1. |
- Andersson, Elin, 1975, et al.
(författare)
-
Type-dependent E6/E7 mRNA expression of single and multiple high-risk human papillomavirus infections in cervical neoplasia.
- 2012
-
Ingår i: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. - : Elsevier BV. - 1873-5967. ; 54:1, s. 61-5
-
Tidskriftsartikel (refereegranskat)abstract
- Coinfection with multiple HPV types is common in cervical lesions, but the biological significance of the individual infections is difficult to establish. Expression of oncogenic E6/E7 HPV mRNA is correlated to risk of malignant progression, commercial assays for genotyping E6/E7 mRNA of all HR-HPV are lacking.
|
|
2. |
|
|
3. |
- Arroyo Mühr, Laila Sara, et al.
(författare)
-
Improving human papillomavirus (HPV) testing in the cervical cancer elimination era : The 2021 HPV LabNet international proficiency study
- 2022
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 154, s. 105237-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Proficient Human Papillomavirus (HPV) genotyping services are essential to support HPV and cervical cancer elimination strategies, in particular to support HPV vaccine research. Objectives: To perform a global HPV genotyping proficiency study, with evaluation in relation to previous proficiency studies. Study design: The proficiency panel contained 44 coded samples (40 samples containing one or more purified HPV types (HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/68a/68b) in human DNA, 1 human DNA control and 3 DNA extraction controls). Proficiency required detection of both single and multiple infections of 50 International Units of HPV 16/18, of 500 genome equivalents for other HPV types and no false positivity. Results: One hundred and thirty-two laboratories submitted 211 datasets. Most assays used (182/211 datasets) were commercially available. An all-time high of 75% of the datasets were 100% proficient. One or more false positives were found in 17.5% of datasets. Among laboratories who participated in the 2019 proficiency study, full proficiency increased from 25% in 2019 to 60% in 2021. The high overall proficiency was mostly attributable to a large number of new laboratories, which used similar assays. Conclusions: The worldwide deterioration in comparability and reliability of HPV testing found in 2019 is now reversed and an overall increase in proficiency is found.
|
|
4. |
|
|
5. |
|
|
6. |
- Carozzi, F. M., et al.
(författare)
-
Effectiveness of HPV vaccination in women reaching screening age in Italy
- 2016
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 84, s. 74-81
-
Tidskriftsartikel (refereegranskat)abstract
- Background and objectives A randomized trial was conducted in Tuscany, Italy, to evaluate the effectiveness of HPV vaccination for 25 year old (yo) women who attend at the first time cervical cancer screening. The trial also evaluated immune response after vaccination, reductions of cytological abnormalities and the impact of vaccination on screening activity. Study design During 2010–2011, all 25 yo women who were invited to the Florence cervical cancer screening programme were also asked to participate in the trial. Enrolled women were randomized into study and control groups. Those in the study group were offered HPV vaccination after the usual Pap test. The cytology distribution and prevalence for any high risk (hr) HPV type were compared at the subsequent screening round in an intention-to-treat analysis. The impact of HPV vaccination was evaluated per protocol comparing vaccinated women with the control group. Results Our results showed a reduction in HPV prevalence at recall for any hr-HPV type but it was not statistically significant, being 17.1% vs 21.4%, p = 0.20 in the study and control groups, respectively. If we restricted the analysis to vaccinated women, strong reductions of the HPV 16,18,31,33,45 and HPV 31,33,45 infections were observed, being 5.3% vs 12.8%, p < 0.01 and 2.1% vs 6.5%, p = 0.02, respectively. Significant reductions for any hr-HPV infection and for HPV 16 infection were also observed in women HPV 16/18 negative at enrolment, being 12% vs 21.4%, p < 0.01 and 0.6% vs 6.7%, p-value < 0.01, respectively. In women hr-HPV negative at enrolment no infections due to HPV 16 or HPV 18 were observed and there was a big reduction for any hr-HPV infection (7.1% vs 21.4% p < 0.01). A strong antibody response was observed not only for HPV 16 & 18 but also for their related types. Conclusions Our findings suggest that HPV vaccination at the age 25 is beneficial if it is offered to hr-HPV negative women. Our data will assist in developing a cost effectiveness model for choosing the best strategy to integrate screening and vaccination for the coming years. Clinical trial registration number is NCT02296255.
|
|
7. |
|
|
8. |
- Darlin, Lotten, et al.
(författare)
-
Vaginal self-sampling without preservative for human papillomavirus testing shows good sensitivity.
- 2013
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 56:1, s. 52-56
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Several strategies have been used to reach non-attending women in organized cervical-cancer-screening programs, with varying success. Self-sampling (SS) for HPV is effective for increasing coverage in screening programs, but requires expensive commercial sampling kits. OBJECTIVE: We aimed to evaluate if vaginal SS, without commercial preservatives was adequate for HPV testing. STUDY DESIGN: Women with abnormal cervical smears as determined from the organized screening program were invited to a colposcopy clinic. The 121 women were asked to insert a cotton swab into the vagina and rotate it, put the cotton swab into a sterile cryotube, break the upper part of the stick and put the cap on. Thereafter, the gynaecologist collected a liquid based cytology (LBC) sample. The presence of HPV-types in SS and LBC samples was analysed with PCR and luminex-based typing. RESULTS: High-risk-HPV (hr-HPV) DNA was found in 65 of the tested 108 SS (60%; 95% CI 0.50-0.69), whereas LBC found hr-HPV in 64/108 samples (59%; 95% CI 0.49-0.69). The agreement between sampling with SS and LBC was good, kappa value 0.67 (95% CI; 0.53-0.81). The sensitivity for SS with hr-HPV to find HSIL was 81% (95% CI; 67-95%), specificity 49% (95% CI; 37-60%) and the sensitivity for LBC with hr-HPV to find HSIL was 90% (95% CI 80-100%), specificity53% (95% CI; 42-65%). CONCLUSIONS: This new vaginal self-sampling method detects hr-HPV-infections with similar sensitivity as a cervical smear taken by a gynaecologist. This self-sampling method is cost-effective and well tolerated, and the kit is suitable for regular mail transport.
|
|
9. |
|
|
10. |
- de la Fuente, Luis, et al.
