An update on Genital Herpes

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An update on Genital Herpes

• Kevin Ault, MD
• Department of Obstetrics and Gynecology
• University of Iowa

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An update on Genital Herpes
Source ASHA 98
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Why an update?

• New epidemiology data
• New serological testing
• New drugs
• New ACOG practice bulletin

• New prospects for a vaccine
• New research trial here
• New interest from the CDC/NIH

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Trauma of ContractingGenital Herpes
Im 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?
AIDS infected
Having genital herpes
Breaking up with a significant other
Getting fired from your job
Saying Very Traumatic.
Failing a course in school
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Update on Genital Herpes

• Biology, epidemiology and transmission
• Diagnosis
• Use of serological tests
• Treatment
• Pregnancy and HSV
• The future.

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Biology of Herpesvirsus

• Herpesvirus family HSV 1 2, EBV, CMV, VZV
  and HHV 6-8
• Periods of latency and reactivation
• Older serological tests not really useful but
  newer tests differentiate between HSV - 1, HSV
  2 and other herpesvirus

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Genital herpes simplex virus infections - Initial
visits to physicians' offices United States,
1966-1998
SOURCE National Disease and Therapeutic Index
and the CDC 98.
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National Health and Nutritional Examination
Survey or NHANES
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Genital herpes HSV-2 - seroprevalence according
to age in NHANES II (1976-1980) and NHANES III
(1988-1994)
Note Bars indicate 95 confidence intervals.
Source Fleming et al 97 and CDC 98.
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HSV 2 and The tip of the iceberg
Recognized infection
9.2
90.8 Unrecognized and asymptomatic infection
Iceberg represents all those withHSV-2 antibody
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Trends in HSV-2 Seroprevalence1978-1991
Relative Increase in Women 32
Relative Increase in Men 27
Age-adjustedHSV-2 sero-prevalence()
Age-adjustedHSV-2 sero-prevalence()
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Transmission of HSV

• Approximately 15 of genital HSV is HSV 1
• Transmission in discordant couples 10 - 20
• Daily culture positive shedding 14

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Diagnosis of genital herpes

• Leading cause of genital ulcer disease in the
  USA
• Differential diagnosis would include syphilis
  and chancroid
• Usually multiple vesicular lesions 3 mm and
  painful

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Diagnosis of genital herpes (continued)

• First clinical episode is associated with
  systematic symptoms myalgia, headache,
  inguinal adenopathy and urinary retention
• Natural history of recurrence is highly variable
• Viral culture is the gold standard but beware
  of the false negative

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Primary HSV
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Primary HSV
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Recurrent HSV
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Diagnosis of genital herpes serological testing

• Several new serological tests will reliably
  distinguish an antibody response to members of
  the Herpesvirus family
• Antibodies will become positive several weeks
  after a initial outbreak
• Clinical guidelines for use are currently
  lacking

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Diagnosis the case of the discordant couple

• Jim and Beth are senior medical students. They
  have been dating for four years. Both have three
  lifetime partners. Neither has a history of
  STDs or HSV. Upon returning from their
  honeymoon, Jim has painful ulcers on his penis.

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Diagnosis the case of the discordant couple
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Treatment of genital HSV

• Three drugs now available and are
  therapeutically equivalent
• All drugs are purine analogues
• Acyclovir was the first drug and is now generic,
  however suffers from poor
• bioavailability
• All three drugs work via viral thymidine kinase
  and viral DNA polymerase

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Valacyclovir is a prodrug of acyclovir
0
0
N
N
NH
NH
NH2
N
NH2
N
N
N
HO
O
Acyclovir
0
0
0
0H
NH2
Valacyclovir
0
NH2
Perry 96
L-Valine
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1998 CDC recommendations for the treatment of the
first outbreak of genital HSV

• Valacyclovir 1000 mg po BID
• Acyclovir 200 mg five times a day
• Acyclovir 400 mg TID
• Famciclovir 250 mg po TID

Treatment for 7-14 days
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1998 CDC recommendations for the treatment of
recurrent genital HSV

• Valacyclovir 500 mg po BID
• Acyclovir 200 mg five times a day
• Acyclovir 400 mg TID
• Famciclovir 125 mg BID

Duration of therapy 5 days
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1998 CDC recommendations for the suppression of
recurrent genital HSV

• Valacyclovir 500 mg po once a day
• Valacyclovir 1000 mg po once a day
• Acyclovir 400 mg po BID
• Famciclovir 250 mg po BID

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Suppression of recurrent genital HSV

• Based on frequency and severity of outbreaks
• Suppression is associated with decreased viral
  shedding
• Suppression is associated with improved quality
  of life

Baker 99 and Patel et al 99
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Pregnancy and HSV

• Approximately 2,000 infected newborns annually
  and incidence is increasing
• Virus is passed intrapartum from mother to
  newborn
• Localized, neurological or disseminated
  infection in the newborn
• Most infected newborns born to women without a
  history of HSV

ACOG Practice Bulletin 6, October 99
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Pregnancy and HSV (continued)

• Cesarean delivery is indicated in women with
  active genital lesions or symptoms of vulvar
  pain or burning
• Cesarean delivery is not warranted in women
  with a history of HSV infection but no active
  genital disease during labor
• Summary no lesions no C/S

ACOG Bulletin99 and Roberts et al 95
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Pregnancy and HSV (continued)

• No known adverse affects of acyclovir during
  pregnancy
• Recommended for women with primary outbreaks
  during pregnancy
• One randomized trial has shown a decrease in C/S
  in women treated with acyclovir
• Unknown effect on transmission

Scott et al 96, CDC 98
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Primary vs. recurrent infection during pregnancy
and the risk of transmission to the newborn
n 15,923 Brown et al 91, n 7,046 Brown et al
97
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Primary vs. recurrent infection during pregnancy
and the risk of transmission to the newborn

• Risk of transmission from primary disease 33
  to 50
• Risk from recurrent disease 0 to 3

Brown et al 91, 97
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Pregnancy and HSV transmission possible use of
serological testing

• Most cases are in asymptomatic women
• Risk is associated with recent infection /
  primary disease whether women has symptoms or
  not
• Should women be screened with serological
  testing?

Brown et al 98
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Pregnancy and HSV transmission (continued)

• If seronegative, then test partner and counsel
  to avoid potential transmission
• Problem 1 partners will not have a history
• Problem 2 Pandoras Box
• Problem 3 the temptation of C/S

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Vaccines for HSV - 2

• Previous vaccines have not worked
• New formulation glycoprotein gD2 with a novel
  adjuvant
• Effective in HSV 1 - / 2 women 73-74
• Not effective in women who where
• HSV 1 / 2 or males

Spruance at ASM / ICAAC 00
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Immunomodulation for HSV - 2

• R-848 is a daughter molecule of imiquimod aka
  resiquimod
• Forty seven patients with 6 or greater
  recurrences enrolled in phase II trial
• Mean time to recurrence 169 days vs. 57 days
  for placebo (p lt 0.01)
• A phase III trial is planned at the University
  of Iowa beginning 2 - 2001

Spruance et al at ASM / ICAAC 00
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Conclusions - An update on genital herpes

• Genital infections with HSV are increasing
• 90 of such infections have no symptoms
• A variety of well studied treatments are
  available

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Conclusions - An update on genital herpes

• No lesions no C/S
• Treatment of genital herpes during pregnancy
  with acyclovir may be beneficial in some cases
• Role of serological tests is unclear
• The future vaccines and immunomodulators