This determination provides an independent experimental measure of the frequency of past WNV infection in the general US population, as reflected by the plasma/blood donor community, and the results correlate well with results of previously published theoretical extrapolations (1), which estimated that 1% of the population has already been infected with WNV
This determination provides an independent experimental measure of the frequency of past WNV infection in the general US population, as reflected by the plasma/blood donor community, and the results correlate well with results of previously published theoretical extrapolations (1), which estimated that 1% of the population has already been infected with WNV. The increasing levels of WNV neutralizing antibodies in IGIV lots from US plasma and the particularly high titers in donors who have had a WNV infection suggest the possibility of preparing IGIV products with sufficiently high titers to be useful for WNV prophylaxis or treatment. cases). The cumulative infection rate for each year during 1999C2008 was then calculated by dividing the infections occurring up to a specific year by the US population for that year (determined by US Census Bureau estimates [www.census.gov/popest/states/NST-ann-est.html]). Although WNV was first introduced into the United States in 1999, only in 2003 did the mean WNV neutralization titers of IGIV lots released to the market start to increase markedly (Figure 1). SB-568849 According to extrapolations from the CDF WNV screening of the US blood supply (1), by 2003, an estimated 0.5% of the US population SB-568849 had been infected with WNV, although most infections were asymptomatic. Open in a separate window Figure 1 West Nile virus (WNV) neutralization titers of US plasma-derived immune globulin intravenous (human) (IGIV) lots SB-568849 by year of production and estimated percentage of the US population with past WNV infection by year. WNV neutralization titers were determined either for retention or lot release samples of 3 IGIV products produced during 1998C2005 or for a considerable proportion of Gammagard Liquid/KIOVIG lots produced during 2006C2008. Results are shown as mean SEM (limit of detection <0.8) by year of product release. For 5% of IGIV samples, titers were multiplied by 2 for comparison with the 10% IGIV samples at equivalent immunoglobulin concentrations. The percentage of the US donor population with past WNV infection was calculated from the number of neuroinvasive cases reported per year and the estimated ratio of neuroinvasive cases to total cases of WNV infection. A delay of 1 1 year occurs between the collection of plasma and the release of IGIV lots to SB-568849 the market; thus, the WNV-positive IGIV lots in 2003 reflect the larger number of WNV infections occurring in 2002. Using the same extrapolations from the US blood supply (1), we found that the 0.1% annual increments in the proportion of the US population with past WNV infection follow a straight line (r2 = 0.9996), generally paralleled by the mean WNV neutralization titers of IGIV lots. During 2005C2008, when large numbers of lots of a single IGIV product (Gammagard Liquid) could be analyzed, the WNV neutralization titer increased by 3.6 per year (r2 = 0.9793). US plasma-derived IGIV lots released during 2008 showed variable WNV neutralization titers ranging from 2.8 to 69.8; mean SEM titer was 21 1 (n = 256) (Figure 2). Compared with titers shown to be protective in an animal model of WNV infection (equivalent to >21 by the current assay) (2), 40% of the 2008 IGIV lots had higher titers. Open in a separate window Figure 2 West Nile virus (WNV) neutralization by US plasma-derived immune globulin intravenous (human) (IGIV) released in 2008 and plasma from donors with SB-568849 past WNV infection (past WNV), confirmed by nucleic acid testing. WNV neutralization titers are shown as the mean SEM (limit of detection <0.8 for undiluted IGIVs and <7.7 for prediluted sera). NT50, 50% neutralization titer. Plasma obtained from persons with NAT-confirmed WNV infection had even higher titers; mean SEM titer was 208 40 for 30 persons available for testing. When results were corrected for the immunoglobulin (Ig) G concentration in.