(författare)
-
HTLV infection among young injection and non-injection heroin users in Spain: Prevalence and correlates
- 2006
-
Ingår i: Journal of Clinical Virology. - : Elsevier. - 1386-6532 .- 1873-5967. ; 35:3, s. 244-249
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlthough some studies have described the epidemiology of infection with HIV or hepatitis B and C in young users in Spain – one of the European countries with the highest prevalences – there are no studies of the prevalence of HTLV infection and the most important associated factors.ObjectivesTo evaluate the prevalence and main determinants of HTLV-1 and HTLV-2 infection in young heroin users (including both injection (IDUs) and non-injection drug users (NIDUs)) recruited outside health care services in three of Spain's principal cities.Study designCross-sectional cohort study. All participants (981) were street-recruited by chain referral procedures between April 2001 and December 2003. Face-to-face interviews were conducted using a structured questionnaire and dried blood spot samples were collected for serological testing.ResultsNo sample was positive for HTLV-1 and 27 samples were positive for HTLV-2; all of these were found only in Spanish IDUs in the cities of Madrid (17, 6.2%) and Barcelona (10, 3.5%). The only two factors significantly associated with HTLV infection in the logistic regression analysis were HIV infection (OR 5.7; 95% CI 2.2–14.8) and having injected in the last 30 days (OR 6.5; 95% CI 1.4–29.8). Having been in prison (OR 2.4; 95% CI 0.9–6.4) and HCV infection (OR 3.8; 95% CI 0.5–30.7), which were strongly and significantly associated in the bivariate analysis, were no longer significant in the logistic analysis. Almost the same variables were selected in the tree analysis, in which subjects could be classified into three groups: high prevalence (28.5%, HIV+ and HBV+ who had injected in the last 30 days), medium prevalence (17.8%) and low (<3%) or zero prevalence (HIV−, HCV− and HBV−).ConclusionsHTLV-1 was not detected among young Spanish heroin users. HTLV-2 was not found in NIDUs (perhaps due to the low rate of sexual transmission); it was found only in IDUs from Madrid and Barcelona, but not in those from Seville. Its prevalence is very low and the main correlates of infection were HIV infection and injection as the usual route of heroin administration.
|
|
11. |
|
|
12. |
- Eklund, Carina, et al.
(författare)
-
Continuing global improvement in human papillomavirus DNA genotyping services : The 2013 and 2014 HPV LabNet international proficiency studies
- 2018
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 101, s. 74-85
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Accurate and internationally comparable human papillomavirus (HPV) DNA detection and typing services are essential for HPV vaccine research and surveillance. Objectives: This study assessed the proficiency of different HPV typing services offered routinely in laboratories worldwide. Study design: The HPV Laboratory Network (LabNet) has designed international proficiency panels that can be regularly issued. The HPV genotyping proficiency panels of 2013 and 2014 contained 43 and 41 coded samples, respectively, composed of purified plasmids of sixteen HPV types (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68a and 68b) and 3 extraction controls. Proficient typing was defined as detection in both single and multiple infections of 50 International Units of HPV 16 and HPV 18 and 500 genome equivalents for the other 14 HPV types, with at least 97% specificity. Results: Ninety-six laboratories submitted 136 datasets in 2013 and 121 laboratories submitted 148 datasets in 2014. Thirty-four different HPV genotyping assays were used, notably Linear Array, HPV Direct Flow-chip, GenoFlow HPV array, Anyplex HPV 28, Inno-LiPa, and PGMY-CHUV assays. A trend towards increased sensitivity and specificity was observed. In 2013, 59 data sets (44%) were 100% proficient compared to 86 data sets (59%) in 2014. This is a definite improvement compared to the first proficiency panel, issued in 2008, when only 19 data sets (26%) were fully proficient. Conclusion: The regularly issued global proficiency program has documented an ongoing worldwide improvement in comparability and reliability of HPV genotyping services.
|
|
13. |
- Eklund, Carina, et al.
(författare)
-
The 2019 HPV Labnet international proficiency study : Need of global Human Papillomavirus Proficiency Testing
- 2021
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 141, s. 104902-
-
Tidskriftsartikel (refereegranskat)abstract
- Background:: Accurate and internationally comparable human papillomavirus (HPV) testing services are essential for cervical cancer elimination programs. The WHO HPV Laboratory Network started issuing international HPV testing proficiency panels in 2008. Objectives:: We report the results of the 2019 global proficiency study and evaluate the proficiency over time. Study design:: The proficiency panel contained 40 coded samples containing mixes of purified HPV types (HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/68a/68b) and 4 controls. Proficiency required detection of both single and multiple infections of 50 International Units of HPV 16/18, of 500 genome equivalents (10x higher concentration) for other HPV types, and no false positives (stricter requirement compared to previous panels). Results:: Seventy-eight laboratories submitted 110 datasets with 38 different assays. Most samples (38/44) were reported with 100% proficiency in most datasets. Mostly commercial assays were used (88/110 datasets). Overall, 47.3% of the datasets were 100% proficient. False positivity was detected in at least one sample in 30.1% of datasets. When analysing all datasets ever since 2008 using exactly the same proficiency criteria, there was a steady improvement up to 2017 (the proportion of datasets being completely proficient increased from 25% to 73%). However, in the 2019 proficiency testing the proportion of fully proficient datasets dropped to 50%. Conclusions:: Although we initially documented a worldwide improvement in comparability and reliability of HPV testing services, the trend now appears to be reversed. In response, the International HPV Reference Center will provide support for improved quality of laboratory services, including issuing of global proficiency panels every year.
|
|
14. |
- Faust, Helena, et al.
(författare)
-
Serum antibodies to human papillomavirus (HPV) pseudovirions correlate with natural infection for 13 genital HPV types.
