{"title":"Characterizing the genetics of bronchiolitis by viral etiology: Is there a shared role in asthma development?","authors":"Brittney M Snyder,Tina V Hartert","doi":"10.1093/infdis/jiae468","DOIUrl":"https://doi.org/10.1093/infdis/jiae468","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246948","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}
Camila D Odio, Christina Yek, Chloe M Hasund, Somnang Man, Piseth Ly, Sreynik Nhek, Sophana Chea, Chanthap Lon, Charlie Voirin, Rekol Huy, Rithea Leang, Chea Huch, Elaine W Lamirande, Stephen S Whitehead, L Fabiano Oliveira, Jessica E Manning, Leah C Katzelnick
Background Seroprevalence studies are the standard for disease surveillance, and serology determined eligibility for the first dengue vaccine. Expanding flavivirus co-circulation and vaccination complicate testing. We evaluate the accuracy of a common dengue virus serological assay, examine immunity to non-dengue flaviviruses as a contributor to decreased performance, and assess whether alternative cut points may improve assay performance. Methods Children (n = 770) aged 2–9 years in Kampong Speu, Cambodia were enrolled in a prospective longitudinal study, and PanBio indirect dengue virus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) was performed. Plaque reduction neutralization tests (PRNTs) using dengue viruses were performed on a subset to assess the accuracy of the IgG ELISA, and PRNTs with Zika, Japanese encephalitis, and West Nile viruses evaluated immunity to non-dengue flaviviruses. Receiver operating curve analysis identified an alternative cut point to improve IgG ELISA accuracy. Results The dengue IgG ELISA had a lower specificity than previously reported (58% vs 93%–100%). Of those with false-positive IgG results, 46% had detectable neutralizing antibodies against other flaviviruses including 14% against West Nile virus. A higher IgG cut point improved the test accuracy in this population. Conclusions Physicians and public health authorities should be alert for West Nile in Cambodia. Immunity to non-dengue flaviviruses can impact dengue surveillance. Clinical Trials Registration NCT03534245.
{"title":"Immunity to Non-Dengue Flaviviruses Impacts Dengue Virus Immunoglobulin G Enzyme-Linked Immunosorbent Assay Specificity in Cambodia","authors":"Camila D Odio, Christina Yek, Chloe M Hasund, Somnang Man, Piseth Ly, Sreynik Nhek, Sophana Chea, Chanthap Lon, Charlie Voirin, Rekol Huy, Rithea Leang, Chea Huch, Elaine W Lamirande, Stephen S Whitehead, L Fabiano Oliveira, Jessica E Manning, Leah C Katzelnick","doi":"10.1093/infdis/jiae422","DOIUrl":"https://doi.org/10.1093/infdis/jiae422","url":null,"abstract":"Background Seroprevalence studies are the standard for disease surveillance, and serology determined eligibility for the first dengue vaccine. Expanding flavivirus co-circulation and vaccination complicate testing. We evaluate the accuracy of a common dengue virus serological assay, examine immunity to non-dengue flaviviruses as a contributor to decreased performance, and assess whether alternative cut points may improve assay performance. Methods Children (n = 770) aged 2–9 years in Kampong Speu, Cambodia were enrolled in a prospective longitudinal study, and PanBio indirect dengue virus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) was performed. Plaque reduction neutralization tests (PRNTs) using dengue viruses were performed on a subset to assess the accuracy of the IgG ELISA, and PRNTs with Zika, Japanese encephalitis, and West Nile viruses evaluated immunity to non-dengue flaviviruses. Receiver operating curve analysis identified an alternative cut point to improve IgG ELISA accuracy. Results The dengue IgG ELISA had a lower specificity than previously reported (58% vs 93%–100%). Of those with false-positive IgG results, 46% had detectable neutralizing antibodies against other flaviviruses including 14% against West Nile virus. A higher IgG cut point improved the test accuracy in this population. Conclusions Physicians and public health authorities should be alert for West Nile in Cambodia. Immunity to non-dengue flaviviruses can impact dengue surveillance. Clinical Trials Registration NCT03534245.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142275615","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}
