Project description:Human infection with Puumala virus (PUUV), the most common hantavirus in Central Europe, causes nephropathia epidemica (NE), a disease characterized by acute kidney injury and thrombocytopenia. To determine the clinical phenotype of hantavirus-infected patients and their long-term outcome and humoral immunity to PUUV, we conducted a cross-sectional prospective survey of 456 patients in Germany with clinically and serologically confirmed hantavirus-associated NE during 2001-2012. Prominent clinical findings during acute NE were fever and back/limb pain, and 88% of the patients had acute kidney injury. At follow-up (7-35 mo), all patients had detectable hantavirus-specific IgG; 8.5% had persistent IgM; 25% had hematuria; 23% had hypertension (new diagnosis for 67%); and 7% had proteinuria. NE-associated hypertension and proteinuria do not appear to have long-term consequences, but NE-associated hematuria may. All patients in this study had hantavirus-specific IgG up to years after the infection.
Project description:Nephropathia Epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) and linked to hantavirus infection, is endemic in the Republic of Tatarstan. Several genetic markers of HFRS severity have been identified previously, including human leukocyte antigen (HLA) complexes and nucleotide polymorphism in the tumor necrosis factor alpha (TNFα) gene. Still, our understanding of the genetic markers of NE severity remains incomplete. The frequency of the C-C chemokine receptor type 5 (CCR5) gene wild type and gene with 32-base-pair deletion (Δ32CCR5) genotypes in 98 NE samples and 592 controls was analyzed using PCR. Along with the serum levels of 94 analytes, a lack of differences in the CCR5 genotype distribution between NE cases and the general population suggests that the CCR5 genotype does not affect susceptibility to hantavirus infection. However, in NE cases, significant variation in the serum levels of the host matrix metalloproteases between functional CCR5 homozygous and Δ32CCR5 heterozygous patients was detected. Also, the oliguric phase was longer, while thrombocyte counts were lower in functional CCR5 homozygous as compared to heterozygous NE cases. Our data, for the first time, presents the potential role of the CCR5 receptor genotype in NE pathogenesis. Our data suggests that NE pathogenesis in functional CCR5 homozygous and heterozygous NE patients differs, where homozygous cases may have more disintegration of the extracellular matrix and potentially more severe disease.
Project description:Nephropathia epidemica (NE) is a zoonotic disease caused by hantaviruses transmitted from rodents, endemic in the Republic of Tatarstan, Russia. The disease presents clinically with mild, moderate, and severe forms, and time-dependent febrile, oliguric, and polyuric stages of the disease are also recognized. The patient's cytokine responses have been suggested to play a central role in disease pathogenesis; however, little is known about the different patterns of cytokine expression in NE in cohorts of different ages and sexes. Serum samples and clinical records were collected from 139 patients and 57 controls (healthy donors) and were used to analyze 48 analytes with the Bio-Plex multiplex magnetic bead-based antibody detection kits. Principal component analysis of 137 patient and 55 controls (for which there was full data) identified two components that individually accounted for >15% of the total variance in results and together for 38% of the total variance. PC1 represented a proinflammatory TH17/TH2 cell antiviral cytokine profile and PC2 a more antiviral cytokine profile with patients tending to display one or the other of these. Severity of disease and stage of illness did not show any correlation with PC1 profiles; however, significant differences were seen in patients with high PC1 profiles vs. lower for a number of individual clinical parameters: High PC1 patients showed a reduced number of febrile days, but higher maximum urine output, higher creatinine levels, and lower platelet levels. Overall, the results of this study point towards a stronger proinflammatory profile occurring in younger NE patients, this being associated with markers of acute kidney injury and low levels of high-density cholesterol. This is consistent with previous work indicating that the pathology of NE is immune driven, with an inflammatory immune response being associated with disease and that this immune response is more extreme in younger patients.