- 2013
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 56:4, s. 336-341
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Serology for human papillomaviruses (HPV) types -16 and -18 is established as an important tool for studies of HPV vaccinology and epidemiology. However, as there are a large number of oncogenic genital types of HPV there is a need for development of high-throughput, validated HPV serological assays that can be used for more comprehensive seroepidemiological studies and for research on multivalent HPV vaccines. OBJECTIVES: To develop a multiplexed pseudovirion-based serological assay (PsV-Luminex) encompassing 21 HPV types and validate the method by correlating the serology with the presence of type specific HPV DNA in cervical samples. STUDY DESIGN: Cervical swabs from 3,291 unvaccinated women attending organized cervical screening in Slovenia were tested with 3 different HPV DNA detection methods and presence of HPV DNA compared to presence of serum antibodies to pseudovirions from 15 genital HPV types (HPV-6,-11,-16,-18,-31,-33,-35,-39,-45,-52,-56,-58,-59,-68,-73). RESULTS: On average 51% of the HPV DNA positive women were seropositive for the same HPV type that was detected in the cervical specimen. We found a strong correlation with presence of HPV DNA and antibodies to the same HPV type for 13/15 genital HPV types (median OR=5.7, CI 95%=2.4-12.9). HPV-52 serology failed the validation and HPV-11 serology could not be validated because only a single woman was positive for HPV-11 DNA. The correlation between serology and HPV DNA status tended to be stronger among women infected with single HPV type (median OR=10.5, CI 95%=2.4-48.4) than among women with multiple HPV infections (median OR=4.6, CI 95%=1.8-11.7). CONCLUSIONS: A multiplexed HPV PsV-Luminex assay has been developed and validated to correlate with natural HPV infection for 13 HPV types, thus enabling more comprehensive studies in HPV epidemiology and vaccine research.
|
|
15. |
|
|
16. |
|
|
17. |
- Gia Phan, Tung, et al.
(författare)
-
New astrovirus in human feces from Burkina Faso
- 2014
-
Ingår i: Journal of Clinical Virology. - : Elsevier. - 1386-6532 .- 1873-5967. ; 60:2, s. 161-164
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A significant fraction of cases of diarrhea, a leading cause of childhood mortality worldwide, remain unexplained. Objectives: To identify viruses in unexplained cases of diarrhea using an unbiased metagenomics approach. Study design: Viral nucleic acids were enriched from the feces from 48 cases of unexplained diarrhea from Burkina Faso, sequenced, and compared against all known viral genomes. Results: The full genome of a highly divergent astrovirus was sequenced in a sample co-infected with parechovirus 1. RT-PCR identified a single astrovirus infection in these 48 patients indicating a low prevalence. Human astrovirus-BF34 was most closely related to mamastrovirus species 8 and 9 also found in human with which it shared 62%, 74%, and 57% amino acid identities over its protease, RNA dependent RNA polymerase and capsid proteins, respectively. Conclusions: Burkina Faso astrovirus is proposed as prototype for a novel species in the genus Mamastrovirus, here tentatively called Mamastrovirus 20, representing the fifth human astrovirus species.
|
|
18. |
- Groome, Michelle J., et al.
(författare)
-
Human metapneumovirus-associated severe acute respiratory illness hospitalisation in HIV-infected and HIV-uninfected South African children and adults
- 2015
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 69, s. 125-132
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Data on human metapneumovirus (HMPV)-associated severe acute respiratory illness (SARI) are limited in settings with high human immunodeficiency virus (HIV) infection prevalence. Objectives: To describe clinical characteristics and seasonality (all sites), and incidence (Soweto only) of HMPV-associated SARI among children and adults. Study design: Active, prospective, hospital-based, sentinel surveillance for patients hospitalised with SARI was conducted at four sites in South Africa from February 2009-December 2013. Upper respiratory tract samples were tested by multiplex real-time polymerase chain reaction assays for HMPV and other respiratory viruses. Incidence of hospitalisation, stratified by age and HIV-infection status, was calculated for one hospital with population denominators. Results: HMPV was identified in 4.1% of patients enrolled, including 5.6% (593/10503) in children and 1.7% in adults (>= 18 years; 119/6934). The majority of adults (84.0%) had an underlying medical condition, including HIV infection in 87/110 (79.1%). HMPV detection occurred perennially with periods of increased detection, which varied from year to year. The incidence of HMPV-associated hospitalisation in Soweto was highest in infants (653.3 per 100,000 person years; 95% confidence interval (CI) 602.2-707.6). The incidence was higher in HIV-infected persons compared to HIV-uninfected persons in age-groups 5-17 years (RR 6.0; 1.1-20.4), 18-44 years (RR 67.6; 38.0-132.6) and 45-64 years (RR 5.3; 3.4-8.3), while not differing in other age-groups. Conclusions: The burden of HMPV-associated SARI hospitalisation among adults occurred predominantly in HIV-infected persons. Among children, infants were at highest risk, with similar burden of hospitalisation in HIV-infected and HIV-uninfected children.
|
|
19. |
- Gustavsson, Inger, et al.
(författare)
-
Comparison between the Hybrid Capture 2 and the hpVIR real-time PCR for detection of human papillomavirus in women with ASCUS or low grade dysplasia
- 2009
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 45:2, s. 85-89
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human papillomavirus (HPV) testing is an important part of cervical carcinoma screening, and the most widely used assay for detection of HPV is Hybrid Capture 2 (HC2). OBJECTIVES: We compare the HC2 with the real-time PCR hpVIR assay for detection of HPV in follow-up smears of 398 women diagnosed with atypical squamous cells of unknown significance (ASCUS) or low grade cervical intraepithelial neoplasia (CIN 1) in their initial smear. STUDY DESIGN: The two assays target the same set of high-risk (HR) HPVs with exception of HPV68. hpVIR identify individual or groups of HPV types as well as their viral load, while HC2 identify HR HPVs without specification of type. RESULTS: 34% (131/391) of the women were positive with HC2 and 45% (175/391) with hpVIR. 16% (63/391) were positive only with hpVIR and among those with cytology available 6% (3/52) had a CIN 2. The 3% (13/391) of women positive only with HC2 either contained low-risk HPVs or copy numbers below the cut-off for the hpVIR assay. CONCLUSION: The hpVIR assay has a similar sensitivity and specificity as HC2, but hpVIR detect a higher frequency of high-risk HPV infections.
|
|
20. |
- Gustavsson, Inger, 1965-, et al.
