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HSV Curriculum
Genital and Perirectal Herpes
Simplex Virus Infection
Herpes Simplex Virus (HSV) Type 2
1
HSV Curriculum
Learning Objectives
1.
2.
3.
4.
Describe the epidemiology of genital HSV in the U.S.
Describe the pathogenesis of genital HSV.
Discuss the clinical manifestations of genital HSV.
Identify the common methods used in the diagnosis of
genital HSV.
5. Describe patient management for genital HSV.
6. Describe public health measures for the prevention of
genital HSV.
7. Summarize appropriate prevention counseling
messages for genital HSV.
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Lessons
I.
II.
III.
IV.
V.
VI.
Epidemiology: Disease in the U.S.
Pathogenesis
Clinical manifestations
Diagnosis
Patient management
Prevention
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HSV Curriculum
History of Herpes Simplex
• Hippocrates first wrote about the herpes
virus in 500 BC
• Shakespeare wrote about herpes in
Romeo and Juliet in 1598
– In Mercutio's speech about Queen Mab, he
wrote, "O'er ladies lips, who straight on
kisses dream, which oft of the angry Mab
with blisters plagues..."
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History of Herpes Simplex
• In the 1920s the first research was carried out
on the herpes virus.
• In 1964, Epstein-Barr virus (EBV) or Herpes
Simplex-4 was first isolated by Michael
Epstein and Yvonne Barr.
– EBV often causes asymptomatic infections; it is
also the leading cause of infectious
mononucleosis, a syndrome which can also be
caused by other herpesviruses such as
cytomegalovirus (CMV).
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HSV Curriculum
History of Herpes Simplex
• In 1988, Acyclovir, a nucleoside
analogue that is an extremely
effective
antiviral drug,
was developed by pharmacologist
Gertrube Elion, who
won the
Nobel Prize in Medicine.
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Lesson I: Epidemiology:
Disease in the U.S.
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Introduction
• Herpes Viruses are a leading cause of human
viral diseases, second only to influenza and
cold viruses.
• Name Herpes comes from the Latin herpes
which, in turn, comes from the Greek word
herpein which means to creep.
HSV Curriculum
Epidemiology
Background and Burden of Disease
• Genital herpes is a chronic, lifelong viral
infection
• Two HSV serotypes – HSV-1 & HSV-2
• HSV-2 causes most cases of recurrent
genital herpes in the U.S.
• Approximately 776,000 new cases
occur each year
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Epidemiology
Background and Burden of Disease
(continued)
• In the U.S., 16.2% of adults aged 14–49
years have HSV-2 antibodies
• HSV-2 antibodies are not routinely
detected until puberty
• HSV-2 seroprevalence is higher in
women than men in all age groups and
varies by race/ethnicity
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Epidemiology
Age-Adjusted Herpes Simplex Virus Type 2
Seroprevalence According to the Lifetime Number of
Sex Partners, by Race/Ethnicity and Sex on
NHANES in 1999-2004
Source: Xu F et al. JAMA, 2006; 296(8):964-973.
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Genital Herpes — Initial Visits to Physicians’
Offices, United States, 1966 – 2012
NOTE: The relative standard errors for genital herpes estimates of more than 100,000 range
from 18% to 30%. See Other Surveillance Data Sources in the Appendix and Table 45.
SOURCE: IMS Health, Integrated Promotional Services™. IMS Health Report, 1966 – 2012.
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Herpes Virus and Common Diseases
•
•
•
•
•
•
•
Everybody knows chickenpox and likely you experienced the disease
as a child, can be dangerous when exposed to it in adulthood
Another common ailment is lip and mouth “cold sores”
Genital Herpes lesions caused by HSV, sexually transmitted
HSV-1 cold sores (mild but annoying diseases)
HSV-2 genital herpes
Varicella zoster: chickenpox
However the Herpes family is huge, over 100 members
HSV-1 Cold sore
HSV-2 Genital Herpes
HSV Curriculum
Epidemiology
• HSV is spread by contact, as the virus is shed in saliva, tears,
genital and other secretions.
• By far the most common form of infection results from a kiss given
to a child or adult from a person shedding the virus.
• Primary infection is usually trivial or subclinical in most
individuals.
– HSV 1 is a disease mainly of very young children ie. those below 5 years.
• There are 2 peaks of incidence, the first at 0 - 5 years and the
second in the late teens, when sexual activity commences.
• About 10% of the population acquires HSV infection through the
genital route and the risk is concentrated in young adulthood.
HSV Curriculum
Epidemiology
• Generally HSV-1 causes infection above the belt and
HSV-2 below the belt.
– In fact, 40% of clinical isolates from genital sores are HSV-1, and
5% of strains isolated from the facial area are HSV-2.
– This data is complicated by oral sexual practices.
• Following primary infection, 45% of orally infected
individuals and 60% of patients with genital herpes will
experience recurrences.
• The actual frequency of recurrences varies widely between
individuals.
– The mean number of episodes per year is about 1.6.
