Pub Date : 2024-10-30DOI: 10.1016/j.jcv.2024.105743
John Prostko , Richard Rothman , Yu-Hsiang Hsieh , Sandra Pearce , Mark Kilbane , Karl McAuley , Edwin Frias , Russell Taylor , Hussain Ali , Carsten Buenning , Jessica Grieshaber , Jenna Bedrava , David Daghfal
Introduction
HCV antibody assays have been used to screen for HCV, but confirmation of acute infection is dependent on RNA or core antigen testing. The aim of the study was to compare the performance of five HCV test methods, including RNA testing, on a US emergency department population.
Methods
Clinical performance metrics were calculated on 708 consenting Johns Hopkins Emergency Department patients who self-reported an increased risk for HCV infection. Detection times of antibody, antigen, and RNA testing were compared using 89 samples from commercially available seroconversion panels. Testing was performed on the Abbott Alinity HCV Ag Next (RUO), Roche Elecsys HCV Duo, Abbott ARCHITECT Anti-HCV, and Elecsys Anti-HCV II assays. RNA testing was performed on the Abbott m2000 system.
Results
Overall, 21 (3.0%) participants tested positive for HCV on at least one test, 11 (52.4%) had chronic, 1 (4.8%) had an acute, and 3 (14.3%) had resolved infections. The Alinity HCV Ag Next assay demonstrated 99.43% specificity when compared to RNA testing. The Alinity HCV Ag Next assay also detected 91.67% of the active infections compared to RNA testing, while the Elecsys HCV Duo Ag assay detected only 58.33%. The seroconversion panel testing demonstrated that the Alinity HCV Ag Next assay detects an infection within 0.8 days of an RNA result.
Conclusion
The Alinity HCV Ag Next assay demonstrated excellent concordance to RNA testing in a US urban E.D. population. This data supports the utility of Alinity HCV Ag Next in diagnosis of active HCV infections.
导言:HCV抗体检测已被用于筛查HCV,但急性感染的确诊则依赖于RNA或核心抗原检测。本研究的目的是在美国急诊科人群中比较包括 RNA 检测在内的五种 HCV 检测方法的性能:方法:对约翰霍普金斯大学急诊科的 708 名自述感染 HCV 风险增高并征得同意的患者计算临床性能指标。使用 89 份来自市售血清转换面板的样本比较了抗体、抗原和 RNA 检测的检测时间。雅培 Alinity HCV Ag Next (RUO)、罗氏 Elecsys HCV Duo、雅培 ARCHITECT Anti-HCV 和 Elecsys Anti-HCV II 分析仪进行了检测。RNA 检测在雅培 m2000 系统上进行:总体而言,21 名参与者(3.0%)至少有一次检测结果呈 HCV 阳性,其中 11 人(52.4%)为慢性感染,1 人(4.8%)为急性感染,3 人(14.3%)为已解决感染。Alinity HCV Ag Next 检测法与 RNA 检测法相比,特异性高达 99.43%。与 RNA 检测相比,Alinity HCV Ag Next 检测法还能检测出 91.67% 的活动感染,而 Elecsys HCV Duo Ag 检测法只能检测出 58.33%。血清转换面板检测表明,Alinity HCV Ag Next 检测试剂盒能在 RNA 检测结果出来后的 0.8 天内检测出感染:结论:Alinity HCV Ag Next 检测法与 RNA 检测法在美国城市 E.D.Population 中的一致性非常好:这些数据支持 Alinity HCV Ag Next 在诊断活动性 HCV 感染中的实用性。
{"title":"Performance evaluation of the Abbott Alinity Hepatitis C antigen next assay in a US urban emergency department population","authors":"John Prostko , Richard Rothman , Yu-Hsiang Hsieh , Sandra Pearce , Mark Kilbane , Karl McAuley , Edwin Frias , Russell Taylor , Hussain Ali , Carsten Buenning , Jessica Grieshaber , Jenna Bedrava , David Daghfal","doi":"10.1016/j.jcv.2024.105743","DOIUrl":"10.1016/j.jcv.2024.105743","url":null,"abstract":"<div><h3>Introduction</h3><div>HCV antibody assays have been used to screen for HCV, but confirmation of acute infection is dependent on RNA or core antigen testing. The aim of the study was to compare the performance of five HCV test methods, including RNA testing, on a US emergency department population.</div></div><div><h3>Methods</h3><div>Clinical performance metrics were calculated on 708 consenting Johns Hopkins Emergency Department patients who self-reported an increased risk for HCV infection. Detection times of antibody, antigen, and RNA testing were compared using 89 samples from commercially available seroconversion panels. Testing was performed on the Abbott Alinity HCV Ag Next (RUO), Roche Elecsys HCV Duo, Abbott ARCHITECT Anti-HCV, and Elecsys Anti-HCV II assays. RNA testing was performed on the Abbott m2000 system.</div></div><div><h3>Results</h3><div>Overall, 21 (3.0%) participants tested positive for HCV on at least one test, 11 (52.4%) had chronic, 1 (4.8%) had an acute, and 3 (14.3%) had resolved infections. The Alinity HCV Ag Next assay demonstrated 99.43% specificity when compared to RNA testing. The Alinity HCV Ag Next assay also detected 91.67% of the active infections compared to RNA testing, while the Elecsys HCV Duo Ag assay detected only 58.33%. The seroconversion panel testing demonstrated that the Alinity HCV Ag Next assay detects an infection within 0.8 days of an RNA result.</div></div><div><h3>Conclusion</h3><div>The Alinity HCV Ag Next assay demonstrated excellent concordance to RNA testing in a US urban E.D. population. This data supports the utility of Alinity HCV Ag Next in diagnosis of active HCV infections.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"175 ","pages":"Article 105743"},"PeriodicalIF":4.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/j.jcv.2024.105742
Kalpana Thangavelu, Hubert D-J Daniel, Rajesh Kannangai, Asha Mary Abraham, Selva Kumar Velladurai, Dr. Shoba Mammen
Background
Rapid fluorescent focus inhibition test (RFFIT), a neutralization-based assay for detecting rabies antibodies, is the gold standard. The National Action Plan for Dog Mediated Rabies Elimination (NAPRE) is a national program that strategizes the establishment of enzyme-linked immunosorbent assays (ELISA) to detect rabies antibodies.