(författare)
-
Type-specific detection of high-risk human papillomavirus (HPV) in self-sampled cervicovaginal cells applied to FTA elute cartridge
- 2011
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 51:4, s. 255-258
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundMost procedures for self-sampling of cervical cells are based on liquid-based media for transportation and storage. An alternative is to use a solid support, such as dry filter paper media.ObjectivesTo evaluate if self-sampling of cervicovaginal fluid using a cytobrush (Viba-brush; Rovers Medical Devices B.V., Oss, The Netherlands) and a solid support such as the Whatman Indicating FTA® Elute cartridge (GE Healthcare, United Kingdom) can be used for reliable typing of human papillomavirus (HPV), as compared to cervical samples obtained by a physician using a cytobrush and the indicating FTA® Elute Micro card and biopsy analysis.Study designA total of 50 women with a previous high-risk (HR) HPV positive test were invited to perform self-sampling using the Viba-brush and the FTA cartridge and thereafter a physician obtained a cervical sample using the cytobrush and a FTA card, together with a cervical biopsy for histology and HPV typing. Detection of HR-HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 was performed using three multiplex real-time polymerase chain reaction (PCR) assays.ResultAll samples contained sufficient amounts of genomic DNA and the self-samples yielded on average 3.5 times more DNA than those obtained by the physician. All women that were positive for HR-HPV in the biopsy sample also typed positive both by self-sampling and physician-obtained sampling. For women with a histological diagnosis of cervical intraepithelial neoplasia grades 2–3 (CIN 2–3) all three HPV samples showed 100% concordance. A higher number of women were HPV positive by self-sampling than by physician-obtained sampling or by biopsy analysis.ConclusionThe Viba-brush and the FTA cartridge are suitable for self-sampling of vaginal cells and subsequent HR-HPV typing.
|
|
21. |
- Gustavsson, Inger, et al.
(författare)
-
Use of FTA card for dry collection, transportation and storage of cervical cell specimen to detect high-risk HPV
- 2009
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 46:2, s. 112-116
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The FTA elute micro card, which enable the collection, transport, and archiving of DNA could be an attractive alternative to a liquid based collection system for detection of human papillomavirus (HPV). OBJECTIVES: To develop a method based on the FTA elute micro card for dry collection of cervical epithelial cell samples, suitable for subsequent PCR-based HPV testing. STUDY DESIGN: The method was evaluated by a comparison of the DNA collected by cytobrush and the regular FTA elute micro card from 50 cervical cell samples. The method was then used to estimate the DNA amount in 1040 samples applied to the indicating FTA elute micro card. RESULT: The agreement in HPV positivity between the cytobrush and FTA samples (94%) was excellent (kappa=0.88, 95% CI 0.748-1). All the 1040 samples on the indicating FTA card had sufficient amounts of genomic DNA (>10 copies of a single copy gene) to be suitable for HPV typing. In 53 of the 1040 women the day in the menstrual cycle was noted, and the copy number during follicular phase day 9-13 was found to be statistically significantly lower than for the other three stages in the menstrual cycle (day 4-8, 14, >14) and during menopause. CONCLUSION: The indicating FTA elute micro card represents a suitable medium for collection of cervical cell samples, although follow-up studies are needed to verify the detection of low frequency HPV types.
|
|
22. |
- Gustavsson, Lars, et al.
(författare)
-
Rectal swabs can be used for diagnosis of viral gastroenteritis with a multiple real-time PCR assay.
- 2011
-
Ingår i: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. - : Elsevier BV. - 1873-5967. ; 51:4, s. 279-82
-
Tidskriftsartikel (refereegranskat)abstract
- Viral agents, especially norovirus, are the most common cause of nosocomial spread of epidemic gastroenteritis (GE). Rapid and reliable detection of these agents could reduce the risk of outbreaks.
|
|
23. |
- Hakacova, Nina, et al.
(författare)
-
First therapeutic use of Artesunate in treatment of human herpesvirus 6B myocarditis in a child.
- 2013
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 57:2, s. 157-160
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human herpesvirus 6 (HHV-6) is an important cause of fulminant or acute viral myocarditis. However, insufficiency of standard antiviral treatment against HHV-6 is an emerging problem. OBJECTIVES: To describe the case of child with HHV-6 myocarditis who was treated by unloading with a left ventricular assist device and Artesunate. STUDY DESIGN: Case report supported by histological and viral diagnoses via a combination of histology/immunohistochemistry and polymerase chain reaction techniques performed on cardiac tissues before and after treatment. RESULTS: Following therapeutic intervention, the clinical status and heart function improved. Endomyocardial biopsies revealed decreased levels of HHV-6B DNA in the myocardium and the disappearance of histological findings in support of lymphocytic myocarditis. Left ventricular assist device could be explanted. No adverse effects of Artesunate were noted. CONCLUSIONS: In addition to existing heart failure treatments, Artesunate can be considered as an effective candidate for clinical use in cases of HHV-6B associated myocarditis.
|
|
24. |
|
|
25. |
|
|
26. |
|
|
27. |
- Johansen, Kari, et al.
