PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Sex Transm Infect. Author manuscript; available in PMC 2011 April 25.
Published in final edited form as:
PMCID: PMC3081652
NIHMSID: NIHMS287153

Herpes Simplex Virus Type 2 Infection Among Young Uncircumcised Men in Kisumu, Kenya

Supriya D. Mehta, MHS, PhD,1 Stephen Moses, MD, MPH,2 Kawango Agot, PhD, MPH,3 Walter Agingu, HDMLS,3 Corette Parker, DrPH,4 Jeckoniah O. Ndinya-Achola, MBChB, MSc,5 and Robert C. Bailey, PhD1

Abstract

Objectives

This analysis sought to identify factors associated with herpes simplex virus type 2 (HSV-2) infection among men aged 18–24 in Kisumu, Kenya.

Methods

We analyzed baseline data from a randomized trial of male circumcision. Participants were interviewed for socio-demographic and behavioral risks. The outcome was HSV-2 by antibody status. Risk factors were considered singly and in combination through logistic regression models.

Results

Among 2,771 uncircumcised men, 766 (27.6%; 95% confidence interval [CI]: 26.0 – 29.3%) tested antibody positive for HSV-2. The median age at first sex was 16 years, and the median number of lifetime sexual partners was 4. HSV-2 seroprevalence increased from 19% among 18 year-olds to 43% among 24 year-olds (p<0.001). In multivariable analysis, statistically significant risks for infection were: increasing age (adjusted odds ratio [AOR] ranged from 1.22–2.58), being married or having a live-in female partner (AOR=1.80; 95% CI: 1.28 – 2.53), preferring “dry” sex (AOR=1.39; 95% CI: 1.14–1.69), reported penile cuts or abrasions during sex (AOR=1.58; 95% CI: 1.32 – 1.91), increasing lifetime sex partners (multiple response categories; AORs ranging 1.65–1.97), and non-student occupation (multiple response categories; AORs ranging 1.44–1.93). Risk decreased with reported condom used at last sex (AOR=0.82; 95% CI: 0.68–0.99).

Conclusion

Primary prevention efforts should be initiated at an early age. The same behavioral interventions used currently for HIV prevention – abstinence, reducing number of sex partners, and increasing condom use – should be effective for HSV-2 prevention.

Keywords: HSV-2, behavioral risk, epidemiology, Kenya, male circumcision

Background

It is estimated that up to 50% of young men in sub-Saharan Africa are infected with genital herpes, caused primarily by herpes simplex virus type 2 [HSV-2] [12]. HSV-2 has been associated with a several fold increase in the risk of HIV acquisition and transmission [1, 34]. HIV viral shedding is increased in the HSV-2/HIV- infected person [46], which in turn increases HIV transmission risk [7]. Susceptibility to HIV in the HSV-2 positive/HIV-negative person is increased through compromised mucosal integrity and recruitment of HIV susceptible cells to the genital tract [4]. The proportion of HIV cases attributable to HSV-2 infection has been estimated at 12–65% in Mwanza, Tanzania [89]), and 23% in Rakai, Uganda [8]. Preventing HSV-2 acquisition may significantly reduce HIV incidence.

In a randomized controlled trial assessing the effect of circumcision on HIV incidence in Kisumu, Kenya, men who were HSV-2 seropositive at baseline were 1.91 times more likely than HSV-2 seronegative men to become HIV-infected during the 24-month follow-up [10]. We sought to identify demographic and behavioral factors associated with HSV-2 among young men enrolled.

Methods

Study Design and Participants

This is a cross-sectional analysis of baseline data, collected between February 2002 and September 2005. The cohort consisted of men aged 18–24 years enrolled in a randomized controlled trial of male circumcision to reduce HIV acquisition in Kisumu, Kenya [10]. Details of recruitment and consent have been reported [10].

For inclusion men had to be uncircumcised, HIV negative, sexually active in the last 12 months, aged 18–24 years, resident in Kisumu District with no plans to move away during follow-up (two years), and have a hemoglobin ≥ 9.0 g/dL. Men were excluded if their foreskin covered less than half the glans, if they had a bleeding disorder, a medical condition contraindicating surgery, or an absolute indication for surgery. Testing for HIV infection was conducted using a parallel double rapid test protocol. Men who were concordant negative were eligible for the study.

The Institutional Review Boards of the University of Illinois at Chicago, the Kenyatta National Hospital, RTI International, and University of Manitoba approved this study.