Project description:In 2018, a local case of nephropathia epidemica was reported in Scania, southern Sweden, more than 500 km south of the previously known presence of human hantavirus infections in Sweden. Another case emerged in the same area in 2020. To investigate the zoonotic origin of those cases, we trapped rodents in Ballingslöv, Norra Sandby, and Sörby in southern Sweden during 2020‒2021. We found Puumala virus (PUUV) in lung tissues from 9 of 74 Myodes glareolus bank voles by screening tissues using a hantavirus pan-large segment reverse transcription PCR. Genetic analysis revealed that the PUUV strains were distinct from those found in northern Sweden and Denmark and belonged to the Finnish PUUV lineage. Our findings suggest an introduction of PUUV from Finland or Karelia, causing the human PUUV infections in Scania. This discovery emphasizes the need to understand the evolution, cross-species transmission, and disease outcomes of this newly found PUUV variant.
Project description:Nephropathis epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS), is an acute zoonotic disease endemic in the Republic of Tatarstan. This study aimed to assess the impact of rosuvastatin on the clinical and laboratory results of NE. A total of 61 NE patients and 30 controls were included in this study; 22 NE patients and 7 controls received a daily dose of rosuvastatin (10 mg) for ten consecutive days. Serum samples were collected on days 1, 5, and 10 after admission to the hospital. These samples were analyzed to determine the levels of lipids, cytokines, and kidney toxicity markers. Our findings indicate that rosuvastatin reduced the duration of the second wave of fever and alleviated back pain and headache symptoms. Additionally, low-density lipoprotein cholesterol (LDL-C) serum levels were significantly decreased on days 5 and 10 upon rosuvastatin treatment. Furthermore, rosuvastatin decreased the levels of cytokines in the serum, particularly proinflammatory cytokines IL-1β and IL-8. NE patients had significantly altered levels of the kidney toxicity markers albumin and osteopontin. The data from our study provide evidence supporting the therapeutic potential of rosuvastatin in NE cases.
Project description:Puumala virus (PUUV) in Europe causes nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS). The incidence of NE is highly heterogeneous spatially, whereas the geographic distribution of the wild reservoir of PUUV, the bank vole, is essentially homogeneous. Our understanding of the processes driving this heterogeneity remains incomplete due to gaps in knowledge. Little is known about the current distribution and genetic variation of PUUV in the areas outside the well-identified zones of NE endemicity. We trapped bank voles in four forests in French regions in which NE is considered non-endemic, but sporadic NE cases have been reported recently. We tested bank voles for anti-PUUV IgG and characterized the S segment sequences of PUUV from seropositive animals. Phylogenetic analyses revealed specific amino-acid signatures and genetic differences between PUUV circulating in non-endemic and nearby NE-endemic areas. We also showed, in temporal surveys, that the amino-acid sequences of PUUV had undergone fewer recent changes in areas non-endemic for NE than in endemic areas. The evolutionary history of the current French PUUV clusters was investigated by phylogeographic approaches, and the results were considered in the context of the history of French forests. Our findings highlight the need to monitor the circulation and genetics of PUUV in a larger array of bank vole populations, to improve our understanding of the risk of NE.
Project description:In Europe, Puumala virus (PUUV) is responsible for nephropathia epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS). Despite the presence of its reservoir, the bank vole, on most of French territory, the geographic distribution of NE cases is heterogeneous and NE endemic and non-endemic areas have been reported. In this study we analyzed whether bank vole-PUUV interactions could partly shape these epidemiological differences. We performed crossed-experimental infections using wild bank voles from French endemic (Ardennes) and non-endemic (Loiret) areas and two French PUUV strains isolated from these areas. The serological response and dynamics of PUUV infection were compared between the four cross-infection combinations. Due to logistical constraints, this study was based on a small number of animals. Based on this experimental design, we saw a stronger serological response and presence of PUUV in excretory organs (bladder) in bank voles infected with the PUUV endemic strain. Moreover, the within-host viral diversity in excretory organs seemed to be higher than in other non-excretory organs for the NE endemic cross-infection but not for the NE non-endemic cross-infection. Despite the small number of rodents included, our results showed that genetically different PUUV strains and in a lesser extent their interaction with sympatric bank voles, could affect virus replication and diversity. This could impact PUUV excretion/transmission between rodents and to humans and in turn at least partly shape NE epidemiology in France.