(författare)
-
Norovirus strains belonging to the GII.4 genotype dominate as a cause of nosocomial outbreaks of viral gastroenteritis in Sweden 1997-2005 - Arrival of new variants is associated with large nation-wide epidemics
- 2008
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 42:2, s. 129-134
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In recent years an increase of the incidence of nosocomial outbreaks caused by noroviruses has been observed throughout Sweden, with high peaks noted in the winter seasons 2002/2003 and 2004/2005, respectively. Objectives: To phylogenetically characterize norovirus strains causing nosocomial outbreaks from 1997 to 2005 and estimate the impact of norovirus-like disease on the Swedish health care system during the peak season 2002/2003 when a new variant of norovirus occurred. Study design: Stool samples from 115 randomly selected nosocomial outbreaks occurring during 1997-2005 throughout Sweden were studied by RT-PCR and sequencing. In addition, to investigate the impact on the health-care system, a questionnaire was distributed to infection control units (n = 90) serving all Swedish hospitals, nursing homes and other health-care institutions during the largest epidemic of nosocomial outbreaks. Results: Sequencing of 279 nucleotides of the norovirus RNA polymerase gene in stools containing norovirus RNA showed that strains belonging to the GII.4 genotype dominated. Each of the two large epidemics was due to a new variant within this cluster. The questionnaire revealed that 30,000-35,000 episodes of nosocomial norovirus-like infections occurred in 80 of 82 major Swedish hospitals affected in 2002/2003. Conclusion: New norovirus variants within the cluster GGII.4 may have a major impact on the health-care system. (c) 2008 Elsevier B.V. All rights reserved.
|
|
28. |
|
|
29. |
|
|
30. |
|
|
31. |
- Laiho, Jutta E., et al.
(författare)
-
Relative sensitivity of immunohistochemistry, multiple reaction monitoring mass spectrometry, in situ hybridization and PCR to detect Coxsackievirus B1 in A549 cells
- 2016
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 77, s. 21-28
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Enteroviruses (EVs) have been linked to the pathogenesis of several diseases and there is a collective need to develop improved methods for the detection of these viruses in tissue samples. Objectives: This study evaluates the relative sensitivity of immunohistochemistry (IHC), proteomics, in situ hybridization (ISH) and RT-PCR to detect one common EV, Coxsackievirus B1 ( CVB1), in acutely infected human A549 cells in vitro. Study design: A549 cells were infected with CVB1 and diluted with uninfected A549 cells to produce a limited dilution series in which the proportion of infected cells ranged from 10-1 to 10-8. Analyses were carried out by several laboratories using IHC with different anti-EV antibodies, ISH with both ViewRNA and RNAScope systems, liquid chromatography multiple reaction monitoring mass spectrometry (LC/MRM/MS/MS), and two modifications of RT-PCR. Results: RT-PCR was the most sensitive method for EV detection yielding positive signals in the most diluted sample (10-8). LC/MRM/MS/MS detected viral peptides at dilutions as high as 10-7. The sensitivity of IHC depended on the antibody used, and the most sensitive antibody (Dako clone 5D8/1) detected virus proteins at a dilution of 10(-6), while ISH detected the virus at dilutions of 10(-4). Conclusions: All methods were able to detect CVB1 in infected A549 cells. RT-PCR was most sensitive followed by LC/MRM/MS/MS and then IHC. The results from this in vitro survey suggest that all methods are suitable tools for EV detection but that their differential sensitivities need to be considered when interpreting the results from such studies.
|
|
32. |
- Leparc-Goffart, Isabelle, et al.
(författare)
-
Development and validation of real-time one-step reverse transcription-PCR for the detection and typing of dengue viruses
- 2009
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 45:1, s. 61-66
-
Tidskriftsartikel (refereegranskat)abstract
- Background:Dengue virus, transmitted by mosquitoes, causes every year 50 million cases of dengue fever. A standardize method for early diagnosis is still needed for clinical diagnosis and epidemiological studies.Objective: To develop and validate for sensitivity, specificity, linearity and precision real-time one-step RT-PCR for the detection of dengue viruses.Study design: Multiple alignments of dengue virus sequence for each serotype were done and used to develop five systems of real-time RT-PCR to detect all dengue virus strains and then identify the serotype. These systems were validated on synthetic RNA transcripts for specificity, sensitivity, precision and linearity and then applied on series of human samples.Results: The specificity of each system was determined by sequence alignments and experimentally tested on different flaviviruses. Methods precision and linearity were statistically validated. Each of these systems allowed the detection of less than one infectious particle and was able to detect and serotype quickly dengue virus in human samples where infectious virus cannot be isolated anymore.Conclusions: These systems are valuable tools for dengue virus diagnosis and epidemiological studies. Standardization and validation of these methods allow an easy transfer to diagnostic laboratories.
|
|
33. |
|
|
34. |
- Löfström, Emma, et al.
(författare)
-
Dynamics of IgG-avidity and antibody levels after Covid-19
- 2021
-
Ingår i: Journal of Clinical Virology. - Amsterdam : Elsevier. - 1386-6532 .- 1873-5967. ; 144
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A potentially important aspect of the humoral immune response to Covid-19 is avidity, the overall binding strength between antibody and antigen. As low avidity is associated with a risk of re- infection in several viral infections, avidity might be of value to predict risk for reinfection with covid-19. Objectives: The purpose of this study was to describe the maturation of IgG avidity and the antibody-levels over time in patients with PCR-confirmed non-severe covid-19. Study design: Prospective longitudinal cohort study including patients with RT-PCR confirmed covid-19. Blood samples were drawn 1, 3 and 6 months after infection. Antibody levels and IgG-avidity were analysed. Results: The majority had detectable s- and n-antibodies (88,1%, 89,1%, N = 75). The level of total n-antibodies significantly increased from 1 to 3 months (median value 28,3 vs 39,3 s/co, p<0.001) and significantly decreased from 3 to 6 months (median value 39,3 vs 17,1 s/co, p<0.001). A significant decrease in the IgG anti-spike levels (median value 37,6, 24,1 and 18,2 RU/ml, p<0.001) as well as a significant increase in the IgG-avidity index (median values 51,6, 66,0 and 71,0%, p<0.001) were seen from 1 to 3 to 6 months. Conclusion: We found a significant ongoing increase in avidity maturation after Covid-19 whilst the levels of antibodies were declining, suggesting a possible aspect of long-term immunity. © 2021 The Authors. Published by Elsevier B.V.
|
|
35. |
- Malm, Kerstin, 1960-, et al.
