Abstract:HFRS is endemic in the north-eastern part of Slovenia; PUUV and DOBV infections coexist, with PUUV being the main causative agent of HFRS. Demographic, clinical and laboratory findings in our patients with HFRS caused by PUUV were mostly in accordance with those published previously, but the ratio of patients with sinus bradycardia, oliguric renal failure and mildly elevated CSF protein concentration was rather high.
“…The most common clinical symptoms reported in our patients (fever, chills, malaise, headache, and back and abdominal pain) were similar to those previously reported in Slovenia, Germany, and Croatia [12,25,26]. However, there are some differences in the frequency of symptoms as well as in disease severity compared to previous Croatian outbreaks.…”
Introduction: Croatia is endemic for hemorrhagic fever with renal syndrome (HFRS), with both Puumala (PUUV) and Dobrava virus (DOBV) documented. Several large outbreaks were recorded in 1995, 2002, and 2012. We analyzed demographic, clinical, laboratory, and virological characteristics of HFRS cases detected in three geographically close natural foci (Ogulin, Slunj, and the Plitvice Lakes surroundings) during the 2014 outbreak. Methodology: From January to December 2014, 122 patients with suspected HFRS were tested for hantavirus IgM/IgG antibodies using an indirect immunofluorescence assay (IFA). Cross-reactive samples were further tested using a western blot (WB). For hospitalized patients from Ogulin area, clinical and laboratory data were analyzed. Results: Acute infection was documented in 57 (46.7%) patients, of whom 75.4% were hospitalized. Ten (8.2%) patients were found to be IgG seropositive. Patients were 15-69 years of age and predominantly male (74.5%). The outbreak started in winter months, with most cases recorded from May to July (80.7%). The most frequently reported symptoms were fever (96.3%), chills/shivering (62.9%), and lumbar pain (48.1%). Mild clinical form was found in 66.7% patients, moderate in 18.5%, and severe in 14.8% patients (all but one infected with PUUV). One patient died. Using IFA, 48.8% patients showed monotypic antibody response, while in 51.2%, cross-reactive antibodies were found. PUUV was confirmed in 94.7% and DOBV in 5.3% HFRS cases by WB. Conclusions: Central mountainous Croatian regions are still highly endemic areas for HFRS. A higher percentage of severe PUUV infections could be at least partly associated with a patient's immune status.
“…The most common clinical symptoms reported in our patients (fever, chills, malaise, headache, and back and abdominal pain) were similar to those previously reported in Slovenia, Germany, and Croatia [12,25,26]. However, there are some differences in the frequency of symptoms as well as in disease severity compared to previous Croatian outbreaks.…”
Introduction: Croatia is endemic for hemorrhagic fever with renal syndrome (HFRS), with both Puumala (PUUV) and Dobrava virus (DOBV) documented. Several large outbreaks were recorded in 1995, 2002, and 2012. We analyzed demographic, clinical, laboratory, and virological characteristics of HFRS cases detected in three geographically close natural foci (Ogulin, Slunj, and the Plitvice Lakes surroundings) during the 2014 outbreak. Methodology: From January to December 2014, 122 patients with suspected HFRS were tested for hantavirus IgM/IgG antibodies using an indirect immunofluorescence assay (IFA). Cross-reactive samples were further tested using a western blot (WB). For hospitalized patients from Ogulin area, clinical and laboratory data were analyzed. Results: Acute infection was documented in 57 (46.7%) patients, of whom 75.4% were hospitalized. Ten (8.2%) patients were found to be IgG seropositive. Patients were 15-69 years of age and predominantly male (74.5%). The outbreak started in winter months, with most cases recorded from May to July (80.7%). The most frequently reported symptoms were fever (96.3%), chills/shivering (62.9%), and lumbar pain (48.1%). Mild clinical form was found in 66.7% patients, moderate in 18.5%, and severe in 14.8% patients (all but one infected with PUUV). One patient died. Using IFA, 48.8% patients showed monotypic antibody response, while in 51.2%, cross-reactive antibodies were found. PUUV was confirmed in 94.7% and DOBV in 5.3% HFRS cases by WB. Conclusions: Central mountainous Croatian regions are still highly endemic areas for HFRS. A higher percentage of severe PUUV infections could be at least partly associated with a patient's immune status.
