Pub Date : 2024-10-09DOI: 10.1016/j.jinf.2024.106305
Gina M. Aloisio , Divya Nagaraj , Ashley M. Murray , Emily M. Schultz , Trevor McBride , Letisha Aideyan , Erin G. Nicholson , David Henke , Laura Ferlic-Stark , Anubama Rajan , Amal Kambal , Hannah L. Johnson , Elina Mosa , Fabio Stossi , Sarah E. Blutt , Pedro A. Piedra , Vasanthi Avadhanula
Background
Respiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe compared to healthy adults is not fully understood.
Methods
We used ex-vivo human nasal organoid platforms from infants and adults to investigate the underlying mechanism of this disease disparity at the initial site of RSV replication, the nasal epithelium.
Results
Infant-derived human nasal organoid-air liquid interface (HNO-ALIs) lines were more susceptible to early RSV replication. Moreover, infant-derived HNO-ALIs elicited a statistically significant greater overall cytokine response, enhanced mucous production, and greater cellular damage compared to their adult counterparts. Furthermore, the adult cytokine response was associated with a superior regulatory cytokine response, which could explain less cellular damage than in infant lines.
Conclusions
Our data highlights substantial differences in how infant and adult upper respiratory tract epithelium responds to RSV infection at the cellular level. These differences in epithelial cellular response can lead to impaired mucociliary clearance, a more dysregulated innate immune response predisposing infants to more severe RSV infection compared to adults.
{"title":"Infant-derived human nasal organoids exhibit relatively increased susceptibility, epithelial responses, and cytotoxicity during RSV infection","authors":"Gina M. Aloisio , Divya Nagaraj , Ashley M. Murray , Emily M. Schultz , Trevor McBride , Letisha Aideyan , Erin G. Nicholson , David Henke , Laura Ferlic-Stark , Anubama Rajan , Amal Kambal , Hannah L. Johnson , Elina Mosa , Fabio Stossi , Sarah E. Blutt , Pedro A. Piedra , Vasanthi Avadhanula","doi":"10.1016/j.jinf.2024.106305","DOIUrl":"10.1016/j.jinf.2024.106305","url":null,"abstract":"<div><h3>Background</h3><div>Respiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe compared to healthy adults is not fully understood.</div></div><div><h3>Methods</h3><div>We used ex-vivo human nasal organoid platforms from infants and adults to investigate the underlying mechanism of this disease disparity at the initial site of RSV replication, the nasal epithelium.</div></div><div><h3>Results</h3><div>Infant-derived human nasal organoid-air liquid interface (HNO-ALIs) lines were more susceptible to early RSV replication. Moreover, infant-derived HNO-ALIs elicited a statistically significant greater overall cytokine response, enhanced mucous production, and greater cellular damage compared to their adult counterparts. Furthermore, the adult cytokine response was associated with a superior regulatory cytokine response, which could explain less cellular damage than in infant lines.</div></div><div><h3>Conclusions</h3><div>Our data highlights substantial differences in how infant and adult upper respiratory tract epithelium responds to RSV infection at the cellular level. These differences in epithelial cellular response can lead to impaired mucociliary clearance, a more dysregulated innate immune response predisposing infants to more severe RSV infection compared to adults.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106305"},"PeriodicalIF":14.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-08DOI: 10.1016/j.jinf.2024.106311
Yitao Li , Zhihua Sun , Xuefeng Liu , Shuo Wei, Yan Zhang, Yining Fuxiang, Jun Qiao, Hui Zhang, Chencheng Xiao
{"title":"Highly Pathogenic Avian Influenza A(H5N1) virus infection in dairy cattle: Threat of bird flu has expanded to open-air farmed livestock","authors":"Yitao Li , Zhihua Sun , Xuefeng Liu , Shuo Wei, Yan Zhang, Yining Fuxiang, Jun Qiao, Hui Zhang, Chencheng Xiao","doi":"10.1016/j.jinf.2024.106311","DOIUrl":"10.1016/j.jinf.2024.106311","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106311"},"PeriodicalIF":14.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Severe coronavirus disease 2019 (COVID-19) often leads to acute respiratory distress syndrome and multi-organ dysfunction, driven by a dysregulated immune response, including a cytokine storm with elevated proinflammatory cytokine levels. Natural killer (NK) cells are part of the innate immune system with a fundamental role in the defense against viral infections. However, during COVID-19 acute infection, they exhibit an altered phenotype and impaired functionality contributing to the immunopathogenesis of the disease. In this work, we have studied a cohort of patients with COVID-19 (ranging from mild to severe) by analyzing IL-15, TGF-β, PlGF and GDF-15 plasma levels and performing multiparametric flow cytometry studies. Our results revealed that severe COVID-19 patients exhibited high levels of IL-15, PlGF and GDF-15, along with an enrichment of an NK cell subset expressing the CD151 tetraspanin, which correlated with IL-15 plasma levels and disease severity. In patients, these CD151+ NK cells displayed a more activated phenotype characterized by an increased expression of HLA-DR, CD38 and granzyme B, a distinct receptor repertoire, with lower levels of CD160 and CD31 and higher levels of CD55 and, remarkably, a higher expression of tissue-resident markers CD103 and the NK cell decidual marker CD9. Last of all, in individuals with severe disease, we identified an expansion of a CD151brightCD9+ NK cell subset, suggesting that these cells play a specific role in COVID-19. Altogether, our findings suggest that CD151+ NK cells may have a relevant role in COVID-19 immunopathogenesis.
