West Nile Virus (WNV) is a member of the Flaviviridae family, the type species of which is Yellow Fever Virus (YFV) (Latin: flavus=yellow). Other members of this family include the Dengue viruses, Japanese Encephalitis, St Louis Encephalitis and Louping Ill Virus. All members of the flaviviridae are arthropod-borne viruses, known as arboviruses for short, which means that they are spread by insects (particularly mosquitoes, sandflies or midges), and ticks. West Nile Virus is transmitted by mosquitoes.

Transmission of West Nile Virus

Like all arboviruses, WNV multiplies in a haematophagous (blood-feeding) arthropod (in this case, Culex mosquito) and is transmitted by bite to a vertebrate in which it also multiplies. A viraemia¹ is produced of a sufficient level that the virus can be transferred to a subsequent blood-feeding arthropod, and so the cycle is perpetuated. The arthropod host is known as the vector, and the principal vertebrate host (usually a mammal or a bird) is known as the reservoir. Hosts for WNV include wild birds (the main reservoir), horses and, more rarely, humans. Crows are particularly susceptible to West Nile Virus.

Mammals, including humans, generally do not develop a viraemia of a sufficient level for the cycle to be perpetuated, and so are known as dead-end or incidental hosts.

As well as Culex species, at least 42 other species of mosquito have tested positive for WNV in the United States. These include Aedes, Anopheles, and Psorophora species.

A vector of particular concern in the United Kingdom is the Asian tiger mosquito (Aedes albopictus)², a tropical species found primarily in Asia and West Africa. However, it has already established itself in Northern Italy (where it has transmitted chikungunya fever) and has been detected in a dozen other European countries, including Germany, France and the Netherlands. Scientists at the Health Protection Agency, Porton Down, have warned that, as the virus can survive temperate climates, it could establish itself across England and Wales in the warm, damp conditions of a British summer. Because the tiger mosquito lays its eggs in water, Porton scientists believe that it could survive in the small pools that collect in tyres sent to Britain on container ships from Asia for recycling.

Geographical Distribution

The virus is named for the region of its initial detection: it was first isolated from the blood of a febrile woman in the West Nile district of Uganda in 1937. Subsequently, the virus was isolated from human patients, birds, and mosquitoes in Egypt in the early 1950s. The virus was soon recognised as the most widespread of the flaviviruses, with geographic distribution including Africa, Europe, West Asia, the Middle East, and North America, including Canada. In temperate zone countries such as the United States and Canada, the disease occurs mainly in late summer and early autumn. Further south, the disease may occur throughout the year.

Signs and Symptoms

As humans are not the primary host, infections in humans are rare and the symptoms are mild - being likened to those of influenza. Most people infected with WNV have no signs or symptoms at all. About 20 percent of people develop a mild infection called West Nile Fever.

Apart from the fever, the symptoms of West Nile Fever also include headache and muscle aches similar to influenza. Occasionally there is a skin rash on the trunk of the body and swollen lymph glands. People thus afflicted tend to be those who are elderly, young, or have compromised immune systems.

These symptoms last only a few days and a full recovery normally ensues.

Much more rarely - ie, in less than one percent of infected people, the virus causes a more serious neurological infection, including encephalitis, meningitis or paralysis. Signs and symptoms of these conditions include:

• High fever
• Severe headache
• Stiff neck
• Disorientation or confusion
• Stupor or coma
• Tremors or muscle jerking
• Signs and symptoms of Parkinson's disease (Parkinsonism)
• Lack of coordination
• Convulsions
• Partial paralysis

Symptoms of encephalitis or meningitis may last several weeks and certain neurological effects, such as paralysis, may be permanent.

Human Outbreaks of West Nile Fever

Since the original isolation of WNV, human outbreaks have been infrequent and sporadic. Notable examples include:

• 1951 - 1954 and 1957: Israel
• 1960s: France
• 1962 - 1964: Mediterranean and central Russia
• 1974: South Africa
• 1970s and 1980s: Belarus and Ukraine
• 1994: Algeria
• 1996: Morocco
• 1996, 1997: Romania
• 1997: Czech Republic
• 1998: Italy
• 2000: Israel
• 2000: Southern France. (Detected in horses. First recorded case since the 1960s)
• 1998 - 2005: United States (Endemic)*

* By 2005, WNV had spread to virtually every State of the USA. Throughout the USA in 2003, there were 9122 cases of West Nile Fever, resulting in 223 deaths. The virus strain afflicting the USA seems to be more virulent than those affecting Europe, Asia and Africa.

