Weijia Xiong, T. Tsang, Ranawaka A.P.M Perera, Nancy H. L. Leung, V. Fang, I. Barr, J. Peiris, B. Cowling
We explored the potential for a biphasic pattern in waning of antibody titers after influenza vaccination. We collected blood samples in a randomized controlled trial of influenza vaccination in children, and tested them with hemagglutination inhibition (HAI) assays for influenza A(H3N2) and influenza B/Victoria lineage. Using piecewise log-linear mixed-effect models, we found evidence for a faster initial waning of antibody titers for the first 1-2 years after vaccination and then slower longer-term declines. Children with higher post-vaccination titers had faster antibody decay.
{"title":"Biphasic waning of hemagglutination inhibition antibody titers after influenza vaccination in children.","authors":"Weijia Xiong, T. Tsang, Ranawaka A.P.M Perera, Nancy H. L. Leung, V. Fang, I. Barr, J. Peiris, B. Cowling","doi":"10.1093/infdis/jiac117","DOIUrl":"https://doi.org/10.1093/infdis/jiac117","url":null,"abstract":"We explored the potential for a biphasic pattern in waning of antibody titers after influenza vaccination. We collected blood samples in a randomized controlled trial of influenza vaccination in children, and tested them with hemagglutination inhibition (HAI) assays for influenza A(H3N2) and influenza B/Victoria lineage. Using piecewise log-linear mixed-effect models, we found evidence for a faster initial waning of antibody titers for the first 1-2 years after vaccination and then slower longer-term declines. Children with higher post-vaccination titers had faster antibody decay.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83422678","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}
K. Louvanto, Prativa Baral, A. Burchell, A. Ramanakumar, M. El-Zein, P. Tellier, F. Coutlée, M. Roger, E. Franco
Abstract Background Human leukocyte antigen (HLA) polymorphism influences innate and adaptive immune responses. Among heterosexual couples in the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study, we examined whether allele sharing in a couple predicted the partners’ infections with the same human papillomavirus (HPV) type. Methods We tested genital samples from 271 couples for 36 HPV genotypes by polymerase chain reaction. We used direct DNA sequencing to type HLA-B07, -DRB1, -DQB1 and -G. Generalized estimating equations were used to examine the associations between the extent of allele sharing and HPV type concordance in which at least 1 of the partners was HPV positive. Results We identified 106 different HLA alleles. The most common HLA alleles among couples were G*01:01:01 (95.6%), G*01:01:02 (60.1%), DQB1*03:01 (57.2%), and DRB1*07:01 (46.9%). Allele sharing was as follows: 19.6% shared none, 43.2% shared 1 only, 25.1% shared 2, and 12.5% shared 3–5. Irrespective of HLA class, grouped or in combination, the extent of allele sharing was not a significant predictor of type-specific HPV concordance in a couple (odds ratio, 1.1 [95% confidence interval, .5–2.1], for 3–5 vs none). Conclusions We found no evidence that the extent of HLA allele concordance influences the likelihood of HPV transmission in newly formed heterosexual couples.
{"title":"Role of Human Leukocyte Antigen Allele Sharing in Human Papillomavirus Infection Transmission Among Heterosexual Couples: Findings From the HITCH Cohort Study","authors":"K. Louvanto, Prativa Baral, A. Burchell, A. Ramanakumar, M. El-Zein, P. Tellier, F. Coutlée, M. Roger, E. Franco","doi":"10.1093/infdis/jiac115","DOIUrl":"https://doi.org/10.1093/infdis/jiac115","url":null,"abstract":"Abstract Background Human leukocyte antigen (HLA) polymorphism influences innate and adaptive immune responses. Among heterosexual couples in the HPV Infection and Transmission Among Couples Through Heterosexual Activity (HITCH) cohort study, we examined whether allele sharing in a couple predicted the partners’ infections with the same human papillomavirus (HPV) type. Methods We tested genital samples from 271 couples for 36 HPV genotypes by polymerase chain reaction. We used direct DNA sequencing to type HLA-B07, -DRB1, -DQB1 and -G. Generalized estimating equations were used to examine the associations between the extent of allele sharing and HPV type concordance in which at least 1 of the partners was HPV positive. Results We identified 106 different HLA alleles. The most common HLA alleles among couples were G*01:01:01 (95.6%), G*01:01:02 (60.1%), DQB1*03:01 (57.2%), and DRB1*07:01 (46.9%). Allele sharing was as follows: 19.6% shared none, 43.2% shared 1 only, 25.1% shared 2, and 12.5% shared 3–5. Irrespective of HLA class, grouped or in combination, the extent of allele sharing was not a significant predictor of type-specific HPV concordance in a couple (odds ratio, 1.1 [95% confidence interval, .5–2.1], for 3–5 vs none). Conclusions We found no evidence that the extent of HLA allele concordance influences the likelihood of HPV transmission in newly formed heterosexual couples.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"51 1","pages":"1175 - 1183"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78421488","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}
