I. Fricke-Galindo, I. Buendía-Roldán, A. Ruiz, Y. Palacios, G. Pérez-Rubio, R. Hernández-Zenteno, Felipe Reyes-Melendres, A. Zazueta-Márquez, Aimé Alarcón-Dionet, Javier Guzmán-Vargas, Omar Andrés Bravo-Gutiérrez, Teresa Quintero-Puerta, I. A. Gutiérrez-Pérez, Karol J Nava-Quiroz, José Luis Bañuelos-Flores, M. Mejía, J. Rojas-Serrano, E. Ramos-Martínez, I. Guzmán-Guzmán, L. Chávez-Galán, R. Falfán-Valencia
Abstract Background The impact of genetic variants in the expression of tumor necrosis factor-α (TNF-α) and its receptors in coronavirus disease 2019 (COVID-19) severity has not been previously explored. We evaluated the association of TNF (rs1800629 and rs361525), TNFRSF1A (rs767455 and rs1800693), and TNFRSF1B (rs1061622 and rs3397) variants with COVID-19 severity, assessed as invasive mechanical ventilation (IMV) requirement, and the plasma levels of soluble TNF-α, TNFR1, and TNFR2 in patients with severe COVID-19. Methods The genetic study included 1353 patients. Taqman assays were used to assess the genetic variants. ELISA was used to determine soluble TNF-α, TNFR1, and TNFR2 in plasma samples from 334 patients. Results Patients carrying TT (TNFRSF1B rs3397) exhibited lower PaO2/FiO2 levels than those with CT + CC genotypes. Differences in plasma levels of TNFR1 and TNFR2 were observed according to the genotype of TNFRSF1B rs1061622, TNF rs1800629, and rs361525. According to the studied genetic variants, there were no differences in the soluble TNF-α levels. Higher soluble TNFR1 and TNFR2 levels were detected in patients with COVID-19 requiring IMV. Conclusions Genetic variants in TNF and TNFRSFB1 influence the plasma levels of soluble TNFR1 and TNFR2, implicated in COVID-19 severity.
{"title":"TNFRSF1B and TNF Variants Are Associated With Differences in Levels of Soluble Tumor Necrosis Factor Receptors in Patients With Severe COVID-19","authors":"I. Fricke-Galindo, I. Buendía-Roldán, A. Ruiz, Y. Palacios, G. Pérez-Rubio, R. Hernández-Zenteno, Felipe Reyes-Melendres, A. Zazueta-Márquez, Aimé Alarcón-Dionet, Javier Guzmán-Vargas, Omar Andrés Bravo-Gutiérrez, Teresa Quintero-Puerta, I. A. Gutiérrez-Pérez, Karol J Nava-Quiroz, José Luis Bañuelos-Flores, M. Mejía, J. Rojas-Serrano, E. Ramos-Martínez, I. Guzmán-Guzmán, L. Chávez-Galán, R. Falfán-Valencia","doi":"10.1093/infdis/jiac101","DOIUrl":"https://doi.org/10.1093/infdis/jiac101","url":null,"abstract":"Abstract Background The impact of genetic variants in the expression of tumor necrosis factor-α (TNF-α) and its receptors in coronavirus disease 2019 (COVID-19) severity has not been previously explored. We evaluated the association of TNF (rs1800629 and rs361525), TNFRSF1A (rs767455 and rs1800693), and TNFRSF1B (rs1061622 and rs3397) variants with COVID-19 severity, assessed as invasive mechanical ventilation (IMV) requirement, and the plasma levels of soluble TNF-α, TNFR1, and TNFR2 in patients with severe COVID-19. Methods The genetic study included 1353 patients. Taqman assays were used to assess the genetic variants. ELISA was used to determine soluble TNF-α, TNFR1, and TNFR2 in plasma samples from 334 patients. Results Patients carrying TT (TNFRSF1B rs3397) exhibited lower PaO2/FiO2 levels than those with CT + CC genotypes. Differences in plasma levels of TNFR1 and TNFR2 were observed according to the genotype of TNFRSF1B rs1061622, TNF rs1800629, and rs361525. According to the studied genetic variants, there were no differences in the soluble TNF-α levels. Higher soluble TNFR1 and TNFR2 levels were detected in patients with COVID-19 requiring IMV. Conclusions Genetic variants in TNF and TNFRSFB1 influence the plasma levels of soluble TNFR1 and TNFR2, implicated in COVID-19 severity.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"48 1","pages":"778 - 787"},"PeriodicalIF":0.0,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82238623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao Li, J. Bilcke, L. Vázquez Fernández, L. Bont, L. Willem, T. Wisløff, M. Jit, P. Beutels
