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BACKGROUND: This study aimed to analyze the correlation between the cycle threshold (Ct) values of severe fever with thrombocytopenia syndrome (SFTS) virus small (S) and middle (M) segments and the SFTS viral load, aiming to estimate the initial viral load and predict prognosis in the early clinical course. METHOD: A retrospective study was conducted with confirmed SFTS patients at Jeju National University Hospital (2016-2022). Patients were categorized into non-fatal and fatal groups. RESULTS: This study included 49 patients with confirmed SFTS (non-fatal group, n = 42; fatal group, n = 7). A significant negative correlation (-0.783) was observed between the log SFTS viral load and Ct values (p < 0.001). This negative correlation was notably stronger in the fatal group (correlation coefficient -0.940) than in the non-fatal group (correlation coefficient -0.345). CONCLUSION: In this study, we established a correlation between SFTS viral load and Ct values for estimating the initial viral load and early predicting prognosis. These results are expected to offer valuable insights for SFTS patient treatment and prognosis prediction.
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Phlebovirus , Reação em Cadeia da Polimerase em Tempo Real , Febre Grave com Síndrome de Trombocitopenia , Carga Viral , Humanos , Phlebovirus/genética , Phlebovirus/isolamento & purificação , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/virologia , Masculino , Feminino , Prognóstico , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real/métodos , Idoso de 80 Anos ou mais , Adulto , RNA Viral/genéticaRESUMO
BACKGROUND: In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. METHODS: To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments. RESULTS: CD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244-/- bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. CONCLUSION: Our study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients.
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Melanoma , Monócitos , Humanos , Animais , Camundongos , Monócitos/metabolismo , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Macrófagos/metabolismo , Linfócitos T CD8-Positivos , Carcinogênese/metabolismo , Microambiente Tumoral , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismoRESUMO
BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a viral pathogen causing significant clinical signs from mild fever with thrombocytopenia to severe hemorrhages. World Health Organization has paid special attention to the dramatic increase in human SFTS cases in China, Japan, and South Korea since the 2010s. The present study investigated the molecular evolution and genetic reassortment of SFTSVs using complete genomic sequences. METHODS/PRINCIPAL FINDING: We collected the complete genome sequences of SFTSVs globally isolated until 2019 (L segment, n = 307; M segment, n = 326; and S segment, n = 564) and evaluated the evolutionary profiles of SFTSVs based on phylogenetic and molecular selection pressure analyses. By employing a time-scaled Bayesian inference method, we found the geographical heterogeneity of dominant SFTSV genotypes in China, Japan, and South Korea around several centuries before and locally spread by tick-born spillover with infrequent long-distance transmission. Purifying selection predominated the molecular evolution of SFTSVs with limited gene reassortment and fixed substitution, but almost all three gene segments appeared to harbor at least one amino acid residue under positive selection. Specifically, the nonstructural protein and glycoprotein (Gn/Gc) genes were preferential selective targets, and the Gn region retained the highest number of positively selected residues. CONCLUSION/SIGNIFICANCE: Here, the large-scale genomic analyses of SFTSVs improved prior knowledge of how this virus emerged and evolved in China, Japan, and South Korea. Our results highlight the importance of SFTSV surveillance in both human and non-human reservoirs at the molecular level to fight against fatal human infection with the virus.
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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with high mortality in Eastern Asia. The disease is caused by the SFTS virus (SFTSV), also known as Dabie bandavirus, which has a segmented RNA genome consisting of L, M, and S segments. Previous studies have suggested differential viral virulence depending on the genotypes of SFTSV; however, the critical viral factor involved in the differential viral virulence is unknown. Here, we found a significant difference in viral replication in vitro and virulence in vivo between two Korean isolates belonging to the F and B genotypes, respectively. By generating viral reassortants using the two viral strains, we demonstrated that the L segment, which encodes viral RNA-dependent RNA polymerase (RdRp), is responsible for the enhanced viral replication and virulence. Comparison of amino acid sequences and viral replication rates revealed a point variation, E251K, on the surface of RdRp to be the most significant determinant for the enhanced viral replication rate and in vivo virulence. The effect of the variation was further confirmed using recombinant SFTSV generated by reverse genetic engineering. Therefore, our results indicate that natural variations affecting the viral replicase activity could significantly contribute to the viral virulence of SFTSV.
