Pub Date : 2025-11-25DOI: 10.1016/j.jcv.2025.105890
María Elena Ceballos , Cinthya Ruiz-Tagle , Angélica Domínguez de Landa , Manuel A. Espinoza , Marcela Ferrés , María Elvira Balcells , Alejandro Afani , Felipe Castañeda , Carlos Palma , Carlos Gallo , Olga López , Yoselyn Castillo , Francisco Salvador , Elizabeth Barthel , Francisco Zamora , Martín Lasso , Michel Serri , Elisabeth Daube , Nicolás Rodríguez , Loreto Rojas
Background
Human Immunodeficiency Virus (HIV) morbi-mortality and transmission have decreased due to antiretroviral therapy (ART). However, treatment failure still occurs when acquiring a strain with resistance mutations. HIV transmitted drug resistance (TDR) is increasing worldwide, and its prevalence in Chile was estimated at 10.4 % in 2018. We aimed to determine the prevalence of TDR and, its associated mutations to evaluate the need to incorporate genotyping studies in ART-naïve people living with HIV in Chile.
Methods
Cross-sectional study conducted in eleven health centers and seven regions in Chile. Participants were ≥ 18 years with a recent (≤12 months) HIV diagnosis, without previous ART exposure. Genotyping of the reverse transcriptase, protease, and integrase was performed using nested polymerase chain reaction followed by Sanger sequencing.
Results
Between February 2023 and May 2024, 168 participants were recruited. The mean age was 35.9 years (range 18–78), 89.3 % were Chilean, and 84.5 % were male. TDR overall prevalence was 16.7 %, and the percentage of TDR by family was 3 % for nucleoside reverse transcriptase inhibitors (NRTIs), 7.1 % for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 0.6 % for protease inhibitors (PIs) and 8.9 % for integrase strand transfer inhibitors (INSTIs). TDR for first-generation INSTIs was 11.9 % and 1.2 % for second-generation INSTIs.
Conclusion
TDR prevalence in Chile has increased and main affected families are first-generation INSTIs and NNRTIs. This result highlights the relevance of initiating ART with second-generation INSTIs or PIs, or incorporating baseline genotyping studies when initiating ART with NNRTIs or first-generation INSTIs.
{"title":"High levels of transmitted drug resistance to INSTIs and NNRTIs in Chile: A nationwide prevalence study","authors":"María Elena Ceballos , Cinthya Ruiz-Tagle , Angélica Domínguez de Landa , Manuel A. Espinoza , Marcela Ferrés , María Elvira Balcells , Alejandro Afani , Felipe Castañeda , Carlos Palma , Carlos Gallo , Olga López , Yoselyn Castillo , Francisco Salvador , Elizabeth Barthel , Francisco Zamora , Martín Lasso , Michel Serri , Elisabeth Daube , Nicolás Rodríguez , Loreto Rojas","doi":"10.1016/j.jcv.2025.105890","DOIUrl":"10.1016/j.jcv.2025.105890","url":null,"abstract":"<div><h3>Background</h3><div>Human Immunodeficiency Virus (HIV) morbi-mortality and transmission have decreased due to antiretroviral therapy (ART). However, treatment failure still occurs when acquiring a strain with resistance mutations. HIV transmitted drug resistance (TDR) is increasing worldwide, and its prevalence in Chile was estimated at 10.4 % in 2018. We aimed to determine the prevalence of TDR and, its associated mutations to evaluate the need to incorporate genotyping studies in ART-naïve people living with HIV in Chile.</div></div><div><h3>Methods</h3><div>Cross-sectional study conducted in eleven health centers and seven regions in Chile. Participants were ≥ 18 years with a recent (≤12 months) HIV diagnosis, without previous ART exposure. Genotyping of the reverse transcriptase, protease, and integrase was performed using nested polymerase chain reaction followed by Sanger sequencing.</div></div><div><h3>Results</h3><div>Between February 2023 and May 2024, 168 participants were recruited. The mean age was 35.9 years (range 18–78), 89.3 % were Chilean, and 84.5 % were male. TDR overall prevalence was 16.7 %, and the percentage of TDR by family was 3 % for nucleoside reverse transcriptase inhibitors (NRTIs), 7.1 % for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 0.6 % for protease inhibitors (PIs) and 8.9 % for integrase strand transfer inhibitors (INSTIs). TDR for first-generation INSTIs was 11.9 % and 1.2 % for second-generation INSTIs.</div></div><div><h3>Conclusion</h3><div>TDR prevalence in Chile has increased and main affected families are first-generation INSTIs and NNRTIs. This result highlights the relevance of initiating ART with second-generation INSTIs or PIs, or incorporating baseline genotyping studies when initiating ART with NNRTIs or first-generation INSTIs.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"182 ","pages":"Article 105890"},"PeriodicalIF":3.4,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623056","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 : 2025-11-17DOI: 10.1016/j.jcv.2025.105889
Ana I. Cubas Atienzar , Christopher T. Williams , Yasemin Cosgun , Fatma Gonca Arslan , Hakan Hedef , Ilkay Bozkurt , Kevin S. Richards , Sian Summers , James Pitman , Shaun Ainsworth , Gino Miele , Cristina Leggio , William Nicholas , Hilary Bower , Benedict Gannon , Tom E. Fletcher , Gulay Korukluoglu , Thomas Edwards
Introduction
Crimean-Congo haemorrhagic fever (CCHF) is a viral haemorrhagic fever classed by the World Health Organization as a priority disease due to the lack of countermeasures. A point-of-care (POC) diagnostic test for rapid detection of positive cases to expedite patient management is not currently available but urgently needed.
