# Presentation: 219451

## Genital Herpes:  Epidemiology and Public Health Perspectives

**H. Hunter Handsfield, M.D.**
**Professor of Medicine**
**University of Washington**
**Director, STD Control Program**
**Public Health - Seattle & King county**

## Herpes Simplex Virus

**Mucocutaneous infection, retrograde infection along sensory nerves, latent infection in cranial nerve or dorsal spinal ganglia, mucocutaneous recurrences**
**HSV-1**
** ****Mostly orolabial (cold sores, fever blisters)**
** ****20-50% of initial genital herpes**
**HSV-2**
**  ****Almost entirely genital; oral infection rare**
**  ****>90% of recurrent genital herpes**

## Genital Herpes: Initial Visits to Physician’s Offices, 1966-2000

**Genital Herpes: Initial Visits to Physician’s Offices, 1966-2000**

**Year**

**Visits x 1,000**

**STD Surveillance 2000:  National**
**Disease and Therapeutic Index**

## Estimated Annual Incidenceof STDs in the United States

**HIV 40,000**

**Kaiser Family Foundation and American Social Health Association. 1998.**

**Total annual incidence 15 million**

**HPV 5.5 million**

**Trichomoniasis 5 million**

**Chlamydia 3 million**

**Gonorrhea 650,000**

**Hepatitis B 77,000**

**Syphilis 70,000**

**Genital herpes 1 million**

## Estimated Prevalences of Leading STDs 

**HIV****(560,000)**

**Herpes (45-60 million)**

**HPV (20 million)**

**Chlamydia (3 million)**

**Hepatitis B****(750,000)**

**Kaiser Family Foundation and American Social Health Association. 1998.**

## HSV-2 Seroprevalence in Men and Women

**HSV-2 Seroprevalence in Men and Women**
**NHANES II and III**

## Prevalence of Genital HSV Infection in Adults in the United States

**HSV-2, NHANES-II (1978)****	****16%**
**HSV-2, NHANES-III (1991)****	****22%      45 million**
**HSV-2 since 1991****	****	****	****  ****	**** 5-15 million (?)**
**Total HSV-2****	****	****	****	****        50-60 million**
**Genital HSV-1 infection****	****	****	****    10 million (??)**
**TOTAL****	****	****	****	****     25-30%****	****  ****>60 million**

## Slide 8

## Perceived Trauma of ContractingGenital Herpes 

**Acquiring AIDS**

**I’m going to read you a list of items that people may or may not consider traumatic. For each one I read, please tell me how traumatic it would be for you personally: very traumatic, somewhat traumatic, not very traumatic, or not traumatic at all.**

**Having genital herpes**

**Breaking up with a significant other**

**Getting fired from a job**

**Failing a course in school**

**Perceived Trauma of Contracting****Genital Herpes**** **

## National STD HotlineDisease-Specific Calls, 1997

- 		              _**No. Calls**_	  _**Percent**_
**Genital herpes                    63,484****	****                47**
**HPV/warts                           33,533                25**
**Chlamydia                           17,341               13**
**Gonorrhea                           11,300****	****                8**
**Syphilis                                 8,753****	****                 7**
**Total                                   134,411**

## Clinical Spectrum of Genital Herpes

**First episode infection**
**Primary infection (~20%)**
**Nonprimary first-episode infection (~40%)**
**First clinical episode of chronic infection (~40%)**
**Recurrent infection**
**Subclinical infection**
**Truly asymptomatic**
**Unrecognized**

## Recurrence Rate After Initial Genital Herpes

**Mean recurrence rate in first year after initial genital HSV-2 infection (N = 457, median FU 391 days)**
**	****	****-  Men****	****	****	****5.2 episodes/yr**
**	****	****-  Women****	****	****	****4.0 episodes/yr**
_**>**_**6 recurrences in first year****	****	****38%**
_**>**_**10 recurrences in first year****	****	****20%**
**Rate gradually declines over several years**
**Recurrence rate much lower for genital HSV-1**

## Natural History of Genital HSV-1 Infection

**83 pts (53 F, 30 M) with primary GH due to HSV-1**
**Followed **_**>**_**6 mo; median 2.7 yr**
**Recurrences in 1st year****	****	****0****	****38%**
**	****	****	****	****	****	****	****1****	****35%**
**	****	****	****	****	****	****	**_**>**_**2****	****27%**
**Days to first recurrence****	****Median 223 d; CI****95**** 170-335 d**
**Mean recurrence rate****	****	****	****Mean rate/yr (range)**
**	****	****	****	****	****	****Yr 1****	****	****1.30 (0-8)**
**	****	****	****	****	****	****Yr 2****	****	****0.70 (0-5)**
**	****	****	****	****	****	****Yr 3****	****	****0.69 (0-4)****	****	****	**

