Search Results (83)

Orthoflaviviruses (formerly flaviviruses) are known for their role in numerous diseases affecting both humans and animals. Despite the worldwide distribution of orthoflaviviruses, individual species are only found in endemic or epidemic regions. However, in recent decades, certain orthoflaviviruses have spread beyond their traditional geographic boundaries, even crossing continents. Given the long-distance movements of birds, the knowledge of zoonotic orthoflaviviruses associated with birds is essential because of their possible introduction into new regions, as was the case with West Nile virus and Usutu virus. A thorough literature review was conducted on zoonotic orthoflaviviruses related to birds, including lesser-known (re-)emerging and neglected orthoflaviviruses that are limited to specific regions and/or avian hosts but have the potential to spread to a wider geographical area and pose a higher risk of transmission to humans. Several of these viruses possess significant zoonotic potential and can cause a wide spectrum of diseases in humans, ranging from mild febrile illnesses (Zika virus) to severe neuroinvasive diseases (tick-borne encephalitis, West Nile, Japanese encephalitis virus) and hemorrhagic fevers (yellow fever, dengue virus). Geographic distribution, hosts, vectors, incidence of human infections, and impact on human and animal health of zoonotic flaviviruses related to birds are critically reviewed. The viruses have been categorized based on the role of birds as an orthoflavivirus host and the clinical presentation in human infections. Full article

Human West Nile virus (WNV) infection is usually asymptomatic. Less than 1% of patients develop neuroinvasive disease (WNND) which may result in permanent neurological impairment. The aim of this study was to assess the functional and cognitive status of patients with WNND approximately one year after the onset of symptoms. This prospective observational cohort study involved patients with WNND. Patients’ functional and cognitive abilities one year post-infection were assessed by telephone interviews using the Modified Rankin Scale (mRS), Barthel Index, and Telephone Interview for Cognitive Status. Sixty-two participants were analyzed. All patients had encephalitis, and 7 (11.3%) also had acute flaccid paresis/paralysis (AFP). At discharge, 40 (64.5%) patients had no or minimal neurological deficit (mRS 0–1), and 14 (22.6%) were functionally dependent (mRS 3–5). One year later, 52 (83.9%) patients were functionally independent (mRS 0–2), none was severely dependent (Barthel index 0–60), and 50 (90.9%) had a Barthel index score of 91–100. Among 14 functionally dependent patients at discharge, 3 (21.4%) remained functionally dependent one year later. During the follow-up, 7 (11.3%) patients died. No significant difference was observed in the fatality rate between patients with and without AFP, mRS 3–5 at discharge, or age over 65. The most common persistent symptoms were muscle weakness, walking instability, and issues with focus and memory. Using TICS, it was found that 33/55 patients (60%) had unimpaired and 2 (3.6%) had moderately or severely impaired cognitive status. The long-term prognosis after WNV encephalitis is satisfying. The majority of patients reached functional independence and 60% had unimpaired cognitive status. Full article

Neuroinvasive arboviruses such as tick-borne encephalitis virus (TBEV), West Nile virus (WNV), Usutu virus (USUV), and Toscana virus (TOSV) have (re-)emerged with increasing incidence and geographic range. We analyzed the epidemiology of arboviral infections in Croatia during the 2024 transmission season. A total of 154 patients with neuroinvasive diseases (NID), 1596 horses, 69 dead birds, and 7726 mosquitoes were tested. Viral RNA was detected using RT-qPCR. IgM/IgG-specific antibodies were detected using commercial ELISA or IFA, with confirmation of cross-reactive samples by virus neutralization test. RT-qPCR-positive samples were Sanger sequenced. Arboviral etiology was confirmed in 33/21.42% of patients with NID. WNV was most frequently detected (17/11.03%), followed by TBEV (10/6.49%), USUV (5/3.24%), and TOSV (1/0.64%). WNV infections were reported in regions previously known as endemic, while in one continental county, WNV was recorded for the first time. USUV infections re-emerged after a six-year absence. In addition to human cases, acute WNV infections were recorded in 11/395 (2.78%) of horses and two dead crows. WNV IgG seropositivity was detected in 276/1168 (23.63%) and TBEV IgG seropositivity in 68/428 (15.88%) horses. None of the tested mosquito pools were positive for WNV and USUV RNA. Phylogenetic analysis showed the circulation of WNV lineage 2 and Usutu Europe 2 lineage. Climate conditions in 2024 in Croatia were classified as extremely warm, which could, at least in part, impact the quite intense arboviral season. The spreading of flaviviruses in Croatia highlights the need for continuous surveillance in humans, animals, and vectors (“One Health”). Full article