Leah H Rubin, Erin N Shirk, Lily Pohlenz, Hayley Romero, Elizabeth Roti, Raha M Dastgheyb, Isabel Santiuste, Jennifer M Coughlin, Todd T Brown, Janice E Clements, Rebecca T Veenhuis
Background Monocytes are susceptible to HIV infection, form HIV reservoirs, and contribute to central nervous system complications (e.g., cognitive impairment) in virally suppressed women with HIV(vsWWH). However, it remains unknown if the quality and/or quantity of the monocyte reservoir contributes to cognition in vsWWH. Methods 62 vsWWH(mean age=56.1, SD=7.1; 93% Black, non-Hispanic; all HIV RNA <250 copies/mL) completed a cognitive test battery, blood draw, and whole blood immunophenotyping. Monocytes and CD4 T cells were isolated from a subset of 53 participants and the HIV reservoir was assessed using cell specific Intact Proviral DNA Assays(IPDA). Demographically-adjusted z-scores were calculated for each outcome using data from participants without HIV in the Women’s Interagency HIV Study. Cognitive outcomes of interest included domain-specific and global z-scores. Results Thirty-Eight percent of vsWWH had detectable intact HIV genomes in monocytes(median=21.5 copies/million). Higher levels of intact HIV genomes per million monocytes were associated with poorer verbal memory(delayed recall: r=0.55, P=0.01; recognition: r=0.46, P=0.04), fine motor skills(r=0.50, P=0.03), and global function(r=0.47, P=0.04). Higher levels of intact HIV genomes in monocytes were associated with percent intermediate monocytes(r=0.60, P=0.008), and the ratio of intact per intermediate monocyte was associated with worse memory(r=-0.59, P=0.008). There were no associations between CD4 reservoir and cognition. Discussion The number of intact HIV genomes per million monocytes were related to poorer cognition and the percentage of intermediate monocytes. These findings suggest that the presence of HIV genomes in general do not relate to cognitive complications, but intact, and therefore potentially replication-competent HIV, may contribute to cognitive complications in vsWWH.
背景 单核细胞易受艾滋病病毒感染，形成艾滋病病毒库，并导致病毒抑制期女性艾滋病病毒感染者（vsWWH）出现中枢神经系统并发症（如认知障碍）。然而，单核细胞储库的质量和/或数量是否会影响女性艾滋病病毒感染者的认知能力仍是未知数。方法 62 名女性艾滋病病毒感染者（平均年龄 56.1 岁，SD=7.1；93% 为黑人，非西班牙裔；所有 HIV RNA 均为 250 拷贝/毫升）完成了认知测试、抽血和全血免疫分型。从 53 名参与者的子集中分离出单核细胞和 CD4 T 细胞，并使用细胞特异性完整病毒 DNA 检测法（IPDA）评估了艾滋病毒储库。利用妇女机构间艾滋病研究（Women's Interagency HIV Study）中未感染艾滋病病毒的参与者的数据，计算出了每项结果的人口统计学调整 Z 分数。相关认知结果包括特定领域和总体 Z 值。结果 38% 的 vsWWH 在单核细胞中检测到完整的 HIV 基因组（中位数=21.5 拷贝/百万）。每百万单核细胞中完整的 HIV 基因组水平越高，语言记忆（延迟回忆：r=0.55，P=0.01；识别：r=0.46，P=0.04）、精细动作技能（r=0.50，P=0.03）和整体功能（r=0.47，P=0.04）越差。单核细胞中较高水平的完整艾滋病毒基因组与中间单核细胞百分比相关（r=0.60，P=0.008），完整单核细胞与中间单核细胞的比率与记忆力较差相关（r=-0.59，P=0.008）。CD4 储存库与认知能力之间没有关联。讨论 每百万单核细胞中完整 HIV 基因组的数量与较差的认知能力和中间单核细胞的比例有关。这些研究结果表明，HIV 基因组的存在一般与认知并发症无关，但完整的、因此可能具有复制能力的 HIV 基因组可能会导致 vsWWH 患者的认知并发症。
{"title":"Intact HIV reservoir in monocytes is associated with cognitive function in virally suppressed women with HIV","authors":"Leah H Rubin, Erin N Shirk, Lily Pohlenz, Hayley Romero, Elizabeth Roti, Raha M Dastgheyb, Isabel Santiuste, Jennifer M Coughlin, Todd T Brown, Janice E Clements, Rebecca T Veenhuis","doi":"10.1093/infdis/jiae460","DOIUrl":"https://doi.org/10.1093/infdis/jiae460","url":null,"abstract":"Background Monocytes are susceptible to HIV infection, form HIV reservoirs, and contribute to central nervous system complications (e.g., cognitive impairment) in virally suppressed women with HIV(vsWWH). However, it remains unknown if the quality and/or quantity of the monocyte reservoir contributes to cognition in vsWWH. Methods 62 vsWWH(mean age=56.1, SD=7.1; 