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To investigate herpes simplex virus type–2 (HSV-2) seropositivity and associated risk factors in Vietnamese women.
Cross-sectional study with personal interviews and gynecological examinations among population-based samples of ever married women, aged 15–69 years, living in Ho Chi Minh City (HCMC) and Hanoi in 1997. Type-specific IgG antibodies against HSV-2 were detected using HerpeSelect ELISA (Focus Diagnostics). Adjusted prevalence ratios were estimated with log-binomial regression.
HSV-2 seroprevalence was higher in 1,106 women from HCMC (30.8%, 95% CI: 28.1–33.4, age-standardized to 2000 world standard population) than in 1,170 women from Hanoi (8.8%, 95% CI: 7.1–10.5). In HCMC, HSV-2 seroprevalence was higher for women who were not married, HPV DNA positive, current hormonal contraceptive users, or had a history of multiple sexual partners or spontaneous abortion. HCMC seroprevalence was inversely associated with educational attainment, age at first intercourse, and age at first pregnancy. In the multivariable model for HCMC, a trend of increasing HSV-2 seroprevalence with age was observed, and prevalence ratios were nearly identical to age-adjusted prevalence ratios for marital status, age at first pregnancy, and HPV DNA positivity.
HSV-2 was notably less prevalent in Hanoi than HCMC, where it was associated with traditional HSV-2 risk factors. These results are likely explained by socio-cultural, historical, economic, and demographic factors related to urban-rural and regional differences. Future population-based studies should include men and never-married women as a next step toward obtaining a more nearly complete picture of HSV-2 epidemiology in Vietnam.
Herpes simplex virus type–2 (HSV-2) infection, one of the most common sexually transmitted infections (STIs) worldwide1, is the main cause of genital ulcers and may increase susceptibility to human immunodeficiency virus (HIV)2,3,4. Since most HSV-2 infections are asymptomatic, seroprevalence data provide a better measure of the burden of genital herpetic disease than clinical data5,6. We analyzed data collected by the International Agency for Research on Cancer (IARC), the National Cancer Institute in Hanoi, and the Hung Vuong Obstetric and Gynecology Hospital in Ho Chi Minh City (HCMC), Vietnam, as part of a multicentric population-based study of sexually transmitted infection prevalence7.
This cross-sectional study recruited married women registered with family planning clinics in an urban area in HCMC (April–October 1997) and a peri-urban district in Hanoi (April-May 1997)8,9. The HCMC sample was drawn from three communes randomly chosen out of the 15 that constitute HCMC District 10. The Hanoi sample was drawn from four randomly selected communes of the 26 communes in Soc Son. In each location (HCMC, Hanoi), 120 women ages 15 years and older were randomly selected within each of eleven age groups. Health workers visited each woman at her home to check exclusion criteria (pregnancy, history of hysterectomy or conization, mental impairment), explain study aims, and obtain written informed consent. Overall, 1,122 in HCMC (87.7% of 1,279 contacted) and 1,246 women in Hanoi (94.4% of 1,320 contacted) came to the commune health centre for a structured interview and gynecological examination, including a 10-ml blood sample and Pap smear. All protocols were approved by the Ministry of Health Board of Vietnam and the Ethical Committee of the IARC, Lyon, France.
Specimens were shipped daily to central laboratories in each study site for processing and storage. Blood samples were centrifuged at 1,500 g. The plasma was placed in Nunc tubes and frozen at –20° for shipment to Lyon for storage. IgG antibodies against HSV-2 were detected from plasma samples using Focus Diagnostics/MRL type specific HSV-2 ELISA assays in a central laboratory in Seattle, Washington. A formal validation study for HSV-2 was conducted in each site by retesting 100 samples with the Western blot, the gold standard test for type-specific HSV serology8,10. Index values of <0.9 were classified as negative, those >1.1 as positive, and others as equivocal, according to manufacturer’s instructions. HPV DNA testing was performed on cervical exfoliated cells with a general primer-mediated GP5+/6+-PCR, and PCR positivity was assessed by using two HPV oligoprobe cocktails to detect 36 individual HPV types8,11.