严重的冠状病毒病2019年最新注册送彩金（COVID-19）通常会导致急性呼吸窘迫综合征和多器官功能障碍，其驱动因素是失调的免疫反应，包括细胞因子风暴和促炎细胞因子水平升高。自然杀伤（NK）细胞是先天性免疫系统的一部分，在抵御病毒感染方面发挥着重要作用。然而，在 COVID-19 急性感染期间，它们会表现出表型改变和功能受损，从而导致疾病的免疫发病机制。在这项工作中，我们通过分析 IL-15、TGF-β、PlGF 和 GDF-15 的血浆水平以及进行多参数流式细胞术研究，对 COVID-19 患者（从轻度到重度不等）进行了研究。我们的研究结果表明，COVID-19 重症患者的 IL-15、PlGF 和 GDF-15 水平较高，表达 CD151 四聚体蛋白的 NK 细胞亚群也较丰富，这与 IL-15 血浆水平和疾病严重程度相关。在患者体内，这些 CD151+ NK 细胞显示出更活化的表型，其特点是 HLA-DR、CD38 和颗粒酶 B 的表达增加，受体谱系独特，CD160 和 CD31 水平较低，CD55 水平较高，而且值得注意的是，组织驻留标记 CD103 和 NK 细胞蜕膜标记 CD9 的表达较高。最后，在病情严重的个体中，我们发现了 CD151brightCD9+ NK 细胞亚群的扩增，这表明这些细胞在 COVID-19 中发挥着特殊作用。总之，我们的研究结果表明，CD151+ NK 细胞可能在 COVID-19 免疫发病机制中发挥了相关作用。
{"title":"CD151 identifies an NK cell subset that is enriched in COVID-19 patients and correlates with disease severity","authors":"Ainhoa Amarilla-Irusta , Olatz Zenarruzabeitia , Arrate Sevilla , Víctor Sandá , Ainara Lopez-Pardo , Gabirel Astarloa-Pando , Raquel Pérez-Garay , Silvia Pérez-Fernández , Susana Meijide , Natale Imaz-Ayo , Eunate Arana-Arri , Laura Amo , Francisco Borrego","doi":"10.1016/j.jinf.2024.106304","DOIUrl":"10.1016/j.jinf.2024.106304","url":null,"abstract":"<div><div>Severe coronavirus disease 2019 (COVID-19) often leads to acute respiratory distress syndrome and multi-organ dysfunction, driven by a dysregulated immune response, including a cytokine storm with elevated proinflammatory cytokine levels. Natural killer (NK) cells are part of the innate immune system with a fundamental role in the defense against viral infections. However, during COVID-19 acute infection, they exhibit an altered phenotype and impaired functionality contributing to the immunopathogenesis of the disease. In this work, we have studied a cohort of patients with COVID-19 (ranging from mild to severe) by analyzing IL-15, TGF-β, PlGF and GDF-15 plasma levels and performing multiparametric flow cytometry studies. Our results revealed that severe COVID-19 patients exhibited high levels of IL-15, PlGF and GDF-15, along with an enrichment of an NK cell subset expressing the CD151 tetraspanin, which correlated with IL-15 plasma levels and disease severity. In patients, these CD151+ NK cells displayed a more activated phenotype characterized by an increased expression of HLA-DR, CD38 and granzyme B, a distinct receptor repertoire, with lower levels of CD160 and CD31 and higher levels of CD55 and, remarkably, a higher expression of tissue-resident markers CD103 and the NK cell decidual marker CD9. Last of all, in individuals with severe disease, we identified an expansion of a CD151<sup>bright</sup>CD9+ NK cell subset, suggesting that these cells play a specific role in COVID-19. Altogether, our findings suggest that CD151+ NK cells may have a relevant role in COVID-19 immunopathogenesis.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106304"},"PeriodicalIF":14.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-05DOI: 10.1016/j.jinf.2024.106306
Giusy Tiseo , Dafna Yahav , Alaa Atamna , Tomer Avni , Manuel Causse , Elena Pérez-Nadales , Alessandra Mularoni , Elena Reigadas , María Olmedo-Samperio , Mario Fernández-Ruiz , Zaira R. Palacios-Baena , Jesus Rodríguez-Baño , Paolo De Simone , Giandomenico Biancofiore , Eman Fares Sabik , Mical Paul , José María Aguado , Ugo Boggi , Patricia Muñoz , Julián Torres-Cisneros , Marco Falcone
Objective
To evaluate the risk of recurrent Clostridioides difficile infection (CDI) in solid-organ transplant (SOT) recipients.
Methods
Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI ≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis.
Results