**Wald A et al, Abstract 442**
***IDSA***** 39 Oct 25-29, 2001**

## What Triggers Recurrent Outbreaks? 

**Oral HSV-1**
**Other infections (“cold sore”, “fever blister”)**
**Actinic/ultraviolet injury**
**Other local trauma (e.g., surgery)**
**Genital HSV-2**
***No clearly documented triggers***
**No good data support stress, diet, menstruation, sex, etc, despite anecdotal reports and strongly held beliefs to the contrary **

## Biomedical Complications of HSV-2 Genital Infection

**Localized neuropathic manifestations**
**Meningitis (isolated, recurrent)**
**Erythema multiforme, Stevens Johnson syndrome**
**Perinatal and maternal morbidity**
**Neonatal herpes**
**Cesarean section**
**Nongenital autoinoculation syndromes (conjunctivitis, keratitis, whitlow)**
**Chronic localized disease in immunodeficient patients (especially HIV/AIDS)**
**Enhanced HIV transmission**
**	**

## Association of HSV-2 Antibody with HIV Seroconversion in 9 Prospective Cohort and Nested Case-control Studies

**Wald A, Link K.**
***J Infect Dis***** January 2002**

##  Probability of HIV Transmission in 174 Monogamous Couples:  Rakai, Uganda

**Wawer M, Gray R, Quinn TC, et al**
**Int’l Retrovirus Meeting 2001**

## Genital Herpes and HIV Transmission

**Other things being equal, HSV-2 seropositive persons have twice the chance of acquiring HIV if sexually exposed**
**On a population basis, HSV-2 infection may be most important STD in the U.S. and worldwide in enhancing HIV transmission efficiency**
**Persons at high risk for HIV (MSM, IDU, and their sex partners) should routinely be offered HSV-2 serological testing and, if positive, counseled about the elevated HIV risk**

## Subclinical Viral Shedding in Genital Herpes

**Present 1-10% *****(PCR 5 - 30%)***** of asymptomatic days in persons with RGH due to HSV-2**
**Max frequency (5-10% of days, *****PCR 20-30%******)***** in first year, then declines; but probably 2-3% of days *****(PCR 4-6%)***** ****for many years**
_**>**_**95% of persons with HSV-2 have Asx shedding**
**Similar frequency in persons with and without Sx**
**Most episodes are symptomatic but unrecognized**
**Accounts for most transmission**
**Substantially reduced by suppressive antiviral therapy (frequency, viral titer)**
**Uncommon in genital HSV-1 infection**

## Psychosocial Impact of Genital Herpes

**Every study of psychosocial impact and every survey of patients with genital herpes has found fear of transmission to sex partners to be among the top 3 (usually no. 1 or 2) sources of concern, anxiety and stress**
**Cited by 37% to 89% of patients**

**  ****Luby & Klinge (1985)**
**  ****Silver et al (1986)**
**  ****Catotti/ASHA (1991)**
**  ****Keller et al (1991)**
**  ****Carney et al (1993)**

**  ****Mindel et al (1993)**
**  ****Carney et al (1994)**
**  ****Mindel et al (1996)**
**  ****IHMF/IHA (2000)**
**  ****IHMF/IHA (2002)**

## Online Herpes Dating Service

- MPwH [Antopia’s “dating site”] is a social resource and dating site for people with herpes and HPV.  Right now it’s May 13, 2003 and we have 36,092 registered members, and 163 are currently logged in.  _Join us now_, and end the aloneness.  Signing up is 100% free and there is no obligation.  Your privacy and confidentiality are assured.

_**Antopia.com**_

## Mean Change From Baseline Recurrent Genital Herpes Quality of Life Score

**Valacyclovir 250 mg BID**

**Valacyclovir 250 mg QD**

**Valacyclovir 1000 mg QD**

**Valacyclovir 500 mg QD**

**Acyclovir 400 mg BID**

**Mean change from baseline**

**Mean Change From Baseline Recurrent Genital Herpes Quality of Life Score**

**Treatment group**

**Patel et al. *****Sex Transm Infect.***** 1999;75:398**

**Mean Change and 95% CI**

## Transmission of Genital HerpesLangenberg AGM, et al.  NEJM 1999;341:1432-8

**Chiron vaccine studies of HSV-2 seronegative persons**
**Monogamous partners of persons with HSV-2 (N = 531)**
**STD clinic patients with bacterial STD in past year or **_**>**_**4 partners in past year (N = 1,862)**
**Follow-up:  11 visits at 2 wk to 3 mo intervals x 18 mo**
**History, genital exam, HSV serology (Western blot), viral cultures of lesions  **
**Repeated safer sex counseling**
**Outcome measures**
**Primary:  HSV-2 seroconversion**
**Secondary:  HSV-1 infection, clinical disease**
**Vaccine and placebo recipients combined**
**Acquisition rates similar in both studies, results combined**

