Reactivation of Genital Herpes Simplex Virus Type 2 Infection in Asymptomatic Seropositive Persons
Anna Wald, M.D., M.P.H., Judith Zeh, Ph.D., Stacy Selke, M.S., Terri Warren, M.S., Alexander J. Ryncarz, Ph.D., Rhoda Ashley, Ph.D., John N. Krieger, M.D., and Lawrence Corey, M.D.
Background Most persons who have serologic evidence of infectionwith herpes simplex virus (HSV) type 2 (HSV-2) are asymptomatic.Historically, it has been assumed that these persons have lessfrequent viral reactivation than those with symptomatic infection.
Methods We conducted a prospective study to investigate genitalshedding of HSV among 53 subjects who had antibodies to HSV-2but who reported having no history of genital herpes, and wecompared their patterns of viral shedding with those in a similarcohort of 90 subjects with symptomatic HSV-2 infection. Genitalsecretions of the subjects in both groups were sampled dailyand cultured for HSV for a median of 94 days.
Results HSV was isolated from the genital mucosa in 38 of the53 HSV-2–seropositive subjects (72 percent) who reportedno history of genital herpes, and HSV DNA was detected by thepolymerase-chain-reaction assay in cultures prepared from genitalmucosal swabs in 6 additional subjects. The rate of subclinicalshedding of HSV in the subjects with no reported history ofgenital herpes was similar to that in the subjects with sucha history (3.0 percent vs. 2.7 percent). Of the 53 subjectswho had no reported history of genital herpes, 33 (62 percent)subsequently reported having typical herpetic lesions; the durationof their recurrences in these subjects was shorter (median,three days vs. five days; P<0.001) and the frequency lower(median, 3.0 per year vs. 8.2 per year; P<0.001) than inthe 90 subjects with previously diagnosed symptomatic infection.Only 1 of these 53 subjects had no clinical or virologic evidenceof HSV infection.
Conclusions Seropositivity for HSV-2 is associated with viralshedding in the genital tract, even in subjects with no reportedhistory of genital herpes.
Source Information
From the Departments of Medicine (A.W., L.C.), Epidemiology (A.W.), Statistics (J.Z.), Laboratory Medicine (S.S., A.J.R., R.A., L.C.), and Urology (J.N.K.), University of Washington, Seattle; Westover Heights Clinic, Portland, Oreg. (T.W.); and the Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle (L.C.). Presented in part at the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, September 15–18, 1996.
Address reprint requests to Dr. Wald at the University of Washington Virology Research Clinic, 1001 Broadway, Suite 320, Seattle, WA 98122, or at annawald{at}u.washington.edu.
Chentoufi, A. A., Binder, N. R., Berka, N., Durand, G., Nguyen, A., Bettahi, I., Maillere, B., BenMohamed, L.
(2008). Asymptomatic Human CD4+ Cytotoxic T-Cell Epitopes Identified from Herpes Simplex Virus Glycoprotein B. J. Virol.
82: 11792-11802
[Abstract][Full Text]
Romanowski, B, Zdanowicz, Y M, Owens, S T
(2008). In search of optimal genital herpes management and standard of care (INSIGHTS): doctors' and patients' perceptions of genital herpes. Sex. Transm. Infect.
84: 51-56
[Abstract][Full Text]
Terry-Allison, T., Smith, C. A., DeLuca, N. A.
(2007). Relaxed Repression of Herpes Simplex Virus Type 1 Genomes in Murine Trigeminal Neurons. J. Virol.
81: 12394-12405
[Abstract][Full Text]
Bellner, L., Karlsson, J., Fu, H., Boulay, F., Dahlgren, C., Eriksson, K., Karlsson, A.
(2007). A Monocyte-Specific Peptide from Herpes Simplex Virus Type 2 Glycoprotein G Activates the NADPH-Oxidase but Not Chemotaxis through a G-Protein-Coupled Receptor Distinct from the Members of the Formyl Peptide Receptor Family. J. Immunol.
179: 6080-6087
[Abstract][Full Text]
Freeman, E. E, Orroth, K. K, White, R. G, Glynn, J. R, Bakker, R., Boily, M.-C., Habbema, D., Buve, A., Hayes, R.
