Browsing by Subject "RENAL SYNDROME"

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  • Koskela, Sirpa; Mäkelä, Satu; Strandin, Tomas; Vaheri, Antti; Outinen, Tuula; Joutsi-Korhonen, Lotta; Pörsti, Ilkka; Mustonen, Jukka; Laine, Outi (2021)
    Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome (HFRS), also called nephropathia epidemica (NE), which is mainly endemic in Europe and Russia. The clinical features include a low platelet count, altered coagulation, endothelial activation, and acute kidney injury (AKI). Multiple connections between coagulation pathways and inflammatory mediators, as well as complement and kallikrein-kinin systems, have been reported. The bleeding symptoms are usually mild. PUUV-infected patients also have an increased risk for disseminated intravascular coagulation (DIC) and thrombosis.
  • Hautala, Timo; Partanen, Terhi; Sironen, Tarja; Rajaniemi, Saara-Mari; Hautala, Nina; Vainio, Olli; Vapalahti, Olli; Kauma, Heikki; Vaheri, Antti (2013)
  • Niskanen, Silja; Jääskeläinen, Anne; Vapalahti, Olli; Sironen, Tarja (2019)
    Puumala virus (PUUV) is the most common cause of hantavirus infection in Europe, with thousands of cases occurring particularly in Northern, Central and Eastern Europe and Russia. It causes a mild form of hemorrhagic fever with renal syndrome also known as nephropathia epidemica (NE) with clinical picture ranging from mild to severe. Currently, the laboratory diagnosis of NE is mainly based on serology. Here, we evaluated a real-time one-step qRT-PCR (PUUV-qRT-PCR) for detection of PUUV with 238 consecutive diagnostic serum samples from patients with suspected PUUV infection. The PUUV-qRT-PCR was both specific and sensitive for PUUV RNA. The analytical sensitivity (limit of detection) was estimated to be four copies of PUUV per reaction. Altogether 28 out of 30 (93%) PUUV IgM positive samples were positive also for PUUV RNA. No false positives were detected and the specificity was thus 100%. Interestingly, one sample was found positive in PUUV-qRT-PCR prior to subsequent IgM and IgG seroconversion. PUUV-qRT-PCR could be used for diagnostics in the early phase of NE infection and might be helpful especially in the rare severe cases when the patient's condition may deteriorate rapidly.
  • Mantula, Paula; Tietavainen, Johanna; Clement, Jan; Niemelä, Onni; Pörsti, Ilkka; Vaheri, Antti; Mustonen, Jukka; Mäkelä, Satu; Outinen, Tuula (2020)
    Transient proteinuria and acute kidney injury (AKI) are characteristics of Puumala virus (PUUV) infection. Albuminuria peaks around the fifth day and associates with AKI severity. To evaluate albuminuria disappearance rate, we quantified albumin excretion at different time points after the fever onset. The study included 141 consecutive patients hospitalized due to acute PUUV infection in Tampere University Hospital, Finland. Timed overnight albumin excretion (cU-Alb) was measured during the acute phase in 133 patients, once or twice during the convalescent phase within three months in 94 patients, and at six months in 36 patients. During hospitalization, 30% of the patients had moderately increased albuminuria (cU-Alb 20-200 mu g/min), while 57% presented with severely increased albuminuria (cU-Alb >200 mu g/min). Median cU-Alb was 311 mu g/min (range 2.2-6460)
  • Ling, Jiaxin; Verner-Carlsson, Jenny; Eriksson, Per; Plyusnina, Angelina; Loehmus, Mare; Jaerhult, Josef D.; van de Goot, Frank; Plyusnin, Alexander; Lundkvist, Ake; Sironen, Tarja (2019)
    Seoul virus (SEOV) is the etiologic agent of hemorrhagic fever with renal syndrome. It is carried by brown rats (Rattus norvegicus), a commensal rodent that closely cohabitates with humans in urban environments. SEOV has a worldwide distribution, and in Europe, it has been found in rats in UK, France, Sweden, and Belgium, and human cases of SEOV infection have been reported in Germany, UK, France, and Belgium. In the search of hantaviruses in brown rats from the Netherlands, we found both serological and genetic evidence for the presence of SEOV in the local wild rat population. To further decipher the relationship with other SEOV variants globally, the complete genome of SEOV in the Netherlands was recovered. SEOV sequences obtained from three positive rats (captured at close trapping locations at the same time) were found highly similar. Phylogenetic analyses demonstrated that two lineages of SEOV circulate in Europe. Strains from the Netherlands and UK, together with the Baxter strain from US, constitute one of these two, while the second includes strains from Europe and Asia. Our results support a hypothesis of diverse routes of SEOV spread into Europe. These findings, combined with other indications on the expansion of the spatial European range of SEOV, suggest an increased risk of this virus for the public health, highlighting the need for increased surveillance.
