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Sexually Transmitted Diseases:
doi: 10.1097/01.olq.0000237774.29010.30
Article

Herpes Simplex Virus Type 2 (HSV-2) Infection in Women Attending an Antenatal Clinic in the South Pacific Island Nation of Vanuatu

Haddow, Lewis J. MB, ChB*; Sullivan, Elizabeth A. MBBS, MPH, MMed†; Taylor, Janette MPhil‡; Abel, Myriam MPH§; Cunningham, Anthony L. MD, FRACP‡; Tabrizi, Sepehr PhD∥; Mindel, Adrian MD, FRCP*

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Abstract

Objective: The objective of this study was to estimate the prevalence and correlates of herpes simplex virus type 2 infection in women in an antenatal clinic in the South Pacific island nation of Vanuatu.

Study Design: A prevalence survey of sexually transmitted infections of pregnant women attending an antenatal clinic at Vila Central Hospital was conducted in 1999–2000. Serum samples were tested for HSV-1 and HSV-2 antibodies by enzyme-linked immunosorbent assay. Results for other sexually transmitted infections and demographic and obstetric variables were analyzed for their association with HSV-2 serostatus.

Results: HSV-2 serum antibody results were obtained on 535 women and HSV-1 results on 134. The seroprevalence of HSV-2 was 30% and HSV-1 was 100%. On multivariate analysis, the independent predictors of HSV-2 infection were age, marital status, and trichomoniasis.

Conclusions: HSV-2 was common in this sample of sexually active women in Vanuatu. This is the first study of HSV in Vanuatu and one of very few studies in the Pacific region.

HERPES SIMPLEX VIRUS TYPE 2 (HSV-2) causes genital herpes and is transmitted during sexual intercourse. Infection causes considerable morbidity and can occasionally cause mother-to-child transmission and death in neonates. It is important to determine the prevalence of HSV-2 in populations for 2 major reasons. First, recent data suggest that prevalent HSV-2 infection is associated with enhanced HIV acquisition1,2 and shedding3,4 and an increase in plasma HIV load,5,6 and conversely that HIV infection leads to enhanced HSV-2 shedding.7 Second, an accurate estimation of the seroprevalence of HSV is needed at the country level for the development of relevant national HIV/sexually transmitted infection (STI) prevention and HSV vaccine policies. There is now the potential availability of a vaccine to reduce HSV-2 infection and perhaps consequent HIV transmission.8

HSV-2 infections are common throughout the world, particularly in parts of Africa.9 There are limited data from the Asia Pacific region. Studies in selected populations, considered to be at high risk for the acquisition of STIs, have shown that HSV-2 occurs in 13% to 75% of patients attending sexually transmitted disease clinics10–13 and 74% to 98% of female sex workers.14,15 In populations considered to be at lower risk for the acquisition of STIs, the prevalence of HSV-2 is generally lower. In women attending antenatal clinics, reported prevalence ranges from 5% to 55%12,16–19 and in women attending family planning clinics 11% to 38%.18,20 Demographic risk factors and behaviors associated with HSV-2 antibodies include increasing age, female gender, ethnic group, previous STIs, young age at first intercourse, lower educational level, and lower social class.

Other workers have shown that adolescents and young adults in the South Pacific Island nation of Vanuatu frequently engage in risky sexual behaviors with low levels of condom use.21–23 Our recent study, conducted of women attending an antenatal hospital clinic in Port Vila, Vanuatu, has shown that STIs are common,24 but HIV has not yet emerged as a major problem.25,26 As a follow-up study, we aimed to estimate the prevalence and correlates of HSV-2 infection in women attending the major urban antenatal clinic in Vanuatu.

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Materials and Methods

Study Design and Patients

A cross-sectional survey of pregnant women attending the first-visit antenatal clinic (ANC) at Vila Central Hospital (VCH) was conducted by the Ministry of Health in 1999–2000. This survey of prevalence of STIs in women in Vanuatu has previously been published.24 Serum samples from the previous study were used as specimens for the current study. Vila Central Hospital is located in Port Vila, the capital and largest town in Vanuatu, population approximately 30,000 (Fig. 1). The majority of pregnancy care for women in Vila and the surrounding villages of Éfaté is delivered through the antenatal clinics at VCH.

