Human Disease

Routes of Transmission

West Nile virus (WNV) is transmitted to humans primarily through the bite of infected mosquitoes (Campbell et al. 2002). However, person-to-person transmission can occur through transfusion of infected blood products or solid organ transplantation (Pealer et al. 2003, Iwamoto et al. 2003). Intrauterine transmission and probable transmission via human milk also have been described but appear to be uncommon (O’Leary et al. 2006, Hinckley et al. 2007). Percutaneous infection and aerosol infection have occurred in laboratory workers, and an outbreak of WNV infection among turkey handlers also raised the possibility of aerosol transmission (CDC 2002, CDC 2003a).

Since 2003, the U.S. blood supply has been routinely screened for WNV RNA; as a result, transfusion associated WNV infection is rare (CDC 2003b). The U.S. Food and Drug Administration (FDA) recommends that blood collection agencies perform WNV nucleic acid amplification test (NAAT) year-round on all blood donations, either in minipools of six or 16 donations (depending on test specifications) or as individual donations. Organ and tissue donors are not routinely screened for WNV infection though a few collection agencies have incorporated screening of donors (Nett et al. 2012, Theodoropoulos et al. 2021).

Clinical Presentation and Evaluation

An estimated 70-80% of human WNV infections are subclinical or asymptomatic (Mostashari et al. 2001, Zou et al. 2010). Most symptomatic persons experience an acute systemic febrile illness that often includes headache, myalgia, or arthralgia; gastrointestinal symptoms and a transient maculopapular rash also are commonly reported (Watson et al. 2004, Hayes et al. 2005, Zou et al. 2010). Less than 1% of infected persons develop neuroinvasive disease, which typically manifests as meningitis, encephalitis, or acute flaccid paralysis (Hayes et al. 2005). WNV meningitis is clinically indistinguishable from aseptic meningitis due to most other viruses (Sejvar and Marfin 2006). Patients with WNV encephalitis usually present with seizures, mental status changes, focal neurologic deficits, or movement disorders (Sejvar and Marfin 2006). WNV acute flaccid paralysis is often clinically and pathologically identical to poliovirus-associated poliomyelitis, with damage of anterior horn cells, and may progress to respiratory paralysis requiring mechanical ventilation (Sejvar and Marfin 2006). WNV-associated Guillain-Barré syndrome has also been reported and can be distinguished from WNV poliomyelitis by clinical manifestations and electrophysiologic testing (Sejvar and Marfin 2006). Cardiac dysrhythmias, myocarditis, rhabdomyolysis, optic neuritis, uveitis, chorioretinitis, orchitis, pancreatitis, and hepatitis have been described rarely with WNV infection (Hayes et al. 2005).

Although people of all age groups appear to be equally susceptible to WNV infection, the incidence of neuroinvasive WNV disease increases with age (McDonald et al. 2021). In addition, among patients with neuroinvasive WNV disease, older adults are more likely to develop encephalitis or meningoencephalitis and have substantially higher case-fatality rates compared with children or younger adults. Solid organ transplant recipients also are at significantly higher risk of severe illness. Severe WNV disease has been described in persons with malignancies, but the relative risk from these or other immunocompromising conditions remains unclear. Hypertension, cerebrovascular disease, chronic renal disease, alcohol abuse, and diabetes mellitus also have been identified as possible risk factors for severe WNV disease, but further research is warranted (Murray et al 2006, Lindsey et al 2012).

The differential diagnosis of arboviral central nervous system disease is broad and includes many infectious (e.g., viral, bacterial, mycoplasmal, protozoal, or mycotic) and noninfectious (e.g., toxic, metabolic, or postinfectious) causes. Other viral causes of acute neurological illness include herpes simplex, enterovirus, rabies, measles, mumps, Epstein-Barr, varicella zoster, and influenza viruses.

References

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CDC. 2002. Laboratory-acquired West Nile virus infections—United States, 2002. MMWR Morb Mortal Wkly Rep. 51: 1133-5.

CDC. 2003a. West Nile virus infection among turkey breeder farm workers—Wisconsin, 2002. MMWR Morb Mortal Wkly Rep. 52: 1017-9.

CDC. 2003b. Detection of West Nile virus in blood donations—United States, 2003. MMWR Morb Mortal Wkly Rep. 52: 769-72.

Hayes EB, Sejvar JJ, Zaki SR, Lanciotti RS, Bode AV, Campbell GL. 2005. Virology, pathology, and clinical manifestations for West Nile virus disease. Emerg Infect Dis. 11: 1174-9.

Hinckley AF, O’Leary DR, Hayes EB. 2007. Transmission of West Nile virus through human breast milk seems to be rare. Pediatrics. 119(3): e666-71.

Iwamoto M, Jernigan DB, Guasch A, et al. 2003. Transmission of West Nile virus from an organ donor to four transplant recipients. N Eng J Med. 348(22): 2196-203.

Lindsey NP, Staples JE, Lehman JA, Fischer M. 2012. Medical risk factors for severe West Nile virus disease, United States, 2008-2010. Am J Trop Med Hyg. 87(1):179-84.

McDonald ES, Mathis S, Martin SW, Staples JE, Fischer M, Lindsey NP. 2021. Surveillance for West Nile virus disease — United States, 2009‒2018.  MMWR Morb Mortal Wkly Rep ;70(1):1-15.

Mostashari F, Bunning ML, Kitsutari PT, et al. 2001. Epidemic West Nile encephalitis, New York, 1999: results of a household-based seroepidemiological survey. Lancet. 358: 261-4. 55

Murray K, Baraniuk S, Resnick M, et al.  Risk factors for encephalitis and death from West Nile virus infection. Epidemiol Infect 2006; 134:1325–32.

Nett RJ, Kuehnert MJ, Ison MG, Orlowski JP, Fischer M, Staples JE. 2012. Current practices and evaluation of screening solid organ donors for West Nile virus. Transpl Infect Dis. 14(3):268-77.

O’Leary DR, Kuhn S, Kniss KL, et al. 2006. Birth outcomes following West Nile virus infection of pregnant women in the United States: 2003-2004. Pediatrics. 117(3): e537-45.

Pealer LN, Marfin AA, Petersen LR, et al. 2003. Transmission of West Nile virus through blood transfusion in the United States in 2002. N Engl J Med. 349(13):1236-45.

Sejvar JJ, Marfin AA. 2006. Manifestations of West Nile neuroinvasive disease. Rev Med Virol. 16(4): 209-24.

Theodoropoulos NM, Greenwald MA, Chin-Hong P, Ison MG. 2021. Testing deceased organ donors for infections: An organ procurement organization survey. Am J Transplant. May;21(5):1924-1930.

Watson JT, Pertel PE, Jones RC, et al. 2004. Clinical characteristics and functional outcomes of West Nile fever. Ann Intern Med. 141: 360-5.

Zou S, Foster GA, Dodd RY, Petersen LR, Stramer SL. 2010. West Nile fever characteristics among viremic persons identified through blood donor screening. J Inf Dis. 202:1354-1361.