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Febre Grave com Síndrome de Trombocitopenia , Humanos , Virulência , RNA Polimerases Dirigidas por DNA/genética , Replicação Viral , RNA Polimerase Dependente de RNA/genéticaRESUMO
Severe fever with thrombocytopenia syndrome virus (SFTSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause the hyperproduction of inflammatory cytokines, which have pathological effects in patient including severe or fatal cytokine storms. To characterize the effect of SFTSV and SARS-CoV-2 infection on the production of cytokines in severe fever with thrombocytopenia syndrome (SFTS) and COVID-19 patients, we performed an analysis of cytokines in SFTS and COVID-19 patients and also investigated the role of interleukin-10 (IL-10) in vitro studies: lipopolysaccharide-induced THP-1-derived macrophages, SFTSV infection of THP-1 cells, and SARS-CoV-2 infection of THP-1 cells. In this study, we found that levels of both IL-10 and IL-6 were significantly elevated, the level of transforming growth factor-ß (TGF-ß) was significantly decreased and IL-10 was elevated earlier than IL-6 in severe and critical COVID-19 and fatal SFTS patients, and inhibition of IL-10 signaling decreased the production of IL-6 and elevated that of TGF-ß. Therefore, the hyperproduction of IL-10 and IL-6 and the low production of TGF-ß have been linked to cytokine storm-induced mortality in fatal SFTS and severe and critically ill COVID-19 patients and that IL-10 can play an important role in the host immune response to severe and critical SARS-CoV-2 and fatal SFTSV infection.
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COVID-19 , Febre Grave com Síndrome de Trombocitopenia , Humanos , Síndrome da Liberação de Citocina , Citocinas , Interleucina-10 , Interleucina-6 , SARS-CoV-2 , Fator de Crescimento Transformador betaRESUMO
BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV) is transmitted through tick bites. Ticks are potential vectors for the bacterium Coxiella burnetii that causes Query fever. Here, we analyzed SFTSV and C. burnetii co-infection rates in ticks in rural areas of Jeju Island, South Korea. METHODS: Free ticks were collected from the natural environment of the island between 2016 and 2019, and SFTSV RNA was extracted. Additionally, ribosomal RNA gene sequencing was used to identify Coxiella species. RESULTS: Haemaphysalis longicornis was the most common tick species followed by H. flava. Tick number gradually increased from April, peaked in August, and was lowest in March. Of all the collected ticks, 82.6% (2,851/3,458) were nymphs, 17.9% (639/3,458) adults, and 0.1% (4/3,458) larvae. SFTSV-infected ticks comprised 12.6% of all ticks; their numbers were the lowest in November-December, increased from January, and were mostly identified in the adult stage during June-August. C. burnetii infections were detected in 4.4% of the SFTSV-infected H. longicornis ticks. C. burnetii co-infection was mainly observed in the nymph stage of H. longicornis, with the highest infection rate in January, followed by December and November. CONCLUSION: Our findings suggest that Jeju Island has a high SFTSV and potential C. burnetii infection in ticks. This study provides important insights regarding SFTS and Q fever risk to humans in South Korea.
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Coinfecção , Coxiella burnetii , Ixodidae , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Carrapatos , Humanos , Animais , Coxiella burnetii/genética , Phlebovirus/genética , República da Coreia/epidemiologiaRESUMO
Infection with severe fever with thrombocytopenia syndrome (SFTS) virus, which can cause hemorrhagic febrile illness, is often transmitted by ticks. We identified 3 patients with SFTS in or near Bangkok, Thailand. Our results underscore a need for heightened awareness by clinicians of possible SFTS virus, even in urban centers.
