West Nile Virus

West Nile Virus (WNV) is an RNA virus of the flavivirus family. It is becoming more common worldwide. It has not so far spread to the UK, but imported cases have been noted.¹

• West Nile virus has been found in: Africa, Europe, the Middle East, west and central Asia, and more recently, North America. WNV is now endemic in Canada.²
• Clinical severity seems to vary between countries and may be related to factors such as age or prevalence of childhood infection. For example, neurological WNV disease seems to be rare in Egypt where childhood WNV infection is common.

Transmission

• The peak transmission is during summer months.
• WNV is transmitted by various mosquito species, of which Culex pipens seems to be important. Mainly, the virus is transmitted between birds and mosquitos.
• Humans, horses, other mammals and reptiles can also be hosts. Humans and horses are "dead end hosts" and do not normally transmit the virus to other mosquitos, because their viraemia is low level and transient.^1,3
• Animal to human transmission is not known. Human to human transmission is rare, but there have been cases of infection occurring transplacentally, via breast feeding, from blood transfusions and following organ transplantation.

Current trends relevant to the UK⁴

• Although WNV has not yet spread to the UK, it is becoming more common in other parts of the world.¹
• In 2006-7 there were 2 imported cases of WNV in the UK (imported from Canada).
• Sporadic cases and outbreaks of disease in humans and horses have occurred in Europe since the 1960s.⁵ In autumn 2008, there were outbreaks of WNV in birds in Austria, and 2 human cases in Northern Italy for the first time.
• So far, in the UK there has been no active disease in birds. The risk of West Nile virus in the UK is considered to be low. However, the situation is being monitored. There is a risk that WNV could be introduced through wild birds in the UK, and DEFRA (Department for Environment, Food and Rural Affairs) continues to test wild birds for WNV.
• The Department of Health has a contingency plan for WNV in the UK.⁶

• Most WNV infections in humans are asymptomatic (e.g. in the 1999 New York outbreak, only 1 in 5 of those infected developed symptoms, and 1 in 150 had neurological WNV disease).
• Incubation period is 2-14 days, usually 2-6 days.
• Usual symptoms are: sudden onset of flu-like illness: high fever, malaise, headache, backache, myalgia and retro-orbital pain.
• Other possible symptoms are: nausea, vomiting, cough and sore throat.
• Possible signs are: facial flushing, conjunctival injection, generalised lymphadenopathy and a rash on the trunk. There may be hepatomegaly and splenomegaly.

Severe illness

There may be:

• Neurological features:
  • Meningitis, encephalitis or myelitis (with muscle weakness) can occur.
  • Usually there is a febrile prodrome of <7 days before neurological symptoms develop.
  • Other possible neurological manifestations are: convulsions, cranial neuropathies, ataxia, optic neuritis, chorioretinitis,⁷ Parkinsonian features or coma.
  • A recent study found that multifocal chorioretinitis may be a specific marker of WNV infection, particularly if there is meningoencephalitis, and suggested that ophthalmological examination should be routine in such cases.⁸
• Other occasional complications are: hepatitis, myocarditis, and pancreatitis.

• The diagnosis requires a high index of clinical suspicion, plus specific laboratory tests.⁹
• In the UK, consider WNV if the person has very recently returned from travel to a warmer climate, especially if there are other reported cases from their travel area.
• In areas where WNV occurs, always consider WNV as a cause of meningitis or encephalitis in all age groups, particularly in late summer. In the USA, also consider other arboviral disease, e.g. St Louis encephalitis.⁹
• Differential diagnosis: there are many other causes of encephalitis and arthropod-borne infections which may enter the differential diagnosis. Travel history is important.
  • Herpes simplex virus (HSV encephalitis) is an important differential diagnosis, as it is treatable with antiviral drugs.
  • Similar viral infections are: St Louis encephalitis, Japanese encephalitis and Murray Valley encephalitis.
  • Other common diseases that may mimic West Nile encephalitis (WNE) include:⁷ subacute bacterial endocarditis, Legionnaires disease, Rocky Mountain spotted fever, Epstein-Barr virus infectious mononucleosis, human herpesvirus type 6 infection, Colorado tick fever, Chandipura virus¹⁰ and systemic lupus erythematosus cerebritis.

• Initially, IgM and IgG antibody tests (by ELISA):
  • However, these are not specific for WNV and should be regarded as screening tests for flaviviruses. They can cross-react with other antibodies, including SLE, dengue and yellow fever. Serologically positive ELISA tests should be followed by the neutralisation test, which is species-specific.^11,12
  • Most patients admitted to hospital have antibodies by day 7.
  • IgM in CSF shows CNS infection.
• Immunocompromised patients can have negative IgM tests, but the virus may be detectable using PCR or other virus detection methods.
• CT, MRI or EEG may be used to look for HSV encephalitis, which tends to show specific changes on cerebral imaging. (This is relevant as HSV has specific treatment.)

• Treatment is supportive; there is no specific antiviral treatment for West Nile virus infection.
• In more severe cases, high dependency care, including ventilation, is required.
• Antiviral treatments which have been proposed or tried are: interferon alpha, ribavirin, or immunoglobulin from previous infected patients. Immunoglobulin had apparently promising results. However, there is no clearly established treatment.
• Rehabilitation for survivors with neurological sequelae is required.

• Most deaths have been reported in those over 50 years old, who generally suffer more severe disease than younger patients.
• Overall fatality rates are 4-14%, but can be higher in older patients.
• Adverse prognostic factors include old age, presence of profound weakness or deep coma, co-existing illness, immunosuppression or failure to produce IgM antibody.
• Persisting neurological symptoms are common, e.g. in one study, two thirds (of patients admitted to hospital for WNV) had persisting symptoms at one year. Another study reported better recovery, with most patients' mental function scoring normal by one year.¹³

• The effects of WNV in pregnancy are largely unknown.
• A study of mothers and their neonates from the USA suggested generally good outcomes of women who may have been exposed to WNV during pregnancy.¹⁴ However, the accompanying editorial comments that this study had limitations, and there may be a possible pattern of congenital WNV infection presenting in the neonate, following WNV infection during the third trimester of pregnancy.¹⁵
• In the USA, reporting of WNV infection during pregnancy is encouraged. There are interim guidelines on testing pregnant women and neonates for suspected WNV.¹⁶
• It may be possible for WNV to be transmitted by breast feeding, but breast feeding is still advised for a woman with WNV. In the one reported case of likely breastfeeding transmission, the baby was well and asymptomatic.¹⁶
• Further information for clinicians and a fact sheet for pregnant women, are available on the USA Centre for Disease Control website.¹⁶

• Reduce mosquito bites: Limit outdoor exposure during peak times of mosquito feeding (usually from dusk to dawn), wear loose fitting clothing that covers up skin as much as possible, use an effective insect repellent (those containing DEET are considered the most effective), insect-proof screens on windows and doors, bed nets and spraying the room with insecticide.
• Do not handle dead birds.¹⁶
• No vaccine is available, although there is a vaccine for horses,¹⁷ and there is research on a vaccine for humans.¹⁸
• Surveillance programmes for mosquito, bird, and horse infection.
• During outbreaks, targeted insecticide spraying has been used to reduce adult mosquito numbers.

West Nile virus was first identified in Uganda in 1937. After this there were reported cases in Africa, Asia and the Middle East. Since the 1990s, there seems to be an increasing frequency and severity of the disease. An outbreak in New York in 1999 marked the arrival of WNV in North America.