191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n = 114,59.7%), vancomycin+metronidazole (n = 39,20.4%), metronidazole (n = 26,13.6%), fidaxomicin (n = 9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77–9.08, p < .001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64–8.14, p = .001) were factors independently associated with recurrence.
Conclusions
Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting.
目的：评估实体器官移植受者复发艰难梭菌感染（CDI）的风险：评估实体器官移植（SOT）受者复发艰难梭菌感染（CDI）的风险：回顾性多中心研究，包括移植后一年内（2017 年 1 月至 2020 年 6 月）首次发生 CDI 的 SOT 受者。主要结局指标为复发，定义为自首次发病后56天内再次发生CDI。采用亚分布危险模型多变量分析法进行竞争风险分析：共纳入 191 名 SOT 受者：101例（52.9%）为肾脏受者，66例（34.6%）为肝脏受者，11例（5.8%）为肺脏受者，8例（4.2%）为胰腺-肾脏同时受者，4例（2.1%）为心脏受者，1例（0.5%）为单纯胰腺受者。首次CDI的治疗方法为：万古霉素（114例，59.7%）、万古霉素+甲硝唑（39例，20.4%）、甲硝唑（26例，13.6%）、非达霉素（9例，4.7%），3名患者未接受任何治疗。首次感染 CDI 后，17/191（8.9%）名患者在 56 天内死亡，且未复发，23/191（12%）名患者复发。在复发 CDI 的患者中，56 天死亡率为 30.4%（7/23 名患者）。在多变量分析中，重症 CDI（sHR4.01，95% CI 1.77-9.08，pConclusions：甲硝唑单药治疗会增加SOT受者复发CDI的风险。在这种情况下应实施旨在降低复发风险的治疗策略。
{"title":"Recurrent Clostridioides difficile infections in solid organ transplant recipients: The international CALIPSO study","authors":"Giusy Tiseo , Dafna Yahav , Alaa Atamna , Tomer Avni , Manuel Causse , Elena Pérez-Nadales , Alessandra Mularoni , Elena Reigadas , María Olmedo-Samperio , Mario Fernández-Ruiz , Zaira R. Palacios-Baena , Jesus Rodríguez-Baño , Paolo De Simone , Giandomenico Biancofiore , Eman Fares Sabik , Mical Paul , José María Aguado , Ugo Boggi , Patricia Muñoz , Julián Torres-Cisneros , Marco Falcone","doi":"10.1016/j.jinf.2024.106306","DOIUrl":"10.1016/j.jinf.2024.106306","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the risk of recurrent <em>Clostridioides difficile</em> infection (CDI) in solid-organ transplant (SOT) recipients.</div></div><div><h3>Methods</h3><div>Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI ≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis.</div></div><div><h3>Results</h3><div>191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n = 114,59.7%), vancomycin+metronidazole (n = 39,20.4%), metronidazole (n = 26,13.6%), fidaxomicin (n = 9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77–9.08, p < .001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64–8.14, p = .001) were factors independently associated with recurrence.</div></div><div><h3>Conclusions</h3><div>Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106306"},"PeriodicalIF":14.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-03DOI: 10.1016/j.jinf.2024.106308
Lada V. Maksimenko, Mariya V. Sivay, Maria E. Antonets, Tatiana V. Tregubchak, Alexei V. Totmenin, Sergei E. Skudarnov, Tatiana S. Ostapova, Svetlana V. Yashenko, Aleksander P. Agafonov, Natalia M. Gashnikova
{"title":"Expanding HIV-1 diversity in Russia: Novel circulating recombinant form between subtypes A6 and B (CRF147_A6B)","authors":"Lada V. Maksimenko, Mariya V. Sivay, Maria E. Antonets, Tatiana V. Tregubchak, Alexei V. Totmenin, Sergei E. Skudarnov, Tatiana S. Ostapova, Svetlana V. Yashenko, Aleksander P. Agafonov, Natalia M. Gashnikova","doi":"10.1016/j.jinf.2024.106308","DOIUrl":"10.1016/j.jinf.2024.106308","url":null,"abstract":"","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 5","pages":"Article 106308"},"PeriodicalIF":14.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-03DOI: 10.1016/j.jinf.2024.106298
Baojiang Wen , Liger Te , Changsen Bai , Wenna Jiang, Duo Zuo, Qianhui Hao, Jiayi Wang, Li Ren
Objectives
China, which has the largest number of patients with primary liver cancer (PLCs), lacks data on the overall prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in PLCs. We aimed to comprehensively assess the seroprevalence of HBV and HCV among PLCs in China.