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Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Carrapatos , Animais , Humanos , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , Tailândia/epidemiologia , Phlebovirus/genéticaRESUMO
Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne viral disease, is prevalent in East Asia and has also been reported in Southeast Asia since 2019. SFTS patients in Vietnam were first reported in 2019. However, the seroprevalence of severe fever with thrombocytopenia syndrome virus (SFTSV) in Vietnam has not been reported. To investigate the seroprevalence of SFTSV in Vietnam, we collected serum samples from 714 healthy residents in Thua Thien Hue and Quang Nam Province, Vietnam, and the seroprevalence of SFTSV was assessed using immunofluorescence antibody assay (IFA), Enzyme-Linked Immunosorbent Assays (ELISAs) and the 50% focus reduction neutralization test (FRNT50) assay. The seroprevalence of anti-SFTSV IgM or IgG was observed to be 3.64% (26/714), high IgM positivity was >80 (0.28%, 2/714) and the titer of neutralizing antibodies against SFTSV ranged from 15.5 to 55.9. In Pakistan, SFTSV infection confirmed using a microneutralization test (MNT) assay (prevalence is 2.5%) and ELISAs showed a high seroprevalence (46.7%) of SFTSV. Hence, the seroprevalence rate in Vietnam is similar to that in Pakistan and the number of SFTS patients could increase in Vietnam.
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Infecções por Bunyaviridae , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Doenças Transmitidas por Carrapatos , Humanos , Estudos Soroepidemiológicos , Vietnã/epidemiologia , Anticorpos Antivirais , Anticorpos Neutralizantes , Imunoglobulina M , Imunoglobulina GRESUMO
BACKGROUND: There is a correlation between the severe fever with thrombocytopenia syndrome (SFTS) viral load and disease severity; however, measurement of viral load is difficult in general laboratory and it takes time to obtain a viral load value. Here, the laboratory parameters for predicting the dynamic changes in SFTS viral load were identified. In addition, we tried to evaluate a specific time point for the early determination of clinical deterioration using dynamic change of laboratory parameters. MATERIALS AND METHODS: This observational study included SFTS patients in Korea (2013 - 2020). Cross-correlation analysis at lagged values was used to determine the temporal correlation between the SFTS viral loads and time-series variables. Fifty-eight SFTS patients were included in the non-severe group (NSG) and 11 in the severe group (SG). RESULTS: In the cross-sectional analyses, 10 parameters -white blood cell, absolute neutrophil cell, lymphocyte, platelet, activated partial thromboplastin time (aPTT), C-reactive protein, aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK)- were assessed within 30 days from the onset of symptoms; they exhibited three different correlation patterns: (1) positive, (2) positive with a time lag, and (3) negative. A prediction score system was developed for predicting SFTS fatality based on age and six laboratory variables -platelet, aPTT, AST, ALT, LDH, and CPK- in 5 days after the onset of symptoms; this scoring system had 87.5% sensitivity and 86.0% specificity (95% confidence interval: 0.831 - 1.00, P <0.001). CONCLUSION: Three types of correlation patterns between the dynamic changes in SFTS viral load and laboratory parameters were identified. The dynamic changes in the viral load could be predicted using the dynamic changes in these variables, which can be particularly helpful in clinical settings where viral load tests cannot be performed. Also, the proposed scoring system could provide timely treatment to critical patients by rapidly assessing their clinical course.
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Severe fever with thrombocytopenia syndrome virus (SFTSV) infection is commonly reported in countries of Northeast Asia including China, Japan and South Korea. The majority of the SFTS patients are elderly and the average fatality rate is more than 10%. A rapid and sensitive diagnostic method to monitor and prevent SFTSV transmission remains an urgent clinical challenge. In this study, we developed a molecular diagnostic technique for detection of SFTSV using the CRISPR-Cas12a system combined with reverse transcription recombinase polymerase amplification (RT-RPA). Using this method, we successfully diagnosed SFTSV infections with the reaction time of 50 min from blood plasma without cross-reactivity to other viruses, supporting its application for rapid and sensitive diagnosis of SFTS.