Methods
We have developed an RT-qPCR assay to be used with the commercially available POC Genedrive® PCR platform enabling viral detection in serum with minimal sample preparation. The sensitivity and specificity of the novel assay in the Genedrive® was evaluated against the RealStar® CCHFV RT-qPCR Kit (Altona Diagnostics, Germany).
Results
The sensitivity and specificity in assay V1 (sample n = 150) were 94.4 % (95 % CI, 88.2–97.9) and 97.6 % (95 % CI, 87.1–99.9). For assay (n = 55) V2 sensitivity was 92.3 % (95 % CI, 74.9–99.5) and specificity was 100 % (95 % CI, 87.7–100).
Conclusions
This study supports the feasibility of diagnosing CCHF using POC RT-qPCR platforms, having the potential to reduce turnaround times, leading to improved clinical management.
{"title":"Development and evaluation of a novel RT-qPCR assay for detection of Crimean Congo haemorrhagic fever virus using the Genedrive® point-of-care platform","authors":"Ana I. Cubas Atienzar , Christopher T. Williams , Yasemin Cosgun , Fatma Gonca Arslan , Hakan Hedef , Ilkay Bozkurt , Kevin S. Richards , Sian Summers , James Pitman , Shaun Ainsworth , Gino Miele , Cristina Leggio , William Nicholas , Hilary Bower , Benedict Gannon , Tom E. Fletcher , Gulay Korukluoglu , Thomas Edwards","doi":"10.1016/j.jcv.2025.105889","DOIUrl":"10.1016/j.jcv.2025.105889","url":null,"abstract":"<div><h3>Introduction</h3><div>Crimean-Congo haemorrhagic fever (CCHF) is a viral haemorrhagic fever classed by the World Health Organization as a priority disease due to the lack of countermeasures. A point-of-care (POC) diagnostic test for rapid detection of positive cases to expedite patient management is not currently available but urgently needed.</div></div><div><h3>Methods</h3><div>We have developed an RT-qPCR assay to be used with the commercially available POC Genedrive® PCR platform enabling viral detection in serum with minimal sample preparation. The sensitivity and specificity of the novel assay in the Genedrive® was evaluated against the RealStar® CCHFV RT-qPCR Kit (Altona Diagnostics, Germany).</div></div><div><h3>Results</h3><div>The sensitivity and specificity in assay V1 (sample n = 150) were 94.4 % (95 % CI, 88.2–97.9) and 97.6 % (95 % CI, 87.1–99.9). For assay (n = 55) V2 sensitivity was 92.3 % (95 % CI, 74.9–99.5) and specificity was 100 % (95 % CI, 87.7–100).</div></div><div><h3>Conclusions</h3><div>This study supports the feasibility of diagnosing CCHF using POC RT-qPCR platforms, having the potential to reduce turnaround times, leading to improved clinical management.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"182 ","pages":"Article 105889"},"PeriodicalIF":3.4,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145594697","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 : 2025-11-14DOI: 10.1016/j.jcv.2025.105888
{"title":"2025 JCV reviewer recognition list and best reviewer awards","authors":"","doi":"10.1016/j.jcv.2025.105888","DOIUrl":"10.1016/j.jcv.2025.105888","url":null,"abstract":"","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"182 ","pages":"Article 105888"},"PeriodicalIF":3.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145819433","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 : 2025-11-10DOI: 10.1016/j.jcv.2025.105887
Kajal M. Patel, Erika A. Roloff, Paa K. Annobil, Pushker Raj
In response to the ongoing clade II mpox (formerly monkeypox) outbreak and the emergence and rapid spread of clade I mpox, public health laboratories need an effective testing method for identifying and monitoring mpox cases. The currently available assays are either labor-intensive, low-throughput, and/or unable to differentiate between clade I and clade II mpox, making them less than ideal for the current global public health emergency. Additionally, the lack of the non-variola Orthopoxvirus target in an mpox assay creates the chance of missing cases due to mutations within the clade-specific target genome regions. We present the development of a fully automated nucleic acid extraction and RT-PCR laboratory-developed test (LDT) for the detection of clade I mpox, clade II mpox, non-variola Orthopoxvirus, and RNase P. This automated assay runs on the Panther Fusion® System, which has an Open Access feature that allows LDTs to utilize the platform’s automated nucleic acid extraction, RT-PCR, and automated results generation features. To assess assay performance, 63 previously tested and 16 contrived specimens were tested. The mpox multiplex LDT demonstrated 100 % positive and negative agreement with the reference assays. Analytical sensitivity was 1.37 × 104 copies/mL for all targets, with amplification efficiencies of 103.8 %, 104.1 %, 96.2 %, and 98.9 % for mpox clade I, mpox clade II, NVO, and RNase P, respectively. The mpox multiplex LDT assay was successfully developed for high-throughput testing and can be rapidly adopted by other laboratories.
