West Nile Virus
Summary
In recent years, there have been serious outbreaks of West Nile Virus in the US, where the outbreaks caused a number of fatalities, and in some parts of Europe. Prof David Williams provides an overview of the virus, its symptoms, treatment and prevention.
Key Points
- West Nile Virus is named after the West Nile district of Uganda where it was discovered.
- Large birds are probably the main hosts, and bites from infected Culex mosquitos transmit the virus to humans.
- Person-to-person spread does not occur other than by blood transfusions, organ donation and transplacentally.
- Infected humans are usually asymptomatic. About 1 in 5 suffer a feverish illness with headache and joint pains, and 1 in 150 suffer nervous system disease usually encephalitis or aseptic meningitis.
- The virus is susceptible to ribavirin and interferon alpha 2B in the laboratory, but the effectiveness of these drugs in patients is not known.
- Prevention is by public control of mosquitos and personal measures against being bitten.
Declaration of interests: No conflict of interests declared
Background
The West Nile Virus is an RNA virus belonging to the Flavivirus group. It is classified in the Japanese encephalitis virus serocomplex. The virus was first isolated and identified in 1937 in the West Nile district of Uganda. It was first linked with encephalitis in 1957 during an outbreak in Israel. Since the mid 1990s the frequency and apparent clinical severity of West Nile Virus outbreaks have increased. Outbreaks have occurred recently in Romania, Russia and the US. In the USA in 2002 and 2003 there were 2900 and 2700 cases respectively of meningoencephalitis with more than 200 deaths in both years. The first cases in the US occurred in the Northeast in 1999, but how or why the virus appeared in the US remains unknown. It has been postulated that travel and commerce may have played a role.
Transmission
The virus can infect humans, birds, and various mammals. However, large birds appear to be the principal hosts, as they are able to survive long-term viremia. Dead crows have become harbingers of human cases, giving new meaning to the phrase, ‘as the crow flies’ (or falls). The mosquito most commonly implicated in transmission belongs to the genus Culex. The mosquito and the virus are able to survive through the winter months.
Humans are infected following a bite by an infected mosquito typically in the late summer months. The virus is located in the mosquito’s salivary glands. Person-to-person spread can occur through blood transfusion and organ donation and more rarely transplacentally.
Clinical manifestations
The majority of infected individuals remain asymptomatic. The incubation period is probably in the range of three to 14 days. Serosurveys conducted during the 1999 New York epidemic indicated that approximately 20% of infected individuals developed a febrile illness (West Nile fever). These patients complained of fever, headache and arthralgias. In earlier outbreaks, rash and lymph adenopathy had been noted as part of this febrile illness.
Approximately one in 150 infections result in neurologic sequelae, most frequently encephalitis. Increasing age is the most significant risk factor for severe neurologic disease and death. The risk markedly increases in individuals aged over 50 years (the incidence is ten times higher than in those aged 0-19 years).
The clues to implicating West Nile Virus as a cause of encephalitis include epidemiologic factors (this is a disease of late summer and early autumn), and the presence of severe muscle weakness. Acute flaccid paralysis has been described fairly frequently and usually represents anterior horn cell involvement.
Encephalitis typically presents with confusion, coma, cranial nerve abnormalities, etc. Aseptic meningitis is the second most frequent presentation, typically with headache, fever and neck stiffness. The CSF findings are non-specific (CSF pleocytosis, elevated protein and normal glucose). MRI studies have shown enhancement of the leptomeninges and periventricular areas in about one-third of patients. Serial MRI studies may show evidence of deep grey matter involvement in the thalamus.
Laboratory diagnosis
The diagnosis is best made by detection of IgM antibodies in the serum or CSF. Since IgM antibodies do not cross the blood-brain barrier, their detection in the CSF strongly suggests CNS infection. The diagnosis can also be made by isolation of the virus or demonstration of specific viral antigen (or genomic-sequences) in tissue, CSF or blood.
Treatment
Treatment is supportive. Ribavirin and interferon alpha-2B have in vitro activity against the virus, but there are no controlled clinical studies of the value of this treatment. The use of intravenous immunogloblin is being studied.
Prevention
This involves the usual personal protective measures of avoiding mosquito bites. Local authorities have intensified mosquito control measures in response to outbreaks. A vaccine is in development; it has not yet been studied clinically.
In August 2002 a report from Georgia and Florida documented transmission of West Nile Virus from a single organ donor to four organ recipients. The organ donor had received numerous transfusions of blood products prior to death and a viremic donor was eventually identified. In July 2003, the FDA recommended blood donor screening for West Nile Virus using a nucleic acid testing programme. A follow up analysis showed that blood donor screening reduced, but did not eliminate, the risk of transfusion transmission.
References
- Petersen LR, Marfin AA. West Nile Virus: a primer for the clinician. Anal of Intern Med 2002; 137:173-9.
- US Center for Disease Control (CDC) website
- Gea-Banaclohe J et al. West Nile Virus: pathogens and therapeutic options. Annals of Intern Med 2004; 140:545-553.
- Solomon T. Flavivirus Encephalitis. N Engl J Med 2004; 351:370-8.
