Pub Date : 2024-03-05DOI: 10.1016/j.jcv.2024.105664
Carlo Pietrasanta , Andrea Ronchi , Laura Bassi , Agnese De Carli , Luca Caschera , Francesco Maria Lo Russo , Beatrice Letizia Crippa , Silvia Pisoni , Riccardo Crimi , Giacomo Artieri , Laura Pellegrinelli , Robertino Dilena , Giorgio Conte , Fabio Mosca , Monica Fumagalli , Lorenza Pugni
Background
Non-polio enteroviruses (EV) and human parechoviruses (HPeV) are known etiological agents of meningoencephalitis in neonates. However, reports of neuroradiological findings and neurodevelopmental outcomes in this population are scarce.
Objectives
to describe clinical characteristics, neuroradiological findings and, in a subset of patients, neurodevelopmental outcomes in a cohort of infants with EV or HPeV meningoencephalitis within 60 days of life.
Study design
clinical/laboratory data, neuroradiological findings (cranial ultrasound, cUS, brain magnetic resonance imaging, MRI), and neurodevelopmental outcomes assessed by Ages and Stages Questionnaires – third edition were prospectively collected.
Results
overall, 32 infants with EV (21, 67.8 %) or HPeV (11, 28.2 %) meningoencephalitis were enrolled. Infants with HPeV (73 %: type 3 HPeV) presented more frequently with seizures (18.2 % vs. 0, p value=0.03), lymphopenia (1120 vs. 2170 cells/mm3, p = 0.02), focal anomalies at electroencephalography (EEG) (63.6 vs. 23.8 %, p = 0.03), and pathological findings at MRI (72.7 % vs. 15.8 %, p value=0.004) compared to those affected by EV. cUS was not significantly altered in any of the enrolled infants. All infants with EV meningoencephalitis evaluated at 12–24 months and at 30–48 months were normal. Two out of the 7 infants with HPeV meningoencephalitis showed some concerns in gross motor (1/7, 14.3 %) or in problem solving (1/7, 14.3 %) function at 30–48 months of age.
Conclusions
In our cohort, neonates infected by HPeV had more severe clinical manifestations, more alterations at brain MRI, and some signs of long-term neurodevelopmental delay. Our data highlight the heterogeneity of manifestations in infants with EV or HPeV meningoencephalitis, and the need for long-term follow-up of those infected by HPeV in the neonatal period.
{"title":"Enterovirus and parechovirus meningoencephalitis in infants: A ten-year prospective observational study in a neonatal intensive care unit","authors":"Carlo Pietrasanta , Andrea Ronchi , Laura Bassi , Agnese De Carli , Luca Caschera , Francesco Maria Lo Russo , Beatrice Letizia Crippa , Silvia Pisoni , Riccardo Crimi , Giacomo Artieri , Laura Pellegrinelli , Robertino Dilena , Giorgio Conte , Fabio Mosca , Monica Fumagalli , Lorenza Pugni","doi":"10.1016/j.jcv.2024.105664","DOIUrl":"10.1016/j.jcv.2024.105664","url":null,"abstract":"<div><h3>Background</h3><p>Non-polio enteroviruses (EV) and human parechoviruses (HPeV) are known etiological agents of meningoencephalitis in neonates. However, reports of neuroradiological findings and neurodevelopmental outcomes in this population are scarce.</p></div><div><h3>Objectives</h3><p>to describe clinical characteristics, neuroradiological findings and, in a subset of patients, neurodevelopmental outcomes in a cohort of infants with EV or HPeV meningoencephalitis within 60 days of life.</p></div><div><h3>Study design</h3><p>clinical/laboratory data, neuroradiological findings (cranial ultrasound, cUS, brain magnetic resonance imaging, MRI), and neurodevelopmental outcomes assessed by Ages and Stages Questionnaires – third edition were prospectively collected.</p></div><div><h3>Results</h3><p>overall, 32 infants with EV (21, 67.8 %) or HPeV (11, 28.2 %) meningoencephalitis were enrolled. Infants with HPeV (73 %: type 3 HPeV) presented more frequently with seizures (18.2 % <em>vs.</em> 0, <em>p</em> value=0.03), lymphopenia (1120 <em>vs.</em> 2170 cells/mm<sup>3</sup>, <em>p</em> = 0.02), focal anomalies at electroencephalography (EEG) (63.6 <em>vs.</em> 23.8 %, <em>p</em> = 0.03), and pathological findings at MRI (72.7 % <em>vs.</em> 15.8 %, <em>p</em> value=0.004) compared to those affected by EV. cUS was not significantly altered in any of the enrolled infants. All infants with EV meningoencephalitis evaluated at 12–24 months and at 30–48 months were normal. Two out of the 7 infants with HPeV meningoencephalitis showed some concerns in gross motor (1/7, 14.3 %) or in problem solving (1/7, 14.3 %) function at 30–48 months of age.</p></div><div><h3>Conclusions</h3><p>In our cohort, neonates infected by HPeV had more severe clinical manifestations, more alterations at brain MRI, and some signs of long-term neurodevelopmental delay. Our data highlight the heterogeneity of manifestations in infants with EV or HPeV meningoencephalitis, and the need for long-term follow-up of those infected by HPeV in the neonatal period.</p></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S138665322400026X/pdfft?md5=f94e9dc1b2b8d099a2a392b433339d79&pid=1-s2.0-S138665322400026X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140053770","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 : 2024-03-03DOI: 10.1016/j.jcv.2024.105663