93% Black, non-Hispanic; all HIV RNA &lt;250 copies/mL) completed a cognitive test battery, blood draw, and whole blood immunophenotyping. Monocytes and CD4 T cells were isolated from a subset of 53 participants and the HIV reservoir was assessed using cell specific Intact Proviral DNA Assays(IPDA). Demographically-adjusted z-scores were calculated for each outcome using data from participants without HIV in the Women’s Interagency HIV Study. Cognitive outcomes of interest included domain-specific and global z-scores. Results Thirty-Eight percent of vsWWH had detectable intact HIV genomes in monocytes(median=21.5 copies/million). Higher levels of intact HIV genomes per million monocytes were associated with poorer verbal memory(delayed recall: r=0.55, P=0.01; recognition: r=0.46, P=0.04), fine motor skills(r=0.50, P=0.03), and global function(r=0.47, P=0.04). Higher levels of intact HIV genomes in monocytes were associated with percent intermediate monocytes(r=0.60, P=0.008), and the ratio of intact per intermediate monocyte was associated with worse memory(r=-0.59, P=0.008). There were no associations between CD4 reservoir and cognition. Discussion The number of intact HIV genomes per million monocytes were related to poorer cognition and the percentage of intermediate monocytes. These findings suggest that the presence of HIV genomes in general do not relate to cognitive complications, but intact, and therefore potentially replication-competent HIV, may contribute to cognitive complications in vsWWH.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245263","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":"Will mortality rates in the next viral pandemic be affected by the COVID-19 experience?","authors":"Prabhavathi Fernandes","doi":"10.1093/infdis/jiae458","DOIUrl":"https://doi.org/10.1093/infdis/jiae458","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245583","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}
Johannes M A Kusters, Maarten F Schim van der Loeff, Janneke C M Heijne, Audrey J King, Hester E de Melker, Titia Heijman, Johannes A Bogaards, Birgit H B van Benthem
Background From 2009 until 2021, bivalent HPV vaccination was offered only to girls in the Netherlands. We aimed to study the impact of girls-only HPV vaccination on genital HPV prevalence among young adults. Methods and findings PASSYON is a biennial repeated cross-sectional study (2009-21) among sexual health clinic clients aged 16-24 years old. Questionnaires elicited data on demographics, sexual behaviour and HPV vaccination status. Genital samples were collected and analysed using a PCR-based assay (SPF10-LiPA25). Type-specific prevalence trends of 12 high-risk (hr) genotypes were analysed as the adjusted average annual change (aAAC), estimated using Poisson GEE models. The relation between aAAC and phylogenetic distance to HPV-16/18 was assessed by means of regression and rank correlation analysis. Questionnaires and genital samples were collected from 8,889 females and 3,300 heterosexual males (HM). 4,829 females reported to be unvaccinated (54·3%). Among females (irrespective of vaccination status), prevalences of HPV-16/18/31/33/35/45 decreased significantly over time. Increasing trends were observed for HPV-39/52/56. Among both HM and unvaccinated females HPV-16/18 prevalence significantly declined, as did HPV-31 among HM. In contrast, HPV-52/58 increased significantly among HM and unvaccinated females. The type-specific aAAC correlated well with the phylogenetic distance to HPV-16/18. Conclusions During twelve years girls-only bivalent HPV vaccination in the Netherlands, decreasing trends of the vaccine types and cross-protected types were observed among females. Herd protection of vaccine-types was observed for HM and unvaccinated females, and one cross-protected type for HM. Increasing prevalence trends of HPV types with large phylogenetic distance to the vaccine types might indicate type-replacement.
