Original Article
Herpes Simplex Virus Type 2 in the United States, 1976 to 1994
N Engl J Med 1997; 337:1105-1111October 16, 1997
- Abstract
Background
Herpes simplex virus type 2 (HSV-2) infection is usually transmitted sexually and can cause recurrent, painful genital ulcers. In neonates the infection is potentially lethal. We investigated the seroprevalence and correlates of HSV-2 infection in the United States and identified changes in HSV-2 seroprevalence since the late 1970s.
Methods
Serum samples and questionnaire data were collected during the National Health and Nutrition Examination Surveys (NHANES) II (1976 to 1980) and III (1988 to 1994). HSV-2 antibody was assessed with an immunodot assay specific for glycoprotein gG-2 of HSV-2.
Results
From 1988 to 1994, the seroprevalence of HSV-2 in persons 12 years of age or older in the United States was 21.9 percent (95 percent confidence interval, 20.2 to 23.6 percent), corresponding to 45 million infected people in the noninstitutionalized civilian population. The seroprevalence was higher among women (25.6 percent) than men (17.8 percent) and higher among blacks (45.9 percent) than whites (17.6 percent). Less than 10 percent of all those who were seropositive reported a history of genital herpes infection. In a multivariate model, the independent predictors of HSV-2 seropositivity were female sex, black race or Mexican-American ethnic background, older age, less education, poverty, cocaine use, and a greater lifetime number of sexual partners. As compared with the period from 1976 to 1980, the age-adjusted seroprevalence of HSV-2 rose 30 percent (95 percent confidence interval, 15.8 to 45.8 percent). The seroprevalence quintupled among white teenagers and doubled among whites in their twenties. Among blacks and older whites, the increases were smaller.
Conclusions
Since the late 1970s, the prevalence of HSV-2 infection has increased by 30 percent, and HSV-2 is now detectable in roughly one of five persons 12 years of age or older nationwide. Improvements in the prevention of HSV-2 infection are needed, particularly since genital ulcers may facilitate the transmission of the human immunodeficiency virus.
Media in This Article
Figure 2
HSV-2 Seroprevalence According to Age in NHANES II (1976 to 1980) and NHANES III (1988 to 1994).Figure 1
HSV-2 Seroprevalence According to the Lifetime Number of Sexual Partners, Adjusted for Age, for Black and White Men and Women in NHANES III (1988 to 1994).Article Activity
- Article
Herpes simplex virus type 2 (HSV-2) causes vesicular and ulcerative lesions in adults1-3 and may cause severe systemic disease in neonates and immunosuppressed hosts.4-6 In addition, genital ulceration caused by HSV-2 may facilitate the transmission of the human immunodeficiency virus (HIV).7-12 Infections with HSV-2 typically affect the genital area, and transmission is usually sexual.6,13,14 In contrast, herpes simplex virus type 1 (HSV-1) commonly causes oropharyngeal infection, and transmission is primarily by nongenital personal contact.2,15 However, both viruses are capable of causing either genital or oropharyngeal infection and can produce mucosal lesions that are clinically indistinguishable. After primary infection, herpes simplex viruses enter a latent state in the nerve ganglia and may emerge later to cause recurrent active infection.
Assessing the extent of HSV-2 infection nationwide is difficult, for several reasons. In most states, HSV-2 infection is not a reportable disease. Furthermore, most people with HSV-2 are unaware of the infection.5,14,16-20 And, although the number of initial visits to physicians' offices for genital HSV infection increased from about 75,000 per year in 1978 to more than 150,000 per year in the early 1990s,21 it is uncertain whether this increase was due to a real increase in incidence or to increased public awareness and improved diagnosis and treatment of genital herpes. For these reasons, serologic methods have been the best way to study the epidemiology of HSV-2. Comprehensive serologic data on HSV-2 in the United States were collected during the second National Health and Nutrition Examination Survey (NHANES II) between 1976 and 1980.22
We report here the results of a nationally representative serologic survey of HSV-2 that was done as part of NHANES III from 1988 to 1994. NHANES III had a larger sample than NHANES II and included information on behavioral risk factors for HSV-2 infection. In addition, the new survey allows us to see changes in HSV-2 seroprevalence over the 13 years between the midpoints of the two surveys. During this period, public awareness of genital herpes and other sexually transmitted diseases increased, and national programs to prevent HIV infection were begun.
Methods
Study Populations and Sample Design
The NHANES program comprises a series of cross-sectional national surveys conducted by the National Center for Health Statistics of the U.S. Centers for Disease Control and Prevention (CDC). Each survey had a complex, stratified, multistage, probability-cluster design for selecting a sample representative of the noninstitutionalized civilian population of the United States.23,24 The total sample was larger in NHANES III (40,000) than in NHANES II (28,000).
In NHANES III, children under 5 years of age, persons 60 years of age or older, Mexican Americans, and blacks were sampled at higher rates than other persons. Race or ethnic group was defined by self-report as non-Hispanic white or non-Hispanic black (referred to as “white” and “black” in this article), or as Mexican American. People who did not place themselves in any of these categories were classified as “other” and were included with the total population.
The poverty-index ratio in NHANES III was calculated by dividing the total family income by the poverty threshold, with adjustment for the family size in the year of the interview, as determined by the Bureau of the Census.25 Residence in a county located in a metropolitan area was defined as urban residence. All other counties were defined as nonurban. Questions about the lifetime number of sexual partners, age at first intercourse, cocaine use, and history of genital herpes were asked of all study participants between 18 and 59 years old. Whether the participant had a history of genital herpes was addressed by the question, “Have you ever had genital herpes?”