Adeline Baron , Alice Moisan , Guillemette Unal , Véronique Lemée , Manuel Etienne , Jean-Christophe Plantier
In the last few years, many manufacturers have developed new kits for plasma HIV-1 RNA quantification. Recently, a solution consisting of the ELITe InGenius® instrument and the HIV1 ELITe MGB®kit has been commercialized worldwide. Our aim was to compare its clinical performance with the Aptima® HIV-1 Quant Dx kit by Hologic, on a panel of HIV-1 group M circulating variants, representative of viral load levels found during the pre- and post-treatment follow-up of patients. The linearity was evaluated on the AcroMetrix® HIV-1 Panel. Clinical specificity was evaluated on 100 plasma samples negative for HIV; and clinical sensitivity and sequential follow-up were evaluated on 166 HIV-1 positive plasma samples from 126 patients. The linearity data showed a difference obtained for each point of less than 0.2 Log cp/mL. No amplification was found for the 100 HIV negative clinical specimens. The overall agreement between the two kits was 83.7 %; the differences corresponded to a slightly higher detection for the Aptima kit (with more samples detected below the lower limit of quantification). A Bland & Altman analysis of the quantifiable samples showed a mean difference of −0.05 Log and Spearman's coefficient was 0.975. Only six samples presented discrepancies (above 0.5 Log), but these differences were overall similar between the two kits. Our study has shown that the HIV1 ELITe MGB® Kit can be successfully used for the monitoring of patients infected with various epidemic HIV-1 strains, and for the precise quantification of the viral load.
{"title":"Evaluation of the ELITechGroup solution for plasma HIV-1 RNA quantification","authors":"Adeline Baron , Alice Moisan , Guillemette Unal , Véronique Lemée , Manuel Etienne , Jean-Christophe Plantier","doi":"10.1016/j.jcv.2024.105663","DOIUrl":"10.1016/j.jcv.2024.105663","url":null,"abstract":"<div><p>In the last few years, many manufacturers have developed new kits for plasma HIV-1 RNA quantification. Recently, a solution consisting of the ELITe InGenius® instrument and the HIV1 ELITe MGB®kit has been commercialized worldwide. Our aim was to compare its clinical performance with the Aptima® HIV-1 Quant Dx kit by Hologic, on a panel of HIV-1 group M circulating variants, representative of viral load levels found during the pre- and post-treatment follow-up of patients. The linearity was evaluated on the AcroMetrix® HIV-1 Panel. Clinical specificity was evaluated on 100 plasma samples negative for HIV; and clinical sensitivity and sequential follow-up were evaluated on 166 HIV-1 positive plasma samples from 126 patients. The linearity data showed a difference obtained for each point of less than 0.2 Log cp/mL. No amplification was found for the 100 HIV negative clinical specimens. The overall agreement between the two kits was 83.7 %; the differences corresponded to a slightly higher detection for the Aptima kit (with more samples detected below the lower limit of quantification). A Bland & Altman analysis of the quantifiable samples showed a mean difference of −0.05 Log and Spearman's coefficient was 0.975. Only six samples presented discrepancies (above 0.5 Log), but these differences were overall similar between the two kits. Our study has shown that the HIV1 ELITe MGB® Kit can be successfully used for the monitoring of patients infected with various epidemic HIV-1 strains, and for the precise quantification of the viral load.</p></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1386653224000258/pdfft?md5=38f71e94941f74678398f058f65734eb&pid=1-s2.0-S1386653224000258-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140044273","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 : 2024-02-28DOI: 10.1016/j.jcv.2024.105661
Daniela Sieghart , Claudia A. Hana , Caroline Dürrschmid , Leonhard X. Heinz , Helmuth Haslacher , Markus Zlesak , Giulia Piccini , Alessandro Manenti , Emanuele Montomoli , Anselm Jorda , Clemens Fedrizzi , Timothy Hasenoehrl , Andrej Zdravkovic , Karolina Anderle , Ursula Wiedermann , Susanne Drapalik , Helmut Steinbrecher , Felix Bergmann , Christa Firbas , Galateja Jordakieva , Helga Radner
Background
Various SARS-CoV-2 variants of concerns (VOCs) characterized by higher transmissibility and immune evasion have emerged. Despite reduced vaccine efficacy against VOCs, currently available vaccines provide protection. Population-based evidence on the humoral immune response after booster vaccination is crucial to guide future vaccination strategies and in preparation for imminent COVID-19 waves.