Crude and age-standardized (2000 world standard population12) HSV-2 seroprevalence and 95% confidence intervals (CIs) were calculated separately for each study area. Age-adjusted (aaPR) and multiply-adjusted prevalence ratios for HSV-2 seropositivity and CIs were calculated by log-binomial regression, with and without controlling for variables significant in the age-adjusted analysis in either HCMC or Hanoi.
After we excluded women without HSV-2 serostatus data (16 HCMC, 76 Hanoi), data from 1,106 women from HCMC and 1,170 women from Hanoi were analyzed. HCMC women had more schooling and were older at first pregnancy (Table I). Fewer HCMC women began coitus before age 19 years. Primary methods of contraception were IUDs (ever used by 55.8% of HCMC women and 43.2% of Hanoi women, not shown) and male condoms (46.7% ever used in HCMC, not shown). Most women reported having had only one sexual partner (93.6% HCMC, 94.6% Hanoi). HPV DNA was found in 9.0% of HCMC women and 1.7% of Hanoi women.
HSV-2 seropositivity was higher in HCMC (34.4%, 95% CI 31.7–37.3; age-standardized: 30.8%, 95% CI: 28.1–33.4) than in Hanoi (9.2%, 95% CI 7.6–10.9; age-standardized: 8.8%, 95% CI: 7.1–10.5) (Table II). In HCMC, HSV-2 seroprevalence increased monotonically with age, from 15.7% to 51.5% (aaPR 3.3: 2.2–4.8). HSV-2 seropositivity was inversely associated with educational attainment. HSV-2 seroprevalence was higher in divorced women and widows. The corresponding associations in Hanoi were weaker and less consistent.
Among HCMC women, HSV-2 prevalence was inversely associated with age at first intercourse (aaPR 1.4: 1.1–1.7 for age < 19 years) and age at first pregnancy (aaPR 1.3: 1.1–1.6 for age < 21 years). HSV-2 prevalence was not related to IUD use, but was higher for women who reported current oral contraceptive use (aaPR 1.5: 1.1–2.2). HSV-2 seroprevalence was higher for nulliparous women. Higher crude HSV-2 prevalence among women reporting 5+ pregnancies likely resulted from confounding by age, since the aaPR for parity were not elevated. HSV-2 was slightly higher for HCMC women who reported a spontaneous abortion, though not for those reporting an induced abortion. Again, the corresponding associations for Hanoi were inconsistent or absent.
HSV-2 prevalence was higher among HCMC women reporting more than one lifetime sexual partner but not among their counterparts from Hanoi. Moreover, most HSV-2 infections (209/381 in HCMC, 77/108 in Hanoi) occurred in women who reported that both she and her husband had each had only one sex partner ever. In HCMC, HSV-2 prevalence was higher among HPV DNA positive women (aaPR 1.4: 1.2–1.7); in Hanoi, only one HPV DNA positive woman was HSV-2 seropositive.
In multiple regression models, the age-related rise in HSV-2 prevalence was still present in HCMC. Multiply-adjusted prevalence ratios for HCMC were slightly higher than the aaPRs for marital status, age at first pregnancy, and HPV DNA positivity, but weaker for having had more than one sex partner (Table III).
Age standardized HSV-2 seroprevalence in ever-married HCMC (30.8%) was nearly 3.5 times that in Hanoi (8.8%) despite similarly low proportions of women reporting multiple lifetime sexual partners and earlier onset of sexual intercourse in HCMC. Underreporting of sexual partner risk factors is likely for both geographical areas, as most HSV-2 seropositive women reported only one lifetime sex partner. The higher HSV-2 seroprevalence in HCMC was likely not due to false positive tests because all specimens were examined in parallel within the same laboratory.