BACKGROUND Every winter, respiratory syncytial virus (RSV) disease results in thousands of cases in Norwegian children under 5 years of age. We aim to assess the RSV-related economic burden and the cost-effectiveness of upcoming RSV disease prevention strategies including year-round maternal immunization and year-round and seasonal monoclonal antibody (mAb) programs. METHODS Epidemiological and cost data were obtained from Norwegian national registries, while quality-adjusted life-years (QALYs) lost and intervention characteristics were extracted from literature and phase 3 clinical trials. A static model was used and uncertainty was accounted for probabilistically. Value of information was used to assess decision uncertainty. Extensive scenario analyses were conducted, including accounting for long-term consequences of RSV disease. RESULTS We estimate an annual average of 13 517 RSV cases and 1572 hospitalizations in children under 5, resulting in 79.6 million Norwegian kroner (~€8 million) treatment costs. At €51 per dose for all programs, a 4-month mAb program for neonates born in November to February is the cost-effective strategy for willingness to pay (WTP) values up to €40 000 per QALY gained. For higher WTP values, the longer 6-month mAb program that immunizes neonates from October to March becomes cost-effective. Sensitivity analyses show that year-round maternal immunization can become a cost-effective strategy if priced lower than mAb. CONCLUSIONS Assuming the same pricing, seasonal mAb programs are cost-effective over year-round programs in Norway. The timing and duration of the cost-effective seasonal program are sensitive to the pattern of the RSV season in a country, so continued RSV surveillance data are essential.
{"title":"Cost-effectiveness of Respiratory Syncytial Virus Disease Prevention Strategies: Maternal Vaccine Versus Seasonal or Year-Round Monoclonal Antibody Program in Norwegian Children.","authors":"Xiao Li, J. Bilcke, L. Vázquez Fernández, L. Bont, L. Willem, T. Wisløff, M. Jit, P. Beutels","doi":"10.1093/infdis/jiac064","DOIUrl":"https://doi.org/10.1093/infdis/jiac064","url":null,"abstract":"BACKGROUND\u0000Every winter, respiratory syncytial virus (RSV) disease results in thousands of cases in Norwegian children under 5 years of age. We aim to assess the RSV-related economic burden and the cost-effectiveness of upcoming RSV disease prevention strategies including year-round maternal immunization and year-round and seasonal monoclonal antibody (mAb) programs.\u0000\u0000\u0000METHODS\u0000Epidemiological and cost data were obtained from Norwegian national registries, while quality-adjusted life-years (QALYs) lost and intervention characteristics were extracted from literature and phase 3 clinical trials. A static model was used and uncertainty was accounted for probabilistically. Value of information was used to assess decision uncertainty. Extensive scenario analyses were conducted, including accounting for long-term consequences of RSV disease.\u0000\u0000\u0000RESULTS\u0000We estimate an annual average of 13 517 RSV cases and 1572 hospitalizations in children under 5, resulting in 79.6 million Norwegian kroner (~€8 million) treatment costs. At €51 per dose for all programs, a 4-month mAb program for neonates born in November to February is the cost-effective strategy for willingness to pay (WTP) values up to €40 000 per QALY gained. For higher WTP values, the longer 6-month mAb program that immunizes neonates from October to March becomes cost-effective. Sensitivity analyses show that year-round maternal immunization can become a cost-effective strategy if priced lower than mAb.\u0000\u0000\u0000CONCLUSIONS\u0000Assuming the same pricing, seasonal mAb programs are cost-effective over year-round programs in Norway. The timing and duration of the cost-effective seasonal program are sensitive to the pattern of the RSV season in a country, so continued RSV surveillance data are essential.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"113 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80659556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evolution of resistance to antibiotics in Neisseria meningitidis: any reasons for concern?","authors":"M. Taha, A. Deghmane","doi":"10.1093/infdis/jiac095","DOIUrl":"https://doi.org/10.1093/infdis/jiac095","url":null,"abstract":"","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"103 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79463751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valeria Ochoa, F. Erra Díaz, E. Ramírez, María Clara Fentini, M. Carobene, J. Geffner, L. Arruvito, F. Remes Lenicov
{"title":"Reply to Kao and Liaw.","authors":"Valeria Ochoa, F. Erra Díaz, E. Ramírez, María Clara Fentini, M. Carobene, J. Geffner, L. Arruvito, F. Remes Lenicov","doi":"10.1093/infdis/jiac081","DOIUrl":"https://doi.org/10.1093/infdis/jiac081","url":null,"abstract":"","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75535488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