Methods
This multicenter, population-based cohort study included 4697 individuals ≥18 years of age who received a booster vaccination. Antibody levels against SARS-CoV-2 receptor binding domain (RBD) and neutralizing antibodies against wild-type (WT) virus and Omicron variants were assessed at baseline (day of booster vaccination) and after four weeks. Safety was evaluated daily within the first week using a participant-completed electronic diary. Antibody levels were compared across different vaccination strategies, taking into account individual host factors.
Results
Our main model including 3838 participants revealed that individuals who received a booster with mRNA-1273 compared to BNT162b2 vaccine had a significantly higher increase (95 %CI) in anti-RBD-antibody levels (37,707 BAU/mL [34,575–40,839] vs. 27,176 BAU/mL [26,265–28,087]), and of neutralization levels against WT (1,681 [1490–1872] vs. 1141 [1004–1278] and Omicron variant (422 [369–474] vs. 329 [284–374]). Neutralizing antibody titres highly correlated with anti-RBD antibodies, with neutralizing capacity 4.4 fold higher against WT compared to Omicron. No differences in safety were found between the two booster vaccines.
Conclusion
Our study underlines the superiority of a booster vaccination with mRNA-1273, independent of the primary vaccination and therefore provides guidance on the vaccination strategy.
{"title":"Immunogenicity and safety of COVID-19 booster vaccination: A population-based clinical trial to identify the best vaccination strategy","authors":"Daniela Sieghart , Claudia A. Hana , Caroline Dürrschmid , Leonhard X. Heinz , Helmuth Haslacher , Markus Zlesak , Giulia Piccini , Alessandro Manenti , Emanuele Montomoli , Anselm Jorda , Clemens Fedrizzi , Timothy Hasenoehrl , Andrej Zdravkovic , Karolina Anderle , Ursula Wiedermann , Susanne Drapalik , Helmut Steinbrecher , Felix Bergmann , Christa Firbas , Galateja Jordakieva , Helga Radner","doi":"10.1016/j.jcv.2024.105661","DOIUrl":"10.1016/j.jcv.2024.105661","url":null,"abstract":"<div><h3>Background</h3><p>Various SARS-CoV-2 variants of concerns (VOCs) characterized by higher transmissibility and immune evasion have emerged. Despite reduced vaccine efficacy against VOCs, currently available vaccines provide protection. Population-based evidence on the humoral immune response after booster vaccination is crucial to guide future vaccination strategies and in preparation for imminent COVID-19 waves.</p></div><div><h3>Methods</h3><p>This multicenter, population-based cohort study included 4697 individuals ≥18 years of age who received a booster vaccination. Antibody levels against SARS-CoV-2 receptor binding domain (RBD) and neutralizing antibodies against wild-type (WT) virus and Omicron variants were assessed at baseline (day of booster vaccination) and after four weeks. Safety was evaluated daily within the first week using a participant-completed electronic diary. Antibody levels were compared across different vaccination strategies, taking into account individual host factors.</p></div><div><h3>Results</h3><p>Our main model including 3838 participants revealed that individuals who received a booster with mRNA-1273 compared to BNT162b2 vaccine had a significantly higher increase (95 %CI) in anti-RBD-antibody levels (37,707 BAU/mL [34,575–40,839] vs. 27,176 BAU/mL [26,265–28,087]), and of neutralization levels against WT (1,681 [1490–1872] vs. 1141 [1004–1278] and Omicron variant (422 [369–474] vs. 329 [284–374]). Neutralizing antibody titres highly correlated with anti-RBD antibodies, with neutralizing capacity 4.4 fold higher against WT compared to Omicron. No differences in safety were found between the two booster vaccines.</p></div><div><h3>Conclusion</h3><p>Our study underlines the superiority of a booster vaccination with mRNA-1273, independent of the primary vaccination and therefore provides guidance on the vaccination strategy.</p></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140001317","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 : 2024-02-28DOI: 10.1016/j.jcv.2024.105662
Yanhong Sun, Wenjian Nie, Dandan Tian, Qing Ye
Monkeypox virus (MPXV) is responsible for causing a zoonotic disease called monkeypox (mpox), which sporadically infects humans in West and Central Africa. It first infected humans in 1970 and, along with the variola virus, belongs to the genus Orthopoxvirus in the poxvirus family. Since the World Health Organization declared the MPXV outbreak a "Public Health Emergency of International Concern" on July 23, 2022, the number of infected patients has increased dramatically. To control this epidemic and address this previously neglected disease, MPXV needs to be better understood and reevaluated. In this review, we cover recent research on MPXV, including its genomic and pathogenic characteristics, transmission, mutations and mechanisms, clinical characteristics, epidemiology, laboratory diagnosis, and treatment measures, as well as prevention of MPXV infection in light of the 2022 and 2023 global outbreaks. The 2022 MPXV outbreak has been primarily associated with close intimate contact, including sexual activity, with most cases diagnosed among men who have sex with men. The incubation period of MPXV infection usually lasts from 6 to 13 days, and symptoms include fever, muscle pains, headache, swollen lymph nodes, and a characteristic painful rash, including several stages, such as macules, papules, blisters, pustules, scabs, and scab shedding involving the genitals and anus. Polymerase chain reaction (PCR) is usually used to detect MPXV in skin lesion material. Treatment includes supportive care, antivirals, and intravenous vaccinia immune globulin. Smallpox vaccines have been designed with four givens emergency approval for use against MPXV infection.