{"title":"A laboratory-developed test for the automated molecular detection of mpox clade I, mpox clade II, and non-variola Orthopoxvirus using the Panther Fusion® System","authors":"Kajal M. Patel, Erika A. Roloff, Paa K. Annobil, Pushker Raj","doi":"10.1016/j.jcv.2025.105887","DOIUrl":"10.1016/j.jcv.2025.105887","url":null,"abstract":"<div><div>In response to the ongoing clade II mpox (formerly monkeypox) outbreak and the emergence and rapid spread of clade I mpox, public health laboratories need an effective testing method for identifying and monitoring mpox cases. The currently available assays are either labor-intensive, low-throughput, and/or unable to differentiate between clade I and clade II mpox, making them less than ideal for the current global public health emergency. Additionally, the lack of the non-variola <em>Orthopoxvirus</em> target in an mpox assay creates the chance of missing cases due to mutations within the clade-specific target genome regions. We present the development of a fully automated nucleic acid extraction and RT-PCR laboratory-developed test (LDT) for the detection of clade I mpox, clade II mpox, non-variola <em>Orthopoxvirus</em>, and RNase P. This automated assay runs on the Panther Fusion® System, which has an Open Access feature that allows LDTs to utilize the platform’s automated nucleic acid extraction, RT-PCR, and automated results generation features. To assess assay performance, 63 previously tested and 16 contrived specimens were tested. The mpox multiplex LDT demonstrated 100 % positive and negative agreement with the reference assays. Analytical sensitivity was 1.37 × 104 copies/mL for all targets, with amplification efficiencies of 103.8 %, 104.1 %, 96.2 %, and 98.9 % for mpox clade I, mpox clade II, NVO, and RNase P, respectively. The mpox multiplex LDT assay was successfully developed for high-throughput testing and can be rapidly adopted by other laboratories.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"181 ","pages":"Article 105887"},"PeriodicalIF":3.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516876","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 : 2025-11-05DOI: 10.1016/j.jcv.2025.105885
Magnus Klinteskog , Anita Koskela von Sydow , Naveed Asghar , Magnus Johansson , Anna J. Henningsson , Martin Sundqvist , Per-Eric Lindgren , Lukas Frans Ocias
Objectives
We aimed to 1) detect tick-borne encephalitis virus (TBEV) RNA in clinical samples from patients with TBE, 2) characterise the detected RNA using Sanger sequencing, and 3) examine whether RNA detection was associated with disease severity.
Methods
We studied 137 patients infected and diagnosed with TBE between 2016 and 2021 in Region Örebro County and Region Värmland. Biobanked serum (n = 129) and cerebrospinal fluid (CSF; n = 110) samples were analysed. Serum was tested for TBEV-specific antibodies, and both serum and CSF for TBEV RNA using PCR. Following nested PCR, the 5′ non-coding region (5′NCR) of five samples underwent Sanger sequencing. Disease severity was assessed based on intensive care unit (ICU) admission, duration of ICU stay and need for mechanical ventilation.
Results
TBEV RNA was detected in 5 serum samples (3.9 %) and 7 CSF samples (6.4 %), representing 10 patients (7.3 %). Patients with detectable RNA were older, more frequently admitted to an ICU (p = 0.04), and more often required mechanical ventilation (p = 0.01) compared to those without detectable TBEV RNA. Sequencing of the 5′NCR in four patients revealed differences from the 5 ´NCR of the Swedish reference strain Torö-2003. The Örebro sequences were identical but differed from the Värmland sequences at two nucleotide positions.
Conclusions
TBEV RNA was detectable in both serum and CSF of TBE patients, and its presence was associated with more frequent ICU admission and need for mechanical ventilation. Sequencing of the 5′NCR revealed genetic variation between TBEV sequences from patients in Örebro and Värmland.