Project description:We report a sequencing analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in wastewater samples collected in the Frankfurt metropolitan area of Germany. The majority of the detected mutations have been identified only in clinical genomes outside Frankfurt, indicating that the sequencing of SARS-CoV-2 RNA in wastewater can provide insights into emerging variants in a city.
Project description:BackgroundAmbient air pollution poses a major risk for the development and aggravation of respiratory diseases. Evidence suggests that even in low-level air pollution environments there is a risk for an increase in adverse respiratory symptoms. We examined whether variations in daily air pollution levels of nitrogen dioxide, ozone, or particulate matter in Berlin, Germany were associated with hospital admissions of chronic obstructive pulmonary disease (COPD) and asthma patients in a time series analysis.MethodsWe calculated single and multi-pollutant models, investigated possible lags in effect, and analysed the influence of meteorological variables on the results. Data from January 2005 through December 2015 were used to quantify the concentration-response.ResultsThe risk ratio for asthma patients to be hospitalised on the same day of NO2 exposure was 1.101 per 10 µg/m3 NO2 increase (95% CI: 1.013 to 1.195), for COPD patients 1.123 (95% CI: 1.081 to 1.168). Neither the exposure to ozone (95% CI: 0.904 to 1.020), PM10 (95% CI: 0.990 to 1.127), nor PM2.5 (95% CI: 0.981 to 1.148) was associated with an increased risk ratio for asthma patients to be hospitalised. Risk ratios for the hospital admission of COPD patients were also not increased due to ozone (95% CI: 0.981 to 1.033), PM10 (95% CI: 0.988 to 1.032), or PM2.5 (95% CI: 0.966 to 1.019) exposure. The presented risk ratios and confidence intervals relate to the day of exposure. We found no increased hospitalisation risks with a delayed occurrence on subsequent days.ConclusionsA quantifiable, statistically significant increase in risk for asthma and COPD exacerbations owing to NO2 exposure at levels well below European regulatory limit values was observed.
Project description:Nephropathia Epidemica (NE), endemic to several Volga regions of Russia, including the Republic of Tatarstan (RT) and the Republic of Mordovia (RM), is a mild form of hemorrhagic fever with renal syndrome caused by infection with rodent-borne orthohantaviruses. Although NE cases have been reported for decades, little is known about the hantavirus strains associated with human infection in these regions. There is also limited understanding of the pathogenesis of NE in the RT and the RM. To address these knowledge gaps, we conducted comparative analyses of patients with NE in the RT and the RM. Clinical symptoms were more severe in patients with NE from the RM with longer observed duration of fever symptoms and hospitalization. Analysis of patient sera showed changes in the levels of numerous cytokines, chemokines, and matrix metalloproteases (MMPs) in patients with NE from both the RT and the RM, suggesting leukocyte activation, extracellular matrix degradation, and leukocyte chemotaxis. Interestingly, levels of several cytokines were distinctly different between patients NE from the RT when compared with those from the RM. These differences were not related to the genetic variation of orthohantaviruses circulating in those regions, as sequence analysis showed that Puumala virus (PUUV) was the causative agent of NE in these regions. Additionally, only the "Russia" (RUS) genetic lineage of PUUV was detected in the serum samples of patients with NE from both the RT and the RM. We therefore conclude that differences in serum cytokine, chemokine, and MMP levels between the RT and the RM are related to environmental factors and lifestyle differences that influence individual immune responses to orthohantavirus infection.