{"title":"Human monkeypox virus: Epidemiologic review and research progress in diagnosis and treatment","authors":"Yanhong Sun, Wenjian Nie, Dandan Tian, Qing Ye","doi":"10.1016/j.jcv.2024.105662","DOIUrl":"10.1016/j.jcv.2024.105662","url":null,"abstract":"<div><p>Monkeypox virus (MPXV) is responsible for causing a zoonotic disease called monkeypox (mpox), which sporadically infects humans in West and Central Africa. It first infected humans in 1970 and, along with the variola virus, belongs to the genus <em>Orthopoxvirus</em> in the poxvirus family. Since the World Health Organization declared the MPXV outbreak a \"Public Health Emergency of International Concern\" on July 23, 2022, the number of infected patients has increased dramatically. To control this epidemic and address this previously neglected disease, MPXV needs to be better understood and reevaluated. In this review, we cover recent research on MPXV, including its genomic and pathogenic characteristics, transmission, mutations and mechanisms, clinical characteristics, epidemiology, laboratory diagnosis, and treatment measures, as well as prevention of MPXV infection in light of the 2022 and 2023 global outbreaks. The 2022 MPXV outbreak has been primarily associated with close intimate contact, including sexual activity, with most cases diagnosed among men who have sex with men. The incubation period of MPXV infection usually lasts from 6 to 13 days, and symptoms include fever, muscle pains, headache, swollen lymph nodes, and a characteristic painful rash, including several stages, such as macules, papules, blisters, pustules, scabs, and scab shedding involving the genitals and anus. Polymerase chain reaction (PCR) is usually used to detect MPXV in skin lesion material. Treatment includes supportive care, antivirals, and intravenous vaccinia immune globulin. Smallpox vaccines have been designed with four givens emergency approval for use against MPXV infection.</p></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140001747","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}
{"title":"Corrigendum to “First international proficiency study on human papillomavirus testing in cervical cancer screening” [J Clin Virol. 2023 Oct;167:105581]","authors":"Emel Yilmaz , Carina Eklund , Camilla Lagheden , Karin Dahlin Robertsson , Marina Lilja , Miriam Elfström , Laila Sara Arroyo Mühr , Joakim Dillner","doi":"10.1016/j.jcv.2024.105660","DOIUrl":"10.1016/j.jcv.2024.105660","url":null,"abstract":"","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1386653224000222/pdfft?md5=de384e563a1ef2871e8d44ace0002989&pid=1-s2.0-S1386653224000222-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139983046","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 : 2024-02-23DOI: 10.1016/j.jcv.2024.105658
Merle M. Böhmer , Viola C. Haring , Barbara Schmidt , Franziska S. Saller , Liza Coyer , Lidia Chitimia-Dobler , Gerhard Dobler , Dennis Tappe , Andrea Bonakdar , Arnt Ebinger , Gertrud Knoll , Lisa Eidenschink , Anette Rohrhofer , Hans Helmut Niller , Katharina Katz , Philip Starcky , Martin Beer , Rainer G. Ulrich , Dennis Rubbenstroth , Markus Bauswein
Background
Zoonotic Borna disease virus 1 (BoDV-1) causes fatal encephalitis in humans and animals. Subsequent to the detection of two paediatric cases in a Bavarian municipality in Germany within three years, we conducted an interdisciplinary One Health investigation. We aimed to explore seroprevalence in a local human population with a risk for BoDV-1 exposure as well as viral presence in environmental samples from local sites and BoDV-1 prevalence within the local small mammal population and its natural reservoir, the bicoloured white-toothed shrew (Crocidura leucodon).
Methods
The municipality's adult residents participated in an anonymised sero-epidemiological study. Potential risk factors and clinical symptoms were assessed by an electronic questionnaire. Small mammals, environmental samples and ticks from the municipality were tested for BoDV-1-RNA. Shrew-derived BoDV-1-sequences together with sequences of the two human cases were phylogenetically analysed.
Results
In total, 679 citizens participated (response: 41 %), of whom 38 % reported shrews in their living environment and 19 % direct shrew contact. No anti-BoDV-1 antibodies were detected in human samples. BoDV-1-RNA was also undetectable in 38 environmental samples and 336 ticks. Of 220 collected shrews, twelve of 40 C. leucodon (30%) tested BoDV-1-RNA-positive. BoDV-1-sequences from the previously diagnosed two paediatric patients belonged to two different subclades, that were also present in shrews from the municipality.
Interpretation
Our data support the interpretation that human BoDV-1 infections are rare even in endemic areas and primarily manifest as severe encephalitis. Sequence analysis linked both previous paediatric human infections to the local shrew population, but indicated independent infection sources.