{"title":"Changes in Genital HPV Prevalence during 12 Years Girls-Only Bivalent HPV Vaccination: Results from a Biennial Repeated Cross-Sectional Study","authors":"Johannes M A Kusters, Maarten F Schim van der Loeff, Janneke C M Heijne, Audrey J King, Hester E de Melker, Titia Heijman, Johannes A Bogaards, Birgit H B van Benthem","doi":"10.1093/infdis/jiae455","DOIUrl":"https://doi.org/10.1093/infdis/jiae455","url":null,"abstract":"Background From 2009 until 2021, bivalent HPV vaccination was offered only to girls in the Netherlands. We aimed to study the impact of girls-only HPV vaccination on genital HPV prevalence among young adults. Methods and findings PASSYON is a biennial repeated cross-sectional study (2009-21) among sexual health clinic clients aged 16-24 years old. Questionnaires elicited data on demographics, sexual behaviour and HPV vaccination status. Genital samples were collected and analysed using a PCR-based assay (SPF10-LiPA25). Type-specific prevalence trends of 12 high-risk (hr) genotypes were analysed as the adjusted average annual change (aAAC), estimated using Poisson GEE models. The relation between aAAC and phylogenetic distance to HPV-16/18 was assessed by means of regression and rank correlation analysis. Questionnaires and genital samples were collected from 8,889 females and 3,300 heterosexual males (HM). 4,829 females reported to be unvaccinated (54·3%). Among females (irrespective of vaccination status), prevalences of HPV-16/18/31/33/35/45 decreased significantly over time. Increasing trends were observed for HPV-39/52/56. Among both HM and unvaccinated females HPV-16/18 prevalence significantly declined, as did HPV-31 among HM. In contrast, HPV-52/58 increased significantly among HM and unvaccinated females. The type-specific aAAC correlated well with the phylogenetic distance to HPV-16/18. Conclusions During twelve years girls-only bivalent HPV vaccination in the Netherlands, decreasing trends of the vaccine types and cross-protected types were observed among females. Herd protection of vaccine-types was observed for HM and unvaccinated females, and one cross-protected type for HM. Increasing prevalence trends of HPV types with large phylogenetic distance to the vaccine types might indicate type-replacement.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233438","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}
Nora Pisanic, Annukka A R Antar, Marissa K Hetrich, Zoe O Demko, Xueyan Zhang, Kristoffer Spicer, Kate L Kruczynski, Barbara Detrick, William Clarke, Maria Deloria Knoll, David L Thomas, Fatimah S Dawood, Vic Veguilla, Ruth A Karron, Yukari C Manabe, Christopher D Heaney
Background High priority efforts are underway to support the development of novel mucosal COVID-19 vaccines, such as the US Government’s Project NextGen and the Center for Epidemic Preparedness Innovations’ goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how to evaluate immunogenicity of mucosal vaccines. This study investigated the role of oral mucosal antibody responses in viral clearance and COVID-19 symptom duration. Methods Participants with PCR-confirmed SARS-CoV-2 infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for RT-PCR and symptom information at up to eight follow-ups from April 2020 to February 2022. Results High and moderate oral fluid anti-spike (S) secretory IgA (SIgA) post infection was associated with significantly faster viral clearance and symptom resolution across age groups with effect sizes equivalent to having COVID-19 vaccine immunity at the time of infection. Those with high and moderate anti-S SIgA cleared the virus 14 days (95% CI: 10-18) and recovered 9-10 days (95% CI: 6-14) earlier. Delayed and higher anti-S IgG was associated with significantly longer time to clearance and recovery. Experiencing symptoms longer than four weeks was associated with lower anti-RBD SIgA 15-30 days after infection onset (p<0.001). Conclusion Robust mucosal SIgA early post infection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new mucosal vaccines.