(författare)
-
Evaluation of the Veris MDx (TM) system for quantification of Hepatitis B DNA and Hepatitis C and HIV-1 RNA in a medium sized University Hospital
- 2016
-
Ingår i: Journal of Clinical Virology. - : Elsevier. - 1386-6532 .- 1873-5967. ; 82, s. S27-S27
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: In the diagnosis and treatment of Hepatitis B (HBV), Hepatitis C (HCV) and HIV, it is crucial to detect and quantify viral nucleic acid. Patients on therapy are monitored continuously to out-rule relapses or reinfections (HCV) while for patients with HIV these tests are important to early on detect potential break-throughs due to resistance development. Quantification methods are today more standardized and fast but still with no opportunity to analyze the samples with full random access. Recently the VERIS MDxTMplatform from Beckman Coulter with this possibility was launched.Objectives: To evaluate a new, random access laboratory instrument for the simultaneous detection and quantification of HBV, HCV and HIV-1.Methods: WHO standards for HBV-DNA, HCV-RNA and HIV-1-RNA provided from the National Institute for Biological Standards and Control (NIBSC) were diluted down to the designated lowest level of detection and analyzed in triplicates on the Veris MDxTM(Beckman Coulter Inc. 250 S. Kraemer Blvd. Brea, CA U.S.A.) instrument. Plasma samples from routine laboratory testing were analyzed and compared to the routine methods used at our hospital or the referral hospital, for HBV; COBAS®AmpliPrep/COBAS® TaqMan®HBV Test, v2.0 (Roche Molecular Diagnostics, 4300 Hacienda Drive, Pleasanton, CA, USA) (Karolinska University Hospital Huddinge), for HCV; COBAS® TaqMan®HCV Test v2.0 for use with the High Pure System (Roche) (Örebro) and for HIV; Aptima HIV-1 Quant Dx Assay (Hologic Inc. 250 Campus Drive Marlborough, MA, USA) (Örebro). 55 samples for HBV, 120 samples for HCV and 60 samples for HIV have been analyzed so far. The absolute majority of samples for HCV and HIV analysis were from patients on treatment. All viral load data were analyzed as log10-transformed values.Results: The Veris MDxTMshowed good compatibility to the designated quantities of the WHO standards (except for HIV-1 where a slight over-quantification could be observed for dilutions in the higher range, i.e. >1000 copies/mL). The limits of detection assigned by the manufacturer could be confirmed. In clinical samples the Veris MDxTM showed similar results to the comparators with a correlation for quantifiable samples of 0.94 (HBV), 0.98 (HCV) and 0.98 (HIV). The Veris MDxTMshowed a slightly higher sensitivity though as DNA/RNA was detected in 4 samples for HBV, 8 for HCV and 7 for HIV when the comparator method did not. The opposite was seen in 0, 0 and 6 samples respectively.Conclusion: The Veris MDxTMfor quantitative analysis of HBV, HCV and HIV nucleic acids showed good correlation to the comparator methods used in this study with a tendency of higher sensitivity for the detection of HBV and HCV. The Instrument provides an easy, fast and flexible method for quantification of RNA and DNA in plasma samples.
|
|
36. |
|
|
37. |
- Mohamed, Nahla, et al.
(författare)
-
Development and evaluation of a broad reacting SYBR-green based quantitative real-time PCR for the detection of different hantaviruses
- 2013
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 56:4, s. 280-285
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hantaviruses are endemic in most parts of the world and cause hundreds of thousand human cases of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) annually throughout Eurasia and the Americas. They are zoonotic viruses, most commonly transmitted to humans by aerosolized rodent excreta. New hantaviruses are frequently discovered in previously unknown reservoir species and geographic areas. Consequently, there is a need to improve hantavirus diagnostics. OBJECTIVES: This paper describes the design and evaluation of a rapid and robust quantitative real-time PCR (QRT-PCR) assay able to detect a wide range of hantaviruses. STUDY DESIGN: Primers with the potential to detect different hantaviruses were designed from conserved regions of different hantavirus L segments, as identified from multiple sequence alignments. RESULTS: By using SYBR-green-based QRT-PCR 100-1000 target molecules of in vitro produced RNA and less than 100 copies of hantavirus RNA from different hantavirus clades and regions of the world were detected. When using the assay on clinical samples from patients with acute HFRS, Puumala hantavirus (PUUV) RNA was confirmed in all previously positive samples. Notably, the broad reacting L-segment QRT-PCR also detected viral RNA in HFRS patient samples, previously negative by a QRT-PCR targeting the S segment of PUUV. CONCLUSIONS: This novel assay provides a powerful tool for diagnosis of hantaviruses from different clades and regions and may also be useful in surveys with the purpose of finding new hantaviruses in rodent or insectivore species.
|
|
38. |
|
|
39. |
- Nenonen, Nancy P, 1943, et al.
(författare)
-
Molecular analysis of an oyster-related norovirus outbreak.
- 2009
-
Ingår i: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. - : Elsevier BV. - 1873-5967. ; 45:2, s. 105-8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Contaminated raw oysters were implicated in a severe outbreak of norovirus (NoV) gastroenteritis affecting 30 restaurant guests. OBJECTIVES: To define the outbreak source by using molecular methods to characterize NoV strains detected in patient and oyster samples. STUDY DESIGN: Molecular epidemiological studies based on nucleotide sequencing and phylogenetic analyses of patient and oyster NoV strains, and comparison to background dataset. RESULTS: NoV genotype (G) I.1 was detected in the one patient stool analyzed by in-house TaqMan real time RT-PCR and classical nested RT-PCR targeting NoV RNA-dependent polymerase (RdRp, 285 nt), and by nested RT-PCR targeting RdRp-capsid-poly(A)-3' (3085 nt). Patient strain showed >or=99% similarity (285 nt) with three NoV strains detected in two of five oysters examined by classical nested RT-PCR (RdRp). A third oyster tested positive for NoV GII.3. Phylogenetic analysis showed clustering of patient and oyster strains related to this outbreak with GI.1 strains from previous local outbreaks, and mussel studies. CONCLUSIONS: Sequence data revealed >or=99% similarity (285 nt) between NoV GI.1 strains detected in patient stool and suspect oysters, linking the contaminated oysters to the outbreak. Identification of human NoV GI and GII strains in oysters indicated contamination of human fecal origin, presumably from inappropriate storage in the harbor. Comparative long-fragment analysis of the patient strain revealed 99% similarity (3085 nt) with NoV GI.1 strains detected in previous outbreaks and environmental mussel studies from West Sweden, 87% with M87661 (Norwalk68) and 96% with L23828 (SRSV-KY-89/89/J). These results indicated considerable genomic stability of NoV GI.1 strains over time.
|
|
40. |
- Nicol, Alcina F., et al.