  • Outinen, Tuula K.; Mantula, Paula; Jaatinen, Pia; Hämäläinen, Mari; Moilanen, Eeva; Vaheri, Antti; Huhtala, Heini; Mäkelä, Satu; Mustonen, Jukka (2019)
    Most cases of hemorrhagic fever with renal syndrome (HFRS) in Europe are caused by the Puumala hantavirus (PUUV). Typical features of the disease are increased vascular permeability, acute kidney injury (AKI), and thrombocytopenia. YKL-40 is an inflammatory glycoprotein involved in various forms of acute and chronic inflammation. In the present study, we examined plasma YKL-40 levels and the associations of YKL-40 with disease severity in acute PUUV infection. A total of 79 patients treated in Tampere University Hospital during 2005-2014 were studied. Plasma YKL-40 was measured in the acute phase, the recovery phase, and one year after hospitalization. Plasma YKL-40 levels were higher during the acute phase compared to the recovery phase and one year after hospitalization (median YKL-40 142 ng/mL, range 11-3320, vs. 45 ng/mL, range 15-529, vs. 32 ng/mL, range 3-213, p <0.001). YKL-40 level was correlated with the length of hospital stay (r = 0.229, p = 0.042), the levels of inflammatory markers-that is, blood leukocytes (r = 0.234, p = 0.040), plasma C-reactive protein (r = 0.332, p = 0.003), and interleukin-6 (r = 0.544, p <0.001), and maximum plasma creatinine level (r = 0.370, p = 0.001). In conclusion, plasma YKL-40 levels were found to be elevated during acute PUUV infection and correlated with the overall severity of the disease, as well as with the degree of inflammation and the severity of AKI.
  • Vaheri, Antti; Henttonen, Heikki; Mustonen, Jukka (2021)
    Finland has the highest incidence of hantavirus infections globally, with a significant impact on public health. The large coverage of boreal forests and the cyclic dynamics of the dominant forest rodent species, the bank vole Myodes glareolus, explain most of this. We review the relationships between Puumala hantavirus (PUUV), its host rodent, and the hantavirus disease, nephropathia epidemica (NE), in Finland. We describe the history of NE and its diagnostic research in Finland, the seasonal and multiannual cyclic dynamics of PUUV in bank voles impacting human epidemiology, and we compare our northern epidemiological patterns with those in temperate Europe. The long survival of PUUV outside the host and the life-long shedding of PUUV by the bank voles are highlighted. In humans, the infection has unique features in pathobiology but rarely long-term consequences. NE is affected by specific host genetics and risk behavior (smoking), and certain biomarkers can predict the outcome. Unlike many other hantaviruses, PUUV causes a relatively mild disease and is rarely fatal. Reinfections do not exist. Antiviral therapy is complicated by the fact that when symptoms appear, the patient already has a generalized infection. Blocking vascular leakage measures counteracting pathobiology, offer a real therapeutic approach.