S. Moon, I. Janssens, K. Kim, B. Stijlemans, S. Magez, M. Radwanska
BACKGROUND Trypanosoma brucei brucei (T. b. brucei) evades host immune responses by multiple means, including the disruption of B cell homeostasis. This hampers anti-trypanosome vaccine development. As the cellular mechanism underlying this pathology has never been addressed, our study focuses on the fate of memory B cells (MBCs) in vaccinated mice upon trypanosome challenge. METHODS A trypanosome variant surface glycoprotein (VSG) and fluorescent phycoerythrin (PE) were used as immunization antigens. Functional and cellular characteristics of antigen-specific MBCs were studied after homologous and heterologous parasite challenge. RESULTS Immunization with AnTat 1.1 VSG triggers a specific antibody response and isotype-switched CD73 +CD273 +CD80 + MBCs, delivering 90% sterile protection against a homologous parasite challenge. As expected, AnTat 1.1 VSG immunization does not protect against infection with heterologous VSG-switched parasites. After successful curative drug treatment, mice were shown to have completely lost their previously induced protective immunity against the homologous parasites, coinciding with the loss of vaccine-induced MBCs. A PE immunization approach confirmed that trypanosome infections cause the general loss of antigen-specific splenic and bone marrow MBCs, and a reduction in antigen-specific IgGs. CONCLUSION Trypanosomosis induces general immunological memory loss. This benefits the parasites by reducing the stringency for antigenic variation requirements.
{"title":"Trypanosoma brucei brucei Infection Depletes Memory B Cells Resulting in Inability of the Host to Recall Protective B Cells Responses.","authors":"S. Moon, I. Janssens, K. Kim, B. Stijlemans, S. Magez, M. Radwanska","doi":"10.1093/infdis/jiac112","DOIUrl":"https://doi.org/10.1093/infdis/jiac112","url":null,"abstract":"BACKGROUND\u0000Trypanosoma brucei brucei (T. b. brucei) evades host immune responses by multiple means, including the disruption of B cell homeostasis. This hampers anti-trypanosome vaccine development. As the cellular mechanism underlying this pathology has never been addressed, our study focuses on the fate of memory B cells (MBCs) in vaccinated mice upon trypanosome challenge.\u0000\u0000\u0000METHODS\u0000A trypanosome variant surface glycoprotein (VSG) and fluorescent phycoerythrin (PE) were used as immunization antigens. Functional and cellular characteristics of antigen-specific MBCs were studied after homologous and heterologous parasite challenge.\u0000\u0000\u0000RESULTS\u0000Immunization with AnTat 1.1 VSG triggers a specific antibody response and isotype-switched CD73 +CD273 +CD80 + MBCs, delivering 90% sterile protection against a homologous parasite challenge. As expected, AnTat 1.1 VSG immunization does not protect against infection with heterologous VSG-switched parasites. After successful curative drug treatment, mice were shown to have completely lost their previously induced protective immunity against the homologous parasites, coinciding with the loss of vaccine-induced MBCs. A PE immunization approach confirmed that trypanosome infections cause the general loss of antigen-specific splenic and bone marrow MBCs, and a reduction in antigen-specific IgGs.\u0000\u0000\u0000CONCLUSION\u0000Trypanosomosis induces general immunological memory loss. This benefits the parasites by reducing the stringency for antigenic variation requirements.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"83 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77646291","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}
Minh Dao Ngo, Stacey Bartlett, H. Bielefeldt-Ohmann, Cheng Xiang Foo, Roma Sinha, Buddhika Jayakody Arachige, Sarah Reed, T. Mandrup-Poulsen, M. Rosenkilde, K. Ronacher
Abstract Background We previously reported that reduced GPR183 expression in blood from tuberculosis (TB) patients with diabetes is associated with more severe TB. Methods To further elucidate the role of GPR183 and its oxysterol ligands in the lung, we studied dysglycemic mice infected with Mycobacterium tuberculosis (Mtb). Results We found upregulation of the oxysterol-producing enzymes CH25H and CYP7B1 and increased concentrations of 25-hydroxycholesterol upon Mtb infection in the lungs of mice. This was associated with increased expression of GPR183 indicative of oxysterol-mediated recruitment of GPR183-expressing immune cells to the lung. CYP7B1 was predominantly expressed by macrophages in TB granulomas. CYP7B1 expression was significantly blunted in lungs from dysglycemic animals, which coincided with delayed macrophage infiltration. GPR183-deficient mice similarly had reduced macrophage recruitment during early infection. Conclusions Taken together, we demonstrate a requirement of the GPR183/oxysterol axis for positioning of macrophages to the site of infection and add an explanation to more severe TB in diabetes patients.