{"title":"Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution.","authors":"Nora Pisanic, Annukka A R Antar, Marissa K Hetrich, Zoe O Demko, Xueyan Zhang, Kristoffer Spicer, Kate L Kruczynski, Barbara Detrick, William Clarke, Maria Deloria Knoll, David L Thomas, Fatimah S Dawood, Vic Veguilla, Ruth A Karron, Yukari C Manabe, Christopher D Heaney","doi":"10.1093/infdis/jiae447","DOIUrl":"https://doi.org/10.1093/infdis/jiae447","url":null,"abstract":"Background High priority efforts are underway to support the development of novel mucosal COVID-19 vaccines, such as the US Government’s Project NextGen and the Center for Epidemic Preparedness Innovations’ goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how to evaluate immunogenicity of mucosal vaccines. This study investigated the role of oral mucosal antibody responses in viral clearance and COVID-19 symptom duration. Methods Participants with PCR-confirmed SARS-CoV-2 infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for RT-PCR and symptom information at up to eight follow-ups from April 2020 to February 2022. Results High and moderate oral fluid anti-spike (S) secretory IgA (SIgA) post infection was associated with significantly faster viral clearance and symptom resolution across age groups with effect sizes equivalent to having COVID-19 vaccine immunity at the time of infection. Those with high and moderate anti-S SIgA cleared the virus 14 days (95% CI: 10-18) and recovered 9-10 days (95% CI: 6-14) earlier. Delayed and higher anti-S IgG was associated with significantly longer time to clearance and recovery. Experiencing symptoms longer than four weeks was associated with lower anti-RBD SIgA 15-30 days after infection onset (p&lt;0.001). Conclusion Robust mucosal SIgA early post infection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new mucosal vaccines.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233270","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}
Cavan Reilly, Eleftherios Mylonakis, Robin Dewar, Barnaby Young, Jacqueline Nordwall, Sanjay Bhagani, Po-ying Chia, Ruby Davis, Clark Files, Adit A Ginde, Timothy Hatlen, Marie Helleberg, Awori Hayanga, Tomas O Jensen, Mamta K Jain, Ioannis Kalomenidis, Kami Kim, Perrine Lallemand, Birgitte Lindegaard, Anupama Menon, Katherine Ognenovska, Garyfallia Poulakou, Birgit Thorup Røge, Angela J Rogers, Katy Shaw-Saliba, Uriel Sandkovsky, Barbara W Trautner, Shikha S Vasudeva, Andrew Vekstein, Kimberley Viens, James Wyncoll, Brian DuChateau, Zhenxing Zhang, Shujiang Wu, Abdel G Babiker, Victoria Davey, Annetine Gelijns, Elizabeth Higgs, Virginia Kan, Jens Lundgren, Gail V Matthews, H Cliff Lane
Background Biomarker guided therapy could improve management of COVID-19 inpatients. Although some results indicate that antibody tests are prognostic, little is known about patient management using point-of-care (POC) antibody tests. Methods COVID-19 inpatients were recruited to evaluate 2 POC tests: LumiraDX and RightSign. Ease of use data was collected. Blood was also collected for centralized testing using established antibody assays (GenScript cPass). A nested case-control study assessed if POC tests conducted on stored specimens were predictive of time to sustained recovery, mortality, and a composite safety outcome. Results While both POC tests exhibited moderate agreement with the GenScript assay (both agreeing with 89% of antibody determinations), they were significantly different from the GenScript assay. Treating the GenScript assay as the gold standard, the LumiraDX assay had 99.5% sensitivity and 58.1% specificity while the RightSign assay had 89.5% sensitivity and 84.0% specificity. The LumiraDX assay frequently gave indeterminant results. Both tests were significantly associated with clinical outcomes. Conclusions Although both POC tests deviated moderately from the GenScript assay, they predicted outcomes of interest. The RightSign test was easier to use and was more likely to detect those lacking antibody compared to the LumiraDX test treating GenScript as the gold standard.
