Mature Glycoprotein G Presents High Performance in Diagnosing Herpes Simplex Virus Type 2 Infection in Sera of Different Tanzanian Cohorts

Abstract

Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted infection in sub-Saharan Africa. Glycoprotein G (gG) of HSV-2 elicits a type-specific antibody response and is widely used for serodiagnosis. gG is cleaved into a secreted portion (sgG-2) and a highly O-glycosylated mature portion (mgG-2). The performances of these two native immunosorbent purified antigens were compared in an enzyme-linked immunosorbent assay (ELISA) format with a commercially available assay (FOCUS2) using sera from blood donors (n = 194) and individuals (n = 198) with genital ulcer disease (GUD) from Tanzania. Discordant results were resolved by Western blotting. The HSV-2 seroprevalence for blood donors was estimated as 42%, and that for the GUD cohort was estimated as 78%. The prevalence increased significantly with age for both cohorts and was higher among human immunodeficiency virus (HIV)-positive individuals than among HIV-negative subjects. In the GUD cohort with a high HSV-2 prevalence, all three assays showed statistically similar performances, with sensitivities between 97% and 99% and specificities in the range of 86% to 91%. In contrast, among blood donors with a lower seroprevalence, the mgG-2-based ELISA presented significantly higher specificity (97%) than the sgG-2 ELISA (89%) and FOCUS2 (74%). Overall, the mgG-2 ELISA gave a high performance, with negative and positive predictive values of 96% for blood donors and a negative predictive value of 95% and a positive predictive value of 97% for the GUD cohort. We conclude that native purified mgG-2 showed the highest accuracy for detection of HSV-2 in patient sera from Tanzania and is therefore suitable for seroprevalence studies as well as in clinical settings.