Objective
We developed an in-house ELISA to screen for rabies antibodies using rabies vaccine antigen to study vaccine response among health care workers (HCWs) who received pre-exposure prophylaxis and a few animal bite victims who received post-exposure prophylaxis with rabies vaccine.
Study design
A prospective study was carried out from April to September 2023 at the Department of Clinical Virology of a tertiary care center in South India. A total of 161 serum specimens, which included 155 serum samples from study participants and 6 samples from a reference laboratory (as controls), were obtained during the study period. Rabies antibody was determined by the in-house standardized ELISA developed using the rabies vaccine and compared with the reference assay, RFFIT. The accuracy indices of the in-house ELISA were estimated by MedCalc software (version 22.023).
Results
A panel of 86 positive and 75 negative serum samples was used for evaluating the in-house standardized ELISA. The sensitivity, specificity, positive and negative predictive values of the in-house ELISA were 98.8 %, 100 %, 100 %, and 98.7 % respectively. The accuracy of the in-house ELISA is 99.4 %.
Conclusion
ELISA can be a practically feasible and less expensive assay compared to RFFIT which is a cumbersome procedure with a long turn-around time of 3–4 days.
{"title":"Standardization and evaluation of an in-house ELISA for the detection of rabies antibody in a tertiary care centre in South India","authors":"Kalpana Thangavelu, Hubert D-J Daniel, Rajesh Kannangai, Asha Mary Abraham, Selva Kumar Velladurai, Dr. Shoba Mammen","doi":"10.1016/j.jcv.2024.105742","DOIUrl":"10.1016/j.jcv.2024.105742","url":null,"abstract":"<div><h3>Background</h3><div>Rapid fluorescent focus inhibition test (RFFIT), a neutralization-based assay for <strong>detecting rabies antibodies</strong>, is the gold standard. <strong>The National Action Plan for Dog Mediated Rabies Elimination (NAPRE) is a national program that strategizes the establishment of enzyme-linked immunosorbent assays (ELISA) to detect rabies antibodies.</strong></div></div><div><h3>Objective</h3><div>We developed an in-house ELISA to screen for <strong>rabies antibodies</strong> using rabies vaccine antigen to study vaccine response among health care workers (HCWs) who received pre-exposure prophylaxis and a few animal bite victims who received post-exposure prophylaxis with rabies vaccine.</div></div><div><h3>Study design</h3><div>A prospective study was carried out from April to September 2023 <strong>at</strong> the Department of Clinical Virology of a tertiary care <strong>center</strong> in South India. A total of 161 serum specimens, which included 155 serum samples from study participants and 6 samples from a reference laboratory (as controls), <strong>were</strong> obtained during the study period. Rabies antibody was determined by the in-house standardized ELISA developed using <strong>the rabies vaccine</strong> and compared with the reference assay, RFFIT. The accuracy indices of the in-house ELISA were estimated by MedCalc software (version 22.023).</div></div><div><h3>Results</h3><div>A panel of 86 positive and 75 negative serum samples was used for evaluating the in-house standardized ELISA. <strong>The sensitivity, specificity, positive and negative predictive values of the in-house ELISA were 98.8 %, 100 %, 100 %, and 98.7 % respectively. The accuracy of the in-house ELISA is 99.4 %.</strong></div></div><div><h3>Conclusion</h3><div>ELISA can be a practically feasible and less expensive assay compared to RFFIT which is a cumbersome procedure with a long turn-around time of 3–4 days.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"175 ","pages":"Article 105742"},"PeriodicalIF":4.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-24DOI: 10.1016/j.jcv.2024.105740
Zsofia Igloi , Laura Pezzi , Remi N. Charrel , Marion Koopmans
Background
Yellow fever virus (YFV) is endemic in the (sub)tropical regions of Africa and South America and is prone to cause epidemics. Molecular testing of YFV by reverse transcription-polymerase chain reaction (RT-PCR) was recently adopted by WHO using blood. Urine is a non-invasive diagnostic specimen which has been proven to be useful in diagnosing several flavivirus infections. Until now, systematic data on the usefulness of urine in YFV molecular diagnostics was lacking.
Methods
We have carried out an extensive literature search using key words “yellow fever AND urine” in PubMed/Medline, Embase and Web of Science.
Results
The search resulted initially in 113 publications. All titles and abstracts were screened and 15 were analyzed in detail. After natural infection (10 articles), the detection ratio of YFV in blood with RT-PCR was 61 % (105/171 samples) vs. 59 % (139/234) in urine from patients with mild/severe infections. YFV could be first detected at average 4.3 days in blood vs. 6.1 days in urine and last detected till 17.2 vs. 31.1 days respectively (significant difference p < 0.05). Viral load over time in blood was not statistically different from urine. Virus could be isolated from blood, urine and semen. Following vaccination, virus was detected longer in patients with vaccine adverse events (VAE) compared to healthy vaccinees (average 34 vs. 25 days, not significant p > 0.05).