{"title":"Evaluation of the feasibility and efficacy of point-of-care antibody tests for biomarker guided management of COVID-19","authors":"Cavan Reilly, Eleftherios Mylonakis, Robin Dewar, Barnaby Young, Jacqueline Nordwall, Sanjay Bhagani, Po-ying Chia, Ruby Davis, Clark Files, Adit A Ginde, Timothy Hatlen, Marie Helleberg, Awori Hayanga, Tomas O Jensen, Mamta K Jain, Ioannis Kalomenidis, Kami Kim, Perrine Lallemand, Birgitte Lindegaard, Anupama Menon, Katherine Ognenovska, Garyfallia Poulakou, Birgit Thorup Røge, Angela J Rogers, Katy Shaw-Saliba, Uriel Sandkovsky, Barbara W Trautner, Shikha S Vasudeva, Andrew Vekstein, Kimberley Viens, James Wyncoll, Brian DuChateau, Zhenxing Zhang, Shujiang Wu, Abdel G Babiker, Victoria Davey, Annetine Gelijns, Elizabeth Higgs, Virginia Kan, Jens Lundgren, Gail V Matthews, H Cliff Lane","doi":"10.1093/infdis/jiae452","DOIUrl":"https://doi.org/10.1093/infdis/jiae452","url":null,"abstract":"Background Biomarker guided therapy could improve management of COVID-19 inpatients. Although some results indicate that antibody tests are prognostic, little is known about patient management using point-of-care (POC) antibody tests. Methods COVID-19 inpatients were recruited to evaluate 2 POC tests: LumiraDX and RightSign. Ease of use data was collected. Blood was also collected for centralized testing using established antibody assays (GenScript cPass). A nested case-control study assessed if POC tests conducted on stored specimens were predictive of time to sustained recovery, mortality, and a composite safety outcome. Results While both POC tests exhibited moderate agreement with the GenScript assay (both agreeing with 89% of antibody determinations), they were significantly different from the GenScript assay. Treating the GenScript assay as the gold standard, the LumiraDX assay had 99.5% sensitivity and 58.1% specificity while the RightSign assay had 89.5% sensitivity and 84.0% specificity. The LumiraDX assay frequently gave indeterminant results. Both tests were significantly associated with clinical outcomes. Conclusions Although both POC tests deviated moderately from the GenScript assay, they predicted outcomes of interest. The RightSign test was easier to use and was more likely to detect those lacking antibody compared to the LumiraDX test treating GenScript as the gold standard.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231459","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}
Bernard Beall, Sopio Chochua, Ben Metcalf, Wuling Lin, Theresa Tran, Zhongya Li, Yuan Li, Meghan L Bentz, Mili Sheth, Gunars Osis, Lesley McGee
Background The Centers for Disease Control and Prevention’s Active Bacterial Core surveillance (ABCs) identified increased serotype 4 invasive pneumococcal disease (IPD), particularly among adults experiencing homelessness (AEH). Methods We quantified IPD cases during 2016-2022. Employing genomic-based characterization of IPD isolates, we identified serotype-switch variants. Recombinational analyses were used to identify the genetic donor and recipient strains that generated a serotype 4 progeny strain. We performed phylogenetic analyses of the serotype 4 progeny and serotype 12F genetic recipient to determine genetic distances. Results We identified 30 inter-related (0-21 nucleotide differences) IPD isolates recovered during 2022–2023, corresponding to a serotype 4 capsular-switch variant. This strain arose through a multi-fragment recombination event between serotype 4/ST10172 and serotype 12F/ST220 parental strains. Twenty-five of the 30 cases occurred within Oregon. Of 29 cases with known residence status, 16 occurred in AEH. Variant emergence coincided with a 2.6-fold increase (57 to 148) of cases caused by the serotype 4/ST10172 donor lineage in 2022 compared to 2019 and its first appearance in Oregon. Most serotypes showed sequential increases of AEH IPD/all IPD ratios during 2016-2022 (for all serotypes combined, 247/2198, 11.2% during 2022 compared to 405/5317, 7.6% for 2018-2019, p<0.001). Serotypes 4 and 12F each caused more IPD than any other serotypes in AEH during 2020-2022 (207 combined reported cases primarily in 4 western states accounting for 38% of IPD in AEH). Conclusion Expansion and increased transmission of serotypes 4 and 12F among adults potentially led to recent genesis of an impactful hybrid “serotype-switch” variant.