Data Collection

All consenting participants underwent standardized medical examination and history, and personal interview to obtain socio-demographic and behavioral risk information. Interviews were conducted by trained, experienced, local language-speaking counsellors in the participant’s language of choice: English, Dho Luo, or Kiswahili. Data on sexual behaviors included: age at first sex, condom use, specific sexual practices, and the number of recent and lifetime sex partners. Three questions assessed the occurrence of penile trauma during sexual intercourse. Five questions assessed specific sexual dysfunctions occurring for 2 or more weeks during the past 6 months [11].

Sexually Transmitted Infection Testing

Methods for STI testing are detailed elsewhere [10, 13]. Briefly, men were tested for Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct) by polymerase chain reaction (PCR)-based methods and for Trichomonas vaginalis (Tv) by culture. Serum specimens were tested for HSV-2 antibody (Kalon HSV-2 IgG ELISA, Kalon Biological Limited, Aldershot, United Kingdom). Syphilis infections were diagnosed by serum antibody testing. Haemophilus ducreyi testing by PCR and culture was conducted if genital ulcers were present. Testing was conducted at the study clinic and the University of Nairobi Department of Medical Microbiology research laboratory.

Data Analysis

The outcome for analysis was HSV-2 serostatus, dichotomized as positive or negative. Explanatory variables were demographics, sexual behaviors, post-coital genital cleaning, coital injury, preference for wet or dry sex, and sexual dysfunction. Differences between explanatory variables and the outcome were assessed by chi-square test for categorical variables. Variables significant at the p<0.20 level in exploratory analysis were examined by univariate logistic regression. Variables significant at the p<0.20 level by likelihood ratio testing were entered into a multivariable logistic regression model using forwards stepwise entry [12]. Those variables with a p-value <0.05 were maintained in the multivariable model. Data were analyzed using Stata/SE 9.2 for Windows (Stata Corp., College Station, TX).

Results

Between February 2002 and September 2005, 2,784 men screened for the main trial consented to participation and were randomized. Results of screening and reasons for exclusion and non-participation have been previously described [10, 13].

Of the 2,776 participants eligible for analysis, 2,771 had HSV-2 testing and were included in this analysis. Among the 2,771 men, 766 tested positive (27.6%; 95% confidence interval [C.I.]: 26.0 – 29.3%). On physical exam, there were 28 men with genital ulcer and 47 (1.7%) men reported painful genital ulcer in the past 6 months. Twenty-eight (1.01%; 95% CI: 0.07 – 1.46%) men had active syphilis (RPR positive and TPHA positive), 2 of whom reported painful genital ulcer in the past 6 months, and none had genital ulcer on exam. Eighty-one men (2.94%; 95% CI: 2.3 – 3.6%) had evidence of prior exposure to syphilis (RPR negative and TPHA positive), four of whom reported painful genital ulcer in the past 6 months, and one had genital ulcer on exam. None of the men tested positive for H. ducreyi. By physical exam there were 12 men with urethral discharge, and 109 (3.9%) men reported urethral discharge in the past 6 months. There were 213 (7.8%; 95% CI: 6.8 – 8.8%) men who tested positive at the baseline visit for non-ulcerative STIs (Ng, Ct, or Tv), 27 (13%) of whom had urethral discharge on exam or by report, compared to 3.5% of men who tested negative for non-ulcerative STI (p<0.001).

Interviews were conducted in English (62%), Dho Luo (36%), and Kiswahili (2%). Participants’ median reported age was 20. The median number of lifetime sex partners was 4 and the median number of years sexually active was 5. Anal insertive sex with a woman was infrequent, reported by 4.0% of men. Sex with a man was reported by 6 participants. Participant socio-demographic and behavioral characteristics are shown in Table 1.

Table 1
Socio-Demographic Characteristics and Behavioral Risks of Participants.

Exploratory Analysis: Factors Associated with HSV-2

The prevalence of infection increased from 19% among 18 year-olds to 43% among 24 year-olds (p<0.001; Figure 1). HSV-2 seropositivity was more prevalent among men reporting coital injuries, preference for dry sex, erectile dysfunction or pain during sex, greater number of sexual partners, and numerous sexual behaviors (Table 2). HSV-2 seropositivity increased with older age, living with their wife or female partner, and employment and income. The prevalence of infection decreased with increasing education, condom use at last sexual intercourse, greater frequency of condom use in the past 6 months, and cleaning one’s penis < 1 hour after sex (Table 2). Age at first sex, alcohol use at the last sex, and living one’s whole life in Kisumu were not associated with infection.