Conclusion
YFV can be detected in urine later but longer. Thus, we see added value for YF molecular diagnostics and sequencing and recommend it besides blood as a standard specimen, especially for late samples post onset.
{"title":"Detection of yellow fever virus genome in urine following natural infection or vaccination: review of current knowledge 1985–2023.","authors":"Zsofia Igloi , Laura Pezzi , Remi N. Charrel , Marion Koopmans","doi":"10.1016/j.jcv.2024.105740","DOIUrl":"10.1016/j.jcv.2024.105740","url":null,"abstract":"<div><h3>Background</h3><div>Yellow fever virus (YFV) is endemic in the (sub)tropical regions of Africa and South America and is prone to cause epidemics. Molecular testing of YFV by reverse transcription-polymerase chain reaction (RT-PCR) was recently adopted by WHO using blood. Urine is a non-invasive diagnostic specimen which has been proven to be useful in diagnosing several flavivirus infections. Until now, systematic data on the usefulness of urine in YFV molecular diagnostics was lacking.</div></div><div><h3>Methods</h3><div>We have carried out an extensive literature search using key words “yellow fever AND urine” in PubMed/Medline, Embase and Web of Science.</div></div><div><h3>Results</h3><div>The search resulted initially in 113 publications. All titles and abstracts were screened and 15 were analyzed in detail. After natural infection (10 articles), the detection ratio of YFV in blood with RT-PCR was 61 % (105/171 samples) vs. 59 % (139/234) in urine from patients with mild/severe infections. YFV could be first detected at average 4.3 days in blood vs. 6.1 days in urine and last detected till 17.2 vs. 31.1 days respectively (significant difference <em>p</em> < 0.05). Viral load over time in blood was not statistically different from urine. Virus could be isolated from blood, urine and semen. Following vaccination, virus was detected longer in patients with vaccine adverse events (VAE) compared to healthy vaccinees (average 34 vs. 25 days, not significant <em>p</em> > 0.05).</div></div><div><h3>Conclusion</h3><div>YFV can be detected in urine later but longer. Thus, we see added value for YF molecular diagnostics and sequencing and recommend it besides blood as a standard specimen, especially for late samples post onset.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"175 ","pages":"Article 105740"},"PeriodicalIF":4.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1016/j.jcv.2024.105737
Ardashel Latsuzbaia , Marianna Martinelli , Chiara Giubbi , Kate Cuschieri , Hana Elasifer , Anna D. Iacobone , Fabio Bottari , Andrea F. Piana , Roberto Pietri , Giancarlo Tisi , Franco Odicino , Clementina E. Cocuzza , Marc Arbyn , European VALHUDES working group
Background
The VALHUDES initiative was established to assess the clinical accuracy of HPV assays to detect cervical precancers using urine and vaginal self-samples compared to cervical clinician-collected samples. Here, the clinical performance of OncoPredict HPV Quantitative Typing (QT) assay (OncoPredict QT) was evaluated.
Methods
490 women referred to colposcopy self-collected a urine and a vaginal specimen using Colli-Pee and FLOQSwab, respectively. Subsequently, a colposcopy was performed, and a cervical sample was collected with Cervex-Brush, followed by biopsy if clinically indicated. Vaginal samples were transported dry and resuspended in 5 mL of eNAT medium, whilst cervical brushings were immediately transferred in 20 mL ThinPrep.
Results
The clinical sensitivity of OncoPredict HPV QT testing for CIN2+ in urine and vaginal self-samples was similar to cervical samples (ratios of 0.99 [95 % CI 0.94–1.05] and 1.00 [95 % CI 0.96–1.04]), respectively, when manufacturer's cut-offs were applied. The specificity for <CIN2 on both self-samples was lower than on cervical samples (urine/cervical ratio = 0.91 [95 % CI 0.84–0.98]; vaginal/cervical ratio = 0.90 [95 % CI 0.84–0.98]). Cut-off optimisation improved specificity without compromising sensitivity. Median viral load values adjusted for cellularity were significantly higher in cervical samples compared to urine or vaginal self-samples, in general for all 12 high-risk HPV and in particular for HPV16, 18, 31, 33, 35, 45, 51, 58 (p < 0.05). No difference was observed in median viral loads between urine and vaginal samples.
Conclusion
Following cut-off optimisation OncoPredict HPV QT assay demonstrated similar accuracy on self-collected versus cervical samples.