{"title":"Increased proportions of invasive pneumococcal disease cases amongs adults experiencing homelessness sets stage for new serotype 4 capsular-switch recombinant","authors":"Bernard Beall, Sopio Chochua, Ben Metcalf, Wuling Lin, Theresa Tran, Zhongya Li, Yuan Li, Meghan L Bentz, Mili Sheth, Gunars Osis, Lesley McGee","doi":"10.1093/infdis/jiae453","DOIUrl":"https://doi.org/10.1093/infdis/jiae453","url":null,"abstract":"Background The Centers for Disease Control and Prevention’s Active Bacterial Core surveillance (ABCs) identified increased serotype 4 invasive pneumococcal disease (IPD), particularly among adults experiencing homelessness (AEH). Methods We quantified IPD cases during 2016-2022. Employing genomic-based characterization of IPD isolates, we identified serotype-switch variants. Recombinational analyses were used to identify the genetic donor and recipient strains that generated a serotype 4 progeny strain. We performed phylogenetic analyses of the serotype 4 progeny and serotype 12F genetic recipient to determine genetic distances. Results We identified 30 inter-related (0-21 nucleotide differences) IPD isolates recovered during 2022–2023, corresponding to a serotype 4 capsular-switch variant. This strain arose through a multi-fragment recombination event between serotype 4/ST10172 and serotype 12F/ST220 parental strains. Twenty-five of the 30 cases occurred within Oregon. Of 29 cases with known residence status, 16 occurred in AEH. Variant emergence coincided with a 2.6-fold increase (57 to 148) of cases caused by the serotype 4/ST10172 donor lineage in 2022 compared to 2019 and its first appearance in Oregon. Most serotypes showed sequential increases of AEH IPD/all IPD ratios during 2016-2022 (for all serotypes combined, 247/2198, 11.2% during 2022 compared to 405/5317, 7.6% for 2018-2019, p&lt;0.001). Serotypes 4 and 12F each caused more IPD than any other serotypes in AEH during 2020-2022 (207 combined reported cases primarily in 4 western states accounting for 38% of IPD in AEH). Conclusion Expansion and increased transmission of serotypes 4 and 12F among adults potentially led to recent genesis of an impactful hybrid “serotype-switch” variant.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170674","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}
Praveen Bathini,Emanuele Brai,Brian J Balin,Lynn Bimler,David B Corry,Davangere P Devanand,Richard L Doty,Garth D Ehrlich,William A Eimer,Tamas Fulop,David L Hahn,Christine J Hammond,Joseph Infanti,Ruth Itzhaki,Richard Lathe,Christopher Scott Little,Rima McLeod,Shima T Moein,Amy R Nelson,George Perry,Or A Shemesh,Rudolph E Tanzi,Wilmore C Webley,Nikki M Schultek,Lavinia Alberi Auber
Sensory functions of organs of the head and neck allow humans to interact with the environment and establish social bonds. With aging, smell, taste, vision, and hearing decline. Evidence suggests that accelerated impairment in sensory abilities can reflect a shift from healthy to pathological aging, including the development of Alzheimer's disease (AD) and other neurological disorders. While the drivers of early sensory alteration in AD are not elucidated, insults such as trauma and infections can affect sensory function. Herein, we review the involvement of the major head and neck sensory systems in AD, with emphasis on microbes exploiting sensory pathways to enter the brain (the "gateway" hypothesis) and the potential feedback loop by which sensory function may be impacted by central nervous system infection. We emphasize detection of sensory changes as first-line surveillance in senior adults to identify and remove potential insults, like microbial infections, that could precipitate brain pathology.
头颈部器官的感官功能使人类能够与环境互动并建立社会联系。随着年龄的增长，嗅觉、味觉、视觉和听觉都会衰退。有证据表明，感官能力的加速衰退可以反映从健康衰老到病理衰老的转变，包括阿尔茨海默病（AD）和其他神经系统疾病的发展。虽然阿尔茨海默病早期感觉改变的驱动因素尚未阐明，但创伤和感染等损伤可能会影响感觉功能。在此，我们回顾了主要的头颈部感觉系统在 AD 中的参与情况，重点是微生物利用感觉通路进入大脑（"网关 "假说）以及感觉功能可能受到中枢神经系统感染影响的潜在反馈回路。我们强调检测感觉变化是对高龄成年人的一线监控，以识别和消除可能引发脑部病变的潜在损伤，如微生物感染。