In NHANES II, preschool children, older people, and people living below the poverty level were oversampled; the upper age limit was 74 years. Race was defined by self-report as “white,” “black,” or “other”; in that study, persons who gave their ancestry as “Hispanic” were classified as “other” so that the results could be compared with those of NHANES III.
Responses to the Surveys
Of the persons originally selected for NHANES III, 82.5 percent were interviewed, and HSV-2 test results were available for 60.2 percent. The reasons that results were unavailable included the inability to locate the selected subject, refusal by that person to be interviewed or to have blood drawn, unsuccessful venipuncture, the need to use serum for other tests, and the loss of serum samples during transportation, storage, or processing. The percentages of selected persons who agreed to be interviewed and the percentages of those for whom HSV-2 test results were available were similar among persons of different sex, race or ethnic group, and age, except that HSV-2 test results were less likely to be available for persons 70 years old or older (51.9 percent).
The rates of college attendance, rates of use of cocaine, and lifetime numbers of sex partners were similar among interviewed persons for whom HSV-2 results were available and those for whom the results were unavailable. The results were more likely to be available for persons living below the poverty level (71.9 percent) than for those living at or above the poverty level (58.1 percent).
An analysis of survey nonresponse in NHANES II has been published elsewhere.26 Nonresponse to the survey did not appear to introduce bias into the overall results.
Serologic Testing
Serum samples in both NHANES II and NHANES III were tested for antibodies to HSV-2 with the same type-specific immunodot test, performed in the same laboratory.22,27,28 The purified glycoprotein gG-2 of HSV-2, which is specific for HSV-2, served as antigen in the assay. The sensitivity of the immunodot test for recurrent, culture-proved genital HSV-2 infection is over 98 percent, and the specificity is over 99 percent.27 The quality of the HSV-2 testing was confirmed during both surveys by testing, with each reaction plate, positive and negative controls derived from pools of reference serum.
In NHANES III, all the available serum samples from persons 12 years of age or older were tested for type-specific HSV-2 antibody. In NHANES II, a subgroup of serum samples was tested for HSV-2, as described previously.22 Subgroup sampling weights were calculated to account for the sampling design and for the unavailability of serum samples according to sex, race or ethnic group, and age group. The final weight for each person in the sample in NHANES II was calculated as the product of the overall survey weight and the subgroup sampling weight.
As previously described,22 in NHANES II serum samples were first screened with a non–type-specific enzyme-linked immunosorbent assay, which detected any antibodies to HSV-1 or HSV-2.27,28 Serum samples that were positive on the non–type-specific screening test were subsequently tested with the type-specific test. Serum samples that were negative on the screening test were then presumptively assigned a negative test result for the type-specific immunodot test, thus limiting the use of the scarce type-specific testing reagent. To ensure that the screening test had a negligible effect on the overall sensitivity or specificity of HSV-2 testing, 245 serum samples from a health maintenance organization that were negative on the screening test were tested with the type-specific test; no type-specific HSV-2 antibody was detected in any of the samples.27
Statistical Analysis
For both surveys, the prevalence estimates were weighted to represent the total U.S. population and to account for oversampling and nonresponse to the household interview and physical examination. The weights were further ratio-adjusted according to age, sex, and race or ethnic group to estimates of the noninstitutionalized civilian U.S. population taken from the Current Population Survey, adjusted for undercounting.29,30 Standard errors were calculated with SUDAAN.31 The approximate standard errors of prevalence ratios were calculated by the delta method.32 For comparisons between NHANES II and III and across population subgroups of NHANES III, the data were age-adjusted to the 1980 U.S. population by the direct method,33 and nonoverlapping 95 percent confidence intervals were taken to indicate statistically significant changes in seroprevalence.
Logistic regression was used to identify predictors of HSV-2 infection. The initial model included demographic and behavioral variables that had univariate odds ratios with 95 percent confidence intervals excluding 1.0. By using stepwise backward elimination, variables with P values greater than 0.05 were then removed from the model.
Results
NHANES III (1988 to 1994)
The seroprevalence of HSV-2 among study participants 12 years of age or older was 21.9 percent (95 percent confidence interval, 20.2 to 23.6 percent) (Table 1Table 1
HSV-2 Seroprevalence in NHANES III (1988 to 1994) According to Sex, Age, and Race or Ethnic Group.). This prevalence corresponds to 45 million infected people in the noninstitutionalized civilian U.S. population. The seroprevalence was higher among women (25.6 percent) than among men (17.8 percent), yielding a female:male prevalence ratio of 1.4 (95 percent confidence interval, 1.2 to 1.7). The seroprevalence was 17.6 percent among whites, 45.9 percent among blacks, and 22.3 percent among Mexican Americans, yielding a black:white prevalence ratio of 2.6 (95 percent confidence interval, 2.3 to 2.9) and a Mexican-American:white prevalence ratio of 1.3 (95 percent confidence interval, 1.1 to 1.4). The female:male prevalence ratios were similar for each race or ethnic group. With increasing age, the overall HSV-2 seroprevalence rose rapidly in the younger age groups and then remained stable among people older than 30 years, in the range of 24 percent to 28 percent.By univariate analysis, HSV-2 seroprevalence was associated with a number of variables (Table 2Table 2
HSV-2 Seroprevalence in NHANES III (1988 to 1994) According to Demographic and Behavioral Factors and History of Herpes.). HSV-2 seroprevalence was higher among persons who were divorced or separated and those who were widowed than among single or married people, those with less education, and those living below the poverty level. There was no statistically significant difference in HSV-2 seroprevalence between urban and nonurban areas, and only a slight variation among the four regions of the United States. As far as behavioral variables were concerned, HSV-2 seroprevalence was higher among those who had ever used cocaine, those who had first had intercourse at the age of 17 or younger, and those with a greater lifetime number of sexual partners.With increasing lifetime numbers of sexual partners, HSV-2 seroprevalence initially rose more sharply for blacks than for whites, even after adjustment for age (Figure 1Figure 1
HSV-2 Seroprevalence According to the Lifetime Number of Sexual Partners, Adjusted for Age, for Black and White Men and Women in NHANES III (1988 to 1994).). For example, the age-adjusted seroprevalence among blacks who reported having one partner over a lifetime was 4.4 times that among whites reporting one partner; this held true both for men and women. By contrast, with increasing lifetime numbers of sexual partners, the seroprevalence among blacks leveled off, whereas it increased sharply among whites.Only 2.6 percent of adults report ever having had genital herpes. Persons with a history of genital herpes had an HSV-2 seroprevalence of 81.5 percent, whereas all other persons had a seroprevalence of 21.6 percent (Table 2). The sensitivity of a self-reported history of genital herpes for the presence of HSV-2 antibody was 9.2 percent overall and was similar for both sexes. In contrast, the sensitivity of a self-reported history of genital herpes for the presence of HSV-2 antibody differed markedly according to race or ethnic group; it was 12.2 percent for whites, 3.7 percent for blacks, and 3.8 percent for Mexican Americans.