Fig. 1
Fig. 1
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Ethical approval for the original STI study was granted by the Ministry of Health, Republic of Vanuatu and University of New South Wales, Australia. Further ethical approval for the testing of sera for HSV-2 antibodies was obtained from Western Sydney Area Health Service, Australia, and the Ministry of Health, Republic of Vanuatu. Samples were fully deidentified for the current study and patient consent for HSV-2 testing was not sought.

Consecutive women were invited by midwives to participate in the study until the sample size of 550 was reached. Women attending the ANC for results or follow up were excluded. Informed consent was obtained for voluntary confidential testing of STIs (gonorrhea, chlamydia, trichomoniasis, and syphilis) and for unlinked anonymous testing for HIV infection.

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Data Collection

Each woman was interviewed by a midwife using a standardized questionnaire. Information collected included gestational age, maternal age, parity, marital status, occupation, place of residence (whether town or village), and island or country of birth. For the purpose of the study, no information was collected on sexual behavior or clinical signs and symptoms. After this, a study obstetrician conducted the standard first-presentation antenatal assessment of history, physical examination, and specimen collection. Testing, treatment, and follow up of STIs have been described previously.24

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Specimen Collection, Transportation, and Testing

Two 5-mL blood samples were obtained from each patient in Serum Separation Gel tubes (Sarstedt, Adelaide, Australia). These were centrifuged and transported to Australia for syphilis and HIV testing as previously described. HIV tests were done on one delinked aliquot of serum. The remainder of this serum was used for HSV antibody detection.

All sera were tested for antibody to HSV-2 using an indirect enzyme-linked immunosorbent assay (ELISA), specifically the HerpeSelect 2 ELISA IgG (Focus Technologies). The manufacturer recommends that an index value of >1.10 is presumptive for the presence of antibody to HSV-2. However, we have found that using this cutoff value yields a high rate of false-positive results (unpublished data). To overcome this problem, a cutoff value of 3.5 was used to determine HSV-2-seropositive sera. Sera that gave an equivocal result in the HerpeSelect 2 ELISA (index values, 0.9–3.5) were resolved using HSV-2 Western blot.27 A randomly selected subset of the sera (25%) was tested for antibodies to HSV-1. Depending on the HSV-2 serostatus of these sera, they were tested by one of 2 strategies. If HSV-2 antibody negative, serum was tested using the Enzygnost anti-HSV IgG ELISA (Behring) for detection of total antibody to HSV. If HSV-2 antibody-positive, the serum was tested using HSV-1 Western blot. This strategy was used as a result of the lack of a low-cost, sufficiently sensitive ELISA for antibody to HSV-1.17,28

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Data Analysis

Variables collected on each woman in the midwife questionnaire were coded in a database. Syphilis was defined as positive if rapid plasma reagin was positive or equivocal and Treponema pallidum hemagglutination was positive. The presence or absence of an STI (chlamydia, gonorrhea, trichomoniasis, and syphilis) was recorded based on the testing protocols described as well as the woman's HSV-2 serostatus. The number of concurrent STIs was also evaluated.

The Mann-Whitney U test was used to compare the age of HSV-2-negative and -positive women, and χ2 tests were performed for all other variables to test for association with HSV-2 seropositivity (Fisher exact test for variables with 1 degree of freedom or Pearson χ2 for other variables). Variables were included in a logistic regression model and were excluded by stepwise selection in which the P value was greater than 0.1. The data were compiled and analyzed using statistical software SPSS for Windows version 13.0 (Chicago, IL).

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Results

In total, 547 women were eligible and all agreed to participate in the study. Valid HSV-2 serology results were obtained on 535 women and HSV-1 results on 134. Women were aged 15 to 46 years with a mean age of 25.8 years. Marital status was given as married by 303 of 530 (57%) women and not recorded in 5. The majority lived in Vila (396 of 530 [75%]) with 113 (21%) living in other villages in Éfaté and 21 (4%) living on other islands. The main islands of birth were Tanna (89 women [17%]), Éfaté (69 [13%]), Ambrym (55 [10%]), Malekula (50 [9%]), Paama (44 [8%]), Pentecost (36 [7%]), and Ambae (36 [7%]). Seven women (1.3%) were born outside of Vanuatu.