Figure 1
Seroprevalence of HSV-2 by Reported Age, with 95% Confidence Intervals.
Table 2
Distribution of Characteristics by HSV-2 Infection Status, HSV-2 Seroprevalence, and Factors Associated with HSV-2 Seropositivity.

The seroprevalence of HSV-2 was increased among men with active syphilis infection (46%; odds ratio [OR]=2.35; 95% CI: 1.11 – 4.97) and men with a history of syphilis infection (42%; OR=1.96; 95% CI: 1.25 – 3.08). HSV-2 seroprevalence was 35% among men with Ng, Ct, or Tv infection compared to 27% among men without any of those infections (OR=1.47; 95% CI: 1.10 – 1.97).

Multivariable Logistic Regression Analysis: Factors Associated with HSV-2

The likelihood of being HSV-2 seropositive increased with age (Table 3). Other risk factors for HSV-2 were being married or living with a female partner (AOR=1.80; 95% CI: 1.28 – 2.53), preference for dry sex (AOR=1.39; 95% CI: 1.14 – 1.70), reporting penile cuts, scratches or abrasions during sex (AOR=1.58; 95% CI: 1.32 – 1.91), having a non-student occupation, and more than one lifetime sex partner. Those who reported using a condom the last time they had sex were less likely to be HSV-2 seropositive (AOR=0.82; 95% CI: 0.68 – 0.99). Frequency of condom use in the past 6 months, assessed in a separate model due to collinearity with condom use at last sex, was not associated with HSV-2 status in a multivariable model. Syphilis and non-ulcerative STI were not analyzed as risks for HSV-2 in multivariable analysis because of the small number of men with these infections relative to the number who were HSV-2 seropositive. No statistically significant two-way interaction terms were identified. The Hosmer-Lemeshow goodness-of-fit test yielded a p-value of 0.45, indicating adequate model fit.

Table 3
Final Results of Stepwise Multivariable Logistic Regression Model for Factors Associated with HSV-2 Seropositivity, N=2,552.

Discussion

Almost 28% of uncircumcised men aged 18–24 residing in Kisumu, Kenya, were HSV-2 seropositive. The high prevalence and increasing prevalence with age, number of lifetime sex partners, non-student occupation, and being married or having a live-in partner were also associated with HSV-2 infection in a study reported by Weiss et al. examining HSV-2 in four African cities, including Kisumu [1]. In our study, the prevalence of infection increased from 15% among men with one lifetime sex partner, to 26% among men with two lifetime sex partners. However, a strong dose-response effect was not observed beyond this, similar to the findings by Weiss et al. [1]. This is likely due to the high prevalence of HSV-2 among young women in Kisumu (51% among women aged 15–24) [1]. Condom use at last sex, an assessment of a single event, was associated with lower risk of HSV-2 infection, and is a condom use measure in the Demographic and Health Survey conducted in several sub-Saharan African countries [14], including Kenya, as well as in U.S. national surveys [15].

Results of some studies suggest dry sex is associated with an increased risk of STI [16] and HIV [1719] in women in Africa, potentially due to the associated abrasions and ulcers [16]. Our study is the first we are aware of to demonstrate an increased risk of HSV-2 with dry sex preference among men. While an association was found for preference for dry sex, actual practices of dry sex were not assessed. In our study, preferring dry sex was associated with older age, being married or having a live-in partner, lower education, increasing number of sex partners, and sexual dysfunction. Further research is necessary to characterize the practice of dry sex geographically and culturally, and to determine whether this precedes STIs.

Less than 2% of men reported having a painful genital ulcer in the past 6 months. We did not collect data on the occurrence or frequency of previous HSV-2 outbreaks. HSV-2 seropositive men were less likely to report condom use the last time they had sex, increasing risk for transmission to their partner. As HSV-2 viral shedding peaks within 24 hours after symptoms [20], individuals could be given specific counseling for symptom recognition, and avoiding sex or using condoms before and after a symptomatic period [2122]. Recent studies have found that single-day oral antiviral therapy (famciclovir) initiated within one hour of prodromal symptoms decreased duration and intensity of genital herpes outbreaks [20, 23]. Current studies are assessing the feasibility of HSV-2 suppressive therapy in preventing HIV transmission and acquisition [24].