{"title":"A Blunted GPR183/Oxysterol Axis During Dysglycemia Results in Delayed Recruitment of Macrophages to the Lung During Mycobacterium tuberculosis Infection","authors":"Minh Dao Ngo, Stacey Bartlett, H. Bielefeldt-Ohmann, Cheng Xiang Foo, Roma Sinha, Buddhika Jayakody Arachige, Sarah Reed, T. Mandrup-Poulsen, M. Rosenkilde, K. Ronacher","doi":"10.1093/infdis/jiac102","DOIUrl":"https://doi.org/10.1093/infdis/jiac102","url":null,"abstract":"Abstract Background We previously reported that reduced GPR183 expression in blood from tuberculosis (TB) patients with diabetes is associated with more severe TB. Methods To further elucidate the role of GPR183 and its oxysterol ligands in the lung, we studied dysglycemic mice infected with Mycobacterium tuberculosis (Mtb). Results We found upregulation of the oxysterol-producing enzymes CH25H and CYP7B1 and increased concentrations of 25-hydroxycholesterol upon Mtb infection in the lungs of mice. This was associated with increased expression of GPR183 indicative of oxysterol-mediated recruitment of GPR183-expressing immune cells to the lung. CYP7B1 was predominantly expressed by macrophages in TB granulomas. CYP7B1 expression was significantly blunted in lungs from dysglycemic animals, which coincided with delayed macrophage infiltration. GPR183-deficient mice similarly had reduced macrophage recruitment during early infection. Conclusions Taken together, we demonstrate a requirement of the GPR183/oxysterol axis for positioning of macrophages to the site of infection and add an explanation to more severe TB in diabetes patients.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"10 1","pages":"2219 - 2228"},"PeriodicalIF":0.0,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84095815","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}
P. G. Choe, Jisu Hong, Jiyoung Park, E. Chang, C. K. Kang, N. Kim, Chang-Han Lee, W. Park, M. Oh
Abstract Background Humoral immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may wane rapidly in persons recovered from mild coronavirus disease 2019 (COVID-19), but little is known about the longevity. Methods Serum samples were obtained 8, 12, and 18 months after infection from 20 patients with mild COVID-19. The binding activities of serum antibodies (IgA, IgG, and IgM) against SARS-CoV-2 antigens of the Wuhan-1 reference strain (wild-type) and the B.1.1.7, P.1, B.1.167.2, and B.1.1.529 variants were measured by enzyme-linked immunosorbent assays. Neutralizing antibody titers were measured using a cytopathic effect-based live virus neutralization assay. Results Serum IgA and IgG antibodies against spike or receptor-binding domain (RBD) protein of wild-type SARS-CoV-2 were detected for up to 18 months, and neutralizing antibodies persisted for 8 to 18 months after infection. However, any significant antibody responses against RBD proteins of SARS-CoV-2 variants were not observed, and median neutralizing antibody titers against the Delta variant at 8, 12, and 18 months were 8–11 fold lower than against wild-type viruses (P < .001). Conclusions Humoral immunity persisted for up to 18 months after SARS-CoV-2 infection in patients with mild COVID-19. Humoral immune activity against more recently circulating variants, however, was reduced in this population.