Nulliparous women accounted for 184 of 534 (34%). Among parous women, 135 (25%) were parity one, 76 (14%) were parity 2, and 139 (26%) were parity 3 or more. Gestational age was first trimester in 104 of 528 (20%), second trimester in 279 (53%), and third trimester in 145 (27%).

The overall seroprevalence of HSV-2 was 158 of 535 (30%). All 134 (100%) of the serum specimens that were tested for HSV-1 were positive. In the current study, only those women who had both STI and HSV-2 testing were included in the analysis. The prevalence of concurrent STIs was as follows: chlamydia, 115 of 533 (22%); gonorrhea, 32 of 533 (6%); trichomoniasis, 146 of 533 (27%); syphilis confirmed on rapid plasma reagin and T. pallidum hemagglutination, 13 of 535 (2.4%). None of the women were HIV antibody-positive. The number of women with no STIs (other than HSV-2) was 325 of 533 (61%), women with one STI numbered 137 (26%), and 71 (13%) had more than one concurrent STI.

On univariate analysis (Table 1), HSV-2 seropositivity was significantly associated with increasing age and concurrent chlamydia, trichomoniasis, and syphilis, but not marital status, gonorrhea, parity, gestational age, place of residence, primary occupation, or place of birth. Older women were also more likely to be married and be parous (data not shown). There were statistical associations between all pairs of other STIs (gonorrhea, chlamydia, trichomoniasis, and syphilis) except gonorrhea and syphilis. The rates of HSV-2 were greater in women with greater numbers of concurrent STIs.

Table 1
Table 1
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Multiple logistic regression was performed, including HSV-2 serostatus as the dependent and age, marital status, and the presence of each other STI as covariates. The number of concurrent STIs was not included because it was a composite variable of all other STI variables. The figures obtained from this final model are shown in Table 2. The independent predictors of HSV-2 infection were age, marital status, and trichomoniasis. Syphilis had the largest odds ratio of 2.89, but the 95% confidence interval crossed 1.0. However, only 13 women had syphilis confirmed on T. pallidum hemagglutination.

Table 2
Table 2
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Discussion

This study shows an HSV-2 seroprevalence of 30% among antenatal clinic attendees in Vila, Vanuatu. The study sample was a large group of young pregnant women with high rates of STIs, who were parous in approximately two thirds of cases and married in just over half. They also displayed a high degree of mobility around Vanuatu with most having been born on islands distant from the clinic. Women with HSV-2-positive serostatus were more likely to be older, unmarried, and have concurrent trichomoniasis or syphilis.

There are no published studies of HSV-2 seroprevalence in Vanuatu. There are few studies of STIs in the Pacific island nations. Seafarers in Kiribati have been found to have a 20% HSV-2 prevalence rate and a 9% chlamydia prevalence.29,30 Nearby Papua New Guinea has been studied in more detail with prevalence rates of HSV-2 of 20% to 39%, depending on age and geographic location, and a demonstrable association with HHV-8-seropositive status.31,32

Previous work has shown high rates of other STIs, particularly chlamydia and trichomoniasis, in this population of antenatal women.24 In that study, younger age and nonmarried status were associated with the presence of an STI. HSV-2 is a lifelong infection; therefore, seropositivity is a marker of lifetime sexual risk, whereas curable or transient STIs may be more representative of recent risk. We have no behavioral data in our sample and rely on limited published work on sexual behavior in Vanuatu. Our study also lacks clinical information that might be of interest.

One further weakness of this study is the absence of demographic variables found in other studies to be associated with HSV-2 status such as ethnicity, educational level, and socioeconomic status. However, the ethnicity of these women is likely to have been fairly uniform, with 98% born in Vanuatu, and residence and primary occupation are surrogates for the other factors.