{"title":"Detection and molecular characterisation of tick-borne encephalitis virus in CSF and serum in relation to disease severity","authors":"Magnus Klinteskog , Anita Koskela von Sydow , Naveed Asghar , Magnus Johansson , Anna J. Henningsson , Martin Sundqvist , Per-Eric Lindgren , Lukas Frans Ocias","doi":"10.1016/j.jcv.2025.105885","DOIUrl":"10.1016/j.jcv.2025.105885","url":null,"abstract":"<div><h3>Objectives</h3><div>We aimed to 1) detect tick-borne encephalitis virus (TBEV) RNA in clinical samples from patients with TBE, 2) characterise the detected RNA using Sanger sequencing, and 3) examine whether RNA detection was associated with disease severity.</div></div><div><h3>Methods</h3><div>We studied 137 patients infected and diagnosed with TBE between 2016 and 2021 in Region Örebro County and Region Värmland. Biobanked serum (n = 129) and cerebrospinal fluid (CSF; n = 110) samples were analysed. Serum was tested for TBEV-specific antibodies, and both serum and CSF for TBEV RNA using PCR. Following nested PCR, the 5′ non-coding region (5′NCR) of five samples underwent Sanger sequencing. Disease severity was assessed based on intensive care unit (ICU) admission, duration of ICU stay and need for mechanical ventilation.</div></div><div><h3>Results</h3><div>TBEV RNA was detected in 5 serum samples (3.9 %) and 7 CSF samples (6.4 %), representing 10 patients (7.3 %). Patients with detectable RNA were older, more frequently admitted to an ICU (p = 0.04), and more often required mechanical ventilation (p = 0.01) compared to those without detectable TBEV RNA. Sequencing of the 5′NCR in four patients revealed differences from the 5 ´NCR of the Swedish reference strain Torö-2003. The Örebro sequences were identical but differed from the Värmland sequences at two nucleotide positions.</div></div><div><h3>Conclusions</h3><div>TBEV RNA was detectable in both serum and CSF of TBE patients, and its presence was associated with more frequent ICU admission and need for mechanical ventilation. Sequencing of the 5′NCR revealed genetic variation between TBEV sequences from patients in Örebro and Värmland.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"181 ","pages":"Article 105885"},"PeriodicalIF":3.4,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145463047","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 : 2025-11-03DOI: 10.1016/j.jcv.2025.105886
Tommaso Clemente , Mehdi Benlarbi , Rebecka Papaioannu Borjesson , Elisa Garlassi , Maria Cristina Moioli , Elisa Fronti , Pierluigi Reali , Leonardo Calza , Maria Mazzitelli , Andrea Giacomelli , Maurizio Zazzi , Maria Mercedes Santoro , Andrés Finzi , Antonella Castagna , on behalf of the PRESTIGIO Study Group
Introduction
Data on soluble gp120 (sgp120) and anti-HIV antibodies are lacking in people with HIV (PWH) and multidrug resistance, characterized by high inflammation and disease burden. We aimed to investigate the relationship between immuno-virological features and sgp120, anti-cluster A, anti-p24, and anti-CD4 binding site (anti-CD4bs) antibodies in 4-class drug-resistant (4DR) individuals.
Methods
Cross-sectional study on PWH with resistance to nucleoside and non-nucleoside reverse transcriptase, protease, and integrase inhibitors. Sgp120, anti-cluster A, anti-p24, and anti-CD4bs antibodies were measured using enzyme-linked immunosorbent assays. K-means clustering based on normalized anti-cluster A and anti-p24 levels identified antibody profiles. Associations with clinical variables were assessed using descriptive statistics and multinomial logistic regression.
Results
Overall, 80 4DR-PWH evaluated. Sgp120 and anti-CD4bs antibodies were detected in 12.5 % and 8.8 %, respectively, and not significantly associated with immuno-virological characteristics.
Based on anti-cluster A and anti-p24 levels, four PWH clusters were identified. Participants with low anti-p24 and high anti-cluster A antibodies showed more frequent detectable viremia (p = 0.018), lower CD4+/CD8+ (p = 0.044), and shorter ART duration (p = 0.025). CD4+ nadir (p = 0.036) followed a similar trend, except with high anti-p24 levels. Recent 4DR onset (p = 0.029) was linked to increasing anti-cluster A antibodies. At multivariable analysis, detectable viremia (p = 0.035) and ART duration (p = 0.022) remained significantly associated with cluster assignment.
Conclusions
Among 4DR-PWH, a specific antibody signature characterized by high anti-cluster A and low anti-p24 levels was associated with unsuppressed viremia and, potentially, immunological impairment. These findings provide preliminary insights into the interplay between anti-HIV humoral responses and immuno-virological features in this fragile population.