Funding
The project was partly financed by funds of the German Federal Ministry of Education and Research (grant numbers: 01KI2005A, 01KI2005C, 01KI1722A, 01KI1722C, 01KI2002 to MaBe, DR, RGU, DT, BS) as well as by the ReForM-A programme of the University Hospital Regensburg (to MaBa) and by funds of the Bavarian State Ministry of Health, Care and Prevention, project “Zoonotic Bornavirus Focal Point Bavaria – ZooBoFo” (to MaBa, MaBe, BS, MMB, DR, PS, RGU).
{"title":"One Health in action: Investigation of the first detected local cluster of fatal borna disease virus 1 (BoDV-1) encephalitis, Germany 2022","authors":"Merle M. Böhmer , Viola C. Haring , Barbara Schmidt , Franziska S. Saller , Liza Coyer , Lidia Chitimia-Dobler , Gerhard Dobler , Dennis Tappe , Andrea Bonakdar , Arnt Ebinger , Gertrud Knoll , Lisa Eidenschink , Anette Rohrhofer , Hans Helmut Niller , Katharina Katz , Philip Starcky , Martin Beer , Rainer G. Ulrich , Dennis Rubbenstroth , Markus Bauswein","doi":"10.1016/j.jcv.2024.105658","DOIUrl":"10.1016/j.jcv.2024.105658","url":null,"abstract":"<div><h3>Background</h3><p>Zoonotic Borna disease virus 1 (BoDV-1) causes fatal encephalitis in humans and animals. Subsequent to the detection of two paediatric cases in a Bavarian municipality in Germany within three years, we conducted an interdisciplinary One Health investigation. We aimed to explore seroprevalence in a local human population with a risk for BoDV-1 exposure as well as viral presence in environmental samples from local sites and BoDV-1 prevalence within the local small mammal population and its natural reservoir, the bicoloured white-toothed shrew (<em>Crocidura leucodon</em>).</p></div><div><h3>Methods</h3><p>The municipality's adult residents participated in an anonymised sero-epidemiological study. Potential risk factors and clinical symptoms were assessed by an electronic questionnaire. Small mammals, environmental samples and ticks from the municipality were tested for BoDV-1-RNA. Shrew-derived BoDV-1-sequences together with sequences of the two human cases were phylogenetically analysed.</p></div><div><h3>Results</h3><p>In total, 679 citizens participated (response: 41 %), of whom 38 % reported shrews in their living environment and 19 % direct shrew contact. No anti-BoDV-1 antibodies were detected in human samples. BoDV-1-RNA was also undetectable in 38 environmental samples and 336 ticks. Of 220 collected shrews, twelve of 40 <em>C. leucodon</em> (30%) tested BoDV-1-RNA-positive. BoDV-1-sequences from the previously diagnosed two paediatric patients belonged to two different subclades, that were also present in shrews from the municipality.</p></div><div><h3>Interpretation</h3><p>Our data support the interpretation that human BoDV-1 infections are rare even in endemic areas and primarily manifest as severe encephalitis. Sequence analysis linked both previous paediatric human infections to the local shrew population, but indicated independent infection sources.</p></div><div><h3>Funding</h3><p>The project was partly financed by funds of the German Federal Ministry of Education and Research (grant numbers: 01KI2005A, 01KI2005C, 01KI1722A, 01KI1722C, 01KI2002 to MaBe, DR, RGU, DT, BS) as well as by the ReForM-A programme of the University Hospital Regensburg (to MaBa) and by funds of the Bavarian State Ministry of Health, Care and Prevention, project “Zoonotic Bornavirus Focal Point Bavaria – ZooBoFo” (to MaBa, MaBe, BS, MMB, DR, PS, RGU).</p></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1386653224000209/pdfft?md5=33d18153498b1f646b5696b76a9dfa2a&pid=1-s2.0-S1386653224000209-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139948196","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 : 2024-02-23DOI: 10.1016/j.jcv.2024.105659
Gregory L. Damhorst , Kaleb McLendon , Evelyn Morales , Zianya M. Solis , Eric Fitts , Heather B. Bowers , Courtney Sabino , Julie Sullivan , Morgan Greenleaf , John D. Roback , Jonathan A. Colasanti , Anandi N. Sheth , Boghuma K. Titanji , Greg S. Martin , Leda Bassit , Wilbur A. Lam , Anuradha Rao
Anorectal and oropharyngeal exposures are implicated in sexual transmission of mpox, but authorized assays in the United States are only validated with cutaneous lesion swabs. Diagnostic assays for anorectal and oropharyngeal swabs are needed to address potential future outbreaks. The Cepheid Xpert® Mpox is the first point-of-care assay to receive FDA emergency use authorization in the United States and would be a valuable tool for evaluating these sample types. Our exploratory study demonstrates 100 % positive agreement with our in-house PCR assay for natural positive anorectal and oropharyngeal specimens and 92 % sensitivity with low-positive spiked specimens. The Xpert® assay detected viral DNA in specimens not detected by our reference PCR assay from four participants with mpox DNA at other sites, suggesting it may be more sensitive at low viral loads. In conclusion, the validation of the Xpert® for oropharyngeal and anorectal sample types can be rapidly achieved if clinical need returns and prospective samples become available.
