia , Leptospira interrogans/isolamento & purificação , Leptospira interrogans/genéticaRESUMO
Phenuiviruses are a class of segmented negative-sense single-stranded RNA viruses, typically consisting of three RNA segments that encode four distinct proteins. The emergence of pathogenic phenuivirus strains, such as Rift Valley fever phlebovirus (RVFV) in sub-Saharan Africa, Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in East and Southeast Asia, and Heartland Virus (HRTV) in the United States has presented considerable challenges to global public health in recent years. The innate immune system plays a crucial role as the initial defense mechanism of the host against invading pathogens. In addition to continued research aimed at elucidating the epidemiological characteristics of phenuivirus, significant advancements have been made in investigating its viral virulence factors (glycoprotein, non-structural protein, and nucleoprotein) and potential host-pathogen interactions. Specifically, efforts have focused on understanding mechanisms of viral immune evasion, viral assembly and egress, and host immune networks involving immune cells, programmed cell death, inflammation, nucleic acid receptors, etc. Furthermore, a plethora of technological advancements, including metagenomics, metabolomics, single-cell transcriptomics, proteomics, gene editing, monoclonal antibodies, and vaccines, have been utilized to further our understanding of phenuivirus pathogenesis and host immune responses. Hence, this review aims to provide a comprehensive overview of the current understanding of the mechanisms of host recognition, viral immune evasion, and potential therapeutic approaches during human pathogenic phenuivirus infections focusing particularly on RVFV and SFTSV.