Herpes

The Herpesvirus Family

Alphaherpesviruses
 Herpes simplex virus type 1 (HSV-1)
 Herpes simplex virus type 2 (HSV-2)
 Varicella-zoster virus (VZV)

Betaherpesviruses
 Cytomegalovirus (CMV)
 Human herpesvirus 6 (HHV-6)
 Human herpesvirus 7 (HHV-7)

Gammaherpesviruses
 Epstein-Barr virus (EBV)
 Human herpesvirus 8 (HHV-8)

2
 The herpesviruses are a group of related, medium- to large-sized DNA
viruses belonging to the family Herpesviridae.
 Approximately 100 herpesviruses have been identified, of which at least
8 infect humans.
 Shown in this slide is an electron micrograph of a herpesvirus.
 In the center of the virion is a double-stranded DNA containing 125,000
to
250,000 base pairs.
 This DNA is surrounded by an icosahedron-shaped protein-protective
layer, known as the capsid, approximately 125 nM in diameter.
 An amorphous layer of viral proteins, called the tegument, surrounds
the
capsid, which is further enclosed by a lipid bilayer envelope derived
from
the host cell and contains glycoprotein spikes.
Herpes Simplex Virus 1 and 2

 HSV-2
- Almost entirely genital; oral infections rare
- >95 % of recurrent genital herpes
- More frequent asymptomatic shedding than HSV-1
- Very low, if any, risk of HSV-1 acquisition
 HSV-1
- Mostly orolabial (cold sores, fever blisters)
- Increasing proportion of cases of primary genital herpes,
especially in younger sexually active patients
- Shorter initial and recurrent outbreaks than HSV-2
- Infrequent recurrences and asymptomatic shedding
- Continued risk for HSV-2 acquisition

4
Type-Specific Methods for Diagnosing
Genital Herpes

 Swab symptomatic area to detect virus

 Culture
 Polymerase Chain Reaction (PCR)

 Draw blood to look for type-specific antibodies

5
Common Manifestations of Genital Herpes

“Classic” Presentation
 Painful vesiculopustular lesions
 Genital ulcers
 Perianal and anal ulcers

Atypical Presentation
 Genital Itching
 Vulvar, scrotal or perianal fissures
 Cervicitis or proctitis
 Urethral or vaginal discharge
 Vulvar or perianal irritation
 Dysuria
 Penile or scrotal irritation
 Painless ulcers

Asymptomatic Presentation

6
Ashley RL, Wald A. Clin Microbiol Rev. 1999;12:1-8.
Commonly Misinterpreted Symptoms

 Women may misinterpret symptoms

 Men may misinterpret symptoms as1
as1  UTI
 Jock itch  Yeast infection
 Folliculitis  Hemorrhoids
 Hemorrhoids  Irritation from sex, condom use, or
 Irritation from condom use, sex, tight feminine products
clothing

• Have a high index of suspicion for GH in patients with recurrent

genitourinary complaints
7
Reference • 1. Ashley RL and Wald A. Clin Microbiol Rev. 1999;12:1-8.
 Genital Herpes Signs and Symptoms Are Attributed to Many
Other Conditions

Undiagnosed Patients Often Attribute

Their Genital Herpes Symptoms to Other Conditions
Possible Overlapping
Patient Reported Conditions Actual
Symptoms
Diagnosis
Genital
UTI Vaginitis Yeast
Herpes
Itching   
   
Burning   
Redness   
  
Discharge 
Pain with urination

Urinary frequency and

urgency

Consider a differential diagnosis of genital herpes for patients with recurrent symptoms

8 RL, Wald A. Clin Microbiol Rev. 1999;12:1-8.

Ashley
Merck Manual
 First Episode Treatment

 Acyclovir 400 mg three times a day for

7-10 days

− Valacyclovir (Valtrex) 1000 mg twice a day

for 7-10 days

− Famciclovir (Famvir) 250 mg three times a day for 7-10 days

9 Sexually Transmitted Diseases Guidelines. 2002.

CDC
 Episodic Therapy

 Acyclovir 400 mg TID for five days

−Valtrex 500 mg BID for three to five days

− Famvir 125 mg BID for five days

10
CDC Sexually Transmitted Diseases Guidelines. 2002.
 Suppressive Therapy
 Acyclovir 400 mg BID daily

 Valtrex 500 mg QD daily for people with 9 or fewer outbreaks per

year

 Valtrex 500 mg BID or 1000 QD for people with 10 or more

outbreaks per year

 Famvir 250 mg BID

11
CDC Sexually Transmitted Diseases Guidelines. 2002.
 Long Term Suppression – Safety Issues

 Safety data available for up to 20 years of constant use (JID, Oct, 2002,
Tyring)

 No safety labs need to be drawn (such as LFT, kidney functions)

 Drug holidays not needed

12
 HSV Resistance is Rare

 Isolation of resistant isolates is <<1% in immunocompetent patients

 Only a few documented cases of clinical resistance

 No detectable increase in resistance since introduction in 1981

 No documented cases of transmission of resistant virus

 Most resistant strains are deficient in viral thymidine kinase (TK-):

these are less virulent than wild-type virus in animal models)

 Recent published model of antiviral resistance predicts that after 25 years of

high antiviral use, only 5 of 10,000 immunocompetent patients will be shedding
drug-resistant virus

Kost RG et al. NEJM. 1993;329:1777-1782. Collins P, Ellis MN. J Med Virol. 1993;1(suppl 1):58-66.
13 F et al. Dermatology. 1995;190:177.
Mouly Corey L, Wald A. In: Sexually Transmitted Diseases. 1999:285-312.
Bacon T et al. Clin Microbiol Rev. 2003;16:114-128 Gershengorn HB et al. BMC Inf Dis .2003;3:1
 HSV-2 Transmission Study Design

Couples (N=1484)

Source Partner Susceptible Partner

HSV-2 HSV-2
Seropositive Seronegative

 Immunocompetent, heterosexual partners, age ≥18, in a stable monogamous

relationship
 Source partner suitable for suppressive therapy, history of 9 or fewer
episodes/year
 Source partners randomized to valacyclovir 500 mg once daily or placebo for 8
months
 Susceptible partner monitored for acquisition of HSV

14
Corey L et al. NEJM. 2004;350:11-20.