{"title":"Sensory Dysfunction, Microbial Infections, and Host Responses in Alzheimer's Disease.","authors":"Praveen Bathini,Emanuele Brai,Brian J Balin,Lynn Bimler,David B Corry,Davangere P Devanand,Richard L Doty,Garth D Ehrlich,William A Eimer,Tamas Fulop,David L Hahn,Christine J Hammond,Joseph Infanti,Ruth Itzhaki,Richard Lathe,Christopher Scott Little,Rima McLeod,Shima T Moein,Amy R Nelson,George Perry,Or A Shemesh,Rudolph E Tanzi,Wilmore C Webley,Nikki M Schultek,Lavinia Alberi Auber","doi":"10.1093/infdis/jiae328","DOIUrl":"https://doi.org/10.1093/infdis/jiae328","url":null,"abstract":"Sensory functions of organs of the head and neck allow humans to interact with the environment and establish social bonds. With aging, smell, taste, vision, and hearing decline. Evidence suggests that accelerated impairment in sensory abilities can reflect a shift from healthy to pathological aging, including the development of Alzheimer's disease (AD) and other neurological disorders. While the drivers of early sensory alteration in AD are not elucidated, insults such as trauma and infections can affect sensory function. Herein, we review the involvement of the major head and neck sensory systems in AD, with emphasis on microbes exploiting sensory pathways to enter the brain (the \"gateway\" hypothesis) and the potential feedback loop by which sensory function may be impacted by central nervous system infection. We emphasize detection of sensory changes as first-line surveillance in senior adults to identify and remove potential insults, like microbial infections, that could precipitate brain pathology.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170675","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}
Katherine J O Yanes,Nathanial A Guanzon,Ricardo Azevedo,Damian G Wheeler,Sunil P Gandhi,Melissa B Lodoen
BACKGROUNDToxoplasma gondii infection of Alzheimer's disease model mice decreases amyloid β plaques. We aimed to determine if there is a brain regional difference in amyloid β reduction in the brains of T. gondii-infected compared to control mice.METHODThree-month-old 5xFAD (AD model) mice were injected with T. gondii or with phosphate-buffered saline as a control. Intact brains were harvested at 6 weeks postinfection, optically cleared using iDISCO+, and brain-wide amyloid burden was visualized using volumetric light-sheet imaging. Amyloid signal was quantified across each brain and computationally mapped to the Allen Institute Brain Reference Atlas to determine amyloid density in each region.RESULTSA brain-wide analysis of amyloid in control and T. gondii-infected 5xFAD mice revealed that T. gondii infection decreased amyloid burden in the brain globally as well as in the cortex and hippocampus, and many daughter regions. Daughter regions that showed reduced amyloid burden included the prelimbic cortex, visual cortex, and retrosplenial cortex. The olfactory tubercle, a region known to have increased monocytes following T. gondii infection, also showed reduced amyloid after infection.CONCLUSIONST. gondii infection of AD mice reduces amyloid burden in a brain region-specific manner that overlaps with known regions of T. gondii infection and peripheral immune cell infiltration.
{"title":"Toxoplasma gondii Infection of Alzheimer's Disease Mice Reduces Brain Amyloid Density Globally and Regionally.","authors":"Katherine J O Yanes,Nathanial A Guanzon,Ricardo Azevedo,Damian G Wheeler,Sunil P Gandhi,Melissa B Lodoen","doi":"10.1093/infdis/jiae227","DOIUrl":"https://doi.org/10.1093/infdis/jiae227","url":null,"abstract":"BACKGROUNDToxoplasma gondii infection of Alzheimer's disease model mice decreases amyloid β plaques. We aimed to determine if there is a brain regional difference in amyloid β reduction in the brains of T. gondii-infected compared to control mice.METHODThree-month-old 5xFAD (AD model) mice were injected with T. gondii or with phosphate-buffered saline as a control. Intact brains were harvested at 6 weeks postinfection, optically cleared using iDISCO+, and brain-wide amyloid burden was visualized using volumetric light-sheet imaging. Amyloid signal was quantified across each brain and computationally mapped to the Allen Institute Brain Reference Atlas to determine amyloid density in each region.RESULTSA brain-wide analysis of amyloid in control and T. gondii-infected 5xFAD mice revealed that T. gondii infection decreased amyloid burden in the brain globally as well as in the cortex and hippocampus, and many daughter regions. Daughter regions that showed reduced amyloid burden included the prelimbic cortex, visual cortex, and retrosplenial cortex. The olfactory tubercle, a region known to have increased monocytes following T. gondii infection, also showed reduced amyloid after infection.CONCLUSIONST. gondii infection of AD mice reduces amyloid burden in a brain region-specific manner that overlaps with known regions of T. gondii infection and peripheral immune cell infiltration.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170775","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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