* Corresponding Author: Yung-Po Liaw, PhD, ORCID: 0000-0003-2046-4964 Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung 40201, Taiwan Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan Medical Imaging and Big Data Center, Chung Shan Medical University Hospital, Taichung, Taiwan Chung Shan Medical University No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City 40201, Taiwan, (TEL) +886 4 36097222 #11838 or +886 4 36097501, (FAX) No Fax liawyp@csmu.edu.tw
{"title":"Infants Younger Than 6 Months Infected With SARS-CoV-2 Show the Highest Respiratory Viral Loads","authors":"Chih-Ching Kao, Y. Liaw","doi":"10.1093/infdis/jiac080","DOIUrl":"https://doi.org/10.1093/infdis/jiac080","url":null,"abstract":"* Corresponding Author: Yung-Po Liaw, PhD, ORCID: 0000-0003-2046-4964 Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung 40201, Taiwan Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan Medical Imaging and Big Data Center, Chung Shan Medical University Hospital, Taichung, Taiwan Chung Shan Medical University No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung City 40201, Taiwan, (TEL) +886 4 36097222 #11838 or +886 4 36097501, (FAX) No Fax liawyp@csmu.edu.tw","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"134 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73254167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Plainvert, Yasmina de Saint Salvy-Tabet, N. Dmytruk, A. Frigo, C. Poyart, Asmaa Tazi
Group B Streptococcus (GBS) is the leading cause of neonatal infections and an important pathogen in pregnancy. However, the features of pregnancy-associated infections are poorly reported. We analyzed 336 cases of GBS invasive infections in women aged 18 to 50 years old, including 242 (72.0%) pregnancy-associated infections. In pregnancy, most cases were intra-amniotic infections (55.8%), occurred preterm (61.3%) and were associated to obstetrical and neonatal complications (81.7%). The GBS clone CC-17 (18.8% of the cases) was overrepresented intrapartum (35.2%; OR = 5.1, 95% CI 1.6-19.3). This work highlights the burden of GBS and of the CC-17 clone infections during pregnancy.
B群链球菌(GBS)是新生儿感染的主要原因，也是妊娠期的重要病原体。然而，妊娠相关感染的特征报道很少。我们分析了336例18至50岁女性的GBS侵袭性感染，其中242例(72.0%)为妊娠相关感染。妊娠期以羊膜内感染为主(55.8%)，发生早产(61.3%)，伴有产科和新生儿并发症(81.7%)。GBS克隆CC-17(18.8%的病例)在产时被过度代表(35.2%;Or = 5.1, 95% ci 1.6-19.3)。这项工作强调了妊娠期间GBS和CC-17克隆感染的负担。
{"title":"Group B Streptococcus invasive infections in women of childbearing age, France, 2012 - 2020 : GBS CC-17 hypervirulence in intrapartum infections.","authors":"C. Plainvert, Yasmina de Saint Salvy-Tabet, N. Dmytruk, A. Frigo, C. Poyart, Asmaa Tazi","doi":"10.1093/infdis/jiac076","DOIUrl":"https://doi.org/10.1093/infdis/jiac076","url":null,"abstract":"Group B Streptococcus (GBS) is the leading cause of neonatal infections and an important pathogen in pregnancy. However, the features of pregnancy-associated infections are poorly reported. We analyzed 336 cases of GBS invasive infections in women aged 18 to 50 years old, including 242 (72.0%) pregnancy-associated infections. In pregnancy, most cases were intra-amniotic infections (55.8%), occurred preterm (61.3%) and were associated to obstetrical and neonatal complications (81.7%). The GBS clone CC-17 (18.8% of the cases) was overrepresented intrapartum (35.2%; OR = 5.1, 95% CI 1.6-19.3). This work highlights the burden of GBS and of the CC-17 clone infections during pregnancy.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73971974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Hou, X. Piao, Ning Jiang, Shuai Liu, Pengfei Cai, Bing Liu, D. McManus, Qijun Chen
Antigens of migrating schistosomula are promising candidates as schistosomiasis vaccine targets, since immune attack on hepatic schistosomula would interrupt the parasites life cycle and reduce egg burden on the host. Here, we report a collection of Schistosoma japonicum schistosomula proteins (SjScP), which are highly expressed in hepatic schistosomula. We found that a number of these SjScPs were highly antigenic and could effectively stimulate humoral immune responses in both human and other mammalian hosts. In particular, SjScP25, SjScP37, SjScP41, SjScP80, SjScP88 showed high potential as biomarkers for schistosomiasis immunodiagnosis. Furthermore, we demonstrated that immunization with several of the recombinant SjScPs were able to protect mice from S. japonicum challenge infection, with SjScP25 generating the most protective results. Our work represents a group of novel schistosome immunogens, which may be promsing schistosomiasis japonica diagonosis and vaccine candidates.
