West Nile virus is a flavivirus that, along with similar viruses such as Japanese encephalitis virus and St. Louis encephalitis virus, has the ability to cause severe central nervous system disease (i.e. meningitis or encephalitis) with subsequent neurological impairments. WNV is the most widespread of the flaviviridae family, and is endemic in many areas of the world. It is also enzootic, cycling through birds (hosts) and mosquitoes (vectors) (May et al., 2011). Many species of mosquitoes can transmit the virus, but in the United States, it is primarily spread by several of the Culex genus. Certain bird species of the Passerine order are most likely to be hosts to the virus (Petersen et al., 2013)
West Nile virus was first identified in 1937 in the blood of a Ugandan woman. At that time, human infection with WNV was uncommon, and the virus was contained to the central region of Africa. From that time until 1991-1992, there were occasional outbreaks of WNV in Africa, but even those were not frequent. However, in the 1990s the disease began to appear in Russia, Romania, Israel, and Greece, possibly due to migratory birds (Petersen et al., 2013). In 1999 it was found for the first time in North America (New York City); only 4 years later, it had reached the west coast, and it spread into South America as well. The disease is now endemic in the United States and other Western hemisphere countries.
West Nile virus is typically caused by mosquitoes who have taken a blood meal from a bird with WNV. Human beings may contract WNV if they, in turn, are bitten by those mosquitoes that now carry the virus. In addition to getting the virus from birds, the mosquitoes can also give it to them. WNV can infect horses as well, and has caused a number of epidemics among horses in both North and South America. Both horses and humans are considered to be “dead-end” hosts (Petersen et al., 2013) since the virus can infect them but not spread from them.
When a mosquito carrying WNV bites a vertebrate such as a bird or human being, its virus-containing saliva is injected into the skin of the host. The virus then begins to replicate in the cells of the epidermis, including keratinocytes, dendritic cells, and Langerhans cells (Petersen et al., 2013). These cells travel to the lymph nodes, where viral replication continues. From there, the virus may move into the bloodstream or the spleen, which can disperse the virus to all other organs, including the brain.
WNV is asymptomatic in approximately 80% of humans infected. Most of the other 20% that are infected experience a mild, flu-like illness. However, 1% of individuals will develop neurological symptoms such as acute flaccid paralysis typical of poliomyelitis, fever, stiff neck, and photophobia of meningitis, or the severe headache, confused thinking, and seizures of encephalitis. Impairment of senses such as hearing or seeing can also occur. The percentage of severe illness has appeared to increase over the past 10 years, but this may be due to errors in diagnosis and lack of subsequent WNV testing, since the milder forms may be indistinguishable from other diseases like influenza. Sensory deficits, paralysis, and cognitive impairment may persist even after the fever and other symptoms resolve (Rossi et al., 2011).
Age and immune system status influence the type and severity of symptoms that the virus causes. Older individuals, those receiving steroids for autoimmune disorders or to prevent transplant rejection, and those with immune system deficits such as HIV are most likely to have severe central nervous system involvement. Recent studies suggest that certain genetic defects can increase susceptibility to WNV, causing those individuals to have more severe illnesses with increased persistent consequences (Loeb et al., 2011); however, replication of these results has been difficult to achieve.
Diagnosis usually rests on examination of cerebrospinal fluid and serological tests, due to the wide variety of presentations and the fact that WNV symptoms overlap with many other disorders. Rossi et al. (2011) note that viremia and/or large amounts of virus in other organs do not imply CNS involvement. In summer, especially when there is a known outbreak occurring in the area, physicians should test for WNV when a patient presents with fever, headache, and neurological symptoms. There is no treatment, other than supportive care, available for WNV, and no vaccine for human (although there is one for horses). Some promising possibilities include combining antivirals such as interferon and ribavirin, and using anti-WNV immunoglobulin.
West Nile encephalitis typically has a death rate of 10%. Chronic CNS symptoms after the acute infection are common (Fredericksen, 2013). Murray et al. (2010) conducted a longitudinal study of patients with confirmed WNV who required hospitalization. Since their illnesses they have been followed every six months with blood tests and a clinical questionnaire. Five years after infection, 60% of the patients who had encephalitis continued to report symptoms such as weakness, fatigue, memory loss, and ataxia (Murray et al., 2010). Johnstone et al. (2011) found that patients who experienced acute flaccid paralysis (WNV poliomyelitis) were most likely to have chronic symptoms due to incomplete recovery. According to Leis and Stokic (2012), these continued symptoms are due to neuronal death during the active infection. Other consequences of WNV were myasthenia gravis, seventh nerve palsy, and autonomic instability (Leis & Stokic, 2012).
Since the spectrum of symptoms caused by WNV encephalitis is so broad, it is not surprising that the post-acute consequences vary widely as well. For instance, Afzal et al. (2014) reported on a unique case of WNV opsoclonus myoclonus syndrome (a combination of rapid eye movements and uncoordinated eyelid movements). Although unnoticeable to the untrained eye, the symptoms persist enough to limit her ability to read and to engage in long tasks requiring use of the eyes. Another unique case, reported by Springer et al. (2012), involved an individual who experienced bulbar palsy and associated respiratory failure. Even after the acute symptoms subsided, he remained tracheostomy and gastrostomy dependent due to weakness of his throat muscles, making it difficult for him to breathe or swallow.
WNV with CNS involvement encompasses a wide range of problems, some of which can persistent after the patient is otherwise recovered. Rehabilitation is often required to bring the person to the highest possible level of functioning.
- Afzal, A., Ashraf, S., Shamim, S. (2014). Opsoclonus myoclonus syndrome: an unusual presentation for West Nile virus encephalitis. Proceedings (Baylor University Medical Center 27 (2): 108-110.
- Fredricksen, B. (2013). The neuroimmune response to West Nile virus (review). Journal of NeuroVirology. doi: 10.1007/s13365-013-0180-z
- Johnstone J., Hanna S. E., Nicolle L. E., Drebot M. A., Neupane B., Mahony J. B., Loeb M. B. (2011). Prognosis of West Nile virus associated acute flaccid paralysis: a case series. Journal of Medical Case Reports 5, 395.10.1186/1752-1947-5-395
- Loeb, M., Eskandarian, S., Rupp, M., Fishman, N., Gasink, L., Patterson, J…. Lemire, M. (2011). Genetic variants and susceptibility to neurological complications following West Nile virus infection. Journal of Infectious Disease, 204 (7): 1031-1037
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- Murray, K., Walker, C., Herrington, E., Lewis, J., McCormick, J.,Beasley, D….Fisher-Hoch, S. (2010). Persistent infection with West Nile virus years after initial infection. Journal of Infectious Disease 201 (1): 2-4.doi: 10.1086/648731
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- Rossi, S., Ross, T., Evans, J. (2011). West Nile virus. Clinical and Laboratory Medicine. 30 (1): 47–65.doi: 10.1016/j.cll.2009.10.006
- Springer, J., Kaldas, K., Barot, N., Kamangar, N. (2012). Isolated bulbar palsy with associated hypercapnic respiratory failure — A Unique presentation of West Nile virus encephalitis. American Thoracic Society International Conference Abstracts.