{"title":"Clinical accuracy of OncoPredict HPV Quantitative Typing (QT) assay on self-samples","authors":"Ardashel Latsuzbaia , Marianna Martinelli , Chiara Giubbi , Kate Cuschieri , Hana Elasifer , Anna D. Iacobone , Fabio Bottari , Andrea F. Piana , Roberto Pietri , Giancarlo Tisi , Franco Odicino , Clementina E. Cocuzza , Marc Arbyn , European VALHUDES working group","doi":"10.1016/j.jcv.2024.105737","DOIUrl":"10.1016/j.jcv.2024.105737","url":null,"abstract":"<div><h3>Background</h3><div>The VALHUDES initiative was established to assess the clinical accuracy of HPV assays to detect cervical precancers using urine and vaginal self-samples compared to cervical clinician-collected samples. Here, the clinical performance of OncoPredict HPV Quantitative Typing (QT) assay (OncoPredict QT) was evaluated.</div></div><div><h3>Methods</h3><div>490 women referred to colposcopy self-collected a urine and a vaginal specimen using Colli-Pee and FLOQSwab, respectively. Subsequently, a colposcopy was performed, and a cervical sample was collected with Cervex-Brush, followed by biopsy if clinically indicated. Vaginal samples were transported dry and resuspended in 5 mL of eNAT medium, whilst cervical brushings were immediately transferred in 20 mL ThinPrep.</div></div><div><h3>Results</h3><div>The clinical sensitivity of OncoPredict HPV QT testing for CIN2+ in urine and vaginal self-samples was similar to cervical samples (ratios of 0.99 [95 % CI 0.94–1.05] and 1.00 [95 % CI 0.96–1.04]), respectively, when manufacturer's cut-offs were applied. The specificity for <CIN2 on both self-samples was lower than on cervical samples (urine/cervical ratio = 0.91 [95 % CI 0.84–0.98]; vaginal/cervical ratio = 0.90 [95 % CI 0.84–0.98]). Cut-off optimisation improved specificity without compromising sensitivity. Median viral load values adjusted for cellularity were significantly higher in cervical samples compared to urine or vaginal self-samples, in general for all 12 high-risk HPV and in particular for HPV16, 18, 31, 33, 35, 45, 51, 58 (<em>p</em> < 0.05). No difference was observed in median viral loads between urine and vaginal samples.</div></div><div><h3>Conclusion</h3><div>Following cut-off optimisation OncoPredict HPV QT assay demonstrated similar accuracy on self-collected versus cervical samples.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"175 ","pages":"Article 105737"},"PeriodicalIF":4.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-21DOI: 10.1016/j.jcv.2024.105741
Rosina Ehmann , Oliver Donoso Mantke , Elaine McCulloch , Amani Yousef , Alastair Ricketts , Harry Staines , Joachim J. Bugert , Roman Wölfel , Hubert G.M. Niesters
Background
Diagnostic capabilities and correspondent External Quality Assessments (EQA) are key for outbreak preparedness. To support diagnostic facilities with a quality assessment of newly established monkeypox virus (MPXV) molecular diagnostic workflows, Quality Control for Molecular Diagnostics (QCMD) and the Bundeswehr Institute of Microbiology (IMB) piloted an international EQA study conducting four challenges from autumn 2022 to summer 2023 during the global mpox outbreak.
Objectives
To assess the performance (sensitivity/specificity) of molecular assays used by diagnostic laboratories.
Study design
Inactivated EQA panels were prepared and distributed containing seven samples of clade Ia and clade IIb MPXV strains at different viral concentrations, two specificity controls with other zoonotic orthopoxviruses (vaccinia and cowpox virus) and a negative control. Assessment was based on reported qualitative testing results.
Results
In this outbreak-related EQA study, a total of 192 laboratories from 37 countries reported 346 qualitative datasets. Overall, core samples were correctly detected by approximately 92 % of participants in all four challenges. While sensitivity performance was acceptable in at least 90 % of datasets correctly reported even for educational MPXV-positive samples with low viral concentration [102 genome equivalents (GE)/mL], several laboratories reported the educational specificity controls as false positives or were unable to differentiate MPXV from related orthopoxviruses.
Conclusions
Mpox is now a globally occurring infection with a demand for quality-assured diagnostic capabilities. The newly established EQA scheme presented here, offers a multi-purpose panel for orthopoxviruses with a focus on MPXV which will continue to ensure diagnostic quality in clinical settings with up-to-date sample panels.
{"title":"International external quality assessment study for detection of monkeypox virus by PCR supporting laboratory preparedness during the 2022–2023 mpox outbreak and beyond","authors":"Rosina Ehmann , Oliver Donoso Mantke , Elaine McCulloch , Amani Yousef , Alastair Ricketts , Harry Staines , Joachim J. Bugert , Roman Wölfel , Hubert G.M. Niesters","doi":"10.1016/j.jcv.2024.105741","DOIUrl":"10.1016/j.jcv.2024.105741","url":null,"abstract":"<div><h3>Background</h3><div>Diagnostic capabilities and correspondent External Quality Assessments (EQA) are key for outbreak preparedness. To support diagnostic facilities with a quality assessment of newly established monkeypox virus (MPXV) molecular diagnostic workflows, Quality Control for Molecular Diagnostics (QCMD) and the Bundeswehr Institute of Microbiology (IMB) piloted an international EQA study conducting four challenges from autumn 2022 to summer 2023 during the global mpox outbreak.</div></div><div><h3>Objectives</h3><div>To assess the performance (sensitivity/specificity) of molecular assays used by diagnostic laboratories.</div></div><div><h3>Study design</h3><div>Inactivated EQA panels were prepared and distributed containing seven samples of clade Ia and clade IIb MPXV strains at different viral concentrations, two specificity controls with other zoonotic orthopoxviruses (vaccinia and cowpox virus) and a negative control. Assessment was based on reported qualitative testing results.</div></div><div><h3>Results</h3><div>In this outbreak-related EQA study, a total of 192 laboratories from 37 countries reported 346 qualitative datasets. Overall, core samples were correctly detected by approximately 92 % of participants in all four challenges. While sensitivity performance was acceptable in at least 90 % of datasets correctly reported even for educational MPXV-positive samples with low viral concentration [10<sup>2</sup> genome equivalents (GE)/mL], several laboratories reported the educational specificity controls as false positives or were unable to differentiate MPXV from related orthopoxviruses.</div></div><div><h3>Conclusions</h3><div>Mpox is now a globally occurring infection with a demand for quality-assured diagnostic capabilities. The newly established EQA scheme presented here, offers a multi-purpose panel for orthopoxviruses with a focus on MPXV which will continue to ensure diagnostic quality in clinical settings with up-to-date sample panels.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"175 ","pages":"Article 105741"},"PeriodicalIF":4.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.jcv.2024.105738
E.J. Gore , L. Gard , P. Bourgeois , D. Kulifaj , E. McCulloch , P.G. Spezia , H.G.M. Niesters , F. Maggi , G. Bond , C. Van Leer-Buter , TTVguideTX consortium partners
Background
Immunosuppressive medication after organ transplantation is usually dosed through therapeutic drug monitoring. Trough levels of antirejection medication however, do not adequately predict rejection or infections. The TTVguideIT trial is a multinational clinical trial evaluating the safety of Torque Teno Virus (TTV) load assessed by qPCR, as an alternative to trough level tacrolimus dosing.
