European College of Equine Internal Medicine consensus statement on equine flaviviridae infections in Europe.

Horses and other equids can be infected with several viruses of the family Flaviviridae, belonging to the genus Flavivirus and Hepacivirus. This consensus statement focuses on viruses with known occurrence in Europe, with the objective to summarize the current literature and formulate clinically relevant evidence-based recommendations regarding clinical disease, diagnosis, treatment, and prevention. The viruses circulating in Europe include West Nile virus, tick-borne encephalitis virus, Usutu virus, Louping ill virus and the equine hepacivirus. West Nile virus and Usutu virus are mosquito-borne, while tick-borne encephalitis virus and Louping ill virus are tick-borne. The natural route of transmission for equine hepacivirus remains speculative. West Nile virus and tick-borne encephalitis virus can induce encephalitis in infected horses. In the British Isle, rare equine cases of encephalitis associated with Louping ill virus are reported. In contrast, equine hepacivirus infections are associated with mild acute hepatitis and possibly chronic hepatitis. Diagnosis of flavivirus infections is made primarily by serology, although cross-reactivity occurs. Virus neutralization testing is considered the gold standard to differentiate between flavivirus infections in horses. Hepacivirus infection is detected by serum or liver RT-PCR. No direct antiviral treatment against flavi- or hepacivirus infections in horses is currently available and thus, treatment is supportive. Three vaccines against West Nile virus are licensed in the European Union. Geographic expansion of flaviviruses pathogenic for equids should always be considered a realistic threat, and it would be beneficial if their detection was included in surveillance programs.

Epidemiology and Clinical Manifestation of West Nile Virus Infections of Equines in Hungary, 2007-2020.

West Nile virus (WNV) is an emerging pathogen in Hungary, causing severe outbreaks in equines and humans since 2007. The aim of our study was to provide a comprehensive report on the clinical signs of West Nile neuroinvasive disease (WNND) in horses in Hungary. Clinical details of 124 confirmed equine WNND cases were collected between 2007 and 2019. Data about the seasonal and geographical presentation, demographic data, clinical signs, treatment protocols, and disease progression were evaluated. Starting from an initial case originating from the area of possible virus introduction by migratory birds, the whole country became endemic with WNV over the subsequent 12 years. The transmission season did not expand significantly during the data collection period, but vaccination protocols should be always reviewed according to the recent observations. There was not any considerable relationship between the occurrence of WNND and age, breed, or gender. Ataxia was by far the most common neurologic sign related to the disease, but weakness, behavioral changes, and muscle fasciculation appeared frequently. Apart from recumbency combined with inappetence, no other clinical sign or treatment regime correlated with survival. The survival rate showed a moderate increase throughout the years, possibly due to the increased awareness of practitioners.

Serum neutralising antibody titres against a lineage 2 neuroinvasive West Nile Virus strain in response to vaccination with an inactivated lineage 1 vaccine in a European endemic area.

In the last decade in Hungary and the neighbouring countries, West Nile Neuroinvasive Disease (WNND) has been caused in dramatically increasing numbers by lineage 2 West Nile Virus (WNV) strains both in horses and in humans. The disease in this geographical region is seasonal, so vaccination of horses should be carefully scheduled to maintain the highest antibody titres during outbreak periods. The objective of this study was to characterise the serum neutralising (SN) antibody titres against a lineage 2 WNV strain in response to vaccination with an inactivated lineage 1 vaccine (Equip® WNV). Thirty-two seronegative horses were enrolled in the study, 22 horses were allocated to the vaccinated group and 10 retained as unvaccinated controls. Horses were vaccinated according to the product's vaccination guidelines. A primary vaccination of two doses administered 28 days apart was initiated approximately 5 months before the WNV outbreak season, followed by a booster vaccination one year later. Blood samples were collected during a 2-year period to monitor production of SN antibodies against lineage 1 and the enzootic lineage 2 WNV strain. Mean antibody titres against lineage 1 WNV were significantly higher (P ≤ 0.05) in the vaccinated group compared to the control group at all-time points after the primary dose of vaccination. Similarly, mean antibody titres against lineage 2 WNV were significantly higher (P ≤ 0.05) in the vaccinated group compared to the control group at all time-points except at 6 months after the primary vaccination. SN antibody titres were significantly higher against lineage 1 than lineage 2 at all-time points. According to the results, vaccination with an inactivated lineage 1 vaccine induces antibodies against both WNV lineages 1 and 2 strains up to 2 years after booster vaccination, but in those geographical regions where lineage 2 strains are responsible for seasonal outbreaks, a booster vaccination should be considered earlier than 12 months after primary vaccination.

Multi-Approach Investigation Regarding the West Nile Virus Situation in Hungary, 2018.

The West Nile virus is endemic in multiple European countries and responsible for several epidemics throughout the European region. Its evolution into local or even widespread epidemics is driven by multiple factors from genetic diversification of the virus to environmental conditions. The year of 2018 was characterized by an extraordinary increase in human and animal cases in the Central-Eastern European region, including Hungary. In a collaborative effort, we summarized and analyzed the genetic and serologic data of WNV infections from multiple Hungarian public health institutions, universities, and private organizations. We compared human and veterinary serologic data, along with NS5 and NS3 gene sequence data through 2018. Wild birds were excellent indicator species for WNV circulation in each year. Our efforts resulted in documenting the presence of multiple phylogenetic subclades with Balkans and Western-European progenitor sequences of WNV circulating among human and animal populations in Hungary prior to and during the 2018 epidemic. Supported by our sequence and phylogenetic data, the epidemic of 2018 was not caused by recently introduced WNV strains. Unfortunately, Hungary has no country-wide integrated surveillance system which would enable the analysis of related conditions and provide a comprehensive epidemiological picture. The One Health approach, involving multiple institutions and experts, should be implemented in order to fully understand ecological background factors driving the evolution of future epidemics.