West Nile Virus
Mary Anne Jackson, MD | Interim Dean - UMKC School of Medicine | Medical Editor, The Link Newsletter
Emerging in New York in 1999, the flavivirus, West Nile Virus (WNV), has been recognized since 1937, and is endemic throughout Africa and parts of the Middle East. It is a member of the Japanese Encephalitis (JE) complex that includes JE and St. Louis encephalitis, and it is known to be amplified in birds, but most commonly is transmitted to humans by the bite from a Culex mosquito. This nationally notifiable infection now is recognized throughout the majority of the U.S.
WNV has an incubation period of two to six days, but may be extended out to 14 days when the disease is recognized in immunocompromised individuals. This year, as of Oct. 16, 2018, 1,976 cases of WNV infection from 49 states have been reported, with 1,176 (60%) of the cases reported as neuroinvasive infections.1
West Nile Virus Neuroinvasive disease incidence by state – United States, 2018 (as of Oct. 16, 2018)1
Infection has been transmitted most commonly by mosquito vector, but also from transfused blood, from organ transplant, from infected pregnant women to their babies, and from breast milk to infant. All blood products have been routinely screened since 2003, and those products testing positive are removed from the blood supply, making the risk of transfusion-associated disease extremely small. Transplanted organs are not tested routinely, and the risk of disease is dependent on a number of host factors and the time of year that the transplant occurs.
While WNF infection is asymptomatic in most, 20% will develop a nonspecific flu-like syndrome associated with fever, headache, gastrointestinal symptoms, transient rash and arthralgia; and one in 150 will present with encephalitis. Rare clinical manifestations include myocarditis, rhabdomyolysis, hepatitis and optic neuritis.
While both meningitis and encephalitis have been reported, encephalitis tends to be associated with seizures, focal neurologic findings and Parkinsonian tremors. An aseptic meningitis presentation more often is noted in younger patients. More severe neuroinvasive disease is less commonly reported in the young, and is more common in those over age 60 years and in organ transplant recipients. Severe weakness has been noted in approximately 50% of those with neuroinvasive infection, and about one-third may progress to frank paralysis, and an acute flaccid paralysis reminiscent of poliomyelitis may be noted, which peaks two to eight days after onset. The mortality rate is estimated at 10% for those presenting with CNS disease.
WNV infection has been described in infants born to infected mothers and subclinical infection has been reported in a breastfeeding infant of an infected mother. Congenital infection may be subclinical; however, in one mother with neuroinvasive disease, the affected newborn had cystic brain findings and chorioretinitis.
Disease is likely under-diagnosed, as most cases are clinically silent; and the majority that are clinically apparent manifest as nonspecific febrile illnesses that are likely thought to be other summer viruses, e.g., enterovirus. When encephalitis is the presentation, the differential includes HSV, other arboviruses, enterovirus and rickettsial infection, all which may present similarly.
CSF examination typically reveals pleocytosis of 100 to 250 cells of which one-half are neutrophils in the first week, proceeding to lymphocyte predominance in week 2.2 If WNV is suspected, serum or CSF antibody testing is diagnostic, with both IgM and IgG tests available. Detectable IgM antibody is present three to eight days after onset, but note that there is cross reactivity with other flaviviruses.
Generally speaking, a positive WNV-specific IgM result from blood or CSF is presumptive evidence of infection. IgG antibodies may persist for years, so a positive test is evidence of previous infection and must be interpreted in the context of the clinical symptoms and signs and IgM results. There is PCR testing available for blood; CSF and tissue and can be ordered through the state health department.
WNV peaks in the summer and the season lasts throughout the fall, so keep this arbovirus in your differential when you encounter individuals with meningitis, encephalitis or meningoencephalitis, and more common etiologies have been excluded. WNV-associated AFM can occur in any age group, and without concurrent co-morbidity and persistent impairment, tends to occur in survivors.
Tyler KL, et al. Neurology 2006; Nash D, et al NEJM 2001