Methods
Prior to, and during the clinical trial, the inter-and intra-laboratory variability, accuracy, and precision of the TTV R-GENE® assay was evaluated through analysis of internal quality control (IQC), external quality assessment (EQA) and linearity panels performed by the thirteen participating clinical virology laboratories, each using their standard testing platforms.
Results
IQC samples with a target of 4 log10 copies/mL (cp/mL) were tested by the participating laboratories 130 times during the implementation phase and 987 times during the trial phase. They showed excellent accuracy, with an inter-laboratory standard deviation (SD) of 0.17 log10 cp/mL, and an intra-laboratory SD of 0.03 to 0.20 log10 cp/mL during the implementation phase, and an inter-laboratory SD of 0.19 log10 cp/mL, and an intra-laboratory SD 0.07 to 0.18 log10 cp/mL during the trial phase. Three EQA panels and three linearity panels showed similarly small variability during implementation as well as within the trial phase.
Conclusion
This data shows that TTV load measurement can be standardized for use in a multinational clinical trial. By using IQC, LP and EQA samples, the quality and integrity of the assay can be compared between laboratories and precise and accurate results can be generated.
{"title":"Validation, implementation and quality control of a Torque Teno Virus qPCR in a multinational clinical trial","authors":"E.J. Gore , L. Gard , P. Bourgeois , D. Kulifaj , E. McCulloch , P.G. Spezia , H.G.M. Niesters , F. Maggi , G. Bond , C. Van Leer-Buter , TTVguideTX consortium partners","doi":"10.1016/j.jcv.2024.105738","DOIUrl":"10.1016/j.jcv.2024.105738","url":null,"abstract":"<div><h3>Background</h3><div>Immunosuppressive medication after organ transplantation is usually dosed through therapeutic drug monitoring. Trough levels of antirejection medication however, do not adequately predict rejection or infections. The TTVguideIT trial is a multinational clinical trial evaluating the safety of Torque Teno Virus (TTV) load assessed by qPCR, as an alternative to trough level tacrolimus dosing.</div></div><div><h3>Methods</h3><div>Prior to, and during the clinical trial, the inter-and intra-laboratory variability, accuracy, and precision of the TTV R-GENE® assay was evaluated through analysis of internal quality control (IQC), external quality assessment (EQA) and linearity panels performed by the thirteen participating clinical virology laboratories, each using their standard testing platforms.</div></div><div><h3>Results</h3><div>IQC samples with a target of 4 log<sub>10</sub> copies/mL (cp/mL) were tested by the participating laboratories 130 times during the implementation phase and 987 times during the trial phase. They showed excellent accuracy, with an inter-laboratory standard deviation (SD) of 0.17 log<sub>10</sub> cp/mL, and an intra-laboratory SD of 0.03 to 0.20 log<sub>10</sub> cp/mL during the implementation phase, and an inter-laboratory SD of 0.19 log<sub>10</sub> cp/mL, and an intra-laboratory SD 0.07 to 0.18 log<sub>10</sub> cp/mL during the trial phase. Three EQA panels and three linearity panels showed similarly small variability during implementation as well as within the trial phase.</div></div><div><h3>Conclusion</h3><div>This data shows that TTV load measurement can be standardized for use in a multinational clinical trial. By using IQC, LP and EQA samples, the quality and integrity of the assay can be compared between laboratories and precise and accurate results can be generated.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"175 ","pages":"Article 105738"},"PeriodicalIF":4.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.jcv.2024.105739
María Belén Colazo Salbetti , Gabriel Boggio , Néstor Dicuatro , Ana Paula Gudiño , Nicolás Olivera , Mauro Pedranti , María Beatriz Isa , Ariel Bertoldi , María José Miranda , Gonzalo Rodriguez Lombardi , Paola Sicilia , Gonzalo Castro , Laura Moreno , María Pilar Adamo
Background
Parvovirus B19 (B19 V) infection during pregnancy can cause adverse fetal outcomes. Our aim was to characterize both clinical and asymptomatic maternal and neonatal cases by studying virological and serological markers of B19 V infection, and to sequence the complete genome of the circulating virus in Argentina.