{"title":"Persistent Antibody Responses up to 18 Months after Mild SARS-CoV-2 Infection","authors":"P. G. Choe, Jisu Hong, Jiyoung Park, E. Chang, C. K. Kang, N. Kim, Chang-Han Lee, W. Park, M. Oh","doi":"10.1093/infdis/jiac099","DOIUrl":"https://doi.org/10.1093/infdis/jiac099","url":null,"abstract":"Abstract Background Humoral immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may wane rapidly in persons recovered from mild coronavirus disease 2019 (COVID-19), but little is known about the longevity. Methods Serum samples were obtained 8, 12, and 18 months after infection from 20 patients with mild COVID-19. The binding activities of serum antibodies (IgA, IgG, and IgM) against SARS-CoV-2 antigens of the Wuhan-1 reference strain (wild-type) and the B.1.1.7, P.1, B.1.167.2, and B.1.1.529 variants were measured by enzyme-linked immunosorbent assays. Neutralizing antibody titers were measured using a cytopathic effect-based live virus neutralization assay. Results Serum IgA and IgG antibodies against spike or receptor-binding domain (RBD) protein of wild-type SARS-CoV-2 were detected for up to 18 months, and neutralizing antibodies persisted for 8 to 18 months after infection. However, any significant antibody responses against RBD proteins of SARS-CoV-2 variants were not observed, and median neutralizing antibody titers against the Delta variant at 8, 12, and 18 months were 8–11 fold lower than against wild-type viruses (P < .001). Conclusions Humoral immunity persisted for up to 18 months after SARS-CoV-2 infection in patients with mild COVID-19. Humoral immune activity against more recently circulating variants, however, was reduced in this population.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76259784","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}
Audrey E Rindler, K. Kusejko, H. Kuster, Kathrin Neumann, Christine Leemann, Marius Zeeb, S. E. Chaudron, D. Braun, R. Kouyos, K. Metzner, H. Günthard
BACKGROUND HIV-1 replication capacity (RC) of transmitted/founder viruses may influence the further course of HIV-1 infection. METHODS Replication capacities (RCs) of 355 whole genome primary HIV-1 isolates derived from samples acquired during acute and recent primary HIV-1 infection (PHI) were determined using a novel high throughput infection assay in primary cells. The RCs were used to elucidate potential factors that could be associated with RC during PHI. RESULTS Increased RC was found to be associated with increased set point viral load (VL), and significant differences in RCs among 13 different HIV-1 subtypes were discerned. Notably, we observed an increase in RCs for primary HIV-1 isolates of HIV-1 subtype B over a 17-year period. Associations were not observed between RC and CD4 count at sample date of RC measurement, CD4 recovery after initiation of antiretroviral treatment (ART), CD4 decline in untreated individuals, and acute retroviral syndrome severity scores. DISCUSSION These findings highlight that RCs of primary HIV-1 isolates acquired during the acute and recent phase of infection are more associated with viral factors, i.e., set point VL, than with host factors. Furthermore, we observed a temporal increase in RC for HIV-1 subtype B viruses over a period of 17 years.
{"title":"The interplay between replication capacity of HIV-1 and surrogate markers of disease.","authors":"Audrey E Rindler, K. Kusejko, H. Kuster, Kathrin Neumann, Christine Leemann, Marius Zeeb, S. E. Chaudron, D. Braun, R. Kouyos, K. Metzner, H. Günthard","doi":"10.1093/infdis/jiac100","DOIUrl":"https://doi.org/10.1093/infdis/jiac100","url":null,"abstract":"BACKGROUND\u0000HIV-1 replication capacity (RC) of transmitted/founder viruses may influence the further course of HIV-1 infection.\u0000\u0000\u0000METHODS\u0000Replication capacities (RCs) of 355 whole genome primary HIV-1 isolates derived from samples acquired during acute and recent primary HIV-1 infection (PHI) were determined using a novel high throughput infection assay in primary cells. The RCs were used to elucidate potential factors that could be associated with RC during PHI.\u0000\u0000\u0000RESULTS\u0000Increased RC was found to be associated with increased set point viral load (VL), and significant differences in RCs among 13 different HIV-1 subtypes were discerned. Notably, we observed an increase in RCs for primary HIV-1 isolates of HIV-1 subtype B over a 17-year period. Associations were not observed between RC and CD4 count at sample date of RC measurement, CD4 recovery after initiation of antiretroviral treatment (ART), CD4 decline in untreated individuals, and acute retroviral syndrome severity scores.\u0000\u0000\u0000DISCUSSION\u0000These findings highlight that RCs of primary HIV-1 isolates acquired during the acute and recent phase of infection are more associated with viral factors, i.e., set point VL, than with host factors. Furthermore, we observed a temporal increase in RC for HIV-1 subtype B viruses over a period of 17 years.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89897645","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}
P. Guisado-Vasco, José Aguarles Gorines, M. M. Carralón González, G. Sotres Fernández, D. Carnevali Ruiz
Abstract Use of interleukin (IL-6) inhibitors has become one of the most complicated clinical issues in treating coronavirus disease 2019 (COVID-19). Recently, randomized open-label platform trials have found that IL-6 inhibitors have a beneficial effect on mortality in severe COVID-19. However, several questions arise around their mechanism of action in this disease, as well as how, when, and at which dose they should be used. IL-6 has both proinflammatory and anti-inflammatory effects, which may modulate the course of COVID-19, whose immunopathogenesis is driven by the innate immune system, autoantibodies, and interferon. Given that patients with delayed seroconversion against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein would be at the highest risk of complications beyond the second week of disease, we propose that considering patient serostatus at admission could optimize the use of IL-6 inhibitors in COVID-19. We predict that the net treatment benefits could be higher in the subgroup of patients with delayed seroconversion as compared to those who seroconvert more rapidly after SARS-CoV-2 infection.