We have found 100% HSV-1 seroprevalence, similar to other developing regions of the world.9 The only vaccine with proven efficacy against genital HSV is ineffective in individuals seropositive for HSV-1; therefore, this vaccine is unlikely to be of use in Vanuatu.8

The 2 most serious health implications of genital herpes infection are neonatal herpes33 and enhanced transmission of HIV. Neonatal herpes is most likely to occur when primary HSV infection occurs during pregnancy, particularly in the third trimester.16,34 With HSV-2 infection prevalent in one third of sexually active women, particularly unmarried women that rises with age, new infections with HSV are likely to be frequent within this population. Therefore, incidence estimates and further studies of men are needed. Incidence could be estimated by longitudinal studies of HSV seroprevalence or possibly by testing for HSV-specific IgM in a large sample.

The transmission of HIV is known to be enhanced in the presence of genital herpes in either the HIV-positive donor or the HIV-negative recipient.35 There were only 2 cases of HIV infection (both AIDS) reported from Vanuatu by December 2004, giving an age-adjusted incidence of 0.8 per 100,000, although surveillance estimates are likely to underestimate the true rates of HIV.25 Our population's high STI rates are notable because there were no cases of HIV identified in over 500 women. Therefore, there is an opportunity for prevention of spread of HIV within this tightly contained community. The rates of HSV-2 that we report here are cause for concern because this disease may contribute to the rapid spread of HIV by sexual transmission.

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References

1. Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: Systematic review and meta-analysis of longitudinal studies. AIDS 2006; 20:73–83.

2. Plummer FA, Simonsen JN, Cameron DW, et al. Cofactors in male-female sexual transmission of human immunodeficiency virus type 1. J Infect Dis 1991; 163:233–239.

3. McClelland RS, Wang CC, Overbaugh J, et al. Association between cervical shedding of herpes simplex virus and HIV-1. AIDS 2002; 16:1425–1430.

4. Mbopi-Keou FX, Gresenguet G, Mayaud P, et al. Interactions between herpes simplex virus type 2 and human immunodeficiency virus type 1 infection in African women: Opportunities for intervention. J Infect Dis 2000; 182:1090–1096.

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.

6. Mole L, Ripich S, Margolis D, Holodniy M. The impact of active herpes simplex virus infection on human immunodeficiency virus load. J Infect Dis 1997; 176:766–770.

7. Nagot N, Foulongne V, Becquart P, et al. Longitudinal assessment of HIV-1 and HSV-2 shedding in the genital tract of west African women. J Acquir Immun Defic Syndr 2005; 39:632–634.

8. Stanberry LR, Spruance SL, Cunningham AL, et al. Glycoprotein-D-adjuvant vaccine to prevent genital herpes. N Engl J Med 2002; 347:1652–1661.

9. Smith JS, Robinson NJ. Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review. J Infect Dis 2002; 186(suppl 1):S3–28.

10. Cowan FM, Johnson AM, Ashley R, Corey L, Mindel A. Antibody to herpes simplex virus type 2 as serological marker of sexual lifestyle in populations. BMJ 1994; 309:1325–1329.

11. Langeland N, Haarr L, Mhalu F. Prevalence of HSV-2 antibodies among STD clinic patients in Tanzania. Int J STD AIDS 1998; 9:104–107.

12. Cunningham AL, Lee FK, Ho DW, et al. Herpes simplex virus type 2 antibody in patients attending antenatal or STD clinics. Med J Aust 1993; 158:525–528.

13. van de Laar MJ, Termorshuizen F, Slomka MJ, et al. Prevalence and correlates of herpes simplex virus type 2 infection: Evaluation of behavioural risk factors. Int J Epidemiol 1998; 27:127–134.

14. Nzila N, Laga M, Thiam MA, et al. HIV and other sexually transmitted diseases among female prostitutes in Kinshasa. AIDS 1991; 5:715–721.

15. Limpakarnjanarat K, Mastro TD, Saisorn S, et al. HIV-1 and other sexually transmitted infections in a cohort of female sex workers in Chiang Rai, Thailand. Sex Transm Infect 1999; 75:30–35.

