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Sep 11

West Nile Virus Infections - 2024 Update

West Nile is the leading cause of mosquito-borne disease in the continental U.S.

Infectious Disease

west nile virus

West Nile virus is again in the news with reports of Dr. Anthony Fauci requiring hospitalization for the disease in August of 2024.[1] 


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]

The Culex Pipiens Mosquito
The Culex Pipiens Mosquito

West Nile virus (WNV), is a Flavivirus, and the leading cause of mosquito-borne disease in the continental U.S.[3]  WNV was first isolated in a woman in the West Nile district of Uganda in 1937, which is how it received its name.[4]  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.[3]


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.[4]  Dying birds may be an indication of a WNV epidemic in an area. Horses may also become infected.


In 2023 there were 2,566 reported cases of WNV in the U.S. from 46 states.  There were  1,840 hospitalizations and 182 deaths attributed to WNV.  1,738 of those reported cases of WNV involved neuroinvasive disease (such as meningitis or encephalitis).[5]  In some previous years there were many more reported cases, with 2,647 cases reported in 2018, and 5,674 cases in 2012.[5]

West Nile virus activity by state 2023[6]
West Nile virus activity by state 2023[6]

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.  Additional studies have also found WNV RNA in an occasional survivor’s urine, but according to the CDC, the long term effects of this are still uncertain.[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.


West Nile Virus 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 for humans are currently available, but there is one for horses.[3] 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.  It is recommended that people with confirmed WNV not donate blood for a minimum of four months after their illness resolves.


Conclusion

West Nile virus 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.  WNV symptoms can range from asymptomatic to life threatening, but care is supportive as no specific treatment has been discovered.  WNV is only one of many mosquito-borne infections around the world.


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References

[1] Gupta S and Dillinger K. Fauci recovering after hospitalization for West Nile virus. CNN. Updated August 26, 2024. Retrieved from: https://www.cnn.com/2024/08/24/health/fauci-west-nile-virus/index.html

[2] 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/

[3] West Nile Virus. CDC. May 15, 2024. Retrieved from: https://www.cdc.gov/west-nile-virus/about/index.html 

[4] West Nile Virus, WHO. 3 October 2017. Retrieved from: https://www.who.int/news-room/fact-sheets/detail/west-nile-virus

[5] Historic Data (1999-2023). CDC. June 18, 2024. Retrieved from: https://www.cdc.gov/west-nile-virus/data-maps/historic-data.html

[6] West Nile Virus Activity by State 2023, 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. May 15, 2024. Retrieved from: https://www.cdc.gov/westnile/healthcareproviders/healthCareProviders-ClinLabEval.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/


Initially posted May 2022, updated August 27, 2024


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