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      Molecular Detection of Orthohantavirus puumalaense in Plasma and Urine Samples from Hospitalized Patients Presenting with a Serologically Confirmed Acute Hantavirus Infection in France

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      a , , b , a , c , a , a , c , d , b , e , for The HANTADIAG Study Group
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      Journal of Clinical Microbiology
      American Society for Microbiology
      France, molecular diagnostic, nephropathia epidemica, orthohantavirus, plasma, Puumala hantavirus, urine, hemorrhagic fever with renal syndrome

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          ABSTRACT

          Molecular detection of Orthohantavirus puumalaense (PUUV) RNA during the course of the disease has been studied in blood of patients in Sweden and Slovenia. The use of urine has been poorly investigated. The aims of this work were to study PUUV RNA detection in plasma from a cohort of patients in France where a different PUUV lineage circulates and to assess the use of urine instead of plasma. Matched plasma and urine samples were collected daily from hospitalized patients presenting with fever, pain, and thrombocytopenia within the last 8 days and testing positive for IgM and IgG against PUUV in serum collected at inclusion and/or approximately 1 month after release. RNA was extracted from samples, and PUUV RNA was detected using real-time reverse transcription-PCR for plasma and urine samples. Sixty-seven patients presented a serologically confirmed acute hantavirus infection. At inclusion, PUUV RNA was detected in plasma from 55 of 62 patients (88.7%) sampled within the first week after disease onset, whereas it was detected in 15 of 60 (25.0%) of matched urine samples. It was then detected from 33 (71.7%) and 2 (4.4%) of 46 patients discharged from the hospital during the second week after disease onset, in plasma and urine, respectively. When PUUV RNA was detected in urine it was also detected in plasma, and not vice versa. Detection of PUUV RNA in plasma from hospitalized patients in France is similar to that observed in Sweden and Slovenia. Urine is not an appropriate sample for this detection.

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          Notice

          SECTION I: USE OF THE CLINICAL PRACTICE GUIDELINE This Clinical Practice Guideline document is based upon the best information available as of February 2011. It is designed to provide information and assist decision-making. It is not intended to define a standard of care, and should not be construed as one, nor should it be interpreted as prescribing an exclusive course of management. Variations in practice will inevitably and appropriately occur when clinicians take into account the needs of individual patients, available resources, and limitations unique to an institution or type of practice. Every health-care professional making use of these recommendations is responsible for evaluating the appropriateness of applying them in the setting of any particular clinical situation. The recommendations for research contained within this document are general and do not imply a specific protocol. SECTION II: DISCLOSURE Kidney Disease: Improving Global Outcomes (KDIGO) makes every effort to avoid any actual or reasonably perceived conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the Work Group. All members of the Work Group are required to complete, sign, and submit a disclosure and attestation form showing all such relationships that might be perceived or actual conflicts of interest. This document is updated annually and information is adjusted accordingly. All reported information is published in its entirety at the end of this document in the Work Group members' Biographical and Disclosure Information section, and is kept on file at the National Kidney Foundation (NKF), Managing Agent for KDIGO.
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            Hantavirus infections

            Over the past few decades understanding and recognition of hantavirus infection has greatly improved worldwide, but both the amplitude and the magnitude of hantavirus outbreaks have been increasing. Several novel hantaviruses with unknown pathogenic potential have been identified in a variety of insectivore hosts. With the new hosts, new geographical distributions of hantaviruses have also been discovered and several new species were found in Africa. Hantavirus infection in humans can result in two clinical syndromes: haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) caused by Old World and New World hantaviruses, respectively. The clinical presentation of HFRS varies from subclinical, mild, and moderate to severe, depending in part on the causative agent of the disease. In general, HFRS caused by Hantaan virus, Amur virus and Dobrava virus are more severe with mortality rates from 5 to 15%, whereas Seoul virus causes moderate and Puumala virus and Saaremaa virus cause mild forms of disease with mortality rates <1%. The central phenomena behind the pathogenesis of both HFRS and HCPS are increased vascular permeability and acute thrombocytopenia. The pathogenesis is likely to be a complex multifactorial process that includes contributions from immune responses, platelet dysfunction and the deregulation of endothelial cell barrier functions. Also a genetic predisposition, related to HLA type, seems to be important for the severity of the disease. As there is no effective treatment or vaccine approved for use in the USA and Europe, public awareness and precautionary measures are the only ways to minimize the risk of hantavirus disease.
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              Detection of dengue virus genome in urine by real-time reverse transcriptase PCR: a laboratory diagnostic method useful after disappearance of the genome in serum.