  • Charbonnel, Nathalie; Pages, Marie; Sironen, Tarja; Henttonen, Heikki; Vapalahti, Olli; Mustonen, Jukka; Vaheri, Antti (2014)
  • Lederer, Sabine; Lattwein, Erik; Hanke, Merle; Sonnenberg, Karen; Stoecker, Winfried; Lundkvist, Ake; Vaheri, Antti; Vapalahti, Olli; Chan, Paul K. S.; Feldmann, Heinz; Dick, Daryl; Schmidt-Chanasit, Jonas; Padula, Paula; Vial, Pablo A.; Panculescu-Gatej, Raluca; Ceianu, Cornelia; Heyman, Paul; Avsic-Zupanc, Tatjana; Niedrig, Matthias (2013)
  • Clement, Jan; Ahlm, Clas; Avsic-Zupanc, Tatjana; Botten, Jason; Chandran, Kartik; Jonsson, Colleen B.; Kariwa, Hiroaki; Klingstrom, Jonas; Klempa, Boris; Krueger, Detlev H.; Leirs, Herwig; Li, Dexin; Liang, Mifang; Markotic, Alemka; Papa, Anna; Schmaljohn, Connie S.; Tischler, Nicole D.; Ulrich, Rainer G.; Vaheri, Antti; Vial, Cecilia; Yanagihara, Richard; Maes, Piet (2020)
    The 2019 11th International Conference on Hantaviruses (ICH 2019) was organized by the International Society for Hantaviruses (ISH), and held on September 1-4, 2019, at the Irish College, in Leuven, Belgium. These ICHs have been held every three years since 1989. ICH 2019 was attended by 158 participants from 33 countries. The current report summarizes research presented on all aspects of hantavirology: ecology; pathogenesis and immune responses; virus phylogeny, replication and morphogenesis; epidemiology; vaccines, therapeutics and prevention; and clinical aspects and diagnosis.
  • Papa, Anna; Vaheri, Antti; LeDuc, James W.; Krueger, Detlev H.; Avsic-Zupanc, Tatjana; Arikawa, Jiro; Song, Jin-Won; Markotic, Alemka; Clement, Jan; Liang, Mifang; Li, Dexin; Yashina, Liudmila N.; Jonsson, Colleen B.; Schmaljohn, Connie S. (2016)
    The 10th International Conference on Hantaviruses, organized by the International Society on Hantaviruses, was held from May 31-June 3, 2016 at Colorado State University, Fort Collins, CO, USA. These conferences have been held every three years since 1980. The current report summarizes research presented on all aspects of hantavirology: ecology and epidemiology, virus replication, phylogeny, pathogenesis, immune response, clinical studies, vaccines and therapeutics. (C) 2016 Elsevier B.V. All rights reserved.
  • Outinen, Tuula K.; Kuparinen, Taru; Jylhava, Juulia; Leppanen, Sonja; Mustonen, Jukka; Makela, Satu; Porsti, Ilkka; Syrjanen, Jaana; Vaheri, Antti; Hurme, Mikko (2012)
  • Douglas, Kirk Osmond; Samuels, Thelma Alafia; Iheozor-Ejiofor, Rommel; Vapalahti, Olli; Sironen, Tarja; Gittens-St. Hilaire, Marquita (2021)
    Background: Hantavirus pulmonary syndrome (HPS) is well-known in South and North America; however, not enough data exist for the Caribbean. The first report of clinical orthohantavirus infection was obtained in Barbados, but no other evidence of clinical orthohantavirus infections among adults in the Caribbean has been documented. Methods: Using enzyme linked immunosorbent assay (ELISA) tests followed by confirmatory testing with immunofluorescent assays (IFA), immunochromatographic (ICG) tests, and pseudotype focus reduction neutralization tests (pFRNT), we retrospectively and prospectively detected orthohantavirus-specific antibodies among patients with febrile illness in Barbados. Results: The orthohantavirus prevalence rate varied from 5.8 to 102.6 cases per 100,000 persons among febrile patients who sought medical attention annually between 2008 and 2016. Two major orthohantavirus epidemics occurred in Barbados during 2010 and 2016. Peak orthohantavis infections were observed observed during the rainy season (August) and prevalence rates were significantly higher in females than males and in patients from urban parishes than rural parishes. Conclusions: Orthohantavirus infections are still occurring in Barbados and in some patients along with multiple pathogen infections (CHIKV, ZIKV, DENV and Leptospira). Orthohantavirus infections are more prevalent during periods of high rainfall (rainy season) with peak transmission in August; females are more likely to be infected than males and infections are more likely among patients from urban rather than rural parishes in Barbados.
