Tatjana Vilibic-Cavlek1,2, Branimir Kristofic3, Vladimir Savic4, Branko Kolaric5,6, Ljubo Barbic7, Irena Tabain1, Ljiljana Peric8,9, Dario Sabadi8,9, Bozana Miklausic10, Tanja Potocnik-Hunjadi11, Sanja Zember12, Vladimir Stevanovic7, Eddy Listes13, Giovanni Savini14. 1. Department of Virology, Croatian Institute of Public Health, Zagreb, Croatia. 2. School of Medicine University of Zagreb, Zagreb, Croatia. 3. Department of Gynecology and Obstetrics, County Hospital Cakovec, Cakovec, Croatia. 4. Poultry Centre, Croatian Veterinary Institute, Zagreb, Croatia. 5. Department of Epidemiology, Andrija Stampar Teaching Institute of Public Health, Zagreb, Croatia. 6. School of Medicine University of Rijeka, Rijeka, Croatia. 7. Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia. 8. Department of Infectious Diseases, Clinical Hospital Centre Osijek, Osijek,Croatia. 9. Medical Faculty, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia. 10. Department of Infectious Diseases, General Hospital "Dr Josip Bencevic", Slavonski Brod, Croatia. 11. Department of Infectious Diseases, County Hospital Cakovec, Cakovec, Croatia. 12. Department of Infectious Diseases, General Hospital Varazdin, Varazdin, Croatia. 13. Croatian Veterinary Institute, Regional Institute Split, Split, Croatia. 14. OIE Reference Centre for West Nile Disease, Istituto Zooprofilattico Sperimentale "G. Caporale", Teramo, Italy.
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.
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.
Authors: Marija Santini; Sara Haberle; Snježana Židovec-Lepej; Vladimir Savić; Marija Kusulja; Neven Papić; Klaudija Višković; Ivana Župetić; Giovanni Savini; Ljubo Barbić; Irena Tabain; Marko Kutleša; Vladimir Krajinović; Tanja Potočnik-Hunjadi; Elizabeta Dvorski; Tamara Butigan; Gordana Kolaric-Sviben; Vladimir Stevanović; Lana Gorenec; Ivana Grgić; Filip Glavač; Armin Mehmedović; Eddy Listeš; Tatjana Vilibić-Čavlek Journal: Pathogens Date: 2022-01-02