In 2018, Croatia reported the largest outbreak of West Nile virus (WNV) infections as well as the re-occurrence of human Usutu virus (USUV) infections. For the first time, fatal WNV and USUV infections were detected in wild birds. We analysed epidemiological characteristics and molecular epidemiology of WNV and USUV infections detected during 2018 transmission season. From April to November, 178 patients with neuroinvasive disease and 68 patients with febrile disease were tested for WNV and USUV. Viral RNA was detected in cerebrospinal fluid (CSF) and urine samples using a real-time RT-PCR. Positive samples were tested by nested RT-PCR and nucleotide sequencing. IgM/IgG antibodies were detected in serum/CSF samples using ELISA | 1947 VILIBIC-CAVLEK Et AL.
Data on the immune response to West Nile virus (WNV) are limited. We analyzed the antiviral cytokine response in serum and cerebrospinal fluid (CSF) samples of patients with WNV fever and WNV neuroinvasive disease using a multiplex bead-based assay for the simultaneous quantification of 13 human cytokines. The panel included cytokines associated with innate and early pro-inflammatory immune responses (TNF-α/IL-6), Th1 (IL-2/IFN-γ), Th2 (IL-4/IL-5/IL-9/IL-13), Th17 immune response (IL-17A/IL-17F/IL-21/IL-22) and the key anti-inflammatory cytokine IL-10. Elevated levels of IFN-γ were detected in 71.7% of CSF and 22.7% of serum samples (p = 0.003). Expression of IL-2/IL-4/TNF-α and Th1 17 cytokines (IL-17A/IL-17F/IL-21) was detected in the serum but not in the CSF (except one positive CSF sample for IL-17F/IL-4). While IL-6 levels were markedly higher in the CSF compared to serum (CSF median 2036.71, IQR 213.82–6190.50; serum median 24.48, IQR 11.93–49.81; p < 0.001), no difference in the IL-13/IL-9/IL-10/IFN-γ/IL-22 levels in serum/CSF was found. In conclusion, increased concentrations of the key cytokines associated with innate and early acute phase responses (IL-6) and Th1 type immune responses (IFN-γ) were found in the CNS of patients with WNV infection. In contrast, expression of the key T-cell growth factor IL-2, Th17 cytokines, a Th2 cytokine IL-4 and the proinflammatory cytokine TNF-α appear to be concentrated mainly in the periphery.
West Nile Virus Neuroinvasive Disease (WNV NID) requires prolonged intensive care treatment, resulting in high mortality and early disability. Long-term results are lacking. We have conducted an observational retrospective study with a prospective follow-up of WNV NID patients treated at the Intensive Care Unit (ICU), University Hospital for Infectious Diseases, Zagreb, Croatia, 2013–2018. Short-term outcomes were vital status, length of stay (LOS), modified Rankin Scale (mRS), and disposition at discharge. Long-term outcomes were vital status and mRS at follow-up. Twenty-three patients were identified, 78.3% males, median age 72 (range 33–84) years. Two patients (8.7%) died in the ICU, with no lethal outcomes after ICU discharge. The median ICU LOS was 19 days (range 5–73), and the median hospital LOS was 34 days (range 7–97). At discharge, 15 (65.2%) patients had moderate to severe/mRS 3–5, 6 (26.0%) had slight disability/mRS 2–1, no patients were symptom-free/mRS 0. Ten (47.6%) survivors were discharged to rehabilitation facilities. The median time to follow-up was nine months (range 6–69). At follow-up, seven patients died (30.5%), five (21.7%) had moderate to severe/mRS 3–5, one (4.3%) had slight disability/mRS 2–1, six (26.1%) had no symptoms/mRS 0, and four (17.4%) were lost to follow-up. Briefly, ten (43.5%) survivors improved their functional status, one (4.3%) was unaltered, and one (4.3%) aggravated. In patients with severe WNV NID, intensive treatment in the acute phase followed by inpatient rehabilitation resulted in significant recovery of functional status after several months.