Methods
Symptomatic patients were included based on maternal and/or fetal-neonatal signs attributable to B19 V infection during gestation. Pregnant patients were analyzed in either the timely diagnosis group (TD, samples obtained when symptoms were present and infection was suspected) or the retrospective diagnosis group (RD, samples collected immediately postpartum), and newborns were analyzed at birth. A sample of asymptomatic individuals was also analyzed. Diagnostic tests (PCR/qPCR/serology) and sequencing were performed on archived serum samples from 2018 to 2023, and clinical data were obtained from medical records.
Results
We studied 328 symptomatic patients, including 185 pregnant patients (73 TD and 112 RD) and 143 newborns. Among them, we identified 27/328 (8.2 %) positive cases (B19V+): 12/73 (16.4 %) in the TD group, 6/112 (5.4 %) in the RD group, and 9/143 (6.3 %) newborns. Within the 77 mother-newborn pairs included, there were 8 (10.4 %) B19 V infections and 6 cases of vertical transmission. Additionally, B19 V infection was detected in 26/310 (8.4 %) asymptomatic patients. Phylogenetic analysis identified genotype 1a as a circulating strain in Argentina.
Conclusions
Our findings highlight the need to raise awareness and enhance diagnostic approaches in Argentina to more effectively identify and manage B19 V infections during pregnancy in our region.
背景:妊娠期感染 Parvovirus B19(B19 V)会对胎儿造成不良影响。我们的目的是通过研究 B19 V 感染的病毒学和血清学标志物来描述临床和无症状孕产妇和新生儿病例的特征,并对阿根廷流行病毒的完整基因组进行测序:方法:根据孕产妇和/或胎儿-新生儿在妊娠期间因 B19 V 感染而出现的体征,纳入有症状的患者。对孕妇的分析分为及时诊断组(TD,在出现症状并怀疑感染时采集样本)或回顾诊断组(RD,产后立即采集样本),新生儿则在出生时进行分析。此外,还对无症状者的样本进行了分析。对2018年至2023年的存档血清样本进行了诊断测试(PCR/qPCR/血清学)和测序,并从病历中获取了临床数据:我们研究了 328 名有症状的患者,包括 185 名孕妇(73 名 TD 和 112 名 RD)和 143 名新生儿。其中,我们发现了27/328(8.2%)例阳性病例(B19V+):TD组12/73(16.4%)例,RD组6/112(5.4%)例,新生儿9/143(6.3%)例。在 77 对母婴中,有 8 例(10.4%)B19 V 感染和 6 例垂直传播。此外,在 26/310 例(8.4%)无症状患者中检测到 B19 V 型感染。系统发育分析确定基因型 1a 是阿根廷的一种流行菌株:我们的研究结果凸显了在阿根廷提高人们对 B19 V 感染的认识和加强诊断方法的必要性,以便更有效地识别和处理本地区的妊娠期 B19 V 感染。
{"title":"Parvovirus B19 remains an underestimated pathogen among infections during gestation in Argentina: Insights through the study of symptomatic and asymptomatic pregnant patients and newborns from Córdoba","authors":"María Belén Colazo Salbetti , Gabriel Boggio , Néstor Dicuatro , Ana Paula Gudiño , Nicolás Olivera , Mauro Pedranti , María Beatriz Isa , Ariel Bertoldi , María José Miranda , Gonzalo Rodriguez Lombardi , Paola Sicilia , Gonzalo Castro , Laura Moreno , María Pilar Adamo","doi":"10.1016/j.jcv.2024.105739","DOIUrl":"10.1016/j.jcv.2024.105739","url":null,"abstract":"<div><h3>Background</h3><div>Parvovirus B19 (B19 V) infection during pregnancy can cause adverse fetal outcomes. Our aim was to characterize both clinical and asymptomatic maternal and neonatal cases by studying virological and serological markers of B19 V infection, and to sequence the complete genome of the circulating virus in Argentina.</div></div><div><h3>Methods</h3><div>Symptomatic patients were included based on maternal and/or fetal-neonatal signs attributable to B19 V infection during gestation. Pregnant patients were analyzed in either the timely diagnosis group (TD, samples obtained when symptoms were present and infection was suspected) or the retrospective diagnosis group (RD, samples collected immediately postpartum), and newborns were analyzed at birth. A sample of asymptomatic individuals was also analyzed. Diagnostic tests (PCR/qPCR/serology) and sequencing were performed on archived serum samples from 2018 to 2023, and clinical data were obtained from medical records.</div></div><div><h3>Results</h3><div>We studied 328 symptomatic patients, including 185 pregnant patients (73 TD and 112 RD) and 143 newborns. Among them, we identified 27/328 (8.2 %) positive cases (B19V+): 12/73 (16.4 %) in the TD group, 6/112 (5.4 %) in the RD group, and 9/143 (6.3 %) newborns. Within the 77 mother-newborn pairs included, there were 8 (10.4 %) B19 V infections and 6 cases of vertical transmission. Additionally, B19 V infection was detected in 26/310 (8.4 %) asymptomatic patients. Phylogenetic analysis identified genotype 1a as a circulating strain in Argentina.</div></div><div><h3>Conclusions</h3><div>Our findings highlight the need to raise awareness and enhance diagnostic approaches in Argentina to more effectively identify and manage B19 V infections during pregnancy in our region.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"175 ","pages":"Article 105739"},"PeriodicalIF":4.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-08DOI: 10.1016/j.jcv.2024.105735
Raissa Rachman , Tanzina Haque , Tristan J Barber , Fiona Burns , Jessica Pinto , Alan Hunter , Russell Durkin , Jennifer Hart
Background
Opt-out Emergency Department blood borne virus (EDBBV) screening was introduced at the Royal Free Hospital under the NHSEI (NHS England and NHS Improvement) programme to expand opt-out testing in local authority areas with high HIV prevalence. This initiative was part of the “Toward Zero” policy towards ending HIV transmission in England by 2030.