West Nile virus (WNV) causes thousands of arboviral infections in the United States each year. Patients with immune-compromising conditions and elderly people are at higher risk of severe WNV neuroinvasive disease (WNND). Despite its broad endemicity nationwide, no U.S. Food and Drug Administration-approved vaccine or therapeutic treatments exist. We summarized existing peer-reviewed literature on the preclinical development of monoclonal antibody (MAb) prophylaxis and therapeutics for the prevention and treatment of WNND. Five bibliographical databases (CINAHL, Cochrane Library, Embase, MEDLINE, and Scopus) were searched for applicable research studies performed from 1 January 1998 to 1 May 2025. In total, 2347 titles and abstracts were screened, 263 full-text publications reviewed, and 25 studies included. Studies included detailed preclinical development and evaluations of MAbs targeting the envelope (E) protein (n = 13), other viral proteins (n = 3), flaviviral cross-protective monoclonal antibodies (n = 4), and novel antibody configurations or delivery methods (n = 5). The most well-studied MAb, E16, targeting E- Domain III (E-DIII), was effective at inhibiting and treating WNND in experimental animal models. No work investigated ways to traffic therapeutic antibodies across the blood–brain barrier. This review summarizes the current research in the development of monoclonal antibody therapeutics for WNV and addresses gaps in the knowledge for future consideration. Full article

The 1999 outbreak of West Nile virus (WNV) in New York City (NYC) marked the first documented introduction of the virus into the western hemisphere, prompting extensive public health surveillance. This study examines the epidemiology of WNV from 2000 to 2019, analyzing 381 human cases, including 66 cases of West Nile Fever (WNF) and 315 cases of West Nile Neuroinvasive Disease (WNND), with 35 fatalities. Simultaneously, 6632 WNV-positive mosquito pools were identified across 16 species. While Culex pipiens and Cx. restuans accounted for 91.4% of positive pools, Cx. salinarius, which comprised only 6.2%, exhibited a stronger correlation with human infections. Human surveillance involved comprehensive case investigations following laboratory-confirmed WNV infections, incorporating structured interviews with patients and healthcare providers. Mosquito surveillance was conducted through weekly collections from 52–71 permanent trap sites, supplemented by approximately 200 additional sites annually in areas with elevated WNV activity. Captured mosquitoes were species-identified, pooled, and tested for WNV RNA via RT-PCR. Findings highlight the dominant role of Culex species, particularly Cx. salinarius, in human WNV transmission, with 69% of cases occurring near WNV-positive mosquito pools. Spatial analyses identified transmission hotspots, emphasizing the importance of species-specific mosquito control strategies. Over the study period, WNV activity has increased in NYC, likely influenced by climate change, as warmer summers and extended breeding seasons align with peak outbreaks. Integrating spatial mapping, climate forecasting, and targeted surveillance could significantly improve WNV mitigation efforts in urban environments. Full article

West Nile virus (WNV) is an important zoonotic pathogen belonging to the Flaviviridae family, which is endemic in some areas and emerging in others. WNV is transmitted by blood-sucking mosquitoes of the genus Culicoides, Aedes, and Anopheles, and the infection can cause different clinical symptoms. The most common and benign illness in humans is West Nile fever (WNF), but a lethal neurological disease (WNND), related to the neuro-invasiveness of WNV lineage 2, represents the highest health risk of WNV infection. The neuro-clinical form is recognized in mammals (land and cetaceans), particularly in humans (elderly or immunosuppressed) and in horses, avian species, and wildlife animals ranging free or in a zoological setting. This review highlights the most relevant data regarding epidemiology, virology, pathogenesis and immunity, clinical signs and differential diagnosis, pathology and imaging, histopathology and gross pathology, economic impact, influence of climate change, and surveillance of WNV. Climate change has favored the wide spread of WNV in many areas of the globe and consequent One-Health and Eco-Health emergencies, influencing the health of human beings, animals, and ecosystems. Full article

