Transmission of Herpes Simplex Virus Type 2 among Factory Workers in Ethiopia

Yenew Kebede 1 2 Wendelien Dorigo-Zetsma 1 Yohannes Mengistu 2 Yared Mekonnen 1 Ab Schaap 1 Dawit Wolday 1 Eduard J. Sanders 1 Tsehaynesh Messele 1 Roel A. Coutinho 0 1 3 Nicole H. T. M. Dukers (ndukers@gggd 0 1 0 Department of STI and AIDS Research, Cluster Infectious Diseases , Municipal Health Service 1 Ethio-Netherlands AIDS Research Project, Ethiopian Health and Nutrition Research Institute , Addis Ababa , Ethiopia 2 Department of Microbiology, Immunology, and Parasitology, Faculty of Medicine, Addis Ababa University 3 Department of Human Retrovirology, Academic Medical Center , Amsterdam , The Netherlands The herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) epidemics are believed to fuel each other, especially in sub-Saharan countries. In Ethiopia during 1997-2002, a retrospective study was conducted to examine risk factors for infection and transmission of HSV-2, in a cohort of 1612 factory workers. Prevalence of HSV-2 seropositivity at enrollment was 40.9%, and incidence of seroconversion was 1.8 seroconversions/100 person-years (PY), which decreased over time. Independent risk factors for seropositivity were having an HSV-2-seropositive partner, female sex, HIV antibodies, positive Treponema pallidum particle agglutination assay result, older age, low education level, and orthodox religion. These same factors were independent risk factors for HSV-2 seroconversion, with the exception of the latter 3. Most HSV-2infected persons did not report symptoms. Among 41 monogamous HSV-2-serodiscordant heterosexual couples, incidence of HSV-2 seroconversion was 20.75 seroconversions/100 PY for women and 4.93 seroconversions/100 PY for men. The high burden of both HSV-2 and HIV infection in Ethiopia warrants stringent control measures. - The public health effect of genital herpes is increasingly recognized. Herpes simplex virus type 2 (HSV-2) infections are the most common cause of genital ulcerations worldwide [1]. In addition to genital herpes, infection with HSV-2 can result in neonatal herpes. It is believed that HSV-2 fuels the HIV epidemic, especially in many developing countries where the majority of transmissions of HIV in adults are heterosexual transmissions [29]. The management of HSV-2 is not only important for its potential effect on the HIV epidemic; it is needed to protect individuals, since infection can cause morbidity and since infection increases the risk for HIV infection. A meta-analysis of prospective studies demonstrated an odds ratio of 2.1 of acquiring an HIV infection when HSV-2 antibodies are present [10]. This association remains after adjusting for confounding factors, such as sexual risk behavior [11, 12]. In Ethiopia, as in other African countries, the prevalence of HSV-2 is high. A previous cross-sectional study among participants in a cohort in Akaki, Ethiopia, showed that half of the adult urban population had antibodies against HSV-2 [13]. Incidence and risk factors for seroconversion in Ethiopia are not known. The present study in this country was therefore conducted among factory workers to determine the incidence of HSV-2, to assess the risk factors for infection, and, especially, to examine the interaction between HSV-2 and HIV. Moreover, since a substantial number of couples were followed over time, the study provided a unique opportunity to investigate transmission of HSV-2 within monogamous HSV-2serodiscordant couples. SUBJECTS AND METHODS Study Population The present study was conducted among factory workers participating in a open cohort set up in 1997 to study HIV infection and disease progression at Wonji and Akaki, 2 study sites near Addis Ababa. After signing an informed-consent form, cohort participants were seen every 6 months for collection of blood samples, counseling for HIV testing (optional), and sexmatched interviews on sociodemographic characteristics and sexual behaviors by use of a structured questionnaire [14]. By December 2002, 1874 persons had entered the cohort. From this population, all 1612 participants who had at least 1 followup visit were included in the present study. Among them were 133 heterosexual couples who were followed over time (a subgroup referred to as couples). HSV-2 Testing Stored plasma samples from cohort participants obtained at enrollment between 1997 and December 2002 were tested for HSV 2 IgG. For participants who were HSV-2 negative at enrollment, the last follow-up sample was tested for HSV-2 IgG. When that sample was found to be positive for HSV-2 IgG, the sample obtained at enrollment was tested. In the case of a person who experienced seroconversion, samples obtained in between were tested to identify the last seronegative and the first seropositive visits. Of the persons who experienced seroconversion, 84.5% had a seroconversion interval of !1 year between the last negative and the first positive samples were obtained. Testing for HSV-2 antibody was performed by use of recombinant IgG2 antigen in a commercially available ELISA kit (HerpeSelect 2 ELISA IgG; Focus Technologies). A cutoff value of 3.0 was used to determine seropositivity. Recently, this test kit was evaluated by use of serum samples from persons from different African countries, showing a sensitivity of 90.5% and a specificity of 97.8% at the cutoff value 3.0 [15]. In a large sample, the interassay agreement value (k) between using serum or plasma samples was 98.9% [16]. We compared 40 paired samples of serum and plasma obtained approximately on the same date, for detection of HSV-2 antibodies, and found that the plasma test result is 88% sensitive and 100% specific, compared with serum test results, resulting in a k of 86%. HIV and Syphilis Testing Plasma samples from the cohort participants were routinely tested for HIV-1 antibodies by use of HIVSPOT (Genelabs Diagnostics), Determine (Abbott Diagnostics), and ELISA (Vironostika HIV Uni-Form II Plus O; Organon Teknika). The samples producing a positive result in at least 1 test were confirmed by use of Western blot test (HIV Blot 2.2; Genelabs Diagnostics). At study entry, plasma samples were also screened for syphilis, by use of the rapid plasma reagin (RPR) test (RPR Nosticon II; Organon Teknika); samples producing a positive result were routinely confirmed by Treponema pallidum particle agglutination assay (TPPA) (Serodia-TP; Fujirebio). Statistical Methods The prevalence of HSV-2 infection was calculated, and risk factors for HSV-2 seropositivity at enrollment were examined by use of a generalized linear model for binomial data, using a log-link function [17]. Since men and women differ with respect to several sociodemographic and behavioral characteristics, all risk estimates were adjusted for sex. Whether risk estimates varied by sex was assessed by adding an interaction term between a risk factor and sex. To identify independent predictors, all variables found to be statistically significant (P ! .05) by bivariate analysi (...truncated)