Methods
We included and pooled observational studies reporting seroprevalence of HBsAg and anti-HCV antibodies among PLCs in China by searching PubMed, Web of Science, Cochrane, Scopus, Embase, CNKI, Wanfang, and CBM. Multivariate meta-regression and subgroup analyses were used to explore sources of heterogeneity, and publication bias was assessed by funnel plots and Egger's test. PROSPERO registration number is CRD42023450382.
Results
A total of 217 eligible studies were included in the meta-analysis. The estimated seroprevalence of HBV and HCV in PLCs was 75.09% (95% CI 73.12–77.02) and 11.82% (95% CI 9.79–14.00), respectively. After stratifying and analysing subgroups by region and study period, we found geographic differences in HBV and HCV prevalence among PLCs, with an overall increasing trend in the proportion of HBV and a decreasing trend in the proportion of HCV as well as co-infections in the last 40 years.
Conclusions
HBV and HCV infections still account for a high proportion of PLCs in China.
{"title":"Relative contribution of hepatitis B and C viruses in primary liver cancer in China: A systematic review and meta-analysis","authors":"Baojiang Wen , Liger Te , Changsen Bai , Wenna Jiang, Duo Zuo, Qianhui Hao, Jiayi Wang, Li Ren","doi":"10.1016/j.jinf.2024.106298","DOIUrl":"10.1016/j.jinf.2024.106298","url":null,"abstract":"<div><h3>Objectives</h3><div>China, which has the largest number of patients with primary liver cancer (PLCs), lacks data on the overall prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) in PLCs. We aimed to comprehensively assess the seroprevalence of HBV and HCV among PLCs in China.</div></div><div><h3>Methods</h3><div>We included and pooled observational studies reporting seroprevalence of HBsAg and anti-HCV antibodies among PLCs in China by searching PubMed, Web of Science, Cochrane, Scopus, Embase, CNKI, Wanfang, and CBM. Multivariate meta-regression and subgroup analyses were used to explore sources of heterogeneity, and publication bias was assessed by funnel plots and Egger's test. PROSPERO registration number is CRD42023450382.</div></div><div><h3>Results</h3><div>A total of 217 eligible studies were included in the meta-analysis. The estimated seroprevalence of HBV and HCV in PLCs was 75.09% (95% CI 73.12–77.02) and 11.82% (95% CI 9.79–14.00), respectively. After stratifying and analysing subgroups by region and study period, we found geographic differences in HBV and HCV prevalence among PLCs, with an overall increasing trend in the proportion of HBV and a decreasing trend in the proportion of HCV as well as co-infections in the last 40 years.</div></div><div><h3>Conclusions</h3><div>HBV and HCV infections still account for a high proportion of PLCs in China.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106298"},"PeriodicalIF":14.3,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.jinf.2024.106303
Martyn Fyles , Christopher E. Overton , Thomas Ward , Emma Bennett , Tom Fowler , Ian Hall