“…Also, DOBV seropositive patients in our study had more severe renal impairment compared with the PUUV and non-id hantavirus positive patients as witnessed by the diuresis, serum urea and creatinine values during the acute stage of the illness. Our results are in line with previous reports from B&H, Croatia and Slovenia that associated DOBV with severe form of HFRS (13,14,15,16,17).…”
Section: Discussionsupporting
confidence: 94%
“…Reports from Croatia and Slovenia where PUUV and DOBV also coexist suggested that DOBV-infected patients exhibited significant differences in illness severity (13,14,15,16). DOBV infected patients suffered more frequently from acute renal failure requiring dialysis treatment, shock, visual disturbances, and severe thrombocytopenia, hemorrhagic complications and disseminated intravascular coagulation than in patients with PUUV infection (17).…”
SummaryDobrava (DOBV) and Puumala (PUUV) viruses are endemic throughout the Balkans and cause high fever with renal syndrome (HFRS). The aim was to assess impact of two different HTV on renal function in HFRS patients during acute stage of illness. We also aimed to assess DOBV and PUUV distribution between symptomatic, HFRS patients and asymptomatic hantavirus antibody positive subjects. The study included 264 symptomatic, HFRS patients and 63 asymptomatic hantavirus antibody positive healthy subjects. In our study, 131 (49,6%) HFRS patients were regarded as PUUV and 69 (26,1%) as DOBV-infected patients, while in 64 (24,2%) of HFRS patients that showed all clinical and biochemical signs of HFRS, the causal hantavirus could not be determined with commercially available tests. DOBV-infected patients were associated with more requirements for haemodialysis treatment, lower diuresis and higher serum creatinine and urea values compared to PUUV-infected patients. PUUV was significantly predominant in asymptomatic hantavirus antibody positive subjects (69,8%) compared to HFRS patients. DOBV was present in 17,5% of asymptomatic subjects and interestingly, the preferential hantavirus serotype could not be determined in 12,7% of the asymptomatic antibody-positive subjects.
“…HTNV (4,000 focus-forming units [FFU] in MEM) was inoculated by intraperitoneal injection into adult mice. After viral challenge, the mice were observed, and body weights were measured at 0 (preinfection) and 7,14,21,28,33,35, and 42 days postinoculation (dpi). At these time points, some of the animals were euthanized, and sera were collected and stored at Ϫ30°C.…”
Section: Virusmentioning
confidence: 99%
“…On the other hand, neutrophilia has been documented in patients with hantavirus infection (26,(35)(36)(37). However, neutrophilia is far less common in viral infections than in bacterial infections (38,39).…”
Hantavirus infections are characterized by vascular hyperpermeability and neutrophilia. However, the pathogenesis of this disease is poorly understood. Here, we demonstrate for the first time that pulmonary vascular permeability is increased by Hantaan virus infection and results in the development of pulmonary edema in C.B-17 severe combined immunodeficiency (SCID) mice lacking functional T cells and B cells. Increases in neutrophils in the lung and blood were observed when pulmonary edema began to be observed in the infected SCID mice. The occurrence of pulmonary edema was inhibited by neutrophil depletion. Moreover, the pulmonary vascular permeability was also significantly suppressed by neutrophil depletion in the infected mice. Taken together, the results suggest that neutrophils play an important role in pulmonary vascular hyperpermeability and the occurrence of pulmonary edema after hantavirus infection in SCID mice.
IMPORTANCEAlthough hantavirus infections are characterized by the occurrence of pulmonary edema, the pathogenic mechanism remains largely unknown. In this study, we demonstrated for the first time in vivo that hantavirus infection increases pulmonary vascular permeability and results in the development of pulmonary edema in SCID mice. This novel mouse model for human hantavirus infection will be a valuable tool and will contribute to elucidation of the pathogenetic mechanisms. Although the involvement of neutrophils in the pathogenesis of hantavirus infection has largely been ignored, the results of this study using the mouse model suggest that neutrophils are involved in the vascular hyperpermeability and development of pulmonary edema in hantavirus infection. Further study of the mechanisms could lead to the development of specific treatment for hantavirus infection.
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