(2007). Proportion of new HIV infections attributable to herpes simplex 2 increases over time: simulations of the changing role of sexually transmitted infections in sub-Saharan African HIV epidemics. Sex. Transm. Infect.
83: i17-i24
[Abstract][Full Text]
Magaret, A. S., Wald, A., Huang, M.-L., Selke, S., Corey, L.
(2007). Optimizing PCR Positivity Criterion for Detection of Herpes Simplex Virus DNA on Skin and Mucosa. J. Clin. Microbiol.
45: 1618-1620
[Abstract][Full Text]
Thapa, M., Kuziel, W. A., Carr, D. J. J.
(2007). Susceptibility of CCR5-Deficient Mice to Genital Herpes Simplex Virus Type 2 Is Linked to NK Cell Mobilization. J. Virol.
81: 3704-3713
[Abstract][Full Text]
Zhu, J., Koelle, D. M., Cao, J., Vazquez, J., Huang, M. L., Hladik, F., Wald, A., Corey, L.
(2007). Virus-specific CD8+ T cells accumulate near sensory nerve endings in genital skin during subclinical HSV-2 reactivation. JEM
204: 595-603
[Abstract][Full Text]
Geretti, A M
(2006). Genital herpes. Sex. Transm. Infect.
82: iv31-iv34
[Full Text]
Gorander, S., Mbwana, J., Lyamuya, E., Lagergard, T., Liljeqvist, J.-A.
(2006). Mature Glycoprotein G Presents High Performance in Diagnosing Herpes Simplex Virus Type 2 Infection in Sera of Different Tanzanian Cohorts. CVI
13: 633-639
[Abstract][Full Text]
Hosken, N., McGowan, P., Meier, A., Koelle, D. M., Sleath, P., Wagener, F., Elliott, M., Grabstein, K., Posavad, C., Corey, L.
(2006). Diversity of the CD8+ T-Cell Response to Herpes Simplex Virus Type 2 Proteins among Persons with Genital Herpes.. J. Virol.
80: 5509-5515
[Abstract][Full Text]
Koelle, D. M., Huang, J., Hensel, M. T., McClurkan, C. L.
(2006). Innate Immune Responses to Herpes Simplex Virus Type 2 Influence Skin Homing Molecule Expression by Memory CD4+ Lymphocytes. J. Virol.
80: 2863-2872
[Abstract][Full Text]
Yim, K. C., Carroll, C. J., Tuyama, A., Cheshenko, N., Carlucci, M. J., Porter, D. D., Prince, G. A., Herold, B. C.
(2005). The Cotton Rat Provides a Novel Model To Study Genital Herpes Infection and To Evaluate Preventive Strategies. J. Virol.
79: 14632-14639
[Abstract][Full Text]
Brown, Z. A., Gardella, C., Wald, A., Morrow, R. A., Corey, L.
(2005). Genital Herpes Complicating Pregnancy. Obstet Gynecol
106: 845-856
[Abstract][Full Text]
Issa, N. C., Espy, M. J., Uhl, J. R., Smith, T. F.
(2005). Sequencing and Resolution of Amplified Herpes Simplex Virus DNA with Intermediate Melting Curves as Genotype 1 or 2 by LightCycler PCR Assay. J. Clin. Microbiol.
43: 1843-1845
[Abstract][Full Text]
Ensor, D.
(2005). The Significance of Herpes Simplex for School Nurses. The Journal of School Nursing
21: 10-16
[Abstract][Full Text]
Hoshino, Y., Dalai, S. K., Wang, K., Pesnicak, L., Lau, T. Y., Knipe, D. M., Cohen, J. I., Straus, S. E.
(2005). Comparative Efficacy and Immunogenicity of Replication-Defective, Recombinant Glycoprotein, and DNA Vaccines for Herpes Simplex Virus 2 Infections in Mice and Guinea Pigs. J. Virol.
79: 410-418
[Abstract][Full Text]
Krantz, I., Lowhagen, G.-B., Ahlberg, B. M., Nilstun, T.
