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West Nile Virus

Cliff Rutter, Pharm. D. Candidate and Jennifer K. Seltzer, Pharm. D.

August 1, 2012

West Nile Virus (WNV) is a member of the Japanese encephalitis virus antigen complex and belongs to the family Flaviviridae.  WNV was first isolated from a patient in the West Nile district of Uganda in 1937. The disease was found only in the Eastern Hemisphere until the virus spread to New York in 1999 and caused 62 cases of encephalitis and seven deaths. Since the mid-1990s, several severe outbreaks of WNV have developed worldwide with many occurring in the United States. 1-3 Typically, human infections with WNV peak in late summer to early fall.2 As of July 30, 2012, there have been 71 invasive neurodegenerative disease cases due to WNV and 40 West Nile fever cases reported to the Texas Department of State Health Services.4 In the Dallas-Ft. Worth area (Dallas, Tarrant, Denton, and Collin Counties), there have been approximately 174 confirmed cases of WNV infection in the past year, and at least three deaths attributed to the disease.5, 6 In July 2012, Travis County experienced its first fatality associated with WNV neurodegenerative disease since 2003.7 The patients who have died in Texas have all been older than 50 years of age.5-7

WNV is primarily transmitted through infected mosquitoes, with Culex pipiens quinquefasciatus (southern house mosquito) being the most commonly implicated mosquito in the southern United States.2 WNV exists in a bird-mosquito-bird cycle in which the bird serves as the amplifying host due to the development of high levels of viremia. 1 Commonly infected birds include crows and jays, but the virus has been found in as many as 320 other species. The infected mosquito injects virus-containing saliva in humans during feeding. WNV is thought to initially replicate in the dermal Langerhans dendritic cells, then travels to lymph nodes to reproduce and produce viremia that spreads to various organs and tissues. Mechanisms by which WNV enter the central nervous system (CNS) are unknown but likely include hematogenous spread, transport by infected cells that traffic the CNS, direct axonal retrograde transport from infected peripheral neurons, and infection or passive transport through endothelium cells.2 Transmission through other routes is rare but may include blood, red blood cell, platelet, and fresh frozen plasma transfusions. Screening of the United States blood supply has vastly reduced the potential for transfusion-transmitted WNV. Organ transplants, transplacental transmission, as well as percutaneous and conjunctival exposure have also been documented to transmit WNV.2, 3

Once infected, the incubation period for WNV ranges from 2 to 14 days, but may be longer in immunosuppressed individuals.2 After a patient recovers from WNV, immunity is considered lifelong and re-infection is rare. Approximately 80% of people infected with WNV are asymptomatic, but 20% of infections manifest as West Nile fever, a self-limiting illness that is indistinguishable from dengue fever.1 Symptoms of West Nile fever, which last from three to five days, include fever, headache, malaise, back pain, myalgias, and anorexia. Some patients will be afebrile or will only develop a low-grade fever. A maculopapular rash involving the chest, back, and arms that lasts for less than one week occurs in 25% to 50% of patients and is associated with a lower risk of neuroinvasive disease and death. 1, 8

Less than one percent of patients develop neuroinvasive disease, which presents as encephalitis, meningitis, flaccid paralysis, or a mixed pattern of disease. Encephalitis is more common in older ages, while meningitis appears to occur more commonly in children. Encephalitis severity ranges from a mild, self-limited confusional state to encephalopathy, coma, and death. Extrapyramidal symptoms are a common manifestation of WNV encephalitis. Course tremor and myoclonus in the upper extremities and Parkinsonian features such as rigidity, postural instability, and bradykinesia are other common neurological manifestations of WNV encephalitis.8 Flaccid paralysis is frequently asymmetrical and may or may not be associated with meningoencephalitis, suggesting poliomyelitis. WNV neuroinvasive disease mortality ranges from 2% to 14% and is increased in elderly patients and patients with advanced disease. 1, 9