Methods
All patients attending the Royal Free Hospital Emergency Department (ED) aged 16 and over were screened for blood borne viruses (HIV/HBV/HCV) unless they opted out. We looked at HIV data from patients seen in ED between the initiation of EDBBV testing on the 12th of April and 12th of August 2022. Hepatitis B and C data was reviewed in a separate study.
Outcome
A total of 12,208 samples from 10,641 patients were screened for HIV. Amongst these samples there were 88 which were positive, giving a seroprevalence of 0.84 %. There were 48 patients who were already known to local HIV services, 35 were known to HIV services outside of our Trust and 5 were new diagnoses.
Conclusion
Our results confirmed our local HIV prevalence to be very high, as per the UK Health Security Agency and supports the need for HIV testing. Opt-out ED BBV screening has been a highly effective method for identifying people living with HIV who are unaware of their status.
背景:根据英国国家医疗服务体系(NHSEI)和英国国家医疗服务体系改进(NHS Improvement)计划,皇家自由医院引入了急诊科血液传播病毒(EDBBV)选择性筛查,在艾滋病高发地区扩大选择性检测范围。这一举措是 "迈向零 "政策的一部分,旨在到 2030 年在英格兰杜绝 HIV 传播:所有在皇家自由医院急诊科(ED)就诊的 16 岁及以上患者都要接受血液传播病毒(HIV/HBV/HCV)筛查,除非他们选择不接受筛查。我们研究了自 2022 年 4 月 12 日开始进行 EDBBV 检测至 8 月 12 日期间急诊科就诊患者的 HIV 数据。乙肝和丙肝数据在另一项研究中进行了审查:共对来自 10,641 名患者的 12,208 份样本进行了艾滋病毒筛查。在这些样本中,有 88 份呈阳性,血清阳性率为 0.84%。其中有 48 名患者已在当地的 HIV 服务机构接受过检测,35 名患者在信托基金以外的 HIV 服务机构接受过检测,5 名患者是新诊断出的:我们的结果证实,根据英国卫生安全局的数据,我们当地的 HIV 感染率非常高,因此有必要进行 HIV 检测。选择不接受 ED BBV 筛查是一种非常有效的方法,可以识别不知道自己感染情况的 HIV 感染者。
{"title":"Opt-out HIV screening in adults attending the Emergency Department of a London teaching hospital","authors":"Raissa Rachman , Tanzina Haque , Tristan J Barber , Fiona Burns , Jessica Pinto , Alan Hunter , Russell Durkin , Jennifer Hart","doi":"10.1016/j.jcv.2024.105735","DOIUrl":"10.1016/j.jcv.2024.105735","url":null,"abstract":"<div><h3>Background</h3><div>Opt-out Emergency Department blood borne virus (EDBBV) screening was introduced at the Royal Free Hospital under the NHSEI (NHS England and NHS Improvement) programme to expand opt-out testing in local authority areas with high HIV prevalence. This initiative was part of the “Toward Zero” policy towards ending HIV transmission in England by 2030.</div></div><div><h3>Methods</h3><div>All patients attending the Royal Free Hospital Emergency Department (ED) aged 16 and over were screened for blood borne viruses (HIV/HBV/HCV) unless they opted out. We looked at HIV data from patients seen in ED between the initiation of EDBBV testing on the 12<sup>th</sup> of April and 12<sup>th</sup> of August 2022. Hepatitis B and C data was reviewed in a separate study.</div></div><div><h3>Outcome</h3><div>A total of 12,208 samples from 10,641 patients were screened for HIV. Amongst these samples there were 88 which were positive, giving a seroprevalence of 0.84 %. There were 48 patients who were already known to local HIV services, 35 were known to HIV services outside of our Trust and 5 were new diagnoses.</div></div><div><h3>Conclusion</h3><div>Our results confirmed our local HIV prevalence to be very high, as per the UK Health Security Agency and supports the need for HIV testing. Opt-out ED BBV screening has been a highly effective method for identifying people living with HIV who are unaware of their status.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"175 ","pages":"Article 105735"},"PeriodicalIF":4.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142501309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-06DOI: 10.1016/j.jcv.2024.105736
Gustaf Leijonhufvud , Tatiany Aparecida Teixeira Soratto , Gabriel Machado Matos , Amanj Bajalan , Claudia Eichler-Jonsson , Britt Gustafsson , Gordana Bogdanovic , Tobias Allander , Gustaf Ljungman , Björn Andersson
Background and Objectives
A large cohort of pediatric patients with various forms of childhood cancer was investigated for the presence of viruses using metagenomics. A total of 476 patient samples, collected between 1989 and 2018, were analyzed, representing various pediatric oncological diagnoses and a control group of non-malignant diagnoses.
Study design
The study was carried out using metagenomic sequencing of serum samples. Viruses were identified and analyzed using bioinformatics methods, followed by Polymerase chain reaction (PCR) confirmation
Results
The results indicate that a wide range of viruses can be detected in the bloodstream of children with newly diagnosed cancer. Nine viral genomes were identified: Human Pegivirus (HPgV), Hepatitis C virus, Parechovirus 1, Rhinovirus C, Human papillomavirus 116, Human polyomavirus 10, Parvovirus B19, and different variants of Torque Teno Virus (TTV). In this study, a previously unknown virus was found belonging to the Iflavirdae family in the order Picornavirales. HPGV was significantly more common in patients with leukemia compared to other conditions.