Even though a verb can assign a variety of thematic roles to the subject, the most typical role for a subject is that of an agent or that of an experiencer for verbs of perception and mental inference. In this paper, we describe constructions where verbs that typically select agent or experiencer subjects occur with subjects expressing thematic roles typical of adverbials: instrument, time or place. We refer to those subjects as permissive subjects. On the other hand, it is argued that in South Slavic languages, non-agents (and non-experiencers) do not show such a strong tendency to occur in the subject position. We performed a translation task to answer the following research question: What range of structures occur in Bosnian translation equivalents of the following English constructions with permissive subjects: Period sees, Money buys, Object seats number, Object sleeps number, Book/ Album/Record sells copies? The quantitative analysis showed that some of the most frequent translation strategies include the following: middle constructions, passive constructions and constructions where the English permissive subject becomes an adverbial in the Bosnian translation equivalent. Moreover, translation equivalents where the English permissive subject is translated as a Bosnian non-agentive/ permissive subject are rather frequent too. Nevertheless, our qualitative analysis shows that the choice of a translation equivalent for the target construction depends on the English target construction itself. For example, in the case of some combinations, we show a correlation between the thematic meaning of a particular permissive subject in English and the choice of a translation equivalent.
a total of 120 patients with neuroinvasive disease from continental Croatian regions were tested for the presence of neuroinvasive zoonotic viruses: tick-borne encephalitis virus (TBEV), West Nile virus (WNV), Usutu virus (USUV), Toscana virus (TOSV), Tahyna virus (TAHV) and lymphocytic choriomeningitis virus (LCMV). Cerebrospinal fluid (CSF) and urine samples were tested for the presence of viral RNA using a real-time RT-PCR and/or nested RT-PCR. Serological tests of serum/CSF samples (IgM/IgG antibodies, IgG avidity) were performed using ELISA (TBEV, WNV, USUV), IFA (TOSV, LCMV) and virus neutralization test (WNV).Results: Etiology was confirmed in 28/23.3% patients: TBEV in 20/16.7% and WNV in 8/6.6% patients by detection of IgM and IgG antibodies of low avidity and/or detection of viral RNA in CSF and urine. Majority of patients with TBEV infection were males (15/75.0%). Although infections were detected in all age groups, 15/75.0% patients were less than 60 years of age. The main clinical symptoms were headache (18/90.0%), weakness (18/90.0%), nausea (12/60.0%) and vomiting (8/40.0%). Fever >39 • C was noted in 16/80.0% patients. CSF leukocyte count ranged from 41-3520/mm 3 with mononuclear cell predominance in 15/75.0% patients. All but one patient fully recovered. WNV infection was reported in 5/62.5% males and 3/37.5% females. All but one patient (7/87.5%) were older than 60 years. Majority of patients reported underlying diseases: hypertension (3/37.5%) and cerebrovascular disease (3/37.5%). The main clinical symptoms were headache (5/62.5%) and weakness (5/62.5%), while fever >39 • C was noted in 4/50.0% patients. CSF leukocyte count ranged from 56-1096/mm 3 with mononuclear cell predominance in 4/50.0% patients. One patient died. USUV, TOSV, TAHV and LCMV infections were not detected during the tested period.Conclusion: TBEV infections were more common in patients less than 60 years of age, while WNV infections were most common in elderly. High fever was noted in 80.0% TBEV cases compared to 50.0% WNV cases. CSF pleocytosis was higher in TBEV infection. Purpose:The Federal Republic of Sudan has experienced 13 outbreaks of undifferentiated febrile illness (UFI) associated with haemorrhage and high case fatality rates (CFR) since 2012. As a range of high consequence pathogens is endemic in Sudan, these outbreaks are of significant concern. We investigated a 2015-16 UFI outbreak in Darfur (469 cases, CFR 25.6%) to explore aetiologies, inform public health interventions and promote development of diagnostic capacity. Methods & Materials:We extracted clinical and epidemiological data from Sudan Ministry of Health databases and matched available legacy samples at the National Public Health Laboratory. Serum samples were tested further at the Rare and Imported Pathogens Laboratory, Public Health England, using a bespoke panel of molecular and serological assays covering a broad range of likely pathogens, including haemorrhagic fever viruses, arboviruses, leptospirosis and rickettsiae.Results: Sixty-five sampl...
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