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.Herpes simplex virus type 2 (HSV-2) infections are common and have spread worldwide, with a reported variation in seroprevalence ranging from less than 1% in children to more than 80% in selected adult populations (13,23,27). After primary infection, HSV-2 establishes latency in sensory ganglia, and after reactivation, HSV-2 can be transmitted by clinical lesions or via asymptomatic shedding (33,35). HSV-2 is sexually transmitted and is the most common cause of genital ulcer disease (GUD) in developing countries (1,8,22). The burden of sexually transmitted diseases (STDs) is high in sub-Saharan Africa, and a major problem is that HSV-2 infection facilitates transmission of human immunodeficiency virus (HIV). It has been estimated that the risk of acquiring HIV is doubled for HSV-2-infected individuals (34), and HSV-2-positive patients present higher HIV viral load than HSV-2-negative HIV-infected patients (26). These data emphasize that identification of HSV-2-infected individuals is important not only for control of HSV-2 transmission but also as a strategy for HIV prevention.The definite diagnosis of HSV-2 infection is achieved by virus isolation (VI) or by the PCR technique using samples from clinical lesions. Both of these methods present high specificity, and PCR is the most sensitive. However, t...

Performance of HerpeSelect and Kalon Assays in Detection of Antibodies to Herpes Simplex Virus Type 2

“…For example, the FDAapproved and widely available HerpeSelect enzyme-linked immunosorbent assay (ELISA) (Focus Technologies) has a high sensitivity and specificity, ranging from 96 to 100%, against the reference HSV-2 Western blot (WB) assay for testing of sera from North American or Western European populations but significantly lower specificity for testing of sera from adult African populations (2,7,16). Moreover, concordance between WB and HerpeSelect assays was found to vary between countries in sub-Saharan Africa (2,6,7,9) and according to human immunodeficiency virus (HIV) serostatus (16). HerpeSelect and other assays were compared in an evaluation study using African sera from population-based surveys, and the Kalon gG2-specific ELISA (Kalon Biologicals) was found to be as sensitive as and more specific than HerpeSelect, with WB as the reference method (16).…”

“…One study reported that the sensitivity of HerpeSelect increased for patients suffering from genital ulcer disease (GUD) compared to that for blood donors (6), perhaps because HerpeSelect may detect primary genital herpes earlier than the Kalon assay or even WB does (1,12).…”

Seroprevalences of Herpes Simplex Virus Type 2, Five Oncogenic Human Papillomaviruses, and Chlamydia trachomatis in Katowice, Poland

“…Furthermore, HSV suppressive therapy significantly reduces genital and plasma HIV-1 RNA levels in dually infected women (28). Seroepidemiological data from worldwide studies performed during the last decade have estimated the HSV-2 seroprevalence to range from 0% in children to more than 80% in selected populations such as STI cohorts in some African countries (14,36). For Poland, data are scarce, but recently, the prevalence of HSV-2 infection was described to vary between 6.5% and 12% from randomly selected serum samples in four geographic regions in Poland, not including Katowice (37).…”

Improved Performance of Enzyme-Linked Immunosorbent Assays and the Effect of Human Immunodeficiency Virus Coinfection on the Serologic Detection of Herpes Simplex Virus Type 2 in Rakai, Uganda

“…Diagnosis of HSV-2 infection in sub-Saharan Africa and developing countries elsewhere, where the prevalence is high, has been problematic. Serologic tests for HSV-2 that use an enzyme-linked immunosorbent assay (ELISA) or dot blot are technically simple and relatively inexpensive (15) but have been complicated by a variable rate of samples with positive HSV-2 ELISA and negative Western blot results (6,8,10,15). In addition, the Western blot assay is expensive, difficult to read, and inefficient for evaluating large numbers of samples for clinical trials (2).…”