In a multivariate model that examined the demographic and behavioral variables associated with HSV-2 status on univariate analysis, differences associated with marital status and age at first sexual intercourse were found not to be statistically significant (P>0.05) and were therefore dropped from the model. In the model, the multivariate independent predictors of HSV-2 serologic status were female sex, black race or Mexican-American ethnic background, older age, less formal education, an income below the poverty level, a greater lifetime number of sexual partners, and having ever used cocaine. The strongest predictors (with odds ratios greater than 3.0) were sex, race or ethnic group, age, and the lifetime number of sexual partners.
Trends in HSV-2 Seroprevalence between NHANES II (1976 to 1980) and NHANES III (1988 to 1994)
The age-adjusted overall prevalence of HSV-2 antibody rose from 16.0 percent in NHANES II to 20.8 percent in NHANES III (Table 3Table 3
Changes in Age-Adjusted HSV-2 Seroprevalence between NHANES II (1976 to 1980) and NHANES III (1988 to 1994).), a relative increase of 30 percent (95 percent confidence interval, 15.8 to 45.8 percent). The relative increases among men and women were similar. Among both whites and blacks there were similar absolute increases, but the relative increases were greater among whites because of the lower base-line prevalence among whites. The age-adjusted HSV-2 seroprevalence among whites increased from 12.7 percent in NHANES II to 16.5 percent in NHANES III, a relative increase of 30 percent (95 percent confidence interval, 9.9 to 54.3 percent). Among blacks, the age-adjusted seroprevalence increased from 43.6 to 47.6 percent, a relative increase of 9 percent (95 percent confidence interval, -1.2 to 20.4 percent).The increases in HSV-2 seroprevalence between NHANES II and NHANES III were concentrated in the younger age groups. There were statistically significant increases overall in the three youngest age groups, encompassing subjects from 12 to 39 years of age (Figure 2Figure 2
HSV-2 Seroprevalence According to Age in NHANES II (1976 to 1980) and NHANES III (1988 to 1994).). Among whites, the seroprevalence increased from 0.96 to 4.5 percent (prevalence ratio, 4.7; 95 percent confidence interval, 1.4 to 16.0) among 12-to-19-year-olds, and from 7.7 to 14.7 percent (prevalence ratio, 1.9; 95 percent confidence interval, 1.3 to 2.8) among 20-to-29-year-olds. Among older whites and among blacks, the increases were smaller and did not reach statistical significance in any age group.Discussion
These findings document the increasing seroprevalence of HSV-2 in the United States during an era in which the acquired immunodeficiency syndrome (AIDS) became recognized and national prevention efforts were initiated. During the period covered by NHANES III (1988 to 1994), the overall seroprevalence of HSV-2 in the United States was 21.9 percent. From NHANES II (1976 to 1980) to NHANES III, the age-adjusted seroprevalence increased by 30 percent, with the greatest relative increases among young whites.
Women were about 45 percent more likely than men to be infected with HSV-2 during both study periods. Potential explanations for this finding include the higher efficiency of HSV-2 transmission from men to women as compared with that from women to men14 and differences between women and men in sexual behavior.34-36 For example, women are more likely than men to choose sexual partners who are older than themselves36 and who therefore have an increased risk of HSV-2 infection.