During the SARS-CoV-2 pandemic, polymerase chain reaction (PCR) and lateral flow device (LFD) tests were frequently deployed to detect the presence of SARS-CoV-2. Many of these tests were singleplex, and only tested for the presence of a single pathogen. Multiplex tests can test for the presence of several pathogens using only a single swab, which can allow for: surveillance of more pathogens, targeting of antiviral interventions, a reduced burden of testing, and lower costs. Test sensitivity, however, particularly in LFD tests, is highly conditional on the viral concentration dynamics of individuals. To inform the use of multiplex testing in outbreak detection it is therefore necessary to investigate the interactions between outbreak detection strategies and the differing viral concentration trajectories of key pathogens. Viral concentration trajectories are estimated for SARS-CoV-2 and Influenza A/B. Testing strategies for the first five symptomatic cases in an outbreak are then simulated and used to evaluate key performance indicators. Strategies that use a combination of multiplex LFD and PCR tests achieve; high levels of detection, detect outbreaks rapidly, and have the lowest burden of testing across multiple pathogens. Influenza B was estimated to have lower rates of detection due to its modelled viral concentration dynamics.
{"title":"Modelling multiplex testing for outbreak control","authors":"Martyn Fyles , Christopher E. Overton , Thomas Ward , Emma Bennett , Tom Fowler , Ian Hall","doi":"10.1016/j.jinf.2024.106303","DOIUrl":"10.1016/j.jinf.2024.106303","url":null,"abstract":"<div><div>During the SARS-CoV-2 pandemic, polymerase chain reaction (PCR) and lateral flow device (LFD) tests were frequently deployed to detect the presence of SARS-CoV-2. Many of these tests were singleplex, and only tested for the presence of a single pathogen. Multiplex tests can test for the presence of several pathogens using only a single swab, which can allow for: surveillance of more pathogens, targeting of antiviral interventions, a reduced burden of testing, and lower costs. Test sensitivity, however, particularly in LFD tests, is highly conditional on the viral concentration dynamics of individuals. To inform the use of multiplex testing in outbreak detection it is therefore necessary to investigate the interactions between outbreak detection strategies and the differing viral concentration trajectories of key pathogens. Viral concentration trajectories are estimated for SARS-CoV-2 and Influenza A/B. Testing strategies for the first five symptomatic cases in an outbreak are then simulated and used to evaluate key performance indicators. Strategies that use a combination of multiplex LFD and PCR tests achieve; high levels of detection, detect outbreaks rapidly, and have the lowest burden of testing across multiple pathogens. Influenza B was estimated to have lower rates of detection due to its modelled viral concentration dynamics.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106303"},"PeriodicalIF":14.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.1016/j.jinf.2024.106302
Line M. Nanque , Anshu Varma , Sanne M. Thysen , Christine S. Benn , Justiniano SD Martins , Aksel KG Jensen , Claudino Correia , Sören Möller , Anita Van den Biggelaar , Peter Aaby , Ane B. Fisker
Objectives
To investigate in a cluster-randomised trial whether a campaign with oral polio vaccine (C-OPV) reduced mortality and morbidity.
Methods
We randomised 222 village clusters under demographic surveillance to an intervention (health check and C-OPV) or control group (health check only). Children aged 0–8 months were eligible. In Cox proportional hazards models with age as the underlying timescale, we compared rates of non-accidental mortality/hospital admission (composite primary outcome) during 12 months of follow-up. Secondary analyses considered non-accidental admission and mortality as separate outcomes. Potential effect modifiers identified in prior studies including sex, season, and timing of the first routine OPV dose (OPV0, scheduled at birth) were assessed.