Almost half of all men reported that their penis had ever been cut, scratched, or abraded during sex, and this was a statistically significant risk for HSV-2 in multivariable analysis. The high prevalence of coital injury reported may be a misclassification of HSV-2 symptoms [25]. However, while there was a higher prevalence of penile cuts or abrasions reported among HSV-2 seropositive men (58%), the prevalence of cuts or abrasions among HSV-2 negative men was still 44%. Conversely, through compromised mucosal integrity, HSV-2 infection may increase men’s risk for penile cuts, abrasions, or scratches, although we are unaware of any evidence for this. Urogenital coital injury has been associated with vigorous coitus, unorthodox sexual positions, and young age [2627]. Penile cuts, scratches, and abrasions may be more common in uncircumcised men [28]. Additional study is needed to determine the cause of penile cuts and abrasions during sex, and how this relates to HSV-2 risk.

Limitations

This analysis is based on data collected from subjects who were recruited, screened and enrolled to a clinical trial. The participants may not be representative of the eligible population and may have a selective behavioral risk profile with respect to HSV-2 infection. This trial excluded men who were HIV-positive at baseline. It is likely that these men would have had higher risk profiles, had higher prevalence of HSV-2, and reported more genital ulcerations [1]. There may have been misreporting of risks due to social desirability or difficulty recalling events.

Conclusions

This analysis identified modifiable behaviors – preference for dry sex, inconsistent condom use, and multiple sex partners – for HSV-2 prevention. Primary HSV-2 prevention efforts should be initiated at an early age prior to first sex. Further study should evaluate the effectiveness of education and behavioral interventions among men already infected in preventing HSV-2 transmission to their partners. The same behavioral interventions used currently for HIV prevention – abstinence, reducing number of sex partners, and increasing condom use – should be effective for HSV-2 prevention.

Acknowledgments

We would like to thank the young men of Kisumu who volunteered for this trial, the UNIM Project staff for their research efforts, and Ian Maclean (University of Manitoba, Winnipeg, Canada) for laboratory protocols and oversight.

Funding: This study was funded by grants from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda Maryland USA, Grant No. AI150440, and the Canadian Institutes of Health Research, Grant No. HCT 44180. Stephen Moses was supported by a CIHR Investigator Award.

Footnotes

Copyright statement: "The Corresponding Author has the right to grant on behalf of all authors and does grant on behalf of all authors, an exclusive licence (or non exclusive for government employees) on a worldwide basis to the BMJ Publishing Group Ltd to permit this article (if accepted) to be published in STI and any other BMJPGL products and sub-licences such use and exploit all subsidiary rights, as set out in our licence http://sti.bmjjournals.com/ifora/licence.pdf)".

Author Contributions:

Supriya D. Mehta: Dr. Mehta developed and conducted statistical analysis, and wrote the first draft of manuscript.

Stephen Moses: Dr. Moses originated the objective of the study, study design and selection of study measurements; assisted with interpretation of analysis and study results, and critical review and revision of the manuscript.

Kawango Agot: Dr. Agot directed and ensured integrity of data collection efforts and study protocol implementation at clinics, assisted with study design and selection of study measurements, and critical review and revision of manuscript.

Walter Agingu: Dr. Agingu developed protocols for biological specimen collection and processing, interpretation and use of laboratory results, and review and revision of manuscript.

Corette Parker: Dr. Parker maintained integrity of data collection, entry, and maintenance, interpretation of analysis and study results, and critical review and revision of manuscript.

Jeckoniah O. Ndinya-Achola: Dr. Ndinya-Achola ensured integrity of data collection efforts and study protocol implementation at clinics, assisted with selection of study measurements, review and revision of manuscript.

Robert C. Bailey: Dr. Bailey originated the objective of the study, study design and selection of study measurements; assisted with interpretation of analysis and study results, and critical review and revision of the manuscript.

Competing Interests: None declared.