We believe that the marked difference in HSV-2 seroprevalence between the two samples is related to socio-cultural, historical, economic, and demographic factors including urbanicity and migration13,14,15. The HCMC sample came from an urban district, and only 44% reported having been born in HCMC. The Hanoi sample was peri-urban, with most women born in Hanoi. The prevalence of HSV-2 and other STIs tends to be higher in urban areas6,16, and the urban-rural ratio in HIV seroprevalence among Vietnamese women is about 2:117. Regional differences are also likely. The HSV-2 prevalence differential parallels the differential in invasive cervical cancer incidence (26.0/100,000/year in HCMC, 6.3/100,000 in Hanoi18,19), for which HSV-2 may be a cofactor with high-risk HPV infection20. Also, HSV-2 seroprevalence in female sex workers is higher in southern provinces (Dong Thap 32.3%, An Giang 33.3% and Kien Giang 29.9%) than in a northern border area (Lai Chau 5.0%)21. Such regional differences could reflect South Vietnam’s greater mid-20th century wartime exposure to social, economic, and political disruption, internal migration, and U.S. military personnel and contractors.
The age standardized HSV-2 prevalence in Hanoi (8.8%) was similar to that reported for several other Asian populations: 9.2% in Manila16, below 7% in Japanese women22,23, and 11% among family planning clients in Dhaka24 and below the 18% in Hong Kong25 and 18.7% among females in Indonesia26 reported by others. The 30.8% in HCMC is higher than these but less than the 41% reported for Jordanian female university students and42.2% among women attending antenatal clinics in Turkey27.
Our cross-sectional findings for HCMC of a positive association between HSV-2 and age, and of greater HSV-2 prevalence for widows and divorced women than for currently married women are consistent with studies in Brazil16, Columbia28, Mexico29, Peru28, Spain28 and the Phillipines16. Similarly, the association of HSV-2 with earlier age at first intercourse is consistent with most6,29 but not all26 reports. The association with history of multiple sexual partners has been regularly observed6,29,30. Higher HSV-2 seroprevalence among users of hormonal contraceptives has been reported for the Philippines16 but not in several other studies16,28. Similarly, our finding of an association between HSV-2 seroprevalence and cervical HPV infection is consistent with previous studies29,31.
Although the data were collected in 1997, to our knowledge the present study remains the largest population-based study of HSV-2 seroprevalence conducted in Vietnam to date. Nevertheless, the samples of ever-married women in HCMC and Hanoi were not designed to be representative of the larger Vietnamese population, nor to test rural-urban or regional differences. Future studies are needed to provide national and regional seroprevalence estimates and to obtain data on men and never-married women.
In conclusion, we observed a moderately high prevalence of HSV-2 and associations with traditional HSV-2 risk factors in an urban general population sample of ever-married women in HCMC. A similarly-obtained sample of ever-married peri-urban women in Hanoi had relatively low HSV-2 seroprevalence, with few risk factor associations observed. Our findings are similar to those seen for HPV DNA prevalence in the same two geographic sites8.
The two surveys were conducted by P.T.H. Anh (in Hanoi) and N.T. Hieu (in HCMC) with the assistance of N.H. Nga, N.B. Duc and N.T. Thuy, respectively. R.H. and N.M. designed the protocol, initiated the prevalence study, completed the field work and HPV testing, assisted by D.M.P. J.S.S. initiated the HSV-2 ancillary study. S.V. checked data accuracy. R.A. carried out testing for anti-HSV-2 antibodies, and P.J.F.S. and C.J.L.M.M. testing for HPV-DNA. L.V. Hoa, V.J.S., and J.S.S. conducted statistical analyses and wrote the first draft of the manuscript. All investigators contributed to the interpretation of the data and to the writing of the paper. We acknowledge the collaboration of all women and staff of the Gynecology Outpatient Clinic and the Cytology Unit of Hung Vuong Hospital. We also thank Dr. D.L.D. Hanh, Dr. N.V.M. Linh and the medical staff of Communes 2, 21 and 14, District 10, HCMC, the Hanoi Cancer Institute and Cancer Registry, the Center of Population and Family Planning of the Soc Son District. The People’s Committee and the staff of the Health Center of the Communes: Hong Ky, Kim Lu, Minh Phu, and Phu Lo supported the study. Mrs. A. Arslan, Ms. S. Hussain and Mr. C. Hsu helped with the preparation of the data. Finally, we thank the anonymous reviewers of an earlier version of the manuscript. Preparation of this article was funded in part by a fellowship grant from the Vietnam Education Foundation (VEF) to L.V. Hoa. The opinions, findings, and conclusions stated herein are those of the authors and do not necessarily reflect those of VEF.