Immunoglobulin G avidity in differentiation between early and late antibody responses to West Nile virus

In 1999 West Nile virus (WNV) surfaced in the United States in the city of New York and spread over successive summers to most of the continental United States, Canada, and Mexico. Because WNV immunoglobulin M (IgM) antibodies have been shown to persist for up to 1 year, residents in areas of endemicity can have persistent WNV IgM antibodies that are unrelated to a current illness with which they present. We present data on the use of IgG avidity testing for the resolution of conflicting data arising from the testing of serum or plasma for antibodies to WNV. Thirteen seroconversion panels, each consisting of a minimum of four samples, were used. All samples were tested for the presence of WNV IgM and IgG antibodies, and the avidity index for the WNV IgG-positive samples was calculated. Panels that exhibited a rise in the WNV IgM level followed by a sequential rise in the WNV IgG level were designated "primary." Panels that exhibited a marked rise in the WNV IgG level followed by a sequential weak WNV IgM response and that had serological evidence of a prior flavivirus infection were designated "secondary." All samples from the "primary" panels exhibited low avidity indices (less than 40%) for the first 20 to 30 days after the recovery of the index sample (the sample found to be virus positive). All of the "secondary" samples had elevated WNV IgG levels with avidity indices of > or =55%, regardless of the number of days since the recovery of the index sample. These data demonstrate that it is possible to differentiate between recent and past exposure to WNV or another flavivirus through the measurement of WNV IgG avidity indices.