Diagnostic significance of immunoglobulin G avidity in symptomatic and asymptomatic West Nile virus infection

Abstract

Introduction: West Nile virus (WNV) immunoglobulin M (IgM) antibodies have been shown to persist for up to 500 days in certain patients. To evaluate the usefulness of immunoglobulin G (IgG) avidity assessment in the diagnosis of WNV infection, we analyzed 54 WNV IgM-and/or IgG-positive serum samples from 39 patients with neuroinvasive disease and 15 asymptomatic cases tested during a seroprevalence investigation. Methods: Serological tests (WNV IgM/IgG antibody detection, IgG avidity) were performed using commercially available enzyme-linked immunosorbent assays. Results: WNV IgM antibodies were detected in 47 (87%) samples. Acute/recent WNV infection was confirmed based on low/borderline avidity index (AI) in 44 IgM-positive samples (93.6%). In three IgM-positive samples (6.4%), high IgG AIs were detected, thus indicating persisting IgM antibodies from previous infections. All IgM-negative samples showed high AIs. Patients with WNV neuroinvasive disease tested within 30 days showed low AIs. In six patients tested 34-50 days after disease onset, AI was borderline (42%-60%), suggesting earlier WNV IgG maturation. Samples with the highest IgM values were associated with the lowest AIs (Spearman's rho coefficient-0.767, p < 0.001). Conclusions: Our results indicate that IgG avidity differentiates current/recent WNV infection from persistent IgM seropositivity from the previous WNV transmission season both in patients with WNV neuroinvasive disease and in asymptomatic persons. A strong negative correlation between IgM antibody levels and AI indicates that in cases with very high IgM levels, determination of IgG avidity may not be necessary. As many patients showed rapid avidity maturation, low IgG avidity is indicative of WNV infection within the previous month.

West Nile Virus and Usutu Virus Co-Circulation in Europe: Epidemiology and Implications

“…The presence of IgM antibodies for WNV, however, is not necessarily a sign of an acute WNV infection as they have been reported to persist for more than a year in certain patients. A combination of IgM levels with IgG avidity determination has been shown to help differentiate a current WNV infection from IgM seropositivity due to the previous WNV transmission season [34].…”

Prevalence and molecular epidemiology of West Nile and Usutu virus infections in Croatia in the ‘One health’ context, 2018

“…WNV IgG‐positive samples were tested for IgG avidity using urea as a denaturing agent. The IgG avidity index (AI) was calculated and expressed as percentage using the extinction values with and without urea treatment and interpreted as follows: <40% low AI, 40%–60% borderline AI, >60% high AI (Vilibic‐Cavlek et al, ).…”

Severe West Nile Virus Neuroinvasive Disease: Clinical Characteristics, Short- and Long-Term Outcomes

“…IgG positive samples were tested for IgG avidity using urea as a denaturing agent. The IgG avidity index (AI) was calculated and expressed as a percentage using the extinction values with and without urea treatment, and interpreted as follows: <40% low AI, 40-60% borderline AI, >60% high AI [55]. Initially reactive samples were confirmed using a VNT.…”