(författare)
-
A summary of the 25th International Papillomavirus Conference 2009: Vaccines, screening, epidemiology and therapeutics
- 2010
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532. ; 47:3, s. 208-215
-
Forskningsöversikt (refereegranskat)abstract
- The 25th International Papillomavirus Conference was held in Malmo, Sweden, on May 8-14, 2009. The conference encompassed all areas of papillomavirus (PV) research, from clinical vaccinology to molecular biology. This review highlights some of the 237 presentations and 887 abstracts which were presented and summarizes sessions on prophylactic vaccines, screening, epidemiology and therapeutics. Important advances included identification of variants in four genes associated with HPV persistence, new HPV detection are likely new infections and not latency reactivation, and development of effective DNA vaccines that targets E6/E7 genes of HPV11. Also, many studies from different countries demonstrated that HPV vaccination provided sustained protection and substantial reduction of disease burden in both women and men, and in HIV-infected neonates. All the references cited are from the abstract book of the IPV Conference. See http://www.hpv2009.org/. (C) 2009 Elsevier B.V. All rights reserved.
|
|
41. |
- Nordgren, Johan, et al.
(författare)
-
SARS-CoV-2 rapid antigen test: High sensitivity to detect infectious virus
- 2021
-
Ingår i: Journal of Clinical Virology. - : ELSEVIER. - 1386-6532 .- 1873-5967. ; 140
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The COVID-19 pandemic has highlighted the need for rapid, cost effective and easy-to-use diagnostic tools for SARS-CoV-2 infections that can be used in point of care settings to limit disease transmission. Objective: We evaluated two rapid antigen immunochromatographic tests, Abbott PanbioTM COVID-19 Ag Rapid Test (Panbio) and Zhejiang Orient Gene/Healgen Biotech Coronavirus Ag rapid test cassette (Orient gene) for detection of infectious SARS-CoV-2. Results: The tests were evaluated on nasopharyngeal samples taken from individuals having respiratory and/or COVID-19 related symptoms, which had been analyzed for SARS-CoV-2 RNA using real-time PCR. In total 156 PCR-positive, and 130 (Panbio) and 176 (Orient Gene) PCR-negative samples were analyzed. Overall sensitivity and specificity were 71.8% and 100% for Panbio and 79.5% and 74.4% for the Orient Gene test respectively. The false positives by the Orient Gene test were verified as SARS-CoV-2 negative by in-house real-time PCR assay and were negative for the four seasonal coronaviruses. Subgroup analysis revealed that the antigen tests had high sensitivity for samples with Ct-values <25 (>88%) and for samples containing infectious viruses as determined by cultivation on Vero cells, 94.1% and 97.1% for the Panbio and Orient gene tests, respectively. Furthermore, both tests had a sensitivity of <50 picogram for nucleocapsid protein. No sample with a Ct-value >27 was shown to contain infectious virus. Conclusion: The results indicate that the rapid antigen tests, especially the Panbio tests may be a valuable tool to detect contagious persons during the ongoing pandemic.
|
|
42. |
- Omarsdottir, Soley, et al.
(författare)
-
High prevalence of cytomegalovirus infection in surgical intestinal specimens from infants with necrotizing enterocolitis and spontaneous intestinal perforation : A retrospective observational study
- 2017
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 93, s. 57-64
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Necrotizing enterocolitis (NEC) is a severe, often fatal gastrointestinal emergency that predominantly affects preterm infants, and there is evidence that neonatal cytomegalovirus (CMV) infection may in some cases contribute to its pathogenesis.Objectives: This study aimed to evaluate the prevalence of CMV in infants with NEC.Study design: Seventy intestinal specimens from 61 infants with NEC, spontaneous intestinal perforation (SIP), or related surgical complications were collected at Karolinska University Hospital and Uppsala University Hospital, Sweden. Ten specimens from autopsied infants without bowel disease served as controls. Samples were analyzed for CMV immediate-early antigen (IEA), CMV late antigen (LA), 5-lipoxigenase (5LO) and CMV-DNA by immunohistochemistry (IHC) and in situ hybridization (ISH), respectively. In 10 index samples, CMV DNA was analyzed with Taqman PCR after laser capture microdissection (LCM) of cells positive for CMV IEA by IHC.Results: CMV IEA was detected by IHC in 57 (81%) and CMV LA in 45 (64%) of 70 intestinal specimens from index cases; 2 (20%) of 10 control specimens were positive for both antigens. 5LO was detected in intestinal tissue section obtained from all examined index and controls. CMV DNA was detected in 4 of 10 samples (40%) after LCM. By ISH, all 13 IHC-IEA-positive samples were positive for CMV DNA; however, 3 of 5 IHC-IEAnegative samples (60%) were also positive.Conclusions: CMV-specific antigens and CMV DNA were highly prevalent in intestinal specimens from infants with NEC, SIP, and related surgical complications. Our findings provide further evidence that neonatal CMV infection contributes to the pathogenesis of these diseases and may affect patient outcome.
|
|
43. |
- Papa, Anna, et al.
