West Nile virus belongs to the Flaviviridae family in the genus Flavivirus. Several lineages of this virus exist, with only lineage 1 present in Europe until recently. Migratory birds serve as animal reservoirs for West Nile virus, which is spread by bites from mosquitoes of the genus Culex. After biting infected birds, the female mosquitoes multiply and then transmit the virus to humans during blood meals.
Transmission and symptoms in humans
Although West Nile virus mainly infects humans when they are bitten by a mosquito vector, cases of transmission by blood transfusion and during organ transplants have been described.
In the majority of cases (80%), infection with West Nile virus is asymptomatic. The symptomatic forms of the disease are characterized by the sudden onset of high fever after an incubation period of 3 to 6 days. Other symptoms include headache and backache, muscle pain, a cough, swollen lymph nodes in the neck, and often also a skin rash, nausea, stomach pain, diarrhea and respiratory problems.
Neurological complications (meningitis and encephalitis) occur in less than 1% of cases. Even more rarely, there can be other complications (hepatitis, pancreatitis and myocarditis). Patients generally recover spontaneously, although they sometimes suffer sequelae. But infection can be fatal, mainly in elderly people.
In horses, a species susceptible to West Nile virus, viral infection results in fever, encephalomyelitis, and paralysis of the hind limbs, and the death rate is high.
Cases of horses infected with West Nile virus have been reported in several countries in Europe and the Mediterranean Basin: in Egypt, Italy (1998), Israel (2000), the United States (1999-2004), France (in the Camargue in 2000 and the Eastern Pyrenees in 2006), Guadeloupe (2002), and Morocco (2003, 2010).
West Nile virus is currently thought to be the second most widespread flavivirus after dengue. It was named after the West Nile district in Uganda, where it was first isolated in 1937 in a woman suffering from high fever. It was then detected in humans, birds and mosquitoes in Egypt in the early 1950s, and has since been found in humans or animals in several countries.
In Africa, the most serious outbreak occurred in 1974, affecting 3,000 people in Cape Province, South Africa, following heavy rainfall. Isolated cases and outbreaks in humans have been observed in Algeria, Azerbaijan, Central African Republic, Democratic Republic of the Congo, Egypt, Ethiopia, India, Madagascar, Morocco, Nigeria, Pakistan, Senegal, Sudan, Tunisia and some European countries.
In Europe, human cases have been reported since the 1960s. But over the past 15 years, the frequency of infections has gathered pace. West Nile virus is currently endemic in several European countries, and its distribution area is growing. It is particularly active in southern Europe. Lineage 2 of the virus was observed in Europe for the first time in 2004, when it appeared in Hungary. In 2010, Greece experienced a major outbreak, with 262 cases. In both continental Greece and southern Italy, severe and sometimes fatal neurological forms have been observed in recent years. In 2018, Europe was faced with a serious outbreak, with case numbers vastly exceeding the total for the previous 10 years.
In France, the first human and equine cases were diagnosed in the early 1960s. The virus re-emerged in horses in the Camargue in 2000, and 7 human cases were reported in 2003 in the Var.
Emergence on the American continent
Since 1999, human cases of West Nile virus fever have been reported on the American continent, and a first outbreak occurred in New York City the same year. Small-scale outbreaks were reported in the United States over the next two years, but in 2002 the virus spread extensively over the continent, affecting 4,156 people in 44 states and claiming 284 lives. This was the largest West Nile virus fever outbreak ever recorded, reaching its peak in 2003, when 9,862 people in 44 states were affected, including 2,866 cases of encephalitis and 264 deaths.
There was a slight decline in 2004, with 2,470 human infections and 88 deaths in the United States. The human toll remained high in 2007, with 3,630 confirmed cases, including 1,217 neurological forms and 124 deaths. In 2008, 1,356 cases were diagnosed, around 50% of which were encephalitis/meningitis forms, and the virus claimed 44 lives. Finally, in 2009, 663 cases were recorded, around half of which were again encephalitis/meningitis forms (source CDC, USA), and there were 30 deaths.
In 2012, the figures published by the US health authorities confirmed that the virus was on the rise again. A total of 4,500 diagnosed cases of West Nile virus infection led to 183 deaths.
Ecology: a mosquito-bird cycle
West Nile virus is naturally transmitted by mosquitoes, mainly belonging to the genus Culex. Any factors that favor the proliferation of mosquito vectors – heavy rainfall, irrigation, above-average temperatures, etc. – may increase the incidence of West Nile virus fever in the regions where it circulates. The virus has also occasionally been isolated on other arthropods, such as ticks.
Wild or domestic birds (ducks, pigeons, etc.) are the main hosts of the virus. Birds, especially migratory birds, that transport West Nile virus in spring from Africa to temperate areas in Europe and Asia play a crucial role in its spread. Mosquitoes become infected when they bite these birds and locally perpetuate the mosquito-bird cycle. Since 1998-1999, in Israel and then in the United States, mortality associated with West Nile virus infection has been observed in some species of birds, especially crows.
Mammals (cattle, dogs, cats, horses, humans, etc.) are considered to be incidental hosts of the virus.
Treatment and prevention
No specific antiviral treatment currently exists for West Nile virus. Only the symptoms are treated.
At present, only an equine vaccine is commercially available. No vaccine is available for humans. Prevention of West Nile virus infection is limited to (individual and collective) protective measures against mosquitoes.
At the Institut Pasteur
At the Institut Pasteur, research programs on West Nile virus focus on both virulence factors and the development of new diagnostic tools. They are run by Nolwenn Jouvenet's team in collaboration with the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) in Maisons-Alfort. Two vaccine candidates for West Nile virus have been jointly developed with the research teams led by Pierre Charneau (Molecular Virology and Vaccinology Unit) for the veterinary aspects and Frédéric Tangy (Viral Genomics and Vaccination Unit) for the medical aspects.
In 2007, the Institut Pasteur coordinated the PREDEMICS program. This collaborative program involved 17 European research and public health organizations. The aim was to study four types of virus from animal reservoirs that have high potential for transmission to humans in Europe – including West Nile virus. The research teams focused their efforts on one key objective: understanding the complex mechanisms that govern interactions between a virus and its host.
The Institut Pasteur was also involved in the EUROWESTNILE European program (2011-2014), in collaboration with ANSES. The aim was to characterize the viral determinants of virulence and to study the virulence of West Nile strains in Europe.
Recently, several teams from the Institut Pasteur, coordinated by Antoine Gessain, joined forces within the DEVA transversal research program, which has led to the development of a molecular diagnostic tool for chikungunya, dengue and West Nile virus on the Institut Pasteur's Paris campus. The tool uses a DNA microarray to analyze body fluids such as blood or serum and diagnose acute viral infection. The microarray can also characterize the genome of the virus or viruses in the infected test sample.
The Institut Pasteur teams working on the topic
led by Frédéric Tangy
led by Pierre Charneau