References

1. Weiss HA, Buve A, Robinson NJ, et al. The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations. AIDS. 2001;15 Suppl 4:S97–S108. [PubMed]
2. Weiss H. Epidemiology of herpes simplex virus type 2 infection in the developing world. Herpes. 2004;11 Suppl 1:24A–35A. [PubMed]
3. del Mar Pujades Rodriguez M, Obasi A, Mosha F, et al. Herpes simplex virus type 2 infection increases HIV incidence: a prospective study in rural Tanzania. AIDS. 2002;16:451–462. [PubMed]
4. Fleming DT, Wasserheit JN. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to sexual transmission of HIV infection [Review] Sex Transm Infect. 1999;75:3–17. [PMC free article] [PubMed]
5. Gray RH, Li X, Wawer MJ, et al. Determinants of HIV-1 load in subjects with early and later HIV infections, in a general-population cohort of Rakai, Uganda. J Infect Dis. 2004;189:1209–1215. [PubMed]
6. Schacker T, Zeh J, Hu HL, Hill E, Corey L. Frequency of symptomatic and asymptomatic herpes simplex virus type 2 reactivations among human immunodeficiency virus-infected men. J Infect Dis. 1998;178:1616–1622. [PubMed]
7. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000;342:921–929. [PubMed]
8. Orroth KK, White RG, Korenromp EL, et al. Empirical observations underestimate the proportion of human immunodeficiency virus infections attributable to sexually transmitted diseases in the Mwanza and Rakai sexually transmitted disease treatment trials: Simulation results. Sex Transm Dis. 2006;33:536–544. [PubMed]
9. Todd J, Grosskurth H, Changalucha J, et al. Risk factors influencing HIV infection incidence in a rural African population: a nested case-control study. J Infect Dis. 2006;193:458–466. [PubMed]
10. Bailey RC, Moses S, Parker CB, et al. Male circumcision for HIV prevention in young men in Kisumu, Kenya: A randomized controlled trial. Lancet. 2007;369:643–656. [PubMed]
11. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: Prevalence and predictors. JAMA. 1999;281:537–544. [PubMed]
12. Hosmer DW, Lemeshow S. Applied Logistic Regression. New York: John Wiley & Sons, Inc.; 2000.
13. Mehta SD, Moses S, Ndinya-Achola JO, et al. Identification of novel risks for non-ulcerative sexually transmitted infections among young men in Kisumu, Kenya. Sex Transm Dis. 2007 [PMC free article] [PubMed]
14. Akwara PA, Madise NJ, Hinde A. Perception of risk of HIV/AIDS and sexual behaviour in Kenya. J Biosoc Sci. 2003;35:385–411. [PubMed]
15. Anderson JE. Condom use and HIV risk among US adults. Am J Public Health. 2003;93:912–914. [PubMed]
16. Schwandt M, Morris C, Ferguson A, Ngugi E, Moses S. Anal and dry sex in commercial sex work, and relation to risk for sexually transmitted infections and HIV in Meru, Kenya. Sex Transm Infect. 2006;82:392–396. [PMC free article] [PubMed]
17. Hira SK, Mangrola UG, Mwale C, et al. Apparent vertical transmission of human immunodeficiency virus type 1 by breast-feeding in Zambia. J Pediatr. 1990;117:421–424. [PubMed]
18. Mann JM, Nzilambi N, Piot P, et al. HIV infection and associated risk factors in female prostitutes in Kinshasa, Zaire. AIDS. 1988;2:249–254. [PubMed]
19. Myer L, Kuhn L, Stein ZA, Wright TC, Jr, Denny L. Intravaginal practices, bacterial vaginosis, and women's susceptibility to HIV infection: epidemiological evidence and biological mechanisms. Lancet Infect Dis. 2005;5:786–794. [PubMed]
20. Aoki FY, Tyring S, Diaz-Mitoma F, Gross G, Gao J, Hamed K. Single-day, patient-initiated famciclovir therapy for recurrent genital herpes: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2006;42:8–13. [PubMed]
21. Wald A. Herpes simplex virus type 2 transmission: risk factors and virus shedding. Herpes. 2004;11 Suppl 3:130A–137A. [PubMed]
22. Patel R. Educational interventions and the prevention of herpes simplex virus transmission. Herpes. 2004;11 Suppl 3:155A–160A. [PubMed]
23. Spruance SL, Bodsworth N, Resnick H, et al. Single-dose, patient-initiated famciclovir: a randomized, double-blind, placebo-controlled trial for episodic treatment of herpes labialis. J Am Acad Dermatol. 2006;55:47–53. [PubMed]
24. Celum CL, Robinson NJ, Cohen MS. Potential effect of HIV type 1 antiretroviral and herpes simplex virus type 2 antiviral therapy on transmission and acquisition of HIV type 1 infection. J Infect Dis. 2005;191 Suppl 1:S107–S114. [PubMed]
25. Sizemore JM, Jr, Lakeman F, Whitley R, Hughes A, Hook EW., 3rd Historical correlates of genital herpes simplex virus type 2 infection in men attending an STD clinic. Sex Transm Infect. 2005;81:303–305. [PMC free article] [PubMed]
26. Eke N. Urological complications of coitus. BJU International. 2002;89:273–277. [PubMed]
27. Verna S. Coital penile trauma with severe paraphimosis. J Eur Acad Dermatol Venereol. 2005;19:134–135. [PubMed]
28. Bailey RC, Plummer FA, Moses S. Male circumcision and HIV prevention: current knowledge and future research directions. Lancet Infect Dis. 2001;1:223–231. [PubMed]