(författare)
-
Recent advances in research on Crimean-Congo hemorrhagic fever
- 2015
-
Ingår i: Journal of Clinical Virology. - : Elsevier. - 1386-6532 .- 1873-5967. ; 64, s. 137-143
-
Tidskriftsartikel (refereegranskat)abstract
- Crimean-Congo hemorrhagic fever (CCHF) is an expanding tick-borne hemorrhagic disease with increasing human and animal health impact. Immense knowledge was gained over the past 10 years mainly due to advances in molecular biology, but also driven by an increased global interest in CCHFV as an emerging/re-emerging zoonotic pathogen. In the present article, we discuss the advances in research with focus on CCHF ecology, epidemiology, pathogenesis, diagnostics, prophylaxis and treatment. Despite tremendous achievements, future activities have to concentrate on the development of vaccines and antivirals/therapeutics to combat CCHF. Vector studies need to continue for better public and animal health preparedness and response. We conclude with a roadmap for future research priorities. (C) 2014 Elsevier B.V. All rights reserved.
|
|
44. |
|
|
45. |
- Paues, Jakob, et al.
(författare)
-
Fatal progressive multifocal leukoencephalopathy in a patient with non-Hodgkin lymphoma treated with rituximab
- 2010
-
Ingår i: Journal of Clinical Virology. - : Elsevier Science B.V., Amsterdam.. - 1386-6532 .- 1873-5967. ; 48:4, s. 291-293
-
Tidskriftsartikel (refereegranskat)abstract
- We report a case of progressive multifocal leukoencephalopathy (PML) in a woman with non-Hodgkin lymphoma treated with chemotherapy in combination with rituximab. She presented with rapid deterioration of vision and subsequently cognitive decline. Magnetic resonance imaging (MRI) of the brain raised the suspicion of PML. The first PCR analysis of the cerebrospinal fluid (CSF) was negative, but a second sample was positive for JC virus DNA. Anti-viral treatment was ineffective and the patient died 7 months after debut of symptoms. Our case emphasizes the importance of the awareness of PML in patients with progressive neurological symptoms treated with antilymphocytic drugs and that consecutive CSF analyses may be needed to detect the JC virus.
|
|
46. |
- Persson, Linn, et al.
(författare)
-
Elevated antibody reactivity to measles virus Ncore protein among patients with multiple sclerosis and their healthy siblings with intrathecal oligoclonal immunoglobulin G production
- 2014
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 61:1, s. 107-112
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with multiple sclerosis (MS) and their healthy siblings with the MS oligoclonal bands (OCB) trait, (a hyperimmune condition in form of two or more CSF enriched OCBs) harbor in cerebrospinal fluid (CSF) and serum elevated immunoglobulin G (IgG) titers against measles crude whole-cell antigen. The underlying mechanism resulting in the increased IgG antibody reactivity to measles remains unclear. The response may represent specific IgG reactivity to measles antigens or unspecific auto-antibodies targeting cellular components in the crude whole virus antigens commonly used in detection assays.
|
|
47. |
|
|
48. |
|
|
49. |
- Rondahl, E., et al.
(författare)
-
The risk of HCV RNA contamination in serology screening instruments with a fixed needle for sample transfer
- 2014
-
Ingår i: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 60:2, s. 172-173
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Hepatitis C diagnostics involve antibody screening and confirmation of current infection by detection of HCV RNA positivity. In screening instruments with fixed pipetting needle, there is a risk of sample carry-over contamination. Objectives: The aim of this study was to evaluate the risk of such contamination in a proposed clinical setting. Study design: In the present study, known HCV RNA positive (n= 149) and negative (n= 149) samples were analysed by anti-HCV Abbott in an Architect instrument in an alternating fashion in order to test for contamination. Results: In subsequent retesting of the previously HCV RNA-negative samples, six samples (4%) were positive by the Cobas Taqman assay with a maximum level of 33. IU/mL. The results show that there is a risk for transfer of HCV in the Architect instrument but they also show that the levels of HCV RNA observed are low. Conclusions: We conclude that complementary HCV RNA testing on samples identified as anti-HCV positive by screening can be recommended because the complementary results are reliable in the majority of cases when either HCV RNA is negative or HCV RNA is positive with a level >1000. IU/mL. In a minority of cases, with low HCV RNA after anti-HCV antibody screening, cross-contamination should be suspected and a new sample requested for HCV RNA testing. This strategy would reduce the need for obtaining a new sample from the vast majority of patients with a newly discovered HCV antibody positivity. © 2014 The Authors.
|
|
50. |
- Rosenbaum, William, et al.
(författare)
-
Hybrid capture-based next-generation sequencing of new and old world Orthohantavirus strains and wild-type Puumala isolates from humans and bank voles
- 2024
-
Ingår i: Journal of Clinical Virology. - : Elsevier. - 1386-6532 .- 1873-5967. ; 172
-
Tidskriftsartikel (refereegranskat)abstract
- Orthohantaviruses, transmitted primarily by rodents, cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in the Americas. These viruses, with documented human-to-human transmission, exhibit a wide case-fatality rate, 0.5–40 %, depending on the virus species, and no vaccine or effective treatment for severe Orthohantavirus infections exists. In Europe, the Puumala virus (PUUV), carried by the bank vole Myodes glareolus, causes a milder form of HFRS. Despite the reliance on serology and PCR for diagnosis, the three genomic segments of Swedish wild-type PUUV have yet to be completely sequenced.We have developed a targeted hybrid-capture method aimed at comprehensive genomic sequencing of wild-type PUUV isolates and the identification of other Orthohantaviruses. Our custom-designed panel includes >11,200 probes covering the entire Orthohantavirus genus. Using this panel, we sequenced complete viral genomes from bank vole lung tissue, human plasma samples, and cell-cultured reference strains. Analysis revealed that Swedish PUUV isolates belong to the Northern Scandinavian lineage, with nucleotide diversity ranging from 2.8 % to 3.7 % among them. Notably, no significant genotypic differences were observed between the viral sequences from reservoirs and human cases except in the nonstructural protein.Despite the high endemicity of PUUV in Northern Sweden, these are the first complete Swedish wild-type PUUV genomes and substantially increase our understanding of PUUV evolution and epidemiology. The panel's sensitivity enables genomic sequencing of human samples with viral RNA levels reflecting the natural progression of infection and underscores our panel's diagnostic value, and could help to uncover novel Orthohantavirus transmission routes.
|
|