In both surveys, blacks were more likely than other racial or ethnic groups to be infected with HSV-2. The disparities may be due to a variety of factors, both current and historical, which include racial and ethnic differences in the prevalence of poverty and low socioeconomic status, access to health care, sexual behavior, health-related behavior, and illicit drug use, as well as the age and sex composition of the population.37-39
Of the other demographic and behavioral factors assessed in NHANES III, the most strongly predictive of HSV-2 infection was the lifetime number of sexual partners. However, this effect was not the same for both sexes or for all races or ethnic groups (Figure 1). In fact, black men and women who reported having had only one sexual partner over their lifetimes were more than four times as likely to be infected with HSV-2 as white men and women with one sexual partner. This observation is consistent with the idea that the pool of potential sexual partners is different for whites and blacks. Since white and black populations have different levels of HSV-2 prevalence and since sexual partnerships tend to form between members of the same race or ethnic group,36,40 whites and blacks will typically face different risks of exposure to HSV-2 with each sexual partner. A similar difference has been observed between white and black women with respect to the risk of pelvic inflammatory disease.41
The great majority of people with serologic evidence of HSV-2 infection in the current study had no history of genital herpes. However, previous studies have demonstrated that many or most seropositive persons shed HSV-2 that is detectable by culture from the genital tract,5,17-19 and many have symptoms, such as itching and discharge, that are directly referable to HSV-2 detectable by culture. Such symptoms, however, are not often recognized as indicating an infection.16,19
Could the increases in HSV-2 seroprevalence among young people in the 13 years between the two surveys be related to changes in sexual behavior? During these years, AIDS was recognized as a public health problem, and large-scale HIV prevention efforts were initiated that might conceivably also have contributed to a reduction in HSV-2 infection. For example, condom use by young men more than doubled between 1979 and 1988.42 Condoms are effective in preventing HIV transmission when they are properly used during every sexual encounter.43 However, their effectiveness against HSV-2 transmission has been less well documented and may be more limited, because HSV-2 lesions can occur on areas of the body not covered by condoms.43-45 On the other hand, despite AIDS-prevention efforts, the prevalence of premarital sexual experience and multiple sexual partners increased among both young whites and young blacks.42,46-48 The increases in some types of risky behavior were more marked among whites.46
These results highlight the ongoing need to prevent HSV-2 and other sexually transmitted infections. A concerted national effort is needed to overcome barriers to the adoption of healthful sexual behavior, as emphasized in a recent report on sexually transmitted diseases from the Institute of Medicine.49 In addition, improvements in the diagnosis and treatment of established HSV-2 infection may have some effect on the transmission of HSV-2, since suppressive therapy with antiviral medications has been shown to decrease viral shedding.50-52 Finally, new preventive techniques, such as the use of HSV-2 vaccines53-57 and topical microbicides58 now under development, are urgently needed.
A primary goal of efforts to reduce HSV-2 infection should be the prevention of new HIV infections, since genital ulcers caused by HSV-2 may independently facilitate HIV transmission.7-12 In the meantime, HSV-2 seroprevalence, as measured by NHANES, provides reliable data on the prevalence of this sexually transmitted disease in the United States. It may therefore be an important indicator to follow as we attempt to promote healthful sexual behavior and prevent sexually transmitted diseases, including HIV infection.
We are indebted to Meena Khare, Akbar Zaidi, and Philip Rhodes for their expert statistical advice; to Peter Kilmarx, Karen Southwick, Kurt Maurer, and Jennifer Madans for their review of the manuscript; and to Robin Buckingham, Lucy Hannah, and Daniel Theodore for their support.
Source Information
From the Division of STD Prevention, National Center for HIV, STD and TB Prevention (D.T.F., R.E.J., S.O.A., M.E.S.L.), the National Center for Health Statistics (G.M.M.), and the Epidemic Intelligence Service, Epidemiology Program Office (D.T.F.), Centers for Disease Control and Prevention, Atlanta; and from the Emory University School of Medicine, Atlanta (A.J.N., F.K.L.).
Address reprint requests to Dr. St. Louis at the Division of STD Prevention, National Center for HIV, STD and TB Prevention, Centers for Disease Control and Prevention, Mailstop E-02, 1600 Clifton Rd., Atlanta, GA 30333.
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The International Working Group on Vaginal Microbicides
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Jeanne S. Sheffield. 2012. Perinatal Infections. , 218-230.
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Wilhelmina M Huston, Marina Harvie, Aruna Mittal, Peter Timms, Kenneth W Beagley. (2012) Vaccination to protect against infection of the female reproductive tract. Expert Review of Clinical Immunology 8:1, 81-94
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Mark R. Schleiss, Janna C. Patterson. 2012. Viral Infections of the Fetus and Newborn and Human Immunodeficiency Virus Infection during Pregnancy. , 468-512.
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Betsy Foxman. 2012. Molecular Tools. , 79-97.
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Elisabeth Puchhammer-Stöckl, Stephan W. Aberle, Harald Heinzl. (2012) Association of age and gender with alphaherpesvirus infections of the central nervous system in the immunocompetent host. Journal of Clinical Virology
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Pragna Patel, Tim Bush, Kenneth H. Mayer, Sheila Desai, Keith Henry, Edgar Turner Overton, Lois Conley, John Hammer, John T. Brooks. (2011) Prevalence and Risk Factors Associated With Herpes Simplex Virus-2 Infection in a Contemporary Cohort of HIV-Infected Persons in the United States. Sexually Transmitted Diseases1
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Katherine E. McGoogan, Allah B. Haafiz, Regino P. González Peralta. (2011) Herpes Simplex Virus Hepatitis in Infants: Clinical Outcomes and Correlates of Disease Severity. The Journal of Pediatrics 159:4, 608-611
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Sanyog Jain, Meghal A. Mistry, Nitin K. Swarnakar. (2011) Enhanced dermal delivery of acyclovir using solid lipid nanoparticles. Drug Delivery and Translational Research 1:5, 395-406
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J. M. Sales, J. L. Brown, R. J. DiClemente, T. L. Davis, M. J. Kottke, E. S. Rose. (2011) Age Differences in STDs, Sexual Behaviors, and Correlates of Risky Sex Among Sexually Experienced Adolescent African-American Females. Journal of Pediatric Psychology
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Christine M. Posavad, Amalia S. Magaret, Lin Zhao, Dawn E. Mueller, Anna Wald, Lawrence Corey. (2011) Development of an interferon-gamma ELISPOT assay to detect human T cell responses to HSV-2. Vaccine 29:40, 7058-7066
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Ferenc Bánhidy, István Dudás, Andrew E. Czeizel. (2011) Trimester dependent preterm births in pregnancy with genital herpes. Central European Journal of Medicine 6:4, 449-455
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I. Mylonas. (2011) Herpes genitalis in der Schwangerschaft. Der Gynäkologe 44:8, 623-629
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Kathleen M. Gutierrez, Richard J. Whitley, Ann M. Arvin. 2011. Herpes Simplex Virus Infections. , 813-833.