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Infecções por Bunyaviridae , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Idoso , Sistemas CRISPR-Cas , Genótipo , Humanos , Phlebovirus/genética , Febre Grave com Síndrome de Trombocitopenia/diagnósticoRESUMO
We report the administration of an anti-interleukin (IL)-6 antibody in a case of severe fever with thrombocytopenia syndrome (SFTS) with an increase in IL-6. On the day of admission, SFTS viral load and IL-6 concentration were 93 831 copies/ml and 5.4 pg/ml, respectively, and tocilizumab was administered. SFTS viral load decreased to 17 821.1 copies/ml on the 3rd day of admission, while IL-6 levels increased to 104.9 pg/ml; SFTS viral load and IL-6 levels had decreased to 2876.4 copies/ml and 48.2 pg/ml on 7th day of admission, respectively. The patient fully recovered no tocilizumab adverse events.
Assuntos
Infecções por Bunyaviridae , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Trombocitopenia , Febre/tratamento farmacológico , Humanos , Interleucina-6 , Trombocitopenia/tratamento farmacológicoRESUMO
Streptococcus equi subsp. zooepidemicus (SEZ) is a highly contagious infectious organism that causes disease in horses. SEZ is seldom isolated from humans; however, zoonotic infections are occasionally reported in individuals exposed to horses and other livestock. Herein, we report three human cases of SEZ in individuals, one with direct horse contact and two among individuals who had eaten raw horse meat. The phylogenetic tree showed that the genotypes of SEZ isolates from two of the cases on Jeju Island, South Korea, were similar to those of isolates from the United Kingdom and the United States of America.
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Doenças dos Cavalos , Infecções Estreptocócicas , Streptococcus equi , Animais , Cavalos , Humanos , Filogenia , Infecções Estreptocócicas/veterinária , Streptococcus equi/genética , ZoonosesRESUMO
BACKGROUND: Skin prick tests are widely used to diagnose allergic sensitization. The influence of obesity on the skin prick test result has not been clearly established, even though the association between allergic disease and obesity is relatively well known. OBJECTIVE: To determine whether a change in body mass index (BMI) contributes to skin reactivity to histamine and allergens in a skin prick test, we performed a 2-year follow-up study on Korean children. METHODS: Skin prick tests for common aeroallergens were performed on elementary school students from Jeju Island, Korea. BMI was calculated using weight and height after measuring both, and demographic characteristics were surveyed. The same tests were repeated after 2 years. RESULTS: The sensitization rate increased during the 2 years between tests and the children's mean BMI also increased, along with their age. The wheal sizes induced by Dermatophagoides pteronyssinus, Dermatophagoides farinae, Japanese cedar, and histamine were significantly increased during 2 years; however, only the histamine reaction associated with increased BMI had statistical significance. Furthermore, other variables-including the number of sensitized allergens-were not related to histamine skin reactivity. CONCLUSION: Histamine skin reactivity increased in children over time and some allergens showed increased specific reactions; however, BMI gain is a specific predictor of histamine reactivity. Further studies are needed to elucidate the clinical significance of these changes.
Assuntos
Alérgenos , Histamina , Índice de Massa Corporal , Criança , Seguimentos , Humanos , República da Coreia/epidemiologia , Testes CutâneosRESUMO
Significant progress has been made on the molecular biology of the severe fever with thrombopenia virus (SFTSV); however, many parts of the pathophysiological mechanisms of mortality in SFTS remain unclear. In this study, we investigated virologic and immunologic factors for fatal outcomes of patients with SFTS. We prospectively enrolled SFTS patients admitted from July 2015 to October 2020. Plasma samples were subjected to SFTSV RNA RT-PCR, multiplex microbead immunoassay for 17 cytokines, and IFA assay. A total of 44 SFTS patients were enrolled, including 37 (84.1%) survivors and 7 (15.9%) non-survivors. Non-survivors had a 2.5 times higher plasma SFTSV load than survivors at admission (p < 0.001), and the viral load in non-survivors increased progressively during hospitalization. In addition, non-survivors did not develop adequate anti-SFTSV IgG, whereas survivors exhibited anti-SFTSV IgG during hospitalization. IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF were significantly elevated in non-survivors compared to survivors and did not revert to normal ranges during hospitalization (p < 0.05). Severe signs of inflammation such as a high plasma concentration of IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF, poor viral control, and inadequate antibody response during the disease course were associated with mortality in SFTS patients.
