West Nile - A Mosquito-Borne Viral Disease
West Nile is the leading cause of mosquito-borne disease in the continental U.S.
Infectious Disease
There are four mosquito-borne viral diseases endemic to the Western Hemisphere; Zika, Dengue, chikungunya, and West Nile. Currently, only West Nile is endemic in the continental US, but clinicians may see the other three diseases in travelers who are either from, or who have visited endemic areas.
No other animal infects and causes disease as effectively as mosquitos, which are the deadliest animals in the world to humans. Infections caused by mosquitos kill over 700,000 people a year.[2]
West Nile virus (WNV), is a Flavivirus, and the leading cause of mosquito-borne disease in the continental U.S.[2] WNV was first isolated in a woman in the West Nile district of Uganda in 1937, which is how it received its name.[3] It is most often spread in the summer and fall by the bite of an infected mosquito. Infections have rarely occurred through organ transplant, blood transfusions and breast milk. Most people infected with WNV are asymptomatic, but about 20% of those who are infected develop a fever and/or other symptoms. Only about 0.7% of infections lead to a serious and sometimes fatal illness.[2]
Mosquitoes of the genus Culex are generally considered the principal vectors of WNV, in particular Culex Pipiens. Birds are the reservoir hosts of WNV. Interestingly, in Europe, Africa, Middle East and Asia, mortality in birds with WNV infection is rare. However, the virus is highly toxic to birds in the Americas.[3] Dying birds may be an indication of a WNV epidemic in an area. Horses may also become infected.
In 2020, 44 states reported WNV infections in people, birds, or mosquitoes. There were 422 reported human cases of neuroinvasive disease (such as meningitis or encephalitis) and 135 cases of non-neuroinvasive disease.[4] In some previous years there were many more reported cases, with 2,647 cases reported in 2018, and 5,674 cases in 2012.[5]
Clinical Presentation and Symptoms [7]
WNV should be considered in anyone in an endemic area presenting with a febrile, or acute neurologic illness, who has had recent exposure to mosquitoes, blood transfusion, or organ transplantation, especially during the summer months. The diagnosis should also be considered in infants whose mother was infected with WNV during pregnancy or while breastfeeding.
The incubation period for WNV disease is typically two to six days but ranges from two to 14 days, and can be longer, up to several weeks, in immunocompromised people.
It is estimated that 70-80% of human WNV infections are subclinical or asymptomatic. Symptomatic WNV presents with an acute, non-specific febrile illness that typically includes headache, weakness, myalgias (muscle aches) , arthralgia (joint pains), gastrointestinal symptoms, and a transient rash.
About 0.7% of infected persons develop neuroinvasive disease, which typically manifests as meningitis (infection of the lining of the brain and spinal cord), encephalitis (infection of the brain) , or acute flaccid paralysis. WNV meningitis is indistinguishable from viral meningitis due to other etiologies, and typically presents with fever, headache, and neck stiffness. WNV encephalitis is more severe and presents with fever, altered mental status, seizures, focal neurologic deficits, or movement disorders such as tremor or parkinsonism. WNV acute flaccid paralysis, also known as WNV poliomyelitis, is clinically and pathologically identical to poliomyelitis, with damage to spinal anterior horn cells that may progress to respiratory paralysis requiring mechanical ventilation. WNV flaccid paralysis often presents as an isolated limb paresis (weakness) or paralysis, and can occur without fever or viral prodrome. WNV-associated Guillain-Barré syndrome and WNV radiculopathy (nerve inflammation) have also been reported, and can be distinguished from WNV poliomyelitis by clinical manifestations, and electrophysiologic testing.
Rarely, cardiac dysrhythmias, myocarditis, rhabdomyolysis(muscle inflammation and breakdown), inflammation of the eye , inflammation of the testicle, pancreatitis, and hepatitis have been described in patients with WNV disease.
Most patients with non-neuroinvasive WNV disease or WNV meningitis recover completely, but fatigue, malaise, and weakness can linger for weeks or months. Patients who recover from WNV encephalitis or WNV poliomyelitis often have residual neurologic deficits. The mortality rate for neuroinvasive disease is approximately 10%, but is higher for patients with WNV encephalitis and WNV poliomyelitis than with WNV meningitis.
One study found that five of 25 patients who had WNV infections diagnosed 1.6 to 6.7 years previously continued to have WNV RNA in their urine, suggesting chronic infection. But, according to the CDC, the implications of this are still unknown.[8,9]
Diagnostic Testing [10]
Routine clinical laboratory studies for WNV are generally nonspecific. In patients with neuroinvasive disease, cerebrospinal fluid(CSF) examination from a spinal tap generally shows increased lymphocytes (a white blood cell typically elevated in viral infections) , but neutrophils (a type of white blood cell typically seen in bacterial infections and unusual in a viral infection) may predominate early in the course of the illness. Brain MRI is frequently normal, but abnormalities in the basal ganglia, thalamus, and brainstem may be seen in patients with encephalitis, and in the anterior spinal cord in patients with WNV poliomyelitis.[7]
Laboratory diagnosis is typically made by testing of serum or CSF for WNV-specific IgM antibodies which are usually detectable three to eight days after the onset of illness, and can persist for 30 to 90 days. The absence of WNV IgM antibodies on an initial sample does not rule out the diagnosis of WNV infection, and a convalescent sample may need to be drawn. Unfortunately, cross-reactive antibodies from other flaviviruses are common, and all positive IgM results should be confirmed with a plaque-reduction neutralization test (PRNT), which requires acute and convalescent serum, and can differentiate which Flavivirus species is causing the infection.
