The epidemiology and natural history of genital herpes simplex virus (HSV) infection
Genital infection with herpes simplex virus type 2 (HSV -2) is increasingly common worldwide. The aims of this thesis were to investigate the epidemiology and natural history of genital herpes among GUM attendees with symptomatic genital herpes, and among HIV-l infected individuals. In our study of GUM attendees in the UK, we demonstrated HSV -1 to account for 9% of first episodes of genital herpes. These findings are in contrast with observations made elsewhere in the UK, where HSV -1 has accounted for >50% of first-episode cases. As most individuals with genital HSV -2 infection remain clinically misdiagnosed, the need for improved diagnostic methods to detect genital HSV infection is warranted. We compared the performance of virus culture and PCR in patients clinically diagnosed with genital herpes. PCR increased HSV detection in patients with both early and late presentations and in first and recurrent diseases. PEG precipitation was the most sensitive specimen preparation method of choice. A HSV positive PCR was also associated with heterosexuals, early presentation, and visible genital ulceration. HSV -1 and HSV -2 genital infections were also associated with white and black ethnicity respectively. This suggests that host susceptibility and behavioural factors may influence the epidemiological patterns of genital herpes. Current data support the use of HSV type-specific serology and PCR to diagnose HSV infections. In addition to PCR, we evaluated the performance of type-specific serology (HerpeSelect EIA, Focus Technologies, Cypress, California, USA) for the diagnosis of HSV infection. Our findings indicated that increasing the assay cut-off from 1.1 to 3.1 increased specificity and maintained sensitivity. By performing an inhibition EIA using an inhibition value of ~60% we minimised false positive results from Ugandan and Kenyan sera. Recent data has implicated HSV-2 as a co-factor in HIV transmission. We therefore investigated the seroepidemiology of HSV infection among 850 HIV-infected individuals. HSV-2 seroprevalence was 63% and increased with age and was associated with female gender, heterosexuals and black ethnicity. A follow-up of 123 HSV-2 seronegative persons revealed a HSV -2 seroconversion rate of 10% which was associated with HPV infection and gonorrhoea. Only 21 % of the seroconverters received a clinical diagnosis of genital herpes, and this was more likely in persons diagnosed HIV -1 positive before 1997 (preHAART era). To investigate the effects of HAART on HSV-specific immunity, we studied the kinetics of HAART-induced reconstitution of HSV-specific T-cell responses in HIV-l infected persons at different stages of clinical disease using an ELISPOT assay. Successful HAART proved to resolve HSV-specific immunity restoration which coincided with HAART-induced CD4 gain. HSV-specific IFN-y responses correlated with CD4 counts. Responses similar to those of HIV -negative healthy controls were seen at CD4 counts >450 cells/mm3.