West Nile Virus Seroprevalence and Cross-Neutralization in Sera from Eastern and Central Sudan

Objectives: In regions with co-existing flaviviruses, the diagnosis of previous West Nile virus (WNV) infections is challenging due to cross-reacting antibodies. The aim of the study was to determine the frequency of previous WNV infections in sera from three Sudanese states by excluding potentially dengue virus (DENV) and ZIKV cross-reacting sera and to determine the percentage of WNV cross-neutralizing sera from individuals with previous DENV infection. Methods: Serum samples from Kassala, North Kordofan, and Red Sea state were screened for antibodies against DENV by ELISA. Sera without DENV antibodies (N = 106) and a matched set of sera with DENV antibodies (N = 108) was selected. In all blood samples the frequency of WNV-neutralizing antibodies and the antibody titers were measured with microplate neutralization assays. DENV and Zika virus (ZIKV) microplate neutralization assays were performed with all WNV neutralizing sera of the DENV negative group. Results: A fraction of 30.2% of the DENV antibody negative sera neutralized WNV. The seroprevalence increased with age from 9.5% to 41.7%. Men and women were equally affected. The percentage of DENV positive sera that neutralized WNV was 83.3%. DENV positive sera had higher WNV neutralization titers than DENV negative sera. Conclusions: A significant fraction of the DENV antibody negative sera from three regions in Sudan showed serologic evidence of previous WNV infection. In comparison, the large majority of DENV antibody positive sera had WNV neutralizing antibodies. Studies are needed to identify clinical cases of WNV infection and to determine whether individuals with cross-neutralizing antibodies are protected from WNV disease.