  • Rissanen, Ilona; Stass, Robert; Zeltina, Antra; Li, Sai; Hepojoki, Jussi; Harlos, Karl; Gilbert, Robert J. C.; Huiskonen, Juha T.; Bowden, Thomas A. (2017)
    Hantaviruses are zoonotic pathogens that cause severe hemorrhagic fever and pulmonary syndrome. The outer membrane of the hantavirus envelope displays a lattice of two glycoproteins, Gn and Gc, which orchestrate host cell recognition and entry. Here, we describe the crystal structure of the Gn glycoprotein ectodomain from the Asiatic Hantaan virus (HTNV), the most prevalent pathogenic hantavirus. Structural overlay analysis reveals that the HTNV Gn fold is highly similar to the Gn of Puumala virus (PUUV), a genetically and geographically distinct and less pathogenic hantavirus found predominantly in northeastern Europe, confirming that the hantaviral Gn fold is architecturally conserved across hantavirus clades. Interestingly, HTNV Gn crystallized at acidic pH, in a compact tetrameric configuration distinct from the organization at neutral pH. Analysis of the Gn, both in solution and in the context of the virion, confirms the pH-sensitive oligomeric nature of the glycoprotein, indicating that the hantaviral Gn undergoes structural transitions during host cell entry. These data allow us to present a structural model for how acidification during endocytic uptake of the virus triggers the dissociation of the metastable Gn-Gc lattice to enable insertion of the Gc-resident hydrophobic fusion loops into the host cell membrane. Together, these data reveal the dynamic plasticity of the structurally conserved hantaviral surface. IMPORTANCE Although outbreaks of Korean hemorrhagic fever were first recognized during the Korean War (1950 to 1953), it was not until 1978 that they were found to be caused by Hantaan virus (HTNV), the most prevalent pathogenic hantavirus. Here, we describe the crystal structure of HTNV envelope glycoprotein Gn, an integral component of the Gn-Gc glycoprotein spike complex responsible for host cell entry. HTNV Gn is structurally conserved with the Gn of a genetically and geographically distal hantavirus, Puumala virus, indicating that the observed alpha/beta fold is well preserved across the Hantaviridae family. The combination of our crystal structure with solution state analysis of recombinant protein and electron cryo-microscopy of acidified hantavirus allows us to propose a model for endosome-induced reorganization of the hantaviral glycoprotein lattice. This provides a molecular-level rationale for the exposure of the hydrophobic fusion loops on the Gc, a process required for fusion of viral and cellular membranes.
  • Libraty, Daniel H.; Makela, Satu; Vlk, Jennifer; Hurme, Mikko; Vaheri, Antti; Ennis, Francis A.; Mustonen, Jukka (2012)
  • Hepojoki, Jussi; Vaheri, Antti; Strandin, Tomas (2014)
  • Hautala, Timo; Hautala, Nina; Mahonen, Saara-Mari; Sironen, Tarja; Paakko, Eija; Karttunen, Ari; Salmela, Pasi I.; Vainio, Olli; Rytky, Seppo; Pljusnin, Aleksandr; Vaheri, Antti; Vapalahti, Olli; Kauma, Heikki (2011)