16. Brown ZA, Selke S, Zeh J, et al. The acquisition of herpes simplex virus during pregnancy. N Engl J Med 1997; 337:509–515.

17. Mindel A, Taylor J, Tideman RL, et al. Neonatal herpes prevention: A minor public health problem in some communities. Sex Transm Infect 2000; 76:287–291.

18. Bogaerts J, Ahmed J, Akhter N, et al. Sexually transmitted infections among married women in Dhaka, Bangladesh: Unexpected high prevalence of herpes simplex type 2 infection. Sex Transm Infect 2001; 77:114–119.

19. Arvaja M, Lehtinen M, Koskela P, Lappalainen M, Paavonen J, Vesikari T. Serological evaluation of herpes simplex virus type 1 and type 2 infections in pregnancy. Sex Transm Infect 1999; 75:168–171.

20. Breinig MK, Kingsley LA, Armstrong JA, Freeman DJ, Ho M. Epidemiology of genital herpes in Pittsburgh: Serologic, sexual, and racial correlates of apparent and inapparent herpes simplex infections. J Infect Dis 1990; 162:299–305.

21. Corner H, Rissel C, Smith B, et al. Sexual health behaviours among Pacific Island youth in Vanuatu, Tonga and the Federated States of Micronesia. Health Promot J Austr 2005; 16:144–150.

22. Mitchell J. Young People Speak, a Report on the Vanuatu Young People's Project Vanuatu Cultural Centre. Port Vila, Vanuatu: Vanuatu Young People's Project, 1998.

23. Niras E. Vanuatu: Young people in Port Vila are sexually active but practising safe sex is not always a priority. Pacific AIDS Alert Bull 2000; 19:7.

24. Sullivan EA, Abel M, Tabrizi S, et al. Prevalence of sexually transmitted infections among antenatal women in Vanuatu, 1999–2000. Sex Transm Dis 2003; 30:362–366.

25. Zenner D, Russell S. Sexually transmitted diseases and HIV/AIDS in Vanuatu: A cause for concern and action. N Z Med J 2005; 118:U1610.

26. WHO Regional Offices for the Western Pacific and South-East Asia. HIV/AIDS in Asia and the Pacific Region 2003. Geneva: World Health Organization, 2004.

27. Ho DW, Field PR, Irving WL, Packham DR, Cunningham AL. Detection of immunoglobulin M antibodies to glycoprotein G-2 by Western blot (immunoblot) for diagnosis of initial herpes simplex virus type 2 genital infections. J Clin Microbiol 1993; 31:3157–3164.

28. Ho DW, Field PR, Sjogren-Jansson E, Jeansson S, Cunningham AL. Indirect ELISA for the detection of HSV-2 specific IgG and IgM antibodies with glycoprotein G (gG-2). J Virol Methods 1992; 36:249–264.

29. WHO Regional Offices for the Western Pacific and South-East Asia. Prevalence surveys of sexually transmitted infections among seafarers and women attending antenatal clinics in Kiribati 2002–2003. Manila, Philippines. Geneva: World Health Organization, 2003.

30. Sullivan EA, Koro S, Tabrizi S, et al. Prevalence of sexually transmitted diseases and human immunodeficiency virus among women attending prenatal services in Apia, Samoa. Int J STD AIDS 2004; 15:116–119.

31. Suligoi B, Danaya RT, Sarmati L, et al. Infection with human immunodeficiency virus, herpes simplex virus type 2, and human herpes virus 8 in remote villages of southwestern Papua New Guinea. Am J Trop Med Hyg 2005; 72:33–36.

32. Rezza G, Danaya RT, Wagner TM, et al. Human herpesvirus-8 and other viral infections, Papua New Guinea. Emerg Infect Dis 2001; 7:893–895.

33. Kimberlin DW. Neonatal herpes simplex infection. Clin Microbiol Rev 2004; 17:1–13.

34. Brown ZA, Wald A, Ashley Morrow R, Selke S, Zeh J, Corey L. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA 2003; 289:203–209.

35. Wald A, Link K. Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: A meta-analysis. J Infect Dis 2002; 185:45–52.

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