In Europe, zoonotic Leptospira spp. and orthohantaviruses are mainly associated with specific rodent hosts. These pathogens cause febrile human diseases with similar symptoms and disease progression. ...In Lithuania, the presence of Dobrava‐Belgrade orthohantavirus (DOBV), Tula orthohantavirus (TULV) and Leptospira spp. in rodent reservoirs is still unknown, and Puumala orthohantavirus (PUUV) was detected in bank voles (Clethrionomys glareolus) at only one site. Therefore, we collected and screened 1617 rodents and insectivores from Lithuania for zoonotic (re‐)emerging Leptospira and orthohantaviruses. We detected Leptospira DNA in six rodent species, namely striped field mouse (Apodemus agrarius), yellow‐necked mouse (Apodemus flavicollis), bank vole, common vole (Microtus arvalis), field vole (Microtus agrestis) and root vole (Microtus oeconomus). Leptospira DNA was detected with an overall mean prevalence of 4.4% (range 3.7%–7.9% per rodent species). We detected DOBV RNA in 5.6% of the striped field mice, PUUV RNA in 1% of bank voles and TULV RNA in 4.6% of common voles, but no Leptospira DNA in shrews and no hantavirus‐Leptospira coinfections in rodents. Based on the complete coding sequences of the three genome segments, two distant DOBV phylogenetic lineages in striped field mice, one PUUV strain in bank voles and two TULV strains in common voles were identified. The Leptospira prevalence for striped field mice and yellow‐necked mice indicated a significant negative effect of the distance to water points. The detection of (re‐)emerging human pathogenic Leptospira and three orthohantaviruses in rodent reservoirs in Lithuania calls for increased awareness of public health institutions and allows the improvement of molecular diagnostics for pathogen identification.
We report complete coding sequences of Orthohantavirus dobravaense (Dobrava virus) Igneada strains and phylogenetic characterization of all available complete coding sequences. Our analyses suggested ...separation of host-dependent lineages, followed by geographic clustering. Surveillance of orthohantaviruses using complete genomes would be useful for assessing public health threats from Dobrava virus.
1. Stochastic processes play an important role in the infectious disease dynamics of wildlife, especially in species subject to large population oscillations. 2. Here, we study the case of a free ...ranging population of yellow-necked mice (Apodemus flavicollis) in northern Italy, where circulation of Dobrava-Belgrade hantavirus (DOBV) has been detected intermittently since 2001, until an outbreak emerged in 2010. 3. We analysed the transmission dynamics of the recent outbreak using a computational model that accounts for seasonal changes of the host population and territorial behaviour. Model parameters were informed by capture-mark-recapture data collected over 14 years and longitudinal seroprevalence data from 2010 to 2013. 4. The intermittent observation of DOBV before 2010 can be interpreted as repeated stochastic fadeouts after multiple introductions of infectious rodents migrating from neighbouring areas. We estimated that only 20% of introductions in a naïve host population results in sustained transmission after 2 years, despite an effective reproduction number well above the epidemic threshold (mean 4·5, 95% credible intervals, CI: 0·65-15·8). Following the 2010 outbreak, DOBV has become endemic in the study area, but we predict a constant probability of about 4·7% per year that infection dies out, following large population drops in winter. In the absence of stochastic fadeout, viral prevalence is predicted to continue its growth to an oscillating equilibrium around a value of 24% (95% CI: 3-57). 5. We presented an example of invasion dynamics of a zoonotic virus where stochastic fadeout have played a major role and may induce future extinction of the endemic infection.
Members of the Dobrava-Belgrade virus (DOBV) species are hantaviruses carried by different Apodemus mice as reservoir hosts and causing haemorrhagic fever with renal syndrome (HFRS) in humans. In ...Central Europe, the Kurkino genotype of DOBV, associated with the striped field mouse, Apodemus agrarius, is prevalent. This paper presents the first extensive study of the serological and molecular diagnostics, epidemiology and clinics of DOBV-Kurkino infections in Central Europe. Serum samples from 570 German patients living in the habitat of A. agrarius (north and northeast Germany) and exhibiting febrile disease, were analysed. All samples were tested by ELISA, subsets of samples were also analysed by immunoblot, neutralization assay, and RT-PCR. A group of 86 individuals was confirmed as DOBV-infected. The virus neutralization assay allowed a reliable identification of DOBV antibodies during both acute and convalescent phases of infection. However, differentiation of relevant DOBV genotypes was not possible by neutralization test but required molecular analysis. Whereas DOBV IgM antibodies tend to persist in the infected organism, RNAaemia seems to be short. Nucleotide sequences were amplified from four patients, and their analysis demonstrated infection by DOBV-Kurkino. With respect to the initial results, the high degree of identity of local patient-derived and A. agrarius-derived virus sequences may allow a closer allocation of the geographical place where the human infection occurred. In contrast to moderate/severe HFRS caused by the DOBV genotypes Dobrava or Sochi, all available data showed a mild clinical course of HFRS caused by DOBV-Kurkino infection without lethal outcomes.
Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. Interferon (IFN) responses play an important role in HFRS pathogenesis and early IFN-β response is delayed by ...pathogenic hantaviruses. The severity of HFRS caused by Dobrava virus (DOBV) and Puumala virus (PUUV) varies. Our aim was to determine whether differences in early activation of IFN type 1-induced antiviral state influence HFRS severity. Peripheral blood mononuclear cells (PBMCs) from healthy donors and HFRS patients were stimulated with DOBV or PUUV and expression of selected genes was measured. PUUV, but not DOBV, activated IFN type 1-induced antiviral state in stimulated PBMCs, and IFNβ, STAT-1, and MxA were highly upregulated. Upregulation of MxA was earlier in acute-phase PBMCs and higher in convalescent-phase PBMCs from patients with mild compared with severe PUUV infection. Our study showed that delayed IFN type 1-induced antiviral state could contribute to HFRS severity, particularly in PUUV infection.
Patients with haemorrhagic fever with renal syndrome (HFRS) may present without significant oliguria. We compared different initial clinical symptoms and laboratory findings in patients who developed ...oliguric acute renal failure (ARF) with those in patients who did not develop oliguric ARF. Overall, 128 patients with serologically confirmed HFRS were hospitalized at the University Hospital for Infectious Disease, Zagreb, Croatia between January 1999 and December 2010. Clinical signs and laboratory findings were extracted from medical charts, and were assessed for their relationship to the development of oliguric ARF. Puumala virus infection was diagnosed in 101 (79%) patients, and Dobrava-Belgrade virus infection in 27 (21%). Oliguria or anuria developed in 30% of patients. We identified the following risk factors for the development of oliguria and anuria on multivariable analysis: conjunctival hyperaemia or bleeding (relative risk (RR) 1.84, 95% CI 1.09–3.10; p 0.023), diarrhoea (RR 1.45, 95% CI 1.07–1.97; p 0.017), serum sodium of ≤133 mM (RR 2.21, 95% CI 1.34–3.64; p 0.002), and dipstick protein value of >1.5 g/L (RR 1.59, 95% CI 1.09–2.33; p 0.016), as well as hiking in the forest (RR 1.92, 95% CI 1.13–3.26; p 0.016). Our findings may help physicians in the earlier identification of patients with a more severe form of HFRS caused by Puumala and Dobrava-Belgrade viruses. Particular attention should be given to findings such as conjunctival hyperaemia or bleeding, diarrhoea, a low serum sodium level, and proteinuria.
It is generally accepted that the pathogenesis of hantavirus infections is the result of virus-mediated host immune response. Hantaviruses, and mainly Dobrava–Belgrade virus, are present in Greece, ...and cause to humans hemorrhagic fever with renal syndrome (HFRS). Serum IL-6, IL-8, IL-10, TNF-α and sTNFR1 levels were measured in 29 HFRS Greek patients. Significant higher sTNFR1, IL-6, IL-8 and IL-10 levels were observed in severe than in mild/moderate cases, while TNF-α did not seem to be associated with disease severity. Correlations between cytokine levels and their fluctuation over time after onset of the illness, along with comparisons from previously published data on the field, led in building an immune response pattern for HFRS.
Hantaviruses include several zoonotic pathogens that cause different syndromes in humans, with mortality rates ranging from 12 to 40%. Most commonly, humans get infected through the inhalation of ...aerosols or dust particles contaminated with virus-containing rodent excreta. Hantaviruses are specifically associated with the host species, and human cases depend on the presence and the dynamics of reservoir hosts. In this letter, we report the identification of Dobrava-Belgrade virus (DOBV) in the yellow-necked mouse (Apodemus flavicollis) from Italy. The virus was detected in the mountainous area of the province of Udine, bordering Austria and Slovenia, during an event of enhanced mortality in wild mice and voles. Despite serological evidence in rodents and humans that suggested the circulation of hantaviruses in Italy since 2000, this is the first virological confirmation of the infection. Phylogenetic analyses across the whole genome of the two detected viruses confirmed the host-specificity of DOBV sub-species and showed the highest identity with viruses identified in Slovenia and Croatia from both A. flavicollis and humans, with no signs of reassortment. These findings highlight the need for ecologists, veterinarians and medical doctors to come together in a coordinated approach in full compliance with the One Health concept.
Dobrava-Belgrade virus (DOBV) is a human pathogen that has evolved in, and is hosted by, mice of several species of the genus
Apodemus
. We propose a subdivision of the species
Dobrava-Belgrade virus
...into four related genotypes – Dobrava, Kurkino, Saaremaa, and Sochi – that show characteristic differences in their phylogeny, specific host reservoirs, geographical distribution, and pathogenicity for humans.
During 2008-2018, we collected samples from rodents and patients throughout the Czech Republic and characterized hantavirus isolates. We detected Dobrava-Belgrade and Puumala orthohantaviruses in ...patients and Dobrava-Belgrade, Tula, and Seewis orthohantaviruses in rodents. Increased knowledge of eco-epidemiology of hantaviruses will improve awareness among physicians and better outcomes of patients.
PDF