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C Gardella, Z Brown. (2011) Prevention of neonatal herpes. BJOG: An International Journal of Obstetrics & Gynaecology 118:2, 187-192
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Lisa K. Gilbert, Brooke A. Levandowski, Craig M. Roberts. (2010) Characteristics Associated With Genital Herpes Testing Among Young Adults: Assessing Factors From Two National Data Sets. Journal of American College Health 59:3, 143-150
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Michael J. Cannon, D. Scott Schmid, Terri B. Hyde. (2010) Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Reviews in Medical Virology 20:4, 202-213
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R. F. Gillum, Cheryl L. Holt. (2010) Religious Involvement and Seroprevalence of Six Infectious Diseases in US Adults. Southern Medical Journal 103:5, 403-408
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Pinaki Mandal, Carlos Alberto Pujol, Elsa Beatriz Damonte, Tuhin Ghosh, Bimalendu Ray. (2010) Xylans from Scinaia hatei: Structural features, sulfation and anti-HSV activity. International Journal of Biological Macromolecules 46:2, 173-178
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Daniel W. Dye, Gary T. Simmons. (2010) Fatal Herpes Virus Type I Infection in a Newborn. The American Journal of Forensic Medicine and Pathology 31:1, 89-91
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Thaveechai Vachirayonstien, Duanthanorm Promkhatkaew, Malee Bunjob, Asawachai Chueyprom, Pranee Chavalittumrong, Pathom Sawanpanyalert. (2010) Molecular evaluation of extracellular activity of medicinal herb Clinacanthus nutans against herpes simplex virus type-2. Natural Product Research 24:3, 236-245
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Silke Nolkemper, Jürgen Reichling, Karl Heinz Sensch, Paul Schnitzler. (2010) Mechanism of herpes simplex virus type 2 suppression by propolis extracts. Phytomedicine 17:2, 132-138
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Sharmistha Sinha, Akram Astani, Tuhin Ghosh, Paul Schnitzler, Bimalendu Ray. (2010) Polysaccharides from Sargassum tenerrimum: Structural features, chemical modification and anti-viral activity. Phytochemistry 71:2-3, 235-242
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S. K. Lai, Y.-Y. Wang, K. Hida, R. Cone, J. Hanes. (2010) Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses. Proceedings of the National Academy of Sciences 107:2, 598-603
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Anthony G. Brazzale, Darren B. Russell, Anthony L. Cunningham, Janette Taylor, William J. H. McBride. (2010) Seroprevalence of herpes simplex virus type 1 and type 2 among the Indigenous population of Cape York, Far North Queensland, Australia. Sexual Health 7:4, 453
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Hossein Sadeghi-Nejad, Marlene Wasserman, Wolfgang Weidner, Daniel Richardson, David Goldmeier. (2010) Sexually Transmitted Diseases and Sexual Function. Journal of Sexual Medicine 7:1pt2, 389-413
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Erina Petrera, Celia E. Coto. (2009) Therapeutic effect of meliacine, an antiviral derived from Melia azedarach L., in mice genital herpetic infection. Phytotherapy Research 23:12, 1771-1777
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Işıl Maral, Aydan Biri, Ümit Korucuoğlu, Coşkun Bakar, Meltem Çırak, M. Ali Bumin. (2009) Seroprevalences of herpes simplex virus type 2 and Chlamydia trachomatis in Turkey. Archives of Gynecology and Obstetrics 280:5, 739-743
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Kenneth H. Fife, Barbara Van Der Pol, Alexis M. Roth, Juanita Brand, Janet N. Arno, Jyl Madlem, Beth E. Juliar, Barry P. Katz, James A. Williams, Gregory D. Zimet, J Dennis Fortenberry. (2009) Implementation of Routine Access to Herpes Simplex Virus Type 2 Antibody Testing in a Public Health Sexually Transmitted Disease Clinic. Sexually Transmitted Diseases 36:11, 724-728
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K. P. Smith, N. A. Christakis. (2009) Association Between Widowhood and Risk of Diagnosis With a Sexually Transmitted Infection in Older Adults. American Journal of Public Health 99:11, 2055-2062
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Jeffrey B. Bingenheimer, Arline T. Geronimus. (2009) Behavioral Mechanisms in HIV Epidemiology and Prevention: Past, Present, and Future Roles. Studies in Family Planning 40:3, 187-204
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Marco Rusnati, Elisa Vicenzi, Manuela Donalisio, Pasqua Oreste, Santo Landolfo, David Lembo. (2009) Sulfated K5 Escherichia coli polysaccharide derivatives: A novel class of candidate antiviral microbicides. Pharmacology & Therapeutics 123:3, 310-322
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Gunilla Malm. (2009) Neonatal herpes simplex virus infection. Seminars in Fetal and Neonatal Medicine 14:4, 204-208
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Andrew Page, Richard Taylor, Juliet Richters, Jonathan Shaw, Janette Taylor, Anthony Cunningham, Adrian Mindel. (2009) Upstairs and Downstairs. Sexually Transmitted Diseases 36:6, 344-349
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Amanda Psyrri, Panagiotis Gouveris, Jan Baptist Vermorken. (2009) Human papillomavirus-related head and neck tumors: clinical and research implication. Current Opinion in Oncology 21:3, 201-205
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P. Chayavichitsilp, J. V Buckwalter, A. C. Krakowski, S. F. Friedlander. (2009) Herpes Simplex. Pediatrics in Review 30:4, 119-130
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SJ van Hal, DE Dwyer. 2009. Herpes Simplex: Viruses and Infections. .