{"title":"Anti-cluster A and anti-p24 antibodies in people with multidrug-resistant HIV: Preliminary observations from the PRESTIGIO registry","authors":"Tommaso Clemente , Mehdi Benlarbi , Rebecka Papaioannu Borjesson , Elisa Garlassi , Maria Cristina Moioli , Elisa Fronti , Pierluigi Reali , Leonardo Calza , Maria Mazzitelli , Andrea Giacomelli , Maurizio Zazzi , Maria Mercedes Santoro , Andrés Finzi , Antonella Castagna , on behalf of the PRESTIGIO Study Group","doi":"10.1016/j.jcv.2025.105886","DOIUrl":"10.1016/j.jcv.2025.105886","url":null,"abstract":"<div><h3>Introduction</h3><div>Data on soluble gp120 (sgp120) and anti-HIV antibodies are lacking in people with HIV (PWH) and multidrug resistance, characterized by high inflammation and disease burden. We aimed to investigate the relationship between immuno-virological features and sgp120, anti-cluster A, anti-p24, and anti-CD4 binding site (anti-CD4bs) antibodies in 4-class drug-resistant (4DR) individuals.</div></div><div><h3>Methods</h3><div>Cross-sectional study on PWH with resistance to nucleoside and non-nucleoside reverse transcriptase, protease, and integrase inhibitors. Sgp120, anti-cluster A, anti-p24, and anti-CD4bs antibodies were measured using enzyme-linked immunosorbent assays. K-means clustering based on normalized anti-cluster A and anti-p24 levels identified antibody profiles. Associations with clinical variables were assessed using descriptive statistics and multinomial logistic regression.</div></div><div><h3>Results</h3><div>Overall, 80 4DR-PWH evaluated. Sgp120 and anti-CD4bs antibodies were detected in 12.5 % and 8.8 %, respectively, and not significantly associated with immuno-virological characteristics.</div><div>Based on anti-cluster A and anti-p24 levels, four PWH clusters were identified. Participants with low anti-p24 and high anti-cluster A antibodies showed more frequent detectable viremia (p = 0.018), lower CD4<sup>+</sup>/CD8<sup>+</sup> (p = 0.044), and shorter ART duration (p = 0.025). CD4<sup>+</sup> nadir (p = 0.036) followed a similar trend, except with high anti-p24 levels. Recent 4DR onset (p = 0.029) was linked to increasing anti-cluster A antibodies. At multivariable analysis, detectable viremia (p = 0.035) and ART duration (p = 0.022) remained significantly associated with cluster assignment.</div></div><div><h3>Conclusions</h3><div>Among 4DR-PWH, a specific antibody signature characterized by high anti-cluster A and low anti-p24 levels was associated with unsuppressed viremia and, potentially, immunological impairment. These findings provide preliminary insights into the interplay between anti-HIV humoral responses and immuno-virological features in this fragile population.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"181 ","pages":"Article 105886"},"PeriodicalIF":3.4,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458506","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 : 2025-10-24DOI: 10.1016/j.jcv.2025.105884
Arvid Edén , Amanda Ahlin , Magnus Lindh , Johan Westin
Background
Human herpesvirus 6 (HHV-6) is included in syndromic panels for diagnostics of CNS infections, but the clinical significance of the detection is often unclear.
Objective
To investigate the clinical importance of detectable HHV-6 DNA in CSF.
Study design
We retrospectively investigated the clinical significance of detection of HHV-6 DNA in all clinical CSF samples that were analyzed between 2010 and 2021 using in-house PCR or the FilmArray meningitis/encephalitis (ME) panel. The clinical significance of HHV-6 was evaluated by review of electronic medical records (EMR) and categorized as unlikely, possible or likely for each case.
Results
Of 8778 samples from 8222 individuals, HHV-6 DNA was detected in CSF in 113 (1.4 %). After EMR review, the clinical importance of HHV-6 was categorized as likely in three (3 %; including one with meningoencephalitis), possible in 15 (14 %) and unlikely in 95 (83 %) cases. No significant difference in HHV-6 DNA levels was seen between these categories. Seven of ten initiated antiviral therapies were unnecessary (integrated HHV-6 n = 4; primary infection without CNS complications n = 3).
Conclusions
In this large clinical sample, nearly all HHV-6 detections were either of unlikely diagnostic importance or did not require specific medical interventions. Moreover, in most cases where antiviral therapy was initiated, treatment was either erroneous (integration) or unmotivated (limited disease). These results indicate that the utility of including HHV-6 in routine syndromic diagnostic panels for CNS infections is questionable, and that appropriate guidance from the laboratory to aid attending clinicians is prudent to avoid unnecessary, expensive and potentially toxic therapy.
