Evaluation of Immunoglobulin M (IgM) and IgG Enzyme Immunoassays in Serologic Diagnosis of West Nile Virus Infection

Abstract

A unique urban encephalitis epidemic in Romania signaled the emergence of neurological infection due to West Nile (WN) virus as a novel public health threat in Eastern Europe and provided an opportunity to evaluate patterns of immunoglobulin G (IgG) and IgM reactivity in IgM capture and IgG enzyme-linked immunosorbent assays (ELISAs). WN virus infection was diagnosed serologically in 236 of 290 patients from whom acute serum or cerebrospinal fluid (CSF) samples were available. In 37% of serum samples and in 25% of CSF samples collected in the first week of illness, anti-WN virus IgM antibody was detected in the absence of virus-specific IgG. The switch to an IgG antibody response occurred after 4 to 5 days of illness and earlier in CSF than in serum. A specific humoral immune response was detected in the CSF before the serum in some patients for whom paired CSF and serum samples from the same day were available. IgM antibody in convalescent serum samples persisted beyond 2 months after the onset of illness in more than 50% of patients. ELISA optical density values and antibody concentrations were well correlated for both IgM and IgG immunoassays. Anti-WN virus IgM antibody in acute-phase samples did not cross-react significantly with flaviviruses in other antigenic groups.

Immunoglobulin M–Capture Enzyme-Linked Immunosorbent Assay Testing of Cerebrospinal Fluid and Serum from Horses Exposed to West Nile Virus by Vaccination or Natural Infection

“…In humans infected with WN virus, anti-WN virus IgM antibody was detected in 37% of serum samples and 25% of CSF samples collected during the 1st 7 days of illness. 9 The switch to IgG antibody production occurred after 4-5 days of illness; however, IgM antibody persisted in more than 50% of patients for 2 months after the onset of clinical signs. Examination of these data suggests that anti-WN virus IgM levels measured by MAC-ELISA in serum may vary depending on time from initial exposure.…”

“…7,8 Testing of humans for diagnosis of WN encephalitis in flavivirus endemic areas relies on production of IgM in serum and CSF, a 4-fold rise or fall in IgG levels during the acute and convalescent period, or both. 9 In about 30% of human cases, the development of IgM in the CSF precedes the development of IgM in the serum. The development of IgM antibody in the CSF is considered independent of a serum IgM response; thus, the development of antibody within CSF is highly diagnostic for WN virus infection in humans.…”

Infectious encephalitis: Management without etiological diagnosis 48 hours after onset

“…IgM sensitivity in CSF is good, reported at 94% (89% if sampled < 8 days) [156], while it usually is negative in blood the first 15 days after symptom onset [157]. Antibodies remain in the CSF for a long time after the end of the infection, for more than two months in 50% of patients [155,158] and may even stay longer as specific IgM were detected in the CSF samples of three patients 110, 141, and 199 days following WNV encephalitis [159]. Viral genome detection by PCR may also be performed, but its sensitivity is lower: 57% in CSF and 14% in plasma [156].…”

Emerging viral infections

“…Serology with acute and convalescent sera remains the primary means of laboratory confirmation of WNV infection; a panel of other flaviviruses also should be included in the comparison [181]. A presumptive diagnosis can be made with enzyme immunoassays and immunofluorescent antibody assays for anti-WNV IgM, although such IgM can persist in patients several months after acute infection [206]. Isolation of WNV from clinical specimens has proved difficult; molecular assays exist, but because of the low magnitude and transient viremia in humans, they are of limited clinical value [181,207].…”