West Nile Virus

WNV was first isolated 1937 in the West Nile District in Uganda. It is a zoonotic neuropathic virus, infecting mainly birds but also mammals, including humans, where infection with WNV can lead to neurological symptoms such as encephalitis. WNV is transmitted via mosquitoes.

transmission cycleIn humans, first signs of WN-disease are observed 2–6 days post infection, but the incubation period may extend to 2 weeks. 20% of the infected persons develop flu-like symptoms with high fever. However, in about 1% of the cases, a WNV infection can lead to a severe neuro-invasive disease. Within this group the mortality rate can reach 20%. In particular older and immune-suppressed persons are at risk.

The virus belongs to the Flaviviridae family, which also includes several other clinically relevant viruses including Dengue Virus, Yellow Fever Virus, Tick Born Encephalitis virus and Japanese encephalitis virus. Among mosquito-borne flaviviruses, WNV has the broadest vector and host range. Flaviviruses have an icosahedral structure of ~50 nm diameter. The virion’s envelop comprises virus-specific glycosylated proteins, surrounding the capsid which contains the viral RNA genome.

Phylogenetic analyses have revealed that most WNV isolates worldwide can be assigned to two major lineages. Lineage 1 consists of isolates from North Africa, Europe, India, Israel, USA and Australia (Kunjin-virus), whereas lineage 2 comprises isolates from West, Central and East Africa including Madagascar. The two lineages share 76–77% identity on the RNA level and 93–94% identity on the amino acid level.

WNV is a zoonotic virus circulating in birds. The role of birds in the enzootic cycle of the virus is well documented. Many avian species are susceptible and develop high viral serum titres during the acute phase of infection. During a time window of 4–5 days these WNV titres are high enough to transmit the virus to blood sucking mosquitoes and infect them. Such serum concentrations have been observed in birds only, hence the mammalian hosts such as humans and horses provide a dead end for WNV. However, in rare cases WNV can be transmitted among humans via blood transfusion or organ transplantation. Transplacental transmission has been documented as well.

WNV has come into the focus of public interest following its introduction into the USA in 1999. Starting from New York City, the epidemic spread over the entire continent and reached countries in Latin America. In the United States, between 1999 and 2010, more than 30,000 human cases were confirmed that required clinical attention. These were associated with more than 1,200 deaths. Based on seroprevalence studies several million humans have been infected but not diagnosed. Horses were affected as well, and experienced even higher mortality rates than humans. In addition, WNV has led to a dramatic decrease in the populations of many American bird species.

WNV in Europe

Although the European situation is currently less dramatic compared to the USA, WNV is being detected more frequently over the last five years, especially in southern Europe, where both major WNV lineages seem to be endemic today. Epidemiological data demonstrate the spreading of WNV and imply the occurrence of novel WNV variants over the last 15 years with increased virulence and epidemic potential both for birds and for mammals.

Most documented cases of WNV infection derive from the veterinary sector, and outbreaks very often affect birds and horses. Several studies demonstrated that birds in Europe, even in Germany and the UK, had WNV specific antibodies or detectable viral RNA in their blood. Recent outbreaks among horses were seen in 1998 in the Tuscany region / Italy and, since 2008, in Northeastern Italy and in the Camargue / France (2002 and 2008). Human WNV cases in Europe have up to now clustered in Southern Europe. WNV of the lineage 2 seems to be endemic in Hungary, where between 2003 and 2007 on average of six cases of WNV neuroinvasive infection were recorded per year. In 2008, this number increased to 14 by October, and the virus now affects the whole country. In the same year a WNV outbreak among humans was observed in the Emilia Romagna and Veneto regions of Northeastern Italy with 9 confirmed cases of WNV diseases. In 2009, 16 human cases were reported from Italy, showing a larger geographical distribution than 2008. In 2010, major outbreaks occurred in Romania and Greece, caused by pathogenic lineage 2 WNV strains. More than 200 people suffered from neurological symptoms, more than 20 cases were fatal. Also in 2010, WNV cases were reported from Russia, Italy, Turkey, Israel and Morocco. It should be noted that numbers of confirmed human cases probably underestimate the true extent of the disease due to the heterogeneous nature of symptoms associated with WNV infection.

Prevention

Only veterinary WNV vaccines are currently on the market. Equine WNV vaccines in the USA led to a significant decrease in the number of severe clinical signs associated with WNV infections among horses, and the first veterinary vaccine was also licensed in Europe. There is no human vaccine available to date, neither is a specific treatment to counteract WNV caused disease. Hence, at the moment the only way to prevent an infection with WNV is to avoid mosquito bites. There is also a high demand for novel diagnostic tools that minimize cross-reactivity with other flaviviral infections.

The development of safe and efficient vaccine candidates for the protection of humans and of innovative diagnostic systems are major goals of the West Nile Shield Project.