人类疱疹病毒6 （HHV-6）被包括在诊断中枢神经系统感染的综合征组中，但检测的临床意义往往不清楚。目的探讨脑脊液中检测HHV-6 DNA的临床意义。我们回顾性研究了2010年至2021年间使用内部PCR或FilmArray脑膜炎/脑炎（ME）面板分析的所有临床脑脊液样本中检测HHV-6 DNA的临床意义。通过电子病历（EMR）评估HHV-6的临床意义，并将每个病例分类为不太可能、可能或可能。结果8222人8778份脑脊液中检出HHV-6 DNA 113份（1.4 %）。在EMR审查后，HHV-6的临床重要性在3例（3 %，包括1例脑膜脑炎）中被分类为可能，在15例（14 %）中被分类为可能，在95例（83 %）中被分类为不可能。这些类别之间HHV-6 DNA水平无显著差异。10个初始抗病毒治疗中有7个是不必要的（综合HHV-6 n = 4；无中枢神经系统并发症的原发感染n = 3）。结论在这个大的临床样本中，几乎所有的HHV-6检测要么不太可能具有诊断重要性，要么不需要特殊的医疗干预。此外，在大多数开始抗病毒治疗的病例中，治疗要么是错误的（整合），要么是无动机的（有限的疾病）。这些结果表明，将HHV-6纳入中枢神经系统感染的常规综合征诊断小组的效用值得怀疑，并且实验室的适当指导可以帮助主治临床医生谨慎地避免不必要的、昂贵的和潜在毒性的治疗。
{"title":"Detection of human herpesvirus type 6 DNA in cerebrospinal fluid is rarely clinically significant","authors":"Arvid Edén , Amanda Ahlin , Magnus Lindh , Johan Westin","doi":"10.1016/j.jcv.2025.105884","DOIUrl":"10.1016/j.jcv.2025.105884","url":null,"abstract":"<div><h3>Background</h3><div>Human herpesvirus 6 (HHV-6) is included in syndromic panels for diagnostics of CNS infections, but the clinical significance of the detection is often unclear.</div></div><div><h3>Objective</h3><div>To investigate the clinical importance of detectable HHV-6 DNA in CSF.</div></div><div><h3>Study design</h3><div>We retrospectively investigated the clinical significance of detection of HHV-6 DNA in all clinical CSF samples that were analyzed between 2010 and 2021 using in-house PCR or the FilmArray meningitis/encephalitis (ME) panel. The clinical significance of HHV-6 was evaluated by review of electronic medical records (EMR) and categorized as unlikely, possible or likely for each case.</div></div><div><h3>Results</h3><div>Of 8778 samples from 8222 individuals, HHV-6 DNA was detected in CSF in 113 (1.4 %). After EMR review, the clinical importance of HHV-6 was categorized as likely in three (3 %; including one with meningoencephalitis), possible in 15 (14 %) and unlikely in 95 (83 %) cases. No significant difference in HHV-6 DNA levels was seen between these categories. Seven of ten initiated antiviral therapies were unnecessary (integrated HHV-6 n = 4; primary infection without CNS complications n = 3).</div></div><div><h3>Conclusions</h3><div>In this large clinical sample, nearly all HHV-6 detections were either of unlikely diagnostic importance or did not require specific medical interventions. Moreover, in most cases where antiviral therapy was initiated, treatment was either erroneous (integration) or unmotivated (limited disease). These results indicate that the utility of including HHV-6 in routine syndromic diagnostic panels for CNS infections is questionable, and that appropriate guidance from the laboratory to aid attending clinicians is prudent to avoid unnecessary, expensive and potentially toxic therapy.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"181 ","pages":"Article 105884"},"PeriodicalIF":3.4,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358012","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 : 2025-10-20DOI: 10.1016/j.jcv.2025.105883
Adino Tesfahun Tsegaye , Megan A. Clarke , Beverly Long , Nicole P. Chappell , Sarah A. Phillips , Megan A. Swiger , Anna BuAbbud , Priya Sathyanarayan , Nicolas Wentzensen
Background
Human papillomavirus (HPV) testing using self-collected samples could increase cervical cancer screening among never screened or underscreened populations. This study aimed to evaluate the concordance between self-collected and clinician-collected samples using the Alinity m high risk (HR) HPV extended genotyping assay.
Methods
Self-collected vaginal samples and clinician-collected cervical samples were obtained from 25 to 69-year-old women who had visits for cervical cancer screening, colposcopy, follow up pap test, and/or treatment of cervical dysplasia at the George Washington University Hospital in Washington DC and Sarasota Memorial Health Care System and their affiliates in Florida. Extended genotyping based on the Alinity m HR HPV assay was performed on stored residual samples and the agreement between clinician- and self-collected HPV test results was assessed using positive percent agreement and Cohen’s kappa values.
Results
There were 294 participants who provided paired self and clinician-collected samples. The overall prevalence of any HR-HPV was 26 %(76/293) for clinician-collected samples and 27 %(79/291) for self-collected samples. The positive percent agreement between clinician- and self-collected samples for any HR-HPV was 78 %, and the Cohen’s Kappa value was 0.83(95 %CI:0.76,0.91). For specific HPV genotypes, the positive percent agreement ranged from 72 % for HPV16–79 % for other HR-HPV group A (HPV31/33/52/58); and the Kappa value ranged from 0.83(95 %CI:0.68,0.98) for HPV16–0.87(95 %CI:0.77,0.97) for other HR-HPV group A.
Conclusion
There was a strong test concordance between self-collected and clinician-collected samples using the Alinity m HR HPV assay. Self-collected samples tested with the Alinity m HR HPV assays can be considered an alternative to clinician-collected primary HPV testing.