## Transmission of Genital HerpesLangenberg AGM, et al.  NEJM 1999;341:1432-8

_**Infection Type**__**	**__**Person-Yr**_**	****     **_**Asx**_**	****   **_**Sx**_**	****	**_**Total**_
**Total HSV-2****	****    3,015****	****      3.2****	****   1.9****	****	****  5.1**
**	****Men****	****    ****	****    2,086****	****      3.0****	****   1.4****	****	****  ****4.4**
**	****Women****	****      ****	****       929****	****      3.8****	****   3.0****	****	****  ****6.8**
**	****HSV-1 pos  ****	****    1,868****	****      3.6****	****   1.4****	****	****  5.1**
**	****HSV-1 neg  ****	****    1,147****	****      2.6****	****   2.6****	****	****  5.2**
**Total HSV-1****	****    1,170****	****      0.6****	****   1.0****	****	****  1.6****	**

_**Rate per 100 Person-Yr**_

** ****155 incident HSV-2 infections:  57 (37%) Sx, 98 (63%) Asx**
** ****19 incident HSV-1 infections**

## Transmission of Genital HerpesLangenberg AGM, et al.  NEJM 1999;341:1432-8

**Clinical misdiagnosis was common (20%)**
**13% of incident symptomatic infections were atypical (e.g., urethritis, cystitis, cervicitis, meningitis)**
**15% of asx seroconverters subsequently developed clinically evident disease (likely an underestimate)**
**Half the HSV-1 infections were genital, half oral**
**Incident infection was associated with young age (**_**<**_**30 yr) in women, but not men**
**Incident infection was 2-3 times more common in nonwhites than whites**
**Prior HSV-1 ameliorated incident HSV-2 (more asx infection) but did not influence acquisition rate**
**Study design probably reduced infection rate**

## Other Factors in Genital Herpes Transmission

**Condom use**
**Avoidance of sex when symptomatic**
**Shorter duration of infection**
**Shorter duration of relationship**
**Sexual practices (vaginal, anal, orogenital; interaction with virus type)**
**Circumcision status?**
**Pregnancy?**
**Immunodeficiency and/or HIV status?**

## Protection Against HSV-2 by CondomsWald et al, JAMA 2001;3100-6

**528 monogamous HSV-2-discordant couples**
**261 HSV-2-neg men, 267 HSV-2-neg women**
**18 mo. follow-up**
**Relative transmission risk (hazard ratio) among couples with **_**>**_**25%condom use vs <25% use**
**Male to female****	****	****0.085  (CI****95**** 0.01-0.67)**
**Female to male****	****	**** ****2.02   (CI****95**** 0.32-12.5)**

## Protection Against HSV-2 by CondomsWald et al, National STD Prevention Conference, San Diego, CA, 2002: Abstract LB1

**1,852 HSV-2-seronegative heterosexual M & F**
**At risk for STD (**_**>**_**4 ptr or Hx of STD in past yr)**
**18 mo. follow-up**
**Relative HSV-2 infection risk (hazard ratio) among persons with **_**>**_**65%condom use vs <65% use**
**Men****	****	****	****	****0.58   (CI****95**** 0.37-0.92)**
**Women****	****	****  ****	****0.66   (CI****95**** 0.30-1.46)**

## Efficacy of Condoms in Preventing Genital Herpes:  Summary

**Male Condom**
**Partially effective; previous controversy notwithstanding, probably about equally effective for M    F and F    M**
**Variable acceptability**
**Probably most important in first 6-12 mo**
**Female Condom**
**Might be more effective (larger surface area covered) but no data available**
**Low acceptability**

## Abstinence During Symptoms to Prevent Sexual Transmission of HSV

**Among HSV-2-discordant couples, transmission is less frequent in aware than in unaware couples**
**Requires awareness of infection and recognition of symptoms**
**Partially effective:  Used successfully by many couples for several years**
**Studied primarily for overt recurrent herpes in ongoing partnerships**
**However, no data in serologically diagnosed persons counseled to recognize symptoms**
**Likely less effective in new relationships or when infection is recent**

## Counseling Patients with Newly Diagnosed Genital Herpes 

**Natural history of the disease**
**Potential for recurrences**
**Subclinical shedding**
**Availability and efficacy of suppressive therapy**
**Inform current and future sex partners**
**Availability of type-specific serological testing to diagnose partner and assess risk of acquisition**
**How to reduce transmission risk**
**Avoid sex when symptomatic**
**Condoms**
**Antiviral therapy?**
**Importance and avoidance of neonatal infection**

## Public Health Issues in Genital HerpesThe Six Biggies

**Preventing sexual transmission of HSV**
**Relationship of HSV-2 infection to HIV transmission and its prevention**
**Underdiagnosis of genital ulcer disease**
**Underutilization of type-specific serological testing**
**Undertreatment**
**Poor understanding of psychosocial impact**
**Preventing neonatal herpes and maternal perinatal morbidity**