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Kelly Conner, Alice Wuu, Victoria Maldonado, Brenda L. Bartlett, Stephen K. Tyring. (2009) Vaccines under study: non-HIV vaccines. Dermatologic Therapy 22:2, 168-185
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Barbara Romanowski, Linda N. Myziuk, Sharon L. Walmsley, Sylvie Trottier, Ameeta E. Singh, Stanley Houston, Mark Joffe, Isabelle Chiu. (2009) Seroprevalence and Risk Factors for Herpes Simplex Virus Infection in a Population of HIV-Infected Patients in Canada. Sexually Transmitted Diseases 36:3, 165-169
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Wendy S. Biggs, Rachel M. Williams. (2009) Common Gynecologic Infections. Primary Care: Clinics in Office Practice 36:1, 33-51
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J.M. Martín, G. Villalón, E. Jordá. (2009) Actualización en el tratamiento del herpes genital. Actas Dermo-Sifiliográficas 100:1, 22-32
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Bridget Leyland, Margaret R. Kennedy, Yolanda H. Wimberly, Bruce J. Levine, Thomas L. Cherpes. (2009) Serologic detection of herpes simplex virus type 2 antibodies among pregnant women using a point-of-care test from Focus Diagnostics. Journal of Clinical Virology 44:2, 125-128
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Felipe Uribe-Salas, Oswaldo Palma-Coca, Miguel A. Sánchez-Alemán, María Olamendi, Luís Juárez-Figueroa, Carlos J. Conde-Glez. (2009) Population-based prevalence of antibodies against herpes simplex virus type 2 and socio-demographic characteristics in Mexico. Transactions of the Royal Society of Tropical Medicine and Hygiene 103:2, 151-158
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Umamaheswar Duvvuri, Jeffrey N. Myers. (2009) Contemporary Management of Oropharyngeal Cancer. Current Problems in Surgery 46:2, 119-184
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Shivaprasad Bilichodmath, Sachin B. Mangalekar, Dileep C. G. Sharma, Ashok K. Prabhakar, Sridhar B. Reddy, Nagaraj B. Kalburgi, Sudhir R. Patil, Kishore Bhat. (2009) Herpesviruses in chronic and aggressive periodontitis patients in an Indian population. Journal of Oral Science 51:1, 79-86
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Mark R. Schleiss. (2009) Persistent and Recurring Viral Infections: The Human Herpesviruses. Current Problems in Pediatric and Adolescent Health Care 39:1, 7-23
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Lisa M. Hollier, Kimberly Workowski. (2008) Treatment of Sexually Transmitted Infections in Women. Infectious Disease Clinics of North America 22:4, 665-691
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Jan M.H. Risser, William L. Risser, Amanda L. Risser. (2008) Epidemiology of Infections in Women. Infectious Disease Clinics of North America 22:4, 581-599
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Eileen Stillwaggon. (2008) Race, Sex, and the Neglected Risks for Women and Girls in Sub-Saharan Africa. Feminist Economics 14:4, 67-86
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Robert N. Bowles, Jamie C. Yedowitz, John A. Blaho. (2008) Reconsideration of viral protein immunoblotting for differentiation of human herpes simplex viruses. Diagnostic Microbiology and Infectious Disease 62:2, 167-176
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Claudia Palladino, Jose María Bellón, Santiago Perez-Hoyos, Rosa Resino, Sara Guillén, Dolores Garcia, María Dolores Gurbindo, José Tomás Ramos, María Isabel de José, María Josefa Mellado, María Ángeles Muñoz-Fernández. (2008) Spatial pattern of HIV-1 mother-to-child-transmission in Madrid (Spain) from 1980 till now: demographic and socioeconomic factors. AIDS 22:16, 2199-2205
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Suresh Katragadda, Ritesh Jain, Deep Kwatra, Sudharshan Hariharan, Ashim K. Mitra. (2008) Pharmacokinetics of amino acid ester prodrugs of acyclovir after oral administration: Interaction with the transporters on Caco-2 cells. International Journal of Pharmaceutics 362:1-2, 93-101
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Ravi S. Talluri, Swapan K. Samanta, Ripal Gaudana, Ashim K. Mitra. (2008) Synthesis, metabolism and cellular permeability of enzymatically stable dipeptide prodrugs of acyclovir. International Journal of Pharmaceutics 361:1-2, 118-124
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Bruce G. Trigg, Peter R. Kerndt, Getahun Aynalem. (2008) Sexually Transmitted Infections and Pelvic Inflammatory Disease in Women. Medical Clinics of North America 92:5, 1083-1113
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Amanda Psyrri, Barbara Burtness. (2008) Viruses in head and neck cancers: prevention and therapy. Expert Review of Anticancer Therapy 8:9, 1365-1371