背景：人乳头瘤病毒（HPV）检测使用自我收集的样本可以增加宫颈癌筛查从未筛查或筛查不足的人群。本研究旨在评估使用Alinity m高风险（HR） HPV扩展基因分型检测的自我采集和临床采集样本之间的一致性。方法：在华盛顿特区的乔治华盛顿大学医院和佛罗里达州的萨拉索塔纪念医疗保健系统及其附属机构进行宫颈癌筛查、阴道镜检查、随访巴氏试验和/或宫颈发育不良治疗的25至69岁妇女中，收集自阴道样本和临床收集的宫颈样本。对储存的剩余样本进行基于Alinity m HR HPV检测的扩展基因分型，并使用阳性一致性百分比和Cohen’s kappa值评估临床医生和自己收集的HPV检测结果之间的一致性。结果：有294名参与者提供了配对的自我和临床收集的样本。临床采集样本的HR-HPV总患病率为26 %(76/293)，自行采集样本的HR-HPV总患病率为27 %（79/291）。临床医生和自己收集的任何HR-HPV样本的阳性率为78 %，Cohen's Kappa值为0.83（95 %CI:0.76,0.91）。对于特定的HPV基因型，HPV16-79的阳性率为72% %，其他HR-HPV A组（HPV31/33/52/58）的阳性率为 %；hpv16组的Kappa值为0.83(95 %CI:0.68,0.98)，其他HR-HPV a组的Kappa值为0.87（95 %CI:0.77,0.97）。结论：使用Alinity m HR HPV检测方法自行采集的样本与临床采集的样本具有很强的一致性。用Alinity m HR HPV检测检测的自收集样本可以被认为是临床收集的原发性HPV检测的替代方法。
{"title":"Performance of the Alinity m HR HPV assay on self-collected vaginal samples compared to clinician-collected cervical samples","authors":"Adino Tesfahun Tsegaye , Megan A. Clarke , Beverly Long , Nicole P. Chappell , Sarah A. Phillips , Megan A. Swiger , Anna BuAbbud , Priya Sathyanarayan , Nicolas Wentzensen","doi":"10.1016/j.jcv.2025.105883","DOIUrl":"10.1016/j.jcv.2025.105883","url":null,"abstract":"<div><h3>Background</h3><div>Human papillomavirus (HPV) testing using self-collected samples could increase cervical cancer screening among never screened or underscreened populations. This study aimed to evaluate the concordance between self-collected and clinician-collected samples using the Alinity m high risk (HR) HPV extended genotyping assay.</div></div><div><h3>Methods</h3><div>Self-collected vaginal samples and clinician-collected cervical samples were obtained from 25 to 69-year-old women who had visits for cervical cancer screening, colposcopy, follow up pap test, and/or treatment of cervical dysplasia at the George Washington University Hospital in Washington DC and Sarasota Memorial Health Care System and their affiliates in Florida. Extended genotyping based on the Alinity m HR HPV assay was performed on stored residual samples and the agreement between clinician- and self-collected HPV test results was assessed using positive percent agreement and Cohen’s kappa values.</div></div><div><h3>Results</h3><div>There were 294 participants who provided paired self and clinician-collected samples. The overall prevalence of any HR-HPV was 26 %(76/293) for clinician-collected samples and 27 %(79/291) for self-collected samples. The positive percent agreement between clinician- and self-collected samples for any HR-HPV was 78 %, and the Cohen’s Kappa value was 0.83(95 %CI:0.76,0.91). For specific HPV genotypes, the positive percent agreement ranged from 72 % for HPV16–79 % for other HR-HPV group A (HPV31/33/52/58); and the Kappa value ranged from 0.83(95 %CI:0.68,0.98) for HPV16–0.87(95 %CI:0.77,0.97) for other HR-HPV group A.</div></div><div><h3>Conclusion</h3><div>There was a strong test concordance between self-collected and clinician-collected samples using the Alinity m HR HPV assay. Self-collected samples tested with the Alinity m HR HPV assays can be considered an alternative to clinician-collected primary HPV testing.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"181 ","pages":"Article 105883"},"PeriodicalIF":3.4,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400976","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 : 2025-10-20DOI: 10.1016/j.jcv.2025.105882
Martin Ekman , Amir Nematollahi Mahani , Shambhu Ganeshappa Aralaguppe , Tanja Normark , Sofia Stamouli , Lili Andersson-Li , Dan Sun , Sandra Broddesson , Valtteri Wirta , Niklas K. Björkström , Jan Albert , Tobias Allander
Background
Metagenomic sequencing has emerged as an attractive, general, and agnostic diagnostic method, in particular for detection of viruses. However, its application faces limitations, including reduced sensitivity due to background nucleic acid content of samples, and the search for an optimized protocol is still ongoing.
Methods
We report the development of a metagenomic sequencing protocol for diagnostic use and its performance in detecting DNA and RNA viruses in three different sample materials: serum, cerebrospinal fluid (CSF) and nasopharyngeal swabs (NPS).
Results
Sensitivity was higher for RNA viruses than for DNA viruses, and also higher in CSF than in serum and lowest in NPS. We characterized the background nucleic acids and found higher DNA than RNA levels in CSF and serum and overall highest nucleic acid levels in NPS, intermediate in serum and lowest in CSF. These differences largely explained the observed variability in sensitivity between sample preparations and sample materials.
Conclusions
Our results highlight the need to consider sample-type specific characteristics in efforts to improve the sensitivity of metagenomic assays e.g. via host depletion protocols.