Viral cultures and RT-PCR testing can be performed on serum, CSF, and tissue specimens that are collected early in the course of illness, and can confirm an infection. Immunohistochemistry can detect WNV antigen in tissue biopsy specimens. Initial negative results of these tests do not rule out a WNV infection.
Treatment [11]
There are no specific treatments for WNV disease, other than supportive management. Patients with meningitis may require pain control for headaches, antiemetics and IV rehydration as needed for nausea and vomiting. Patients with encephalitis require ICU monitoring for the development of elevated intracranial pressure and seizures. WNV encephalitis or WNV poliomyelitis patients should be monitored for the ability to protect their airway from aspiration (swallowed liquids or saliva going into the lung and causing pneumonia.). Acute neuromuscular respiratory failure may develop in WNV poliomyelitis requiring prolonged ventilatory support.
No WNV vaccines are currently available. Prevention of WNV disease depends on community mosquito control programs, personal protective measures to decrease exposure to infected mosquitoes, and screening of blood and organ donors.
Conclusion
Mosquito-borne viral diseases can present initially as a non-specific illness, making diagnosis difficult. Laboratory testing may help, but initially can be negative, requiring convalescent testing to make a firm diagnosis. Of the four mosquito-borne viral infections in the Western Hemisphere, dengue is the deadliest, and in endemic areas initially treating for dengue is recommended until an alternate diagnosis is confirmed. West Nile virus is the only one of the four infections which is currently endemic in the continental U.S., the others are typically seen in travelers who are either from, or who have visited endemic areas. Fortunately, with its threat of fetal abnormalities, Zika virus spread has significantly declined, but around the world dengue and chikungunya infections remain significant health issues.
The infections discussed in our series are just a small portion of the infections that mosquitos can transmit, which include both viruses and parasites, and are listed below.
Mosquito-borne Viruses[12]
Cache Valley
Chikungunya
Eastern equine encephalitis
Jamestown Canyon
Japanese encephalitis
La Crosse encephalitis
Rift Valley fever
Ross River virus disease
St. Louis encephalitis
West Nile
Yellow fever
Mosquito Borne-Parasites
Dirofilariasis (dog heartworm)
Lymphatic filariasis
Malaria
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References
[1] Nuwer R. Mosquitoes Kill More Humans Than Human Murderers Do. SMITHSONIANMAG.COM. April 30, 2014. Retrieved from: https://www.smithsonianmag.com/smart-news/mosquitoes-kill-more-humans-human-murderers-do-180951272/
[2] West Nile Virus. CDC. Last reviewed: June 3, 2020. Retrieved from: https://www.cdc.gov/westnile/index.html
[3] West Nile Virus, WHO. October 3, 2017. Retrieved from: https://www.who.int/news-room/fact-sheets/detail/west-nile-virus
[4] Preliminary Maps & Data for 2020. CDC. Last reviewed: January 5, 2021. Retrieved from: https://www.cdc.gov/westnile/statsmaps/preliminarymapsdata2020/index.html
[5] West Nile Virus, Final Cumulative Maps & Data for 1999–2019. CDC. last reviewed: November 24, 2020. Retrieved from: https://www.cdc.gov/westnile/statsmaps/cumMapsData.html#one
[6] West Nile Virus Activity by State 2020, CDC. Last reviewed: January 5, 2021. Retrieved from: https://www.cdc.gov/westnile/statsmaps/preliminarymapsdata2020/activitybystate2020.html
[7] West Nile Virus, Clinical Evaluation & Disease. CDC. Last reviewed: December 10, 2018. Retrieved from: https://www.cdc.gov/westnile/healthcareproviders/healthCareProviders-ClinLabEval.html
[8] West Nile Virus, Possible Persistence of West Nile Virus Infection. CDC. last reviewed: December 10, 2018. Retrieved from: https://www.cdc.gov/westnile/healthcareproviders/healthCareProviders-PersistentInfections.html
[9] Murray K et al. Persistent Infection with West Nile Virus Years after Initial Infection. J Infect Dis. (2010) 201 (1): 2-4. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791189/
[10] West Nile Virus, Diagnostic Testing. CDC. Last reviewed: December 10, 2018. Retrieved from: https://www.cdc.gov/westnile/healthcareproviders/healthCareProviders-Diagnostic.html
[11] West Nile Virus, Treatment & Prevention. CDC. Last reviewed: December 10, 2018. Retrieved from: https://www.cdc.gov/westnile/healthcareproviders/healthCareProviders-TreatmentPrevention.html
[12] Mosquitoes and Diseases: A-Z. CDC. last reviewed: March 6, 2020. Retrieved from: https://www.cdc.gov/mosquitoes/about/diseases.html