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Yo Hoshino, Lesley Pesnicak, Kennichi C. Dowdell, Juan Lacayo, Timothy Dudek, David M. Knipe, Stephen E. Straus, Jeffrey I. Cohen. (2008) Comparison of immunogenicity and protective efficacy of genital herpes vaccine candidates herpes simplex virus 2 dl5-29 and dl5-29-41L in mice and guinea pigs. Vaccine 26:32, 4034-4040
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(2008) Letters to the Editor. Journal of Paediatrics and Child Health 44:7-8, 471-472
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Adolfo C Fernandez-Obregon, Dhrumil Shah, Amanda I Howell, Imane Tiyal Bentahar, Lester Carrodeguas, Arifa Siddiqui, Julia A Ejiogu. (2008) Challenges in anti-infective therapy for skin conditions: part 1. Expert Review of Dermatology 3:3, 367-394
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Joseph John SASADEUSZ, Julie Elizabeth SILVERS, Helen Elizabeth KENT, Wayne DEVENISH, Jane HOCKING, Suzanne Marie GARLAND. (2008) Prevalence of HSV-2 antibody in a Melbourne antenatal population attending a tertiary obstetric hospital. The Australian and New Zealand Journal of Obstetrics and Gynaecology 48:3, 266-272
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Julia A. Schillinger, Christy M. McKinney, Renu Garg, R Charon Gwynn, Kellee White, Francis Lee, Susan Blank, Lorna Thorpe, Thomas Frieden. (2008) Seroprevalence of Herpes Simplex Virus Type 2 and Characteristics Associated With Undiagnosed Infection: New York City, 2004. Sexually Transmitted Diseases 35:6, 599-606
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Stephanie A.S. Staras, W Dana Flanders, Sheila C. Dollard, Robert F. Pass, John E. McGowan, Michael J. Cannon. (2008) Influence of Sexual Activity on Cytomegalovirus Seroprevalence in the United States, 1988???1994. Sexually Transmitted Diseases 35:5, 472-479
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Odilon da Silva Nunes, Ricardo de Souza Pereira. (2008) Regression of herpes viral infection symptoms using melatonin and SB-73: comparison with Acyclovir. Journal of Pineal Research 44:4, 373-378
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Victoria Arama, Radu Vladareanu, Raluca Mihailescu, Adrian Streinu Cercel, Carina Mihai, Adriana Hristea, Mihaela Iosipenco, Sorin Stefan Arama, Muriel Rabilloud. (2008) Seroprevalence and risk factors associated with herpes simplex virus infection among pregnant women. Journal of Perinatal Medicine 36:3, 206-212
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Katherine T. Chen, Ruth E. Tuomala, Clara Chu, Meei-Li Huang, D. Heather Watts, Carmen D. Zorrilla, Mary Paul, Ron Hershow, Philip Larussa. (2008) No association between antepartum serologic and genital tract evidence of herpes simplex virus-2 coinfection and perinatal HIV-1 transmission. American Journal of Obstetrics and Gynecology 198:4, 399.e1-399.e5
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Rhoda S. Sperling, Kenneth H. Fife, Terri J. Warren, Lynn P. Dix, Clare A. Brennan. (2008) The Effect of Daily Valacyclovir Suppression on Herpes Simplex Virus Type 2 Viral Shedding in HSV-2 Seropositive Subjects Without a History of Genital Herpes. Sexually Transmitted Diseases 35:3, 286-290
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Richard Rupp, David I Bernstein. (2008) The potential impact of a prophylactic herpes simplex vaccine. Expert Opinion on Emerging Drugs 13:1, 41-52
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Lisa M Hollier, George D Wendel, Lisa M Hollier. 2008. Third trimester antiviral prophylaxis for preventing maternal genital herpes simplex virus (HSV) recurrences and neonatal infection. .
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Deven T. Hamilton, Mark S. Handcock, Martina Morris. (2008) Degree Distributions in Sexual Networks: A Framework for Evaluating Evidence. Sexually Transmitted Diseases 35:1, 30-40
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Richard A. Crosby, Sara Head, Gregory Moore, Adewale Troutman. (2008) Is suspicion of genital herpes infection associated with avoiding sex? A clinic-based study. Sexual Health 5:3, 279
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Amanda Psyrri, Daniel DiMaio. (2008) Human papillomavirus in cervical and head-and-neck cancer. Nature Clinical Practice Oncology 5:1, 24-31
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Frances M Cowan, Jean H Humphrey, Robert Ntozini, Kuda Mutasa, Rhoda Morrow, Peter Iliff. (2008) Maternal Herpes simplex virus type 2 infection, syphilis and risk of intra-partum transmission of HIV-1: results of a case control study. AIDS 22:2, 193-201
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W. Lawrence Drew, Kim S. Erlich. 2008. Management of Herpesvirus Infections (Cytomegalovirus, Herpes Simplex Virus, and Varicella-Zoster Virus). , 437-461.