{"title":"Flipped Inflammatory Time and the Role of Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2: Optimizing Tocilizumab Against Coronavirus Disease 2019","authors":"P. Guisado-Vasco, José Aguarles Gorines, M. M. Carralón González, G. Sotres Fernández, D. Carnevali Ruiz","doi":"10.1093/infdis/jiac090","DOIUrl":"https://doi.org/10.1093/infdis/jiac090","url":null,"abstract":"Abstract Use of interleukin (IL-6) inhibitors has become one of the most complicated clinical issues in treating coronavirus disease 2019 (COVID-19). Recently, randomized open-label platform trials have found that IL-6 inhibitors have a beneficial effect on mortality in severe COVID-19. However, several questions arise around their mechanism of action in this disease, as well as how, when, and at which dose they should be used. IL-6 has both proinflammatory and anti-inflammatory effects, which may modulate the course of COVID-19, whose immunopathogenesis is driven by the innate immune system, autoantibodies, and interferon. Given that patients with delayed seroconversion against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein would be at the highest risk of complications beyond the second week of disease, we propose that considering patient serostatus at admission could optimize the use of IL-6 inhibitors in COVID-19. We predict that the net treatment benefits could be higher in the subgroup of patients with delayed seroconversion as compared to those who seroconvert more rapidly after SARS-CoV-2 infection.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"254 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75936811","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}
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}
Ankur Sharma, B. Jenkins, Adovi Akue, L. Lambert, Sachy Orr-Gonzalez, Marvin L. Thomas, Almahamoudou Mahamar, B. S. Diarra, A. Dicko, M. Fried, P. Duffy
Plasmodium falciparum (Pf)-infected erythrocytes that display the variant surface antigen VAR2CSA bind chondroitin sulfate A (CSA) to sequester in placental intervillous spaces, causing severe sequelae for mother and offspring. Here, we establish a placental malaria (PM) monkey model. Pregnant Aotus infected with CSA-binding Pf-CS2 parasites during 3rd trimester developed pronounced sequestration of late-stage parasites in placental intervillous spaces that express VAR2CSA and bind specifically to CSA. Similar to immune multigravid women, a monkey infected with Pf-CS2 parasites over successive pregnancies acquired antibodies against VAR2CSA, with potent functional activity that was boosted upon subsequent pregnancy infections. Aotus also developed functional antibodies after multiple acute PM episodes and subsequent VAR2CSA immunization. In summary, Pf infections in pregnant Aotus monkeys recapitulate all the prominent features of human PM infection and immunity, and this model can be useful for basic mechanistic studies and preclinical studies to qualify candidate PM vaccines.
{"title":"Plasmodium falciparum in Aotus nancymaae: A New Model for Placental Malaria.","authors":"Ankur Sharma, B. Jenkins, Adovi Akue, L. Lambert, Sachy Orr-Gonzalez, Marvin L. Thomas, Almahamoudou Mahamar, B. S. Diarra, A. Dicko, M. Fried, P. Duffy","doi":"10.1093/infdis/jiac096","DOIUrl":"https://doi.org/10.1093/infdis/jiac096","url":null,"abstract":"Plasmodium falciparum (Pf)-infected erythrocytes that display the variant surface antigen VAR2CSA bind chondroitin sulfate A (CSA) to sequester in placental intervillous spaces, causing severe sequelae for mother and offspring. Here, we establish a placental malaria (PM) monkey model. Pregnant Aotus infected with CSA-binding Pf-CS2 parasites during 3rd trimester developed pronounced sequestration of late-stage parasites in placental intervillous spaces that express VAR2CSA and bind specifically to CSA. Similar to immune multigravid women, a monkey infected with Pf-CS2 parasites over successive pregnancies acquired antibodies against VAR2CSA, with potent functional activity that was boosted upon subsequent pregnancy infections. Aotus also developed functional antibodies after multiple acute PM episodes and subsequent VAR2CSA immunization. In summary, Pf infections in pregnant Aotus monkeys recapitulate all the prominent features of human PM infection and immunity, and this model can be useful for basic mechanistic studies and preclinical studies to qualify candidate PM vaccines.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80235033","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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