Background: West Nile virus (WNV) is a mosquito-borne RNA virus, with birds as reservoirs and humans as incidental hosts. WNV often causes asymptomatic infections, but severe neuroinvasive disease occurs in fewer than 1% of human cases. Recent climatic changes and occupational exposure have increased its spread, particularly in Southern Italy. This study aimed to assess WNV seroprevalence and occupational risks among outdoor workers to guide targeted public health interventions. Methods: This cross-sectional study was conducted in the Apulia region, southeastern Italy, from November 2023 to April 2024. Participants completed a detailed questionnaire on socio-demographics, occupational exposure, travel history, and health symptoms. Blood samples were analyzed using enzyme-linked immunosorbent assay (ELISA) and neutralization assays to detect WNV-specific antibodies. Results: 250 outdoor workers in southeastern Italy were recruited, including agricultural workers, veterinarians, forestry workers, and livestock breeders. The latter showed the highest WNV prevalence at 6.5%. Protective measures such as repellent use (β = −0.145, OR = 0.95, p = 0.019) and personal protective equipment (PPE) usage (β = −0.12, OR = 0.94, p = 0.04) significantly reduced the likelihood of WNV infection. Conclusions: The study highlights the significant occupational risk posed by WNV to outdoor workers involved in livestock breeding in Southern Italy, likely due to their frequent exposure to mosquito-prone environments. Tailored public health strategies and education programs are needed to protect high-risk outdoor workers from WNV, amidst the backdrop of changing climatic conditions that favor increased transmission. Full article

Neuroinvasive flaviviruses such as tick-borne encephalitis virus (TBEV) and West Nile virus (WNV) are widely distributed in continental Croatian regions. We analyzed clinical characteristics, laboratory parameters, and molecular epidemiology of neuroinvasive flavivirus infections in eastern Croatia. A total of 43 patients with confirmed flavivirus infection hospitalized from 2017 to 2023 were included in the study. Reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect flavivirus RNA in clinical samples (cerebrospinal fluid; CSF, urine). ELISA was used for IgM and IgG antibody detection in serum and CSF with confirmation of cross-reactive samples by virus neutralization test. WNV was detected more frequently (74.4%) than TBEV (25.6%). A statistically significant age difference was found between WNV patients (median 65 years) and TBEV patients (median 36 years). Comorbidities were more frequently detected in WNV patients (hypertension 56.3 vs. 18.2%; diabetes 31.3 vs. 0%). Meningitis was the most common clinical presentation in both TBE and WNV neuroinvasive disease (WNND; 63.6 and 59.4%, respectively). In addition, some rare clinical presentations of WNND were also detected (cerebellitis, polyradiculoneuritis). No significant differences in the frequency of clinical symptoms were observed between WNV and TBEV-infected patients (fever 93.7 vs. 100%; malaise 78.1 vs. 100%; headache 75.0 vs. 100%; nausea 50.0 vs. 63.6%; vomiting 34.4 vs. 54.6%). Comparative analysis of total and differential leukocyte blood count showed similar results. However, CSF pleocytosis was higher in TBE patients, with a significant difference in the neutrophil and lymphocyte count (WNND median 48.5% and 51.5%; TBE median 10.0 and 90.0%, respectively). The length of hospital stay was 12 days for WNND and 9 days for TBE. Phylogenetic analysis of detected WNV strains revealed the presence of WNV lineage 2 in eastern Croatia. Full article

Neuroinvasive West Nile Virus disease (WNND) can cause lasting cognitive and motor impairments, impacting autonomy and quality of life. Given the scarcity of research on the rehabilitative needs of patients with WNV infection, this study aims to fill a critical gap by assessing the rehabilitation needs of a real-world cohort of WNND patients. We retrospectively analyzed WNND patients who received early Physical Medicine and Rehabilitation (PMR) evaluations during the 2022 outbreak in Veneto, Italy. Data included demographics, comorbidities, length of hospital stay, days at PMR evaluation, and rehabilitation duration until discharge or death, alongside objective examination findings and Barthel Index scores. Among 29 confirmed WNND patients, the median hospital stay was 20 days, with rehabilitation starting after a median of 7 days. Motor weakness affected 48.28% of patients, swallowing issues 6.90%, and respiratory issues 24.13%. A tailored rehabilitation protocol was designed for 96.55% of patients to address functional concerns and prevent complications. Barthel Index scores showed no significant change. Discharge settings were home (58.34%), other departments (25%), and rehabilitation facilities (16.67%). This study highlights the rehabilitation needs of WNND patients, particularly regarding neuromuscular deficits, swallowing, and respiratory issues, stressing the importance of a comprehensive rehabilitation strategy for improved outcomes. Full article