肛门直肠和口咽接触与水痘的性传播有牵连,但美国授权的检测方法只能通过皮肤病变拭子进行验证。需要对肛门直肠和口咽拭子进行诊断检测,以应对未来可能爆发的疫情。Cepheid Xpert® Mpox 是美国第一个获得 FDA 紧急使用授权的护理点检测方法,将成为评估这些样本类型的重要工具。我们的探索性研究表明,对于自然阳性的肛门直肠和口咽标本,Xpert® Mpox 与我们的内部 PCR 检测法的阳性率为 100%,对于低阳性的加标标本,灵敏度为 92%。Xpert® 检测法在四名在其他部位感染了 mpox DNA 的参与者的标本中检测到了我们的参考 PCR 检测法检测不到的病毒 DNA,这表明该检测法对低病毒载量可能更敏感。总之,如果临床需要得到恢复,并且可以获得前瞻性样本,Xpert® 就能很快通过口咽部和肛门直肠样本类型的验证。
{"title":"Performance of the Xpert™ Mpox PCR assay with oropharyngeal, anorectal, and cutaneous lesion swab specimens","authors":"Gregory L. Damhorst , Kaleb McLendon , Evelyn Morales , Zianya M. Solis , Eric Fitts , Heather B. Bowers , Courtney Sabino , Julie Sullivan , Morgan Greenleaf , John D. Roback , Jonathan A. Colasanti , Anandi N. Sheth , Boghuma K. Titanji , Greg S. Martin , Leda Bassit , Wilbur A. Lam , Anuradha Rao","doi":"10.1016/j.jcv.2024.105659","DOIUrl":"10.1016/j.jcv.2024.105659","url":null,"abstract":"<div><p>Anorectal and oropharyngeal exposures are implicated in sexual transmission of mpox, but authorized assays in the United States are only validated with cutaneous lesion swabs. Diagnostic assays for anorectal and oropharyngeal swabs are needed to address potential future outbreaks. The Cepheid Xpert® Mpox is the first point-of-care assay to receive FDA emergency use authorization in the United States and would be a valuable tool for evaluating these sample types. Our exploratory study demonstrates 100 % positive agreement with our in-house PCR assay for natural positive anorectal and oropharyngeal specimens and 92 % sensitivity with low-positive spiked specimens. The Xpert® assay detected viral DNA in specimens not detected by our reference PCR assay from four participants with mpox DNA at other sites, suggesting it may be more sensitive at low viral loads. In conclusion, the validation of the Xpert® for oropharyngeal and anorectal sample types can be rapidly achieved if clinical need returns and prospective samples become available.</p></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139948474","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 : 2024-02-20DOI: 10.1016/j.jcv.2024.105657
Jean Luc Prétet , Laila Sara Arroyo Mühr , Kate Cuschieri , María Dolores Fellner , Rita Mariel Correa , María Alejandra Picconi , Suzanne M. Garland , Gerald L. Murray , Monica Molano , Michael Peeters , Steven Van Gucht , Charlotte Lambrecht , Davy Vanden Broeck , Elizaveta Padalko , Marc Arbyn , Quentin Lepiller , Alice Brunier , Steffi Silling , Kristiane Søreng , Irene Kraus Christiansen , Joakim Dillner
Background
Some high-grade cervical lesions and cervical cancers (HSIL+) test negative for human papillomavirus (HPV). The HPV-negative fraction varies between 0.03 % and 15 % between different laboratories. Monitoring and extended re-analysis of HPV-negative HSIL+ could thus be helpful to monitor performance of HPV testing services. We aimed to a) provide a real-life example of a quality assurance (QA) program based on re-analysis of HPV-negative HSIL+ and b) develop international guidance for QA of HPV testing services based on standardized identification of apparently HPV-negative HSIL+ and extended re-analysis, either by the primary laboratory or by a national HPV reference laboratory (NRL).
Methods
There were 116 initially HPV-negative cervical specimens (31 histopathology specimens and 85 liquid-based cytology samples) sent to the Swedish HPV Reference Laboratory for re-testing. Based on the results, an international QA guidance was developed through an iterative consensus process.
Result
Standard PCR testing detected HPV in 55.2 % (64/116) of initially “HPV-negative” samples. Whole genome sequencing of PCR-negative samples identified HPV in an additional 7 samples (overall 61.2 % HPV positivity). Reasons for failure to detect HPV in an HSIL+ lesion are listed and guidance to identify cases for extended re-testing, including which information should be included when referring samples to an NRL are presented.
Conclusion
Monitoring the proportion of and reasons for failure to detect HPV in HSIL+ will help support high performance and quality improvement of HPV testing services. We encourage implementation of QA strategies based on re-analysis of “HPV negative” HSIL+ samples.