Results
Among 10,175 children (5288 in 111 intervention clusters/4887 in 111 control clusters), we observed 265 deaths/admissions during 7616 person-years at risk (intervention: 129; control: 136). C-OPV did not reduce the composite endpoint, hazard ratio (HR): 0.87, 95%CI: 0.68–1.12 or its separate components. C-OPV reduced the risk in children receiving OPV0<15 days of birth (HR=0.66, 95%CI: 0.46–0.95), but not in other children (p for interaction: 0.03). Interactions for other potential effect modifiers were not statistically significant.
Conclusions
C-OPV had no overall effect on mortality/admissions, but the effect differed by early priming with OPV0.
{"title":"Effect of a campaign with oral polio vaccine on general health: A cluster-randomised trial in rural Guinea-Bissau","authors":"Line M. Nanque , Anshu Varma , Sanne M. Thysen , Christine S. Benn , Justiniano SD Martins , Aksel KG Jensen , Claudino Correia , Sören Möller , Anita Van den Biggelaar , Peter Aaby , Ane B. Fisker","doi":"10.1016/j.jinf.2024.106302","DOIUrl":"10.1016/j.jinf.2024.106302","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate in a cluster-randomised trial whether a campaign with oral polio vaccine (C-OPV) reduced mortality and morbidity.</div></div><div><h3>Methods</h3><div>We randomised 222 village clusters under demographic surveillance to an intervention (health check and C-OPV) or control group (health check only). Children aged 0–8 months were eligible. In Cox proportional hazards models with age as the underlying timescale, we compared rates of non-accidental mortality/hospital admission (composite primary outcome) during 12 months of follow-up. Secondary analyses considered non-accidental admission and mortality as separate outcomes. Potential effect modifiers identified in prior studies including sex, season, and timing of the first routine OPV dose (OPV0, scheduled at birth) were assessed.</div></div><div><h3>Results</h3><div>Among 10,175 children (5288 in 111 intervention clusters/4887 in 111 control clusters), we observed 265 deaths/admissions during 7616 person-years at risk (intervention: 129; control: 136). C-OPV did not reduce the composite endpoint, hazard ratio (HR): 0.87, 95%CI: 0.68–1.12 or its separate components. C-OPV reduced the risk in children receiving OPV0<15 days of birth (HR=0.66, 95%CI: 0.46–0.95), but not in other children (p for interaction: 0.03). Interactions for other potential effect modifiers were not statistically significant.</div></div><div><h3>Conclusions</h3><div>C-OPV had no overall effect on mortality/admissions, but the effect differed by early priming with OPV0.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 6","pages":"Article 106302"},"PeriodicalIF":14.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.1016/j.jinf.2024.106301
Hester H. Stoorvogel , Maartje van Egmond , Heiman F.L. Wertheim , Jeroen A. Schouten , Marlies E.J.L. Hulscher , Lars Peeters , Yvonne Kiers , Sofie Koenders , Tom Sprong , Suzan P. van Mens , Mirjam Tromp , Olivier Richel , Reinier Akkermans , Jaap ten Oever
Objectives
Evidence on the optimal frequency of laboratory testing during outpatient parenteral antimicrobial therapy (OPAT) is lacking. Therefore, we investigated how often and when laboratory abnormalities occur during OPAT and which factors are associated with these abnormalities.
Methods
We performed a multicenter cohort study in four Dutch hospitals among adult patients receiving OPAT and collected routinely obtained laboratory test results. Incidence and incidence rates were calculated for various laboratory abnormalities. Survival analysis was performed to visualize the time to the first occurrence of laboratory abnormalities and Poisson regression analysis to compare the number of abnormalities in the first and second 30 OPAT days among patients receiving OPAT for ≥60 days. Predictors were identified using a multivariable Cox proportional hazard regression model.
Results
45.1% of 1152 included patients developed laboratory abnormalities, but only 2% led to OPAT discontinuation. Hepatotoxicity was most common (33.9 events/1000 OPAT days), with a time-dependent decrease in the occurrence of the first hepatotoxic event, while hypokalemia was rare (1.7 events/1000 OPAT days). In the subgroup of patients receiving ≥60 days of OPAT, nephrotoxicity was more common in days 31–60. We observed partly toxicity-specific associations between antibiotic type, concomitant medication, baseline laboratory values, patient characteristics, and the occurrence of laboratory abnormalities.