(2004). Ethics of screening for asymptomatic herpes virus type 2 infection. BMJ
329: 618-621
[Full Text]
Eriksson, K., Bellner, L., Gorander, S., Lowhagen, G.-B., Tunback, P., Rydberg, K., Liljeqvist, J.-A.
(2004). CD4+ T-cell responses to herpes simplex virus type 2 (HSV-2) glycoprotein G are type specific and differ in symptomatic and asymptomatic HSV-2-infected individuals. J. Gen. Virol.
85: 2139-2147
[Abstract][Full Text]
Wald, A, Ericsson, M, Krantz, E, Selke, S, Corey, L
(2004). Oral shedding of herpes simplex virus type 2. Sex. Transm. Infect.
80: 272-276
[Abstract][Full Text]
Kimberlin, D. W., Rouse, D. J.
(2004). Genital Herpes. NEJM
350: 1970-1977
[Full Text]
Garnett, G P, Dubin, G, Slaoui, M, Darcis, T
(2004). The potential epidemiological impact of a genital herpes vaccine for women. Sex. Transm. Infect.
80: 24-29
[Abstract][Full Text]
Corey, L., Wald, A., Patel, R., Sacks, S. L., Tyring, S. K., Warren, T., Douglas, J. M. Jr., Paavonen, J., Morrow, R. A., Beutner, K. R., Stratchounsky, L. S., Mertz, G., Keene, O. N., Watson, H. A., Tait, D., Vargas-Cortes, M., the Valacyclovir HSV Transmission Study Group,
(2004). Once-Daily Valacyclovir to Reduce the Risk of Transmission of Genital Herpes. NEJM
350: 11-20
[Abstract][Full Text]
Brown, Z. A.
(2004). Use of Herpes Type-specific Serology to Prevent Neonatal Herpes Simplex Virus Infection. NeoReviews
5: e16-21
[Full Text]
Gorander, S., Svennerholm, B., Liljeqvist, J.-A.
(2003). Secreted Portion of Glycoprotein G of Herpes Simplex Virus Type 2 Is a Novel Antigen for Type-Discriminating Serology. J. Clin. Microbiol.
41: 3681-3686
[Abstract][Full Text]
Melville, J, Sniffen, S, Crosby, R, Salazar, L, Whittington, W, Dithmer-Schreck, D, DiClemente, R, Wald, A
(2003). Psychosocial impact of serological diagnosis of herpes simplex virus type 2: a qualitative assessment. Sex. Transm. Infect.
79: 280-285
[Abstract][Full Text]
Posavad, C. M., Wald, A., Hosken, N., Huang, M. L., Koelle, D. M., Ashley, R. L., Corey, L.
(2003). T Cell Immunity to Herpes Simplex Viruses in Seronegative Subjects: Silent Infection or Acquired Immunity?. J. Immunol.
170: 4380-4388
[Abstract][Full Text]
Fisman, D N, Hook, E W III, Goldie, S J
(2003). Estimating the costs and benefits of screening monogamous, heterosexual couples for unrecognised infection with herpes simplex virus type 2. Sex. Transm. Infect.
79: 45-52
[Abstract][Full Text]
Reyes, M., Shaik, N. S., Graber, J. M., Nisenbaum, R., Wetherall, N. T., Fukuda, K., Reeves, W. C., for the Task Force on Herpes Simplex Virus Resista,
(2003). Acyclovir-Resistant Genital Herpes Among Persons Attending Sexually Transmitted Disease and Human Immunodeficiency Virus Clinics. Arch Intern Med
163: 76-80
[Abstract][Full Text]
Barnabas, R V, Carabin, H, Garnett, G P
(2002). The potential role of suppressive therapy for sex partners in the prevention of neonatal herpes: a health economic analysis. Sex. Transm. Infect.
78: 425-429
[Abstract][Full Text]
Sainz, B. Jr, Halford, W. P.
(2002). Alpha/Beta Interferon and Gamma Interferon Synergize To Inhibit the Replication of Herpes Simplex Virus Type 1. J. Virol.