Of concern are the facts that, since the mid-1990s, there has been an increase in the frequency of the disease in humans, an apparent increase in the severity of the human disease and high avian death rates associated with the human outbreaks in Israel and the United States.

Treatment

As the symptoms are so mild, treatment is not generally sought; and the infection is allowed to run its course and resolve itself. In more serious cases, supportive measures are the ones most commonly taken, as West Nile has no specific antiviral treatment. The patients are kept hydrated and attempts are made to reduce fever. Treatment with ribavirin, an antiviral drug, can be helpful within the first few days of infection.

Prevention

As there is no cure, prevention is obviously the best policy. In areas of known outbreaks, wild bird species (particularly crows) are monitored to assist in the tracking of the virus. Birds found dead are examined for signs of the virus, and spraying of pesticide and other mosquito-abatement measures are taken in areas where infected birds are found.

Other precautions against infection where West Nile Virus is known to be present involve prevention of exposure to mosquitoes, including:

• Avoiding areas where mosquitoes live at dusk and at dawn (their peak feeding/biting times)
• Wearing long-sleeved shirts and long trousers when going outdoors for extended periods
• Using insect repellents
• Draining areas of standing water (mosquito breeding grounds)
• Installing screens on the windows of your home

What About a Vaccine?

A vaccine is available to protect horses from WNV. However, no vaccine is yet available for humans, although work to develop one is in progress.

Thus, in November 2003, the Anglo-American biotechnology company, Acambis, commenced Phase 1 clinical trials³ of the first West Nile Virus vaccine intended for use in humans. The Acambis vaccine is based on the vaccine already licensed for preventing yellow fever. It is a chimeric virus vaccine, containing genes from two different viruses - Yellow Fever and West Nile - in which some of the Yellow Fever Virus genes have been replaced with genes encoding the surface protein of West Nile Virus.

The Situation in Britain

The increased prevalence of WNV in mainland Europe and America, which has claimed hundreds of lives in recent years, has led to fears that it could become endemic in Britain. Indeed, in 2004, two Irish tourists returned home from a holiday in Portugal, infected with WNV.

In the past, malaria - another mosquito-borne infection - used to be prevalent in the Kent and Essex marshes, although no cases have been reported since the early 20th Century. However, global warming has led to fears that the climate will become warm enough for mosquitoes to proliferate. Indeed, scientists say that the climate in southern parts of Britain is already wet and warm enough to enable mosquito eggs to survive for months, even over winter.

Alexander the Great

Alexander the Great (356BC-323BC), King of Macedonia, died at the tragically early age of 32, of a 'fever' following a prolonged drinking session. From then on there has been much speculation as to the real cause of his death - was it alcohol related or could he even have been murdered? Certainly his death occurred at a time when there was concern among his generals that he was planning to annex Arabia to his already large Empire. There has also been speculation that his fever was due to the mosquito-borne disease, malaria. More recently, there has been the intriguing possibility that his death might have been due to another mosquito-borne disease: West Nile Fever. The Greek biographer, Plutarch records that shortly before Alexander's death, birds had been seen pecking at each other, mid-flight, and then dropped at his feet, dead:

When [Alexander] arrived before the walls of [Babylon], he saw a large number of ravens flying about and pecking one another, and some of them fell dead in front of him.

This was perceived as a bad omen for Alexander.

Ravens belong to a family of birds that are particularly susceptible to the pathogen, and a similar phenomenon was observed with birds from the same family during the 1999 outbreak of West Nile Fever in New York State.

Summary

Although WNV is not a serious threat to most humans at the present time, it can cause severe epidemics, and an attitude of caution is warranted. lf the virus is reported to be in your area, take steps to protect yourself from it, and pay attention to local news regarding movement of the virus. Though currently your location may not be threatened by it, the increase in air travel has made the spread of disease far easier and, thanks to a transatlantic airliner harbouring a mosquito, or an infected traveller unwittingly carrying the disease to a new location, this virus could soon come to a mosquito near you!