              The reemergence of dengue virus (DENV) infection has created a requirement for improved laboratory diagnostic procedures. In this study, DENV genome detection in urine was evaluated as a diagnostic method. The DENV genome was detected by real-time reverse transcriptase PCR (RT-PCR) in urine and serum of dengue patients. The detection rate of DENV genome in urine was 25% (2/8) on disease days 0 to 3 and 32% (7/22) on days 4 to 5. The rate was 50% or higher on days 6 to 16, 52% (11/21) on days 6 to 7, 78% (7/9) on days 8 to 9, 80% (4/5) on days 10 to 11, 50% (2/4) on days 12 to 13, and 60% (3/5) on days 14 to 16. The last positive urine sample was on day 16. The detection rates in serum were highest on days 0 to 3 and were greater than 50% on days 0 to 7. Detection rates decreased thereafter, and the last positive detection was on day 11. These results indicate that the time frames for positive detection differ between urine and serum samples, whereby detection rates of 50% or higher are evident between days 6 to 16 for urine samples and days 0 to 7 for serum samples. Nucleotide sequences of PCR products were identical between urine and serum samples. The detection of DENV genome in urine samples by real-time RT-PCR is useful to confirm DENV infection, particularly after viremia disappears.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                J Clin Microbiol
                J Clin Microbiol
                jcm
                Journal of Clinical Microbiology
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                0095-1137
                1098-660X
                24 July 2023
                August 2023
                24 July 2023
                : 61
                : 8
                : e00372-23
                Affiliations
                [a ] Institut Pasteur, Université Paris Cité, Unité Environnement et Risques Infectieux, Centre National de Référence Hantavirus, Paris, France
                [b ] Institut Pasteur, Université Paris Cité, Unité Epidémiologie des Maladies Emergentes, Paris, France
                [c ] Institut Pasteur, Université Paris Cité, Centre de Recherche Translationnelle, Paris, France
                [d ] Centre Hospitalier Intercommunal nord Ardennes, Laboratoire de Biologie Médicale, Charleville- Mézières, France
                [e ] Centre Hospitalier Intercommunal nord Ardennes, Service de Médecine Interne et Maladies Infectieuses, Charleville- Mézières, France
                Institut Pasteur, Université Paris Cité, Unité Environnement et Risques Infectieux, Centre National de Référence Hantavirus, Paris, France.
                Institut Pasteur, Université Paris Cité, Unité Environnement et Risques Infectieux, Centre National de Référence Hantavirus, Paris, France.
                Institut Pasteur, Université Paris Cité, Unité Environnement et Risques Infectieux, Centre National de Référence Hantavirus, Paris, France.
                Institut Pasteur, Université Paris Cité, Unité Environnement et Risques Infectieux, Centre National de Référence Hantavirus, Paris, France.
                Institut Pasteur, Université Paris Cité, Unité Epidémiologie des Maladies Emergentes, Paris, France.
                Institut Pasteur, Université Paris Cité, Centre de Recherche Translationnelle, Paris, France.
                Institut Pasteur, Université Paris Cité, Unité Epidémiologie des Maladies Emergentes, Paris, France.
                Institut Pasteur, Université Paris Cité, Centre de Recherche Translationnelle, Paris, France.
                Centre Hospitalier Intercommunal nord Ardennes, Service de Médecine Interne et Maladies Infectieuses, Charleville- Mézières, France.
                Centre Hospitalier Intercommunal nord Ardennes, Laboratoire de Biologie Médicale, Charleville- Mézières, France.
                Institut Pasteur, Université Paris Cité, Unité Environnement et Risques Infectieux, Centre National de Référence Hantavirus, Paris, France.
                Centre Hospitalier Intercommunal nord Ardennes, Service de Néphrologie, Charleville- Mézières, France.
                Hôpital Nord Franche-Comté, Service d’Infectiologie, Trévenans, France.
                Hôpital Nord Franche-Comté, Laboratoire de Biologie Médicale, Trévenans, France.
                Centre Hospitalier Universitaire de Besançon, Service des Maladies Infectieuses et Tropicales, Besançon, France.
                Centre Hospitalier Universitaire de Besançon, Laboratoire de Virologie, Besançon, France.
                Centre Hospitalier Universitaire Dijon-Bourgogne, Département d’Infectiologie, Dijon, France.
                Centre Hospitalier Universitaire Dijon-Bourgogne, Laboratoire de Sérologie-Virologie, Dijon, France.
                Centre Hospitalier de Laon, Service de Médecine Interne - Maladies Infectieuses, Laon, France.
                Centre Hospitalier de Laon, Service des Urgences, Laon, France.
                Centre Hospitalier de Laon, Laboratoire d’Analyses Médicales - Hygiène Hospitalière, Laon, France.
                CHRU-Nancy, Université de Lorraine, Service Maladies Infectieuses et Tropicales, Nancy, France; Université de Lorraine, APEMAC, Nancy, France.
                CHRU-Nancy, Université de Lorraine, Département de Microbiologie, Laboratoire de Virologie, Nancy, France.
                Centre Hospitalier Universitaire de Reims, Service de Médecine Interne, Maladies Infectieuses et Immunologie Clinique, Reims, France.
                Centre Hospitalier Universitaire de Reims, Service de Néphrologie, Reims, France.
                Centre Hospitalier Universitaire de Reims, Laboratoire de Bactériologie-Virologie-Hygiène-Parasitologie-Mycologie, Reims, France.
                Centre Hospitalier Louis Jaillon, Service de Médecine, Saint-Claude, France.
                Centre Hospitalier de Lons-le Saunier, Laboratoire de Biologie Médicale, Lons-le-Saunier, France.
                Centre Hospitalier de Verdun Saint-Mihiel, Service territorial Dialyse et Néphrologie, Verdun, France.
                Centre Hospitalier de Verdun Saint-Mihiel, Laboratoire de Biologie Médicale, Verdun, France.
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                Author notes

                The authors declare no conflict of interest.

                Author information
                https://orcid.org/0000-0002-3712-941X
                https://orcid.org/0000-0003-2892-4216
                Article
                00372-23 jcm.00372-23
                10.1128/jcm.00372-23
                10446862
                37486218
                e852c6b2-3b3e-4275-bda9-33998ca4820d
                Copyright © 2023 Reynes et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 28 March 2023
                : 31 May 2023
                : 5 June 2023
                Page count
                Figures: 1, Tables: 3, Equations: 0, References: 31, Pages: 9, Words: 5986
                Funding
                Funded by: Direction Generale de l'Offre de Soins (French Ministry of Health and Prevention);
                Award ID: PHRC-N 2014.0063
                Award Recipient :
                Categories
                Virology
                virology, Virology
                Custom metadata
                August 2023

                Microbiology & Virology
                france,molecular diagnostic,nephropathia epidemica,orthohantavirus,plasma,puumala hantavirus,urine,hemorrhagic fever with renal syndrome

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