76: 11541-11550
[Abstract][Full Text]
Schacker, T. W., Conant, M., Thoming, C., Stanczak, T., Wang, Z., Smith, M.
(2002). Imiquimod 5-Percent Cream Does Not Alter the Natural History of Recurrent Herpes Genitalis: a Phase II, Randomized, Double-Blind, Placebo-Controlled Study. Antimicrob. Agents Chemother.
46: 3243-3248
[Abstract][Full Text]
Ikoma, M., Liljeqvist, J.-A., Groen, J., Glazenburg, K. L., The, T. H., Welling-Wester, S.
(2002). Use of a Fragment of Glycoprotein G-2 Produced in the Baculovirus Expression System for Detecting Herpes Simplex Virus Type 2-Specific Antibodies. J. Clin. Microbiol.
40: 2526-2532
[Abstract][Full Text]
Garnett, G P
(2002). The geographical and temporal evolution of sexually transmitted disease epidemics. Sex. Transm. Infect.
78: i14-19
[Abstract][Full Text]
Korenromp, E L, Bakker, R, Gray, R, Wawer, M J, Serwadda, D, Habbema, J D F
(2002). The effect of HIV, behavioural change, and STD syndromic management on STD epidemiology in sub-Saharan Africa: simulations of Uganda. Sex. Transm. Infect.
78: i55-63
[Abstract][Full Text]
Ribes, J. A., Steele, A. D., Seabolt, J. P., Baker, D. J.
(2001). Six-Year Study of the Incidence of Herpes in Genital and Nongenital Cultures in a Central Kentucky Medical Center Patient Population. J. Clin. Microbiol.
39: 3321-3325
[Abstract][Full Text]
Wald, A., Langenberg, A. G. M., Link, K., Izu, A. E., Ashley, R., Warren, T., Tyring, S., Douglas, J. M. Jr, Corey, L.
(2001). Effect of Condoms on Reducing the Transmission of Herpes Simplex Virus Type 2 From Men to Women. JAMA
285: 3100-3106
[Abstract][Full Text]
Storek, J., Dawson, M. A., Storer, B., Stevens-Ayers, T., Maloney, D. G., Marr, K. A., Witherspoon, R. P., Bensinger, W., Flowers, M. E. D., Martin, P., Storb, R., Appelbaum, F. R., Boeckh, M.
(2001). Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood
97: 3380-3389
[Abstract][Full Text]
Gilson, R. J C, Mindel, A.
(2001). Recent advances: Sexually transmitted infections. BMJ
322: 1160-1164
[Full Text]
Koelle, D. M., Chen, H. B., Gavin, M. A., Wald, A., Kwok, W. W., Corey, L.
(2001). CD8 CTL from Genital Herpes Simplex Lesions: Recognition of Viral Tegument and Immediate Early Proteins and Lysis of Infected Cutaneous Cells. J. Immunol.
166: 4049-4058
[Abstract][Full Text]
Koelle, D. M., Schomogyi, M., McClurkan, C., Reymond, S. N., Chen, H. B.
(2000). CD4 T-Cell Responses to Herpes Simplex Virus Type 2 Major Capsid Protein VP5: Comparison with Responses to Tegument and Envelope Glycoproteins. J. Virol.
74: 11422-11425
[Abstract][Full Text]
Ohana, B., Lipson, M., Vered, N., Srugo, I., Ahdut, M., Morag, A.
(2000). Novel Approach for Specific Detection of Herpes Simplex Virus Type 1 and 2 Antibodies and Immunoglobulin G and M Antibodies. CVI
7: 904-908
[Abstract][Full Text]
Da Costa, X., Kramer, M. F., Zhu, J., Brockman, M. A., Knipe, D. M.
(2000). Construction, Phenotypic Analysis, and Immunogenicity of a UL5/UL29 Double Deletion Mutant of Herpes Simplex Virus 2. J. Virol.
74: 7963-7971
[Abstract][Full Text]
Goldman, B. D.
(2000). Herpes Serology for Dermatologists. Arch Dermatol
136: 1158-1161
[Abstract][Full Text]
Previous