WNV should be suspected in patients presenting with acute febrile illness, meningitis, encephalitis, or flaccid paralysis during mosquito season. Diagnosis can be made through serologic testing and nucleic acid testing. IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) should be conducted in patients with suspected West Nile fever. MAC-ELISA testing has a high positive predictive value for the diagnosis of WNV in patients with clinical features suggestive of WNV infection. In patients with suspected neuroinvasive disease, cerebrospinal fluid (CSF) obtained from a lumbar puncture should be analyzed by MAC-ELISA testing.9 IgM antibodies do not cross the blood-brain barrier, and any that are found by MAC-ELISA testing must come from synthesis due to local antigen exposure from WNV.10  Nucleic acid testing may be of benefit in severely immunocompromised patients who are potentially  infected and not producing IgM antibodies.9 Further CSF studies typically reveal pleocytes with elevated protein and normal glucose levels.10

Therapeutic options for WNV infection target supportive care, as there are no specific approved treatments available for WNV. Instead, prevention is the primary mechanism to control WNV disease.9,10 Prevention measures include using mosquito repellents containing N,N-diethyl-meta-toluamide (DEET), avoiding outdoor activity during peak mosquito activity during dawn and dusk, wearing protective clothing, and eliminating potential mosquito breeding grounds by removing standing water.9,10 Mosquito control programs to reduce the number of adult mosquitoes during peak season have been used to limit the spread of human infection. Programs are directed at eliminating breeding sites and utilizing larvicides to reduce mosquito populations.9 Ribavirin inhibits WNV replication in vitro, but has not demonstrated clinical efficacy in uncontrolled, non-blinded studies.9,10 Interferon has shown efficacy in vitro and in animal models but no human studies have been conducted for treating WNV infection.9 Recent studies evaluating interferon efficacy in treating Japanese encephalitis have shown no clinical benefit and interferon's utility against WNV is now being questioned.10 Human vaccines are not currently available, but data for potential vaccines are promising.9

Texas authorities state that the mild winter and recent heavy rain have created breeding grounds for mosquitoes carrying WNV and that this year's WNV season will be more intense than previous years. It is important to remember the "four Ds" for precautions: stay indoors at dusk and dawn, when mosquitoes are most active; dress in long sleeves and pants when outside; use a mosquito repellent containing DEET on exposed skin and clothing; and drain standing water.7

References:

  1. Vaughn DW, Barrett A, Solomon T. Flaviviruses (Yellow fever, dengue, dengue hemorrhagic fever, Japanese encephalitis, West Nile encephalitis, St. Louis encephalitis, tick-borne encephalitis) In: Mandell GL, Bennett JE, Dolin R. Mandell: Mandell, Douglas, and Bennett's Principles and practice of infectious diseases. 7th Ed. Churchstone Livingston. Philadelphia, PA. 2009.
  2. Petersen LR. Epidemiology and pathogenesis of West Nile virus infection. In: UpToDate, Basow, DS (Ed). UpToDate. Waltham, MA. 2012.
  3. Centers for Disease Control and Prevention. West Nile Virus. Available at: http://www.cdc.gov/ncidod/dvbid/westnile/index.htm. Accessed July 18, 2012.
  4. Texas Department of State Health Services. West Nile Virus in Texas. Available at: http://www.dshs.state.tx.us/idcu/disease/arboviral/westNile/. Accessed July 18, 2012.
  5. Third West Nile virus death confirmed in Dallas County. WFAA. Available at: http://www.wfaa.com/news/health/Third-death-in-164063696.html. Accessed July 30, 2012.
  6. West Nile cases surging in north Texas. WFAA. Available at: http://www.wfaa.com/news/health/West-Nile-virus-cases-surging-in-North-Texas-164165516.html. Accessed July 30, 2012.
  7. Roser MA. West Nile claims first Travis County resident since 2003. Austin American Statesman. Available at: http://www.statesman.com/news/local/west-nile-claims-first-travis-county-resident-since-2425637.html. Accessed August 1, 2012.
  8. Petersen LR. Clinical manifestations and diagnosis of West Nile virus infections. In: UpToDate, Basow, DS (Ed). UpToDate. Waltham, MA, 2012.
  9. Petersen LR. Treatment and prevention of West Nile virus infection. In: UpToDate, Basow, DS (Ed). UpToDate. Waltham, MA, 2012.
  10. Tyler KL. West Nile virus infection in the United States. Arch Neurol. 2004;61():1190-5.

 


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