{"title":"Novel Hepatic Schistosomula Antigens as Promising Targets for Immunodiagnosis and Immunoprotection of Schistosomiasis japonica.","authors":"N. Hou, X. Piao, Ning Jiang, Shuai Liu, Pengfei Cai, Bing Liu, D. McManus, Qijun Chen","doi":"10.1093/infdis/jiac077","DOIUrl":"https://doi.org/10.1093/infdis/jiac077","url":null,"abstract":"Antigens of migrating schistosomula are promising candidates as schistosomiasis vaccine targets, since immune attack on hepatic schistosomula would interrupt the parasites life cycle and reduce egg burden on the host. Here, we report a collection of Schistosoma japonicum schistosomula proteins (SjScP), which are highly expressed in hepatic schistosomula. We found that a number of these SjScPs were highly antigenic and could effectively stimulate humoral immune responses in both human and other mammalian hosts. In particular, SjScP25, SjScP37, SjScP41, SjScP80, SjScP88 showed high potential as biomarkers for schistosomiasis immunodiagnosis. Furthermore, we demonstrated that immunization with several of the recombinant SjScPs were able to protect mice from S. japonicum challenge infection, with SjScP25 generating the most protective results. Our work represents a group of novel schistosome immunogens, which may be promsing schistosomiasis japonica diagonosis and vaccine candidates.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"180 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78568097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Veyrenche, A. Pisoni, S. Debiesse, K. Bollore, A. Bedin, A. Makinson, C. Niel, C. Alcocer-Cordellat, A. Mondain, V. Le Moing, P. Van de Perre, E. Tuaillon
Abstract Background SARS-CoV-2 nucleocapsid antigen (N-Ag) can be detected in the blood of patients with Covid-19. We used a highly sensitive and specific assay to explore the presence of N-Ag in urine during the course of Covid-19, and explore its relationship with the severity of the disease. Methods We studied urine and blood N-Ag using highly sensitive immunoassay in 82 patients with a SARS-CoV-2 infection proven by PCR. Results In the first and second weeks of Covid-19, hospitalized patients tested positive for urinary N-Ag (81.25% and 71.79%, respectively), and blood N-Ag (93.75% and 94.87%, respectively). High urinary N-Ag levels were associated with the absence of SARS-CoV-2 nucleocapsid antibodies, admission in intensive care units, high C-reactive protein levels, lymphopenia, eosinopenia, and high lactate dehydrogenase. A higher accuracy was observed for urine N-Ag as a predictor of severe Covid-19 compared to blood N-Ag. Conclusions Our study demonstrate that N-Ag is present in the urine of patients hospitalized in the early phase of Covid-19. As a direct marker of SARS-CoV-2, urinary N-Ag reflects the dissemination of viral compounds in the body. Urine N-Ag may be a useful marker for disease severity of SARS-CoV-2 infections.