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Citocinas/imunologia , Phlebovirus/imunologia , Febre Grave com Síndrome de Trombocitopenia , Idoso , Anticorpos Antivirais/sangue , Progressão da Doença , Feminino , Humanos , Fatores Imunológicos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia , Febre Grave com Síndrome de Trombocitopenia/imunologia , Febre Grave com Síndrome de Trombocitopenia/mortalidade , Febre Grave com Síndrome de Trombocitopenia/virologia , Carga ViralRESUMO
Bacteroides fragilis enterotoxin (BFT) produced by enterotoxigenic B. fragilis (ETBF) causes colonic inflammation. BFT initially contacts intestinal epithelial cells (IECs) and affects the intestinal barrier. Although molecular components of the gut epithelial barrier such as metalloproteinase-7 (MMP-7) and syndecan-2 are known to be associated with inflammation, little has been reported about MMP-7 expression and syndecan-2 shedding in response to ETBF infection. This study explores the role of BFT in MMP-7 induction and syndecan-2 release in IECs. Stimulating IECs with BFT led to the induction of MMP-7 and the activation of transcription factors such as NF-κB and AP-1. MMP-7 upregulation was not affected by NF-κB, but it was related to AP-1 activation. In BFT-exposed IECs, syndecan-2 release was observed in a time- and concentration-dependent manner. MMP-7 suppression was associated with a reduction in syndecan-2 release. In addition, suppression of ERK, one of the mitogen-activated protein kinases (MAPKs), inhibited AP-1 activity and MMP-7 expression. Furthermore, the suppression of AP-1 and ERK activity was related to the attenuation of syndecan-2 release. These results suggest that a signaling cascade comprising ERK and AP-1 activation in IECs is involved in MMP-7 upregulation and syndecan-2 release during exposure to BFT.
Assuntos
Bacteroides fragilis/química , Células Epiteliais/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 7 da Matriz/biossíntese , Metaloendopeptidases/toxicidade , Sindecana-2/metabolismo , Fator de Transcrição AP-1/metabolismo , Regulação para Cima/efeitos dos fármacos , Células HCT116 , Humanos , Metaloendopeptidases/químicaRESUMO
Coxiella burnetii infects humans and wild and domesticated animals. Although reported cases on Jeju Island, off the coast of South Korea, are rare, the region is considered to have a high potential for Q fever. We investigated the seroprevalence of antibodies to C. burnetii in 230 farmers living in ten rural areas on Jeju Island between January 2015 and December 2019. Blood samples were collected and examined for C. burnetii Phase I/II IgM and IgG antibodies. Trained researchers collected ticks from rural areas. Clone XCP-1 16S ribosomal RNA gene sequencing was performed to identify Coxiella species from the collected ticks. The overall seroprevalence of antibodies to C. burnetii in farmers was 35.7%. The seroprevalence was significantly higher in fruit farmers. Of the collected ticks, 5.4% (19/351) of the Haemaphysalis longicornis ticks harbored C. burnetti. A high seroprevalence of antibodies to C. burnetii was observed in this region of Jeju Island, confirming that C. burnetti is endemic. Physicians should thus consider Q fever in the differential diagnosis of patients that present with acute fever after participating in outdoor activities.
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Severe fever with thrombocytopenia syndrome (SFTS) is a new tick-borne viral disease, and most SFTS virus (SFTSV) infections occur via bites from the tick Haemaphysalis longicornis; however, SFTSV transmission can also occur through close contact with an infected patient. SFTS is characterized by acute high fever, thrombocytopenia, leukopenia, elevated serum hepatic enzyme levels, gastrointestinal symptoms, and multiorgan failure and has a 16.2 to 30% mortality rate. In this study, we found that age, dyspnea rates, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, multiorgan dysfunction score (MODS), viral load, IL-6 levels, and IL-10 levels were higher in patients with fatal disease than in patients with nonfatal disease during the initial clinical course of SFTS. In addition, we found that IL-6 and IL-10 levels, rather than viral load and neutralizing antibody titers, in patients with an SFTSV infection strongly correlated with outcomes (for severe disease with an ultimate outcome of recovery or death).