{"title":"Evaluation of a diagnostic metagenomic sequencing assay: Virus detection sensitivity and background nucleic acids in three different sample materials","authors":"Martin Ekman , Amir Nematollahi Mahani , Shambhu Ganeshappa Aralaguppe , Tanja Normark , Sofia Stamouli , Lili Andersson-Li , Dan Sun , Sandra Broddesson , Valtteri Wirta , Niklas K. Björkström , Jan Albert , Tobias Allander","doi":"10.1016/j.jcv.2025.105882","DOIUrl":"10.1016/j.jcv.2025.105882","url":null,"abstract":"<div><h3>Background</h3><div>Metagenomic sequencing has emerged as an attractive, general, and agnostic diagnostic method, in particular for detection of viruses. However, its application faces limitations, including reduced sensitivity due to background nucleic acid content of samples, and the search for an optimized protocol is still ongoing.</div></div><div><h3>Methods</h3><div>We report the development of a metagenomic sequencing protocol for diagnostic use and its performance in detecting DNA and RNA viruses in three different sample materials: serum, cerebrospinal fluid (CSF) and nasopharyngeal swabs (NPS).</div></div><div><h3>Results</h3><div>Sensitivity was higher for RNA viruses than for DNA viruses, and also higher in CSF than in serum and lowest in NPS. We characterized the background nucleic acids and found higher DNA than RNA levels in CSF and serum and overall highest nucleic acid levels in NPS, intermediate in serum and lowest in CSF. These differences largely explained the observed variability in sensitivity between sample preparations and sample materials.</div></div><div><h3>Conclusions</h3><div>Our results highlight the need to consider sample-type specific characteristics in efforts to improve the sensitivity of metagenomic assays e.g. via host depletion protocols.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"181 ","pages":"Article 105882"},"PeriodicalIF":3.4,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400938","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 : 2025-10-15DOI: 10.1016/j.jcv.2025.105881
Osaretin Emmanuel Asowata , Tracy McMillen , Krupa Jani , Brenden Clark , Sejal Morjaria , Mini Kamboj , N.Esther Babady
Background
Enteroviruses (EV) are associated with a range of syndromes including respiratory infections. Non-polio enteroviruses like EV-D68 can cause more severe symptoms in children, and immunocompromised individuals. The goal of this study was to determine the prevalence and genotypes of EV in a pediatric oncology patient population.
Methods
Pediatric patients (<18 years old) testing positive for Rhinovirus/Enterovirus (RV/EV) by multiplexed respiratory pathogens panels between September and December 2022 and 2023 were included in the study. RV/EV positive nasopharyngeal swabs (NPS) specimens were further characterized using pan-enterovirus RT-PCR, EV-D68 RT-PCR and Whole genome sequencing (WGS). Clinical characteristics of EV positive patients and matched controls were extracted from the clinical information system.
Results
Across the two study periods, 3.8 % (9/238) and 3.6 % (8/225) EV were identified in RV/EV positives NPS in 2022 and 2023 respectively. The most prevalent EV species were EV-D68 (3/9, 33 %) and Coxsackievirus A6 (3/9, 33 %). All three patients with EV-D68 were male with an underlying diagnosis of acute lymphoblastic lymphoma or neuroblastoma. Besides, the EV-D68 detections were only from the 2022 NPS samples. There were no differences in symptoms severity between patients with or without EV infections.
Conclusions
The prevalence of EV during the study periods was low in this patient population and not associated with severe symptoms. However, further exploration is required to understand the relationship between EV infection and patient symptoms since this study was limited by the low EV detection. Larger studies are needed to further characterize EV infections in this patient population.
{"title":"Prevalence and epidemiology of enterovirus species in a pediatric oncology patient population","authors":"Osaretin Emmanuel Asowata , Tracy McMillen , Krupa Jani , Brenden Clark , Sejal Morjaria , Mini Kamboj , N.Esther Babady","doi":"10.1016/j.jcv.2025.105881","DOIUrl":"10.1016/j.jcv.2025.105881","url":null,"abstract":"<div><h3>Background</h3><div>Enteroviruses (EV) are associated with a range of syndromes including respiratory infections. Non-polio enteroviruses like EV-D68 can cause more severe symptoms in children, and immunocompromised individuals. The goal of this study was to determine the prevalence and genotypes of EV in a pediatric oncology patient population.</div></div><div><h3>Methods</h3><div>Pediatric patients (<18 years old) testing positive for Rhinovirus/Enterovirus (RV/EV) by multiplexed respiratory pathogens panels between September and December 2022 and 2023 were included in the study. RV/EV positive nasopharyngeal swabs (NPS) specimens were further characterized using pan-enterovirus RT-PCR, EV-D68 RT-PCR and Whole genome sequencing (WGS). Clinical characteristics of EV positive patients and matched controls were extracted from the clinical information system.</div></div><div><h3>Results</h3><div>Across the two study periods, 3.8 % (9/238) and 3.6 % (8/225) EV were identified in RV/EV positives NPS in 2022 and 2023 respectively. The most prevalent EV species were EV-D68 (3/9, 33 %) and Coxsackievirus A6 (3/9, 33 %). All three patients with EV-D68 were male with an underlying diagnosis of acute lymphoblastic lymphoma or neuroblastoma. Besides, the EV-D68 detections were only from the 2022 NPS samples. There were no differences in symptoms severity between patients with or without EV infections.</div></div><div><h3>Conclusions</h3><div>The prevalence of EV during the study periods was low in this patient population and not associated with severe symptoms. However, further exploration is required to understand the relationship between EV infection and patient symptoms since this study was limited by the low EV detection. Larger studies are needed to further characterize EV infections in this patient population.</div></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":"181 ","pages":"Article 105881"},"PeriodicalIF":3.4,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358013","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}
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