{"title":"SARS-CoV-2 nucleocapsid urine antigen in hospitalized patients with Covid-19","authors":"N. Veyrenche, A. Pisoni, S. Debiesse, K. Bollore, A. Bedin, A. Makinson, C. Niel, C. Alcocer-Cordellat, A. Mondain, V. Le Moing, P. Van de Perre, E. Tuaillon","doi":"10.1093/infdis/jiac073","DOIUrl":"https://doi.org/10.1093/infdis/jiac073","url":null,"abstract":"Abstract Background SARS-CoV-2 nucleocapsid antigen (N-Ag) can be detected in the blood of patients with Covid-19. We used a highly sensitive and specific assay to explore the presence of N-Ag in urine during the course of Covid-19, and explore its relationship with the severity of the disease. Methods We studied urine and blood N-Ag using highly sensitive immunoassay in 82 patients with a SARS-CoV-2 infection proven by PCR. Results In the first and second weeks of Covid-19, hospitalized patients tested positive for urinary N-Ag (81.25% and 71.79%, respectively), and blood N-Ag (93.75% and 94.87%, respectively). High urinary N-Ag levels were associated with the absence of SARS-CoV-2 nucleocapsid antibodies, admission in intensive care units, high C-reactive protein levels, lymphopenia, eosinopenia, and high lactate dehydrogenase. A higher accuracy was observed for urine N-Ag as a predictor of severe Covid-19 compared to blood N-Ag. Conclusions Our study demonstrate that N-Ag is present in the urine of patients hospitalized in the early phase of Covid-19. As a direct marker of SARS-CoV-2, urinary N-Ag reflects the dissemination of viral compounds in the body. Urine N-Ag may be a useful marker for disease severity of SARS-CoV-2 infections.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87843622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martina Bottanelli, D. Ceccarelli, L. Galli, A. Castagna, C. Muccini
{"title":"Response to Cyktor Et Al.","authors":"Martina Bottanelli, D. Ceccarelli, L. Galli, A. Castagna, C. Muccini","doi":"10.1093/infdis/jiac070","DOIUrl":"https://doi.org/10.1093/infdis/jiac070","url":null,"abstract":"","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79952678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Krzyżowska, Anders Jarneborn, Karolina Thorn, K. Eriksson, T. Jin
Abstract Tofacitinib, a Janus kinase inhibitor, is a novel immunosuppressive drug for treatment of rheumatoid arthritis. Herpes simplex virus type 1 (HSV-1) may cause encephalitis during primary infection or following reactivation from a latent state. Long-term tofacitinib treatment may increase the risk of this life-threatening condition. The aim of this study was to investigate the effect of tofacitinib on HSV-1 primary infection using a mouse model. Mice pretreated with tofacitinib were intranasally infected with a clinical strain of HSV-1 and monitored for infection severity and antiviral response. Tofacitinib treatment of HSV-1 primary infection resulted in increased viral loads and worsened clinical outcome. Furthermore, tofacitinib promoted M2 anti-inflammatory phenotype of microglia and infiltrating monocytes, as well as inhibited production of inflammatory and antiviral cytokines by macrophages in vitro. Our findings show that treatment with tofacitinib increases severity of herpes simplex encephalitis in mice, by impairing antiviral response induced by monocytes and microglia.
{"title":"Tofacitinib Treatment in Primary Herpes Simplex Encephalitis Interferes With Antiviral Response","authors":"M. Krzyżowska, Anders Jarneborn, Karolina Thorn, K. Eriksson, T. Jin","doi":"10.1093/infdis/jiac040","DOIUrl":"https://doi.org/10.1093/infdis/jiac040","url":null,"abstract":"Abstract Tofacitinib, a Janus kinase inhibitor, is a novel immunosuppressive drug for treatment of rheumatoid arthritis. Herpes simplex virus type 1 (HSV-1) may cause encephalitis during primary infection or following reactivation from a latent state. Long-term tofacitinib treatment may increase the risk of this life-threatening condition. The aim of this study was to investigate the effect of tofacitinib on HSV-1 primary infection using a mouse model. Mice pretreated with tofacitinib were intranasally infected with a clinical strain of HSV-1 and monitored for infection severity and antiviral response. Tofacitinib treatment of HSV-1 primary infection resulted in increased viral loads and worsened clinical outcome. Furthermore, tofacitinib promoted M2 anti-inflammatory phenotype of microglia and infiltrating monocytes, as well as inhibited production of inflammatory and antiviral cytokines by macrophages in vitro. Our findings show that treatment with tofacitinib increases severity of herpes simplex encephalitis in mice, by impairing antiviral response induced by monocytes and microglia.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"9 1","pages":"1545 - 1553"},"PeriodicalIF":0.0,"publicationDate":"2022-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73867558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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