West Nile Virus (WNV) is a zoonotic, vector-borne pathogen affecting humans and animals, particularly in Europe. The virus is primarily transmitted through mosquitoes that infect birds, which serve as the main reservoirs. Humans and horses are incidental hosts. This review focuses on the epidemiology of WNV in southern Europe, particularly its increasing prevalence. Methods included an extensive literature review and analysis of recent outbreaks. WNV is largely asymptomatic in humans, but a small percentage can develop West Nile neuroinvasive disease (WNND), leading to severe neurological symptoms and fatalities. Horses can also suffer from neurological complications, with high mortality rates. Climate change, migratory birds, and mosquito population dynamics contribute to the virus spread across Europe. Control efforts focus on vector management, and while vaccines are available for horses, none has been approved for humans. Surveillance, particularly of bird and mosquito populations, and further research into the virus molecular structure are crucial for understanding and mitigating future outbreaks. Full article

West Nile Virus, an arthropod-borne RNA virus, may result in severe neurological disease. West Nile neuroinvasive disease is characterized by meningitis, encephalitis, and possible acute flaccid paralysis. Here, we report a case of neuroinvasive WNV in a 65-year-old woman hospitalized for hyperpyrexia, chills, intense asthenia, and continuous vomiting. Within days, her clinical condition worsened with the onset of severe neurological symptoms, leading to her death within 10 days despite supportive therapies being administered. The diagnosis of West Nile disease was made through nucleic acid amplification testing (NAAT) on blood and cerebrospinal fluid. However, in the final stages of the illness, cerebrospinal fluid collection was not possible due to the patient’s critical condition, and a nasopharyngeal swab was used instead. The nasopharyngeal swab facilitated the collection of a sample, which was subsequently analyzed for the presence of the virus and allowed for sequencing, showing that it was a strain that had been circulating in Sardinia for some time and had demonstrated its pathogenicity by causing the death of a hawk in 2021. This case report highlights the rapid progression and severity of WNV infection, particularly in vulnerable individuals, and suggests the potential utility of nasopharyngeal swabs as a less invasive option for sample collection. It also underscores the potential for the zoonotic transmission of the virus from birds to humans through vectors, emphasizing the importance of monitoring and controlling WNV outbreaks, especially in regions where such circulation is observed. Full article

(Re-)emerging arboviruses, such as tick-borne encephalitis virus (TBEV), West Nile virus (WNV), and Usutu virus (USUV), are continuously increasing in incidence. We analyzed the epidemiological characteristics of flavivirus infections in humans, sentinel animals, and mosquitoes detected in the 2022 transmission season in Croatia. From April to November 2022, 110 hospitalized patients with neuroinvasive diseases (NID) were tested for the presence of arboviruses. RT-qPCR was used to detect TBEV, WNV, and USUV RNA. An ELISA and virus neutralization tests were used for the detection of flavivirus antibodies. TBEV infection was confirmed in 22 patients with NID. WNV NID was detected in six patients. TBE showed male predominance (81.8%; male-to-female ratio of 4.5:1). All but one WNV patients were males. TBE occurred from April to August, with the majority of patients (83.3%) being detected during the May–June–July period. WNV infections were recorded in August and September. In addition to human cases, asymptomatic WNV infections (IgM positive) were reported in 10 horses. For the first time in Croatia, WNV NID was observed in one horse that presented with neurological symptoms. Furthermore, USUV was confirmed in one dead blackbird that presented with neurological symptoms. A total of 1984 mosquitoes were collected in the City of Zagreb. Two Ae. albopictus pools tested positive for flavivirus RNA: one collected in July (USUV) and the other collected in August (WNV). A phylogenetic analysis of detected human and avian strains confirmed WNV lineage 2 and the USUV Europe 2 lineage. The presented results confirm the endemic presence of neuroinvasive flaviviruses in continental Croatia. The continuous monitoring of virus circulation in humans, sentinel animals, and mosquitoes is needed to reduce the disease burden. Full article