{"title":"Human papillomavirus negative high grade cervical lesions and cancers: Suggested guidance for HPV testing quality assurance","authors":"Jean Luc Prétet , Laila Sara Arroyo Mühr , Kate Cuschieri , María Dolores Fellner , Rita Mariel Correa , María Alejandra Picconi , Suzanne M. Garland , Gerald L. Murray , Monica Molano , Michael Peeters , Steven Van Gucht , Charlotte Lambrecht , Davy Vanden Broeck , Elizaveta Padalko , Marc Arbyn , Quentin Lepiller , Alice Brunier , Steffi Silling , Kristiane Søreng , Irene Kraus Christiansen , Joakim Dillner","doi":"10.1016/j.jcv.2024.105657","DOIUrl":"10.1016/j.jcv.2024.105657","url":null,"abstract":"<div><h3>Background</h3><p>Some high-grade cervical lesions and cervical cancers (HSIL+) test negative for human papillomavirus (HPV). The HPV-negative fraction varies between 0.03 % and 15 % between different laboratories. Monitoring and extended re-analysis of HPV-negative HSIL+ could thus be helpful to monitor performance of HPV testing services. We aimed to a) provide a real-life example of a quality assurance (QA) program based on re-analysis of HPV-negative HSIL+ and b) develop international guidance for QA of HPV testing services based on standardized identification of apparently HPV-negative HSIL+ and extended re-analysis, either by the primary laboratory or by a national HPV reference laboratory (NRL).</p></div><div><h3>Methods</h3><p>There were 116 initially HPV-negative cervical specimens (31 histopathology specimens and 85 liquid-based cytology samples) sent to the Swedish HPV Reference Laboratory for re-testing. Based on the results, an international QA guidance was developed through an iterative consensus process.</p></div><div><h3>Result</h3><p>Standard PCR testing detected HPV in 55.2 % (64/116) of initially “HPV-negative” samples. Whole genome sequencing of PCR-negative samples identified HPV in an additional 7 samples (overall 61.2 % HPV positivity). Reasons for failure to detect HPV in an HSIL+ lesion are listed and guidance to identify cases for extended re-testing, including which information should be included when referring samples to an NRL are presented.</p></div><div><h3>Conclusion</h3><p>Monitoring the proportion of and reasons for failure to detect HPV in HSIL+ will help support high performance and quality improvement of HPV testing services. We encourage implementation of QA strategies based on re-analysis of “HPV negative” HSIL+ samples.</p></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1386653224000192/pdfft?md5=e9801bdb748e0efe4cc4bd6ddb25c7a4&pid=1-s2.0-S1386653224000192-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139924344","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}
BK Polyomavirus is of particular concern for kidney transplant recipients, due to their immunosuppression. This problem is exacerbated by the high effectiveness of antirejection therapies, which also compromise the organism's ability to fight viral infections. The long-term risk is loss of graft function through BKPyV-associated nephropathy (BKPyVAN). The assessment of host immunity and its link to the control of viral infections is a major challenge.
In terms of humoral immunity, researchers have highlighted the prognostic value of the pre-transplantation anti-BKPyV immunoglobulin G titer. However, humoral immunity alone does not guarantee viral clearance, and the correlation between the humoral response and the time course of the infection remains weak.
In contrast, cellular immunity variables appear to be more closely associated with viral clearance, given that the cellular immune response to the kidney transplant is the main target of immunosuppressive treatments in recipients. However, the assessment of the cellular immune response to BK Polyomavirus is complex, and many details still need to be characterized. Here, we review the current state of knowledge about BKPyV cellular immunity, as well as the difficulties that may be encountered in studying it in kidney transplant recipient. This is an essential area of research for optimizing the management of transplant recipients and minimizing the risks associated with insidious BKPyV disease.
{"title":"The value and complexity of studying cellular immunity against BK Polyomavirus in kidney transplant recipients","authors":"Aurélien Aubry , Baptiste Demey , Sandrine Castelain , François Helle , Etienne Brochot","doi":"10.1016/j.jcv.2024.105656","DOIUrl":"10.1016/j.jcv.2024.105656","url":null,"abstract":"<div><p>BK Polyomavirus is of particular concern for kidney transplant recipients, due to their immunosuppression. This problem is exacerbated by the high effectiveness of antirejection therapies, which also compromise the organism's ability to fight viral infections. The long-term risk is loss of graft function through BKPyV-associated nephropathy (BKPyVAN). The assessment of host immunity and its link to the control of viral infections is a major challenge.</p><p>In terms of humoral immunity, researchers have highlighted the prognostic value of the pre-transplantation anti-BKPyV immunoglobulin G titer. However, humoral immunity alone does not guarantee viral clearance, and the correlation between the humoral response and the time course of the infection remains weak.</p><p>In contrast, cellular immunity variables appear to be more closely associated with viral clearance, given that the cellular immune response to the kidney transplant is the main target of immunosuppressive treatments in recipients. However, the assessment of the cellular immune response to BK Polyomavirus is complex, and many details still need to be characterized. Here, we review the current state of knowledge about BKPyV cellular immunity, as well as the difficulties that may be encountered in studying it in kidney transplant recipient. This is an essential area of research for optimizing the management of transplant recipients and minimizing the risks associated with insidious BKPyV disease.</p></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1386653224000180/pdfft?md5=0873b08708568eea289d76a04a7428ab&pid=1-s2.0-S1386653224000180-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139924160","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 : 2024-02-15DOI: 10.1016/j.jcv.2024.105654
Matthias E. Futschik , Samuel Johnson , Elena Turek , David Chapman , Simon Carr , Zareen Thorlu-Bangura , Paul E. Klapper , Malur Sudhanva , Andrew Dodgson , Joanna R. Cole-Hamilton , Nick Germanacos , Raghavendran Kulasegaran-Shylini , Edward Blandford , Sarah Tunkel , Timothy Peto , Susan Hopkins , Tom Fowler
Background
The advent of lateral flow devices (LFDs) for SARS-CoV-2 detection enabled widespread use of rapid self-tests during the pandemic. While self-testing using LFDs is now common, whether self-testing provides comparable performance to professional testing was a key question that remained important for pandemic planning.