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C. Koch, J. Reichling, J. Schneele, P. Schnitzler. (2008) Inhibitory effect of essential oils against herpes simplex virus type 2. Phytomedicine 15:1-2, 71-78
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M. S. Cohen. (2007) Preventing Sexual Transmission of HIV. Clinical Infectious Diseases 45:Supplement 4, S287-S292
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Carolyn Gardella, Julia Barnes, Amalia S. Magaret, Julie Richards, Linda Drolette, Anna Wald. (2007) Prenatal Herpes Simplex Virus Serologic Screening Beliefs and Practices Among Obstetricians. Obstetrics & Gynecology 110:6, 1364-1370
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Rachna Gupta, Terri Warren, Anna Wald. (2007) Genital herpes. The Lancet 370:9605, 2127-2137
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Katherine M Coyne, Simon E Barton. (2007) Epidemiology of sexually transmitted infections. Expert Review of Obstetrics & Gynecology 2:6, 803-816
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Siobhan Sutcliffe, Sabine Rohrmann, Edward Giovannucci, Kenrad E. Nelson, Angelo M. De Marzo, William B. Isaacs, William G. Nelson, Elizabeth A. Platz. (2007) Viral Infections and Lower Urinary Tract Symptoms in the Third National Health and Nutrition Examination Survey. The Journal of Urology 178:5, 2181-2185
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Brian Conway. (2007) Genital herpes: the undiscovered pandemic. Future Virology 2:6, 533-536
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D Malvy, K Ezzedine, F Lançon, B Halioua, A Rezvani, S Bertrais, B Chanzy, J-E Malkin, P Morand, C De Labareyre, S Hercberg, A El Hasnaoui. (2007) Epidemiology of orofacial herpes simplex virus infections in the general population in France: results of the HERPIMAX study. Journal of the European Academy of Dermatology and Venereology 21:10, 1398-1403
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Vinod Mishra, Simona Bignami-Van Assche, Robert Greener, Martin Vaessen, Rathavuth Hong, Peter D Ghys, J Ties Boerma, Ari Van Assche, Shane Khan, Shea Rutstein. (2007) HIV infection does not disproportionately affect the poorer in sub-Saharan Africa. AIDS 21:Suppl 7, S17-S28
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Israel Steiner, Peter GE Kennedy, Andrew R Pachner. (2007) The neurotropic herpes viruses: herpes simplex and varicella-zoster. The Lancet Neurology 6:11, 1015-1028
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Mahnaz Fatahzadeh, Robert A. Schwartz. (2007) Human herpes simplex virus infections: Epidemiology, pathogenesis, symptomatology, diagnosis, and management. Journal of the American Academy of Dermatology 57:5, 737-763
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Kathleen M. Gutierrez. (2007) Rethinking Herpes Simplex Virus Infections in Children and Adolescents. The Journal of Pediatrics 151:4, 336-338
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Richard Whitley, Elizabeth Anne Davis, Nittaya Suppapanya. (2007) Incidence of Neonatal Herpes Simplex Virus Infections in a Managed-Care Population. Sexually Transmitted Diseases 34:9, 704-708
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Julie Richards, Delia Scholes, Selin Caka, Linda Drolette, Amalia Meier Magaret, Patty Yarbro, William Lafferty, Richard Crosby, Ralph Diclemente, Anna Wald. (2007) HSV-2 Serologic Testing in an HMO Population: Uptake and Psychosocial Sequelae. Sexually Transmitted Diseases 34:9, 718-725
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Laura Hokkanen, Jyrki Launes. (2007) Neuropsychological sequelae of acute-onset sporadic viral encephalitis. Neuropsychological Rehabilitation 17:4-5, 450-477
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Maura L. Gillison. (2007) Current topics in the epidemiology of oral cavity and oropharyngeal cancers. Head & Neck 29:8, 779-792
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Joelle M Brown, Anna Wald, Alan Hubbard, Kittipong Rungruengthanakit, Tsungai Chipato, Sungwal Rugpao, Francis Mmiro, David D Celentano, Robert S Salata, Charles S Morrison, Barbra A Richardson, Nancy S Padian. (2007) Incident and prevalent herpes simplex virus type 2 infection increases risk of HIV acquisition among women in Uganda and Zimbabwe. AIDS 21:12, 1515-1523
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D. Hoeller Obrigkeit, J.M. Baron. (2007) Impfstoffe gegen Herpes-simplex-Virus-Infektionen. Der Hautarzt 58:5, 465-466
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Nichole Mahnert, Scott W. Roberts, Vanessa R. Laibl, Jeanne S. Sheffield, George D. Wendel. (2007) The incidence of neonatal herpes infection. American Journal of Obstetrics and Gynecology 196:5, e55-e56
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Meghna Ramaswamy, Anna Maria Geretti. (2007) Interactions and management issues in HSV and HIV coinfection. Expert Review of Anti-infective Therapy 5:2, 231-243
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G. G. Miller, J. S. Dummer. (2007) Herpes Simplex and Varicella Zoster Viruses: Forgotten but Not Gone. American Journal of Transplantation 7:4, 741-747
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A. Sauerbrei, P. Wutzler. (2007) Herpes simplex and varicella-zoster virus infections during pregnancy: current concepts of prevention, diagnosis and therapy. Part 1: Herpes simplex virus infections. Medical Microbiology and Immunology 196:2, 89-94
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Noreen A. Hynes. (2007) Testing for asymptomatic herpes simplex virus type 2: Implications for pretest and post-test counseling. Current Infectious Disease Reports 9:2, 123-124
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Stephen C. Davies, Janette A. Taylor, Endang R. Sedyaningsih-Mamahit, Suriadi Gunawan, Anthony L. Cunningham, Adrian Mindel. (2007) Prevalence and Risk Factors for Herpes Simplex Virus Type 2 Antibodies Among Low- and High-Risk Populations in Indonesia. Sexually Transmitted Diseases 34:3, 132-138
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John R. Williams, Jamie C. Jordan, E Anne Davis, Geoffrey P. Garnett. (2007) Suppressive Valacyclovir Therapy: Impact on the Population Spread of HSV-2 Infection. Sexually Transmitted Diseases 34:3, 123-131
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E. N. Bocharova, L. E. Zavalishina, E. E. Bragina, R. R. Klimova, Yu. K. Gusak, L. F. Kurilo, L. V. Shileiko, A. N. Petrov, G. A. Frank, A. A. Kushch. (2007) Detection of herpes simplex virus genomic DNA in spermatozoa of patients with fertility disorders by in situ hybridization. Doklady Biological Sciences 412:1, 82-86
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