West Nile virus (WNV) is a re-emerging flavivirus, primarily circulating among avian hosts and mosquito vectors, causing periodic outbreaks in humans and horses, often leading to neuroinvasive disease and mortality. Spain has reported several outbreaks, most notably in 2020 with seventy-seven human cases and eight fatalities. WNV has been serologically detected in horses in the Community of Madrid, but to our knowledge, it has never been reported from wild birds in this region. To estimate the seroprevalence of WNV in wild birds and horses in the Community of Madrid, 159 wild birds at a wildlife rescue center and 25 privately owned equines were sampled. Serum from thirteen birds (8.2%) and one equine (4.0%) tested positive with a WNV competitive enzyme-linked immunosorbent assay (cELISA) designed for WNV antibody detection but sensitive to cross-reacting antibodies to other flaviviruses. Virus-neutralization test (VNT) confirmed WNV antibodies in four bird samples (2.5%), and antibodies to undetermined flavivirus in four additional samples. One equine sample (4.0%) tested positive for WNV by VNT, although this horse previously resided in a WN-endemic area. ELISA-positive birds included both migratory and resident species, juveniles and adults. Two seropositive juvenile birds suggest local flavivirus transmission within the Community of Madrid, while WNV seropositive adult birds may have been infected outside Madrid. The potential circulation of flaviviruses, including WNV, in birds in the Madrid Community raises concerns, although further surveillance of mosquitoes, wild birds, and horses in Madrid is necessary to establish the extent of transmission and the principal species involved. Full article

West Nile virus (WNV) neuroinvasive disease (WNND) occurs in approximately 1 percent of WNV-infected patients and typically presents as encephalitis, meningitis, or acute flaccid paralysis (AFP). WNND remains a difficult inpatient diagnosis, creating significant challenges for prognostication and therapy selection. We characterized the clinical and diagnostic features of WNND cases at two major academic medical centers in New York City in routine clinical practice. We retrospectively reviewed the charts of thirty-six patients with WNND, including twenty-six encephalitis, four meningitis, and six AFP cases. The most common presenting symptoms were fever (86.1%) and gastrointestinal symptoms (38.9%) in addition to altered mental status (72.2%), lethargy (63.9%), gait disturbances (46.2%), and headache (44.4%). Fourteen (48.3%) patients displayed acute magnetic resonance imaging (MRI) findings, particularly T2 hyperintensities in the bilateral thalami, brainstem, and deep white matter. New York State Department of Health WNV CSF IgM testing was utilized for diagnosis in 58.3% of patients; however, just 38.1% had the result by discharge, compared to 85.6% of those who underwent serum IgM testing. The median length of stay was 13.5 days, 38.9% were intubated, and three patients (8.9%) died during acute hospitalization. Our findings underscore the morbidity, mortality, and diagnostic challenges of WNND, suggesting the potential utility of serum IgM testing in combination with confirmatory CSF testing to expedite diagnosis in the acute setting. Full article

West Nile Virus (WNV) and Usutu Virus (USUV) are both neurotropic mosquito-borne viruses belonging to the Flaviviridae family. These closely related viruses mainly follow an enzootic cycle involving mosquitoes as vectors and birds as amplifying hosts, but humans and other mammals can also be infected through mosquito bites. WNV was first identified in Uganda in 1937 and has since spread globally, notably in Europe, causing periodic outbreaks associated with severe cases of neuroinvasive diseases such as meningitis and encephalitis. USUV was initially isolated in 1959 in Swaziland and has also spread to Europe, primarily affecting birds and having a limited impact on human health. There has been a recent expansion of these viruses’ geographic range in Europe, facilitated by factors such as climate change, leading to increased human exposure. While sharing similar biological traits, ecology, and epidemiology, there are significant distinctions in their pathogenicity and their impact on both human and animal health. While WNV has been more extensively studied and is a significant public health concern in many regions, USUV has recently been gaining attention due to its emergence in Europe and the diversity of its circulating lineages. Understanding the pathophysiology, ecology, and transmission dynamics of these viruses is important to the implementation of effective surveillance and control measures. This perspective provides a brief overview of the current situation of these two viruses in Europe and outlines the significant challenges that need to be addressed in the coming years. Full article