Methods
Three prospective multi-centre studies were conducted to compare the performance of self- and professional testing using LFDs. Participants tested themselves or were tested by trained (professional) testers at community testing sites in the UK. Corresponding qRT-PCR test results served as reference standard. The performance of Innova, Orient Gene and SureScreen LFDs by users (self) and professional testers was assessed in terms of sensitivity, specificity, and kit failure (void) rates. Impact of age, sex and symptom status was analysed using logistic regression modelling.
Results
16,617 participants provided paired tests, of which 15,418 were included in the analysis. Self-testing with Innova, Orient Gene or SureScreen LFDs achieved sensitivities of 50 %, 53 % or 72 %, respectively, compared to qRT-PCR. Self and professional LFD testing showed no statistically different sensitivity with respect to corresponding qRT-PCR testing. Specificity was consistently equal to or higher than 99 %. Sex and age had no or only marginal impact on LFD performance while sensitivity was significantly higher for symptomatic individuals. Sensitivity of LFDs increased strongly to up to 90 % with higher levels of viral RNA measured by qRT-PCR.
Conclusions
Our results support SARS-CoV-2 self-testing with LFDs, especially for the detection of individuals whose qRT-PCR tests showed high viral concentrations.
{"title":"Rapid antigen testing for SARS-CoV-2 by lateral flow assay: A field evaluation of self- and professional testing at UK community testing sites","authors":"Matthias E. Futschik , Samuel Johnson , Elena Turek , David Chapman , Simon Carr , Zareen Thorlu-Bangura , Paul E. Klapper , Malur Sudhanva , Andrew Dodgson , Joanna R. Cole-Hamilton , Nick Germanacos , Raghavendran Kulasegaran-Shylini , Edward Blandford , Sarah Tunkel , Timothy Peto , Susan Hopkins , Tom Fowler","doi":"10.1016/j.jcv.2024.105654","DOIUrl":"10.1016/j.jcv.2024.105654","url":null,"abstract":"<div><h3>Background</h3><p>The advent of lateral flow devices (LFDs) for SARS-CoV-2 detection enabled widespread use of rapid self-tests during the pandemic. While self-testing using LFDs is now common, whether self-testing provides comparable performance to professional testing was a key question that remained important for pandemic planning.</p></div><div><h3>Methods</h3><p>Three prospective multi-centre studies were conducted to compare the performance of self- and professional testing using LFDs. Participants tested themselves or were tested by trained (professional) testers at community testing sites in the UK. Corresponding qRT-PCR test results served as reference standard. The performance of Innova, Orient Gene and SureScreen LFDs by users (self) and professional testers was assessed in terms of sensitivity, specificity, and kit failure (void) rates. Impact of age, sex and symptom status was analysed using logistic regression modelling.</p></div><div><h3>Results</h3><p>16,617 participants provided paired tests, of which 15,418 were included in the analysis. Self-testing with Innova, Orient Gene or SureScreen LFDs achieved sensitivities of 50 %, 53 % or 72 %, respectively, compared to qRT-PCR. Self and professional LFD testing showed no statistically different sensitivity with respect to corresponding qRT-PCR testing. Specificity was consistently equal to or higher than 99 %. Sex and age had no or only marginal impact on LFD performance while sensitivity was significantly higher for symptomatic individuals. Sensitivity of LFDs increased strongly to up to 90 % with higher levels of viral RNA measured by qRT-PCR.</p></div><div><h3>Conclusions</h3><p>Our results support SARS-CoV-2 self-testing with LFDs, especially for the detection of individuals whose qRT-PCR tests showed high viral concentrations.</p></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":null,"pages":null},"PeriodicalIF":8.8,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1386653224000167/pdfft?md5=daa73e614638408a001b9967885ab74a&pid=1-s2.0-S1386653224000167-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139892936","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}