Conclusions
These results highlight the abundance of systemic virus infections in children, and the value of metagenomic sequencing for hypothesis forming regarding the associations between virus infections and cancer.
{"title":"Metagenomic characterization of viruses in the serum of children with newly diagnosed cancer","authors":"Gustaf Leijonhufvud , Tatiany Aparecida Teixeira Soratto , Gabriel Machado Matos , Amanj Bajalan , Claudia Eichler-Jonsson , Britt Gustafsson , Gordana Bogdanovic , Tobias Allander , Gustaf Ljungman , Björn Andersson","doi":"10.1016/j.jcv.2024.105736","DOIUrl":"10.1016/j.jcv.2024.105736","url":null,"abstract":"<div><h3>Background and Objectives</h3><div>A large cohort of pediatric patients with various forms of childhood cancer was investigated for the presence of viruses using metagenomics. A total of 476 patient samples, collected between 1989 and 2018, were analyzed, representing various pediatric oncological diagnoses and a control group of non-malignant diagnoses.</div></div><div><h3>Study design</h3><div>The study was carried out using metagenomic sequencing of serum samples. Viruses were identified and analyzed using bioinformatics methods, followed by Polymerase chain reaction (PCR) confirmation</div></div><div><h3>Results</h3><div>The results indicate that a wide range of viruses can be detected in the bloodstream of children with newly diagnosed cancer. Nine viral genomes were identified: Human Pegivirus (HPgV), Hepatitis C virus, Parechovirus 1, Rhinovirus C, Human papillomavirus 116, Human polyomavirus 10, Parvovirus B19, and different variants of Torque Teno Virus (TTV). In this study, a previously unknown virus was found belonging to the Iflavirdae family in the order Picornavirales. HPGV was significantly more common in patients with leukemia compared to other conditions.</div></div><div><h3>Conclusions</h3><div>These results highlight the abundance of systemic virus infections in children, and the value of metagenomic sequencing for hypothesis forming regarding the associations between virus infections and cancer.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"175 ","pages":"Article 105736"},"PeriodicalIF":4.0,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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.jcv.2024.105734
William Forson , Ramya Bhatia , Heather Currie , Hana Elasifer , Linzi Connor , Allan Wilson , Kate Cuschieri
Background
HPV self sampling can act as a tool to engage women in cervical screening and population based studies can inform optimal implementation of this approach.
Methods
Self sampling kits were mailed to women who had defaulted from routine screening resident in an entire territorial health board in Scotland. Kit return rates and compliance to colposcopy follow up in those who were HPV mRNA positive were assessed. Concordance of the self-sample with samples taken later at colposcopy was measured alongside PPV of an mRNA positive result for CIN2+.
Results
Of 4173 women invited to participate, 20.5 %, returned their kit and a greater return rate with increasing age was observed. HPV mRNA positivity was 12.0 %, and invalidity rate was approximately 3 %. Compliance to colposcopy follow up was 88.3 % and the PPV for an mRNA test for CIN2+ on a self sample was 25.6 %. hr-HPV concordance on the initial swab and the follow up swab and liquid based cytology (LBC) sample taken at colposcopy was 67.1 % and 30 % respectively.
Conclusions
HPV self sampling using a “mail to all” approach is feasible in Scotland although only 1 in 5 actively responded to the offer. Future work to monitor screening behaviours in those who were invited but did not engage initially will help quantify any additional benefit(s) incurred.
{"title":"High-risk HPV mRNA testing on self-samples offered to those who do not attend for organised cervical screening – real world data from the Dumfries and Galloway region in Scotland","authors":"William Forson , Ramya Bhatia , Heather Currie , Hana Elasifer , Linzi Connor , Allan Wilson , Kate Cuschieri","doi":"10.1016/j.jcv.2024.105734","DOIUrl":"10.1016/j.jcv.2024.105734","url":null,"abstract":"<div><h3>Background</h3><div>HPV self sampling can act as a tool to engage women in cervical screening and population based studies can inform optimal implementation of this approach.</div></div><div><h3>Methods</h3><div>Self sampling kits were mailed to women who had defaulted from routine screening resident in an entire territorial health board in Scotland. Kit return rates and compliance to colposcopy follow up in those who were HPV mRNA positive were assessed. Concordance of the self-sample with samples taken later at colposcopy was measured alongside PPV of an mRNA positive result for CIN2+.</div></div><div><h3>Results</h3><div>Of 4173 women invited to participate, 20.5 %, returned their kit and a greater return rate with increasing age was observed. HPV mRNA positivity was 12.0 %, and invalidity rate was approximately 3 %. Compliance to colposcopy follow up was 88.3 % and the PPV for an mRNA test for CIN2+ on a self sample was 25.6 %. hr-HPV concordance on the initial swab and the follow up swab and liquid based cytology (LBC) sample taken at colposcopy was 67.1 % and 30 % respectively.</div></div><div><h3>Conclusions</h3><div>HPV self sampling using a “mail to all” approach is feasible in Scotland although only 1 in 5 actively responded to the offer. Future work to monitor screening behaviours in those who were invited but did not engage initially will help quantify any additional benefit(s) incurred.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"175 ","pages":"Article 105734"},"PeriodicalIF":4.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142423694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}