Assuntos
Interleucina-10/sangue , Interleucina-6/sangue , Febre Grave com Síndrome de Trombocitopenia/imunologia , Viremia/imunologia , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Aspartato Aminotransferases/sangue , Citocinas/sangue , Dispneia/etiologia , Feminino , Humanos , Interleucina-10/fisiologia , Interleucina-6/fisiologia , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Phlebovirus/imunologia , República da Coreia/epidemiologia , Febre Grave com Síndrome de Trombocitopenia/sangue , Febre Grave com Síndrome de Trombocitopenia/mortalidade , Febre Grave com Síndrome de Trombocitopenia/virologia , Resultado do Tratamento , Carga Viral , Viremia/sangue , Viremia/mortalidadeRESUMO
Incidence of hypervirulent Klebsiella pneumoniae (hvKp) infection has been steadily increasing in the Asia-Pacific rim. The characteristic of hvKp infection is its ability to cause multiple site infections and unpredictable metastatic spread in the community. We describe the first case of mycotic aneurysm caused by hvKp serotype K1 in a previously healthy man and review the literature. Of a total of 13 cases, including our case, three cases were related to hvKp. Among patients with hvKp, the level of mycotic aneurysm in most patients was the infrarenal aorta, and they underwent an aortic graft or coil embolization. All strains were susceptible to most antimicrobial agents, except ampicillin. Early detection of hvKp can help to prevent the metastatic spread of pathogens and be useful for optimal patient care and epidemiologic research.
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BACKGROUND: Orthohantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a significant public health threat worldwide. Despite the significant mortality and morbidity, effective antiviral therapeutics for orthohantavirus infections are currently unavailable. This study aimed to investigate the prevalence of HFRS-associated orthohantaviruses and identify the etiological agent of orthohantavirus outbreaks in southern Republic of Korea (ROK). METHODOLOGY/PRINCIPAL FINDINGS: We collected small mammals on Jeju Island during 2018-2020. We detected the Hantaan virus (HTNV)-specific antibodies and RNA using an indirect immunofluorescence assay test and reverse transcription-polymerase chain reaction on Apodemus agrarius chejuensis (A. chejuensis). The prevalence of anti-HTNV antibodies among rodents was 14.1%. A total of six seropositive mouse harbored HTNV RNA. The amplicon-based next-generation sequencing provided nearly full-length tripartite genomic sequences of six HTNV harbored by A. chejuensis. Phylogenetic and tanglegram analyses were conducted for inferring evolutionary relationships between orthohantaviruses with their reservoir hosts. Phylogenetic analysis showed a novel distinct HTNV genotype. The detected HTNV genomic sequences were phylogenetically related to a viral sequence derived from HFRS patient in southern ROK. Tanglegram analysis demonstrated the segregation of HTNV genotypes corresponding to Apodemus spp. divergence. CONCLUSIONS/SIGNIFICANCE: Our results suggest that A. chejuensis-borne HTNV may be a potential etiological agent of HFRS in southern ROK. Ancestral HTNV may infect A. chejuensis prior to geological isolation between the Korean peninsula and Jeju Island, supporting the co-evolution of orthohantaviruses and rodents. This study arises awareness among physicians for HFRS outbreaks in southern ROK.
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Vírus Hantaan/genética , Vírus Hantaan/isolamento & purificação , Febre Hemorrágica com Síndrome Renal/etiologia , Murinae/virologia , Animais , Anticorpos Antivirais , Vírus Hantaan/classificação , Febre Hemorrágica com Síndrome Renal/virologia , Filogenia , República da Coreia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Roedores , MusaranhosRESUMO
Severe fever with thrombocytopenia syndrome (SFTS), a newly emerging tick-borne viral disease, has been detected in Asia since 2009, and person-to-person transmission is possible. SFTS is characterized by atypical signs, including mild to severe febrile illness similar to that associated with hemorrhagic fever, with 16.2 to 30% mortality. We found that the titers of neutralizing antibodies, play an important role in protective immunity, to SFTS virus (SFTSV) in survivors and healthy residents who lived in endemic areas and who were positive for SFTSV IgG, were higher than those in non-survivor patients. Moreover, the titers were maintained in surviving patients and healthy residents but not in non-surviving patients in South Korea.