Conclusions
While laboratory abnormalities are frequently observed during OPAT, they rarely lead to discontinuation of OPAT. Specific patient, treatment and laboratory characteristics were associated with the occurrence of laboratory abnormalities. Based on our results, we recommend a more personalized laboratory monitoring policy with less blood sampling.
目的：关于门诊肠外抗菌治疗（OPAT）期间实验室检测的最佳频率尚缺乏证据。因此，我们对 OPAT 期间实验室异常发生的频率和时间以及与这些异常相关的因素进行了调查：我们在四家荷兰医院对接受 OPAT 治疗的成年患者进行了一项多中心队列研究，并收集了常规实验室检测结果。我们计算了各种实验室异常的发生率和发病率。对接受 OPAT≥60 天的患者进行了生存分析，以直观显示首次出现实验室异常的时间，并进行了泊松回归分析，以比较接受 OPAT 前 30 天和后 30 天的异常数量。使用多变量考克斯比例危险回归模型确定了预测因素：结果：在纳入的1152名患者中，45.1%的患者出现实验室异常，但只有2%的患者因此停用了OPAT。肝毒性最为常见（33.9 例/1000 OPAT 天），首次肝毒性事件的发生率随时间推移而下降，而低钾血症则很少见（1.7 例/1000 OPAT 天）。在接受 OPAT 治疗≥60 天的患者亚组中，肾毒性在第 31-60 天更为常见。我们观察到抗生素类型、伴随用药、基线实验室值、患者特征与实验室异常发生之间存在部分毒性特异性关联：虽然在 OPAT 期间经常会观察到实验室异常，但它们很少导致 OPAT 的中止。特定的患者、治疗和实验室特征与实验室异常的发生有关。基于我们的研究结果，我们建议采取更个性化的实验室监测政策，减少抽血次数。
{"title":"Occurrence and predictors of laboratory abnormalities during outpatient parenteral antimicrobial therapy – A multicenter cohort study to inform laboratory test monitoring","authors":"Hester H. Stoorvogel , Maartje van Egmond , Heiman F.L. Wertheim , Jeroen A. Schouten , Marlies E.J.L. Hulscher , Lars Peeters , Yvonne Kiers , Sofie Koenders , Tom Sprong , Suzan P. van Mens , Mirjam Tromp , Olivier Richel , Reinier Akkermans , Jaap ten Oever","doi":"10.1016/j.jinf.2024.106301","DOIUrl":"10.1016/j.jinf.2024.106301","url":null,"abstract":"<div><h3>Objectives</h3><div>Evidence on the optimal frequency of laboratory testing during outpatient parenteral antimicrobial therapy (OPAT) is lacking. Therefore, we investigated how often and when laboratory abnormalities occur during OPAT and which factors are associated with these abnormalities.</div></div><div><h3>Methods</h3><div>We performed a multicenter cohort study in four Dutch hospitals among adult patients receiving OPAT and collected routinely obtained laboratory test results. Incidence and incidence rates were calculated for various laboratory abnormalities. Survival analysis was performed to visualize the time to the first occurrence of laboratory abnormalities and Poisson regression analysis to compare the number of abnormalities in the first and second 30 OPAT days among patients receiving OPAT for ≥60 days. Predictors were identified using a multivariable Cox proportional hazard regression model.</div></div><div><h3>Results</h3><div>45.1% of 1152 included patients developed laboratory abnormalities, but only 2% led to OPAT discontinuation. Hepatotoxicity was most common (33.9 events/1000 OPAT days), with a time-dependent decrease in the occurrence of the first hepatotoxic event, while hypokalemia was rare (1.7 events/1000 OPAT days). In the subgroup of patients receiving ≥60 days of OPAT, nephrotoxicity was more common in days 31–60. We observed partly toxicity-specific associations between antibiotic type, concomitant medication, baseline laboratory values, patient characteristics, and the occurrence of laboratory abnormalities.</div></div><div><h3>Conclusions</h3><div>While laboratory abnormalities are frequently observed during OPAT, they rarely lead to discontinuation of OPAT. Specific patient, treatment and laboratory characteristics were associated with the occurrence of laboratory abnormalities. Based on our results, we recommend a more personalized laboratory monitoring policy with less blood sampling.</div></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":"89 5","pages":"Article 106301"},"PeriodicalIF":14.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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