HSV Curriculum
Epidemiology
Transmission
•
HSV-2 is transmitted sexually and perinatally
•
Most genital herpes infections are transmitted
by persons who are
– unaware they are infected with HSV-2 or
– asymptomatic when transmission occurs
•
Efficiency of sexual transmission is greater
from men to women than from women to men
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Epidemiology
Transmission (continued)
•
Likelihood of transmission declines with
increased duration of infection
•
Incubation period after acquisition is 2–12
days (average is 4 days)
•
Drying and soap and water readily
inactivate HSV; fomite transmission unlikely
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HSV Curriculum
Epidemiology
HSV-2 and HIV Infection
•
HSV-2 infection increases the risk of
acquiring HIV infection at least 2-fold
•
HSV-2 infection is also likely to facilitate
transmission of HIV infection from
persons co-infected with both viruses
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Lesson II: Pathogenesis
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Pathogenesis
Virology
• HSV-1 and HSV-2 are members of the
human herpes viruses (herpetoviridae)
• All members of this species establish
latent infection in specific target cells
• Infection persists despite the host’s
immune response, often with recurrent
disease
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HSV Establishes Latent
Infections
• Once infection has taken place HSV can remain dormant for
months, years, lifetime
• Cell types that HSV can infect
– Neurons, B-cells and T-cells
• Examples:
– Shingles which can appear years after first chickepox
infection (varicella zoster, causes both chickenpox and
shingles)
– Genital Herpes outbreaks
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Herpesviridae
The Herpesviridae family comprises large, DNA-containing
enveloped viruses
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Herpesviridae
glycoprotein B (gpB) spikes
visible in membrane
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Herpesviridae
After the primary infection, herpes viruses establish latency
in the infected host
Once a patient has become infected by herpes virus, the
infection remains for life
Intermittently, the latent genome can become activated, in
response to various stimuli, to produce infectious virions
HSV Curriculum
Herpesviridae- Classification
Herpes viruses are classified into three groups based upon of
tissue tropism, pathogenicity and behavior
a herpesviruses
•Fast replicating
•Variable host range
•Typically destroys host cell (lysis)
•Latency established in sensory ganglia
Herpes Simplex virus-1 and 2 (HSV-1/HSV-2)
Varicella-Zoster virus (VZV)
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Herpesviridae- Classification
b herpesviruses
•Slowly replicating
•Restricted host range
•Infected cells enlarge (cytomegalia)
•Latency established in secretory glands, lymphoreticular
cells, kidneys
Cytomegalovirus (CMV)
Human Herpesvirus-6 and 7 (HHV-6/HHV-7)
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Herpesviridae- Classification
g herpesviruses
•Replicate poorly
•Highly restricted host range
•Latency established in lymphoid tissue
(T-cell or B-cell specific)
Epstein-Barr Virus (EBV), a B-cell transforming virus
Human Herpesvirus-8 (HHV-8, KSHV)
HSV Curriculum
Herpesviridae- Replication
PENETRATION
The nucleocapsid enters the cell by direct membrane fusion
with the cell plasma membrane
Capsids are transported to the nucleus
DNA passes into the nucleus, probably via nuclear pores
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Herpesviridae- Replication
Adsorption
and
Penetration
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Herpes Simplex Virus (HSV)
The initial step of the interaction of virus with the cell is binding
to heparan sulfate, which is found on many cell types
Thus, almost any human cell type can be infected by HSV
In many cells, such as endothelial cells and fibroblasts,
infection is lytic
Neurons normally support a latent infection
If early and late proteins are made, the cell is set on a route
to lysis
HSV Curriculum
Herpes Simplex Virus (HSV)
HSV-1 and HSV-2 first infect cells of the mucoepithelia, or
enter through wounds
The site of the initial infection depends on the way in which the
patient acquires the virus
•HSV-1 above the waist
•HSV-2 below the waist
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HSV- Pathology
The virus replicates in the epithelial tissue yielding a
characteristic “fever blister” or “cold sore”
The fluid in this blister is full of infectious virus
The blister ulcerates and forms a crusted lesion that heals
without a scar
HSV Curriculum
HSV- Pathology
The virus replicates in the epithelial tissue yielding a
characteristic “fever blister” or “cold sore”
The fluid in this blister is full of infectious virus
The blister ulcerates and forms a crusted lesion that heals
without a scar
HSV Curriculum
HSV- Latency
HSV also infects neurons that innervate the epithelial tissue
The virus travels along the neuron (retrograde transport)
•oral mucosa
-> trigeminal ganglia
•genital mucosa -> sacral ganglia
A latent infection is established in the nervous tissue
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HSV- Reactivation
Several agents may trigger recurrence
•stress
•exposure to strong sunlight
•fever
The virus can travels back down the nerve axon and arrives
at the mucosa that was initially infected
Vesicles containing infectious virus are formed on the
muscosa and the virus spreads
Recurrent infections are usually less pronounced than the
primary infection and resolve more rapidly
HSV Curriculum
HSV Infections
Oral Herpes
Both HSV-1 and HSV-2
Genital Herpes
Primarily HSV-2 (10% cases HSV-1)
Involve a transient viremia (fever, myalgia, glandular
inflammation in the groin area)
Secondary infections are frequently less severe
Herpes Keratitis
An infection of the eye
Primarily HSV-1
Sometimes recurrent
Leading cause of corneal blindness in the US
HSV Curriculum
HSV Infections
Herpes gladiatorum
Contracted by wrestlers
Spreads by direct contact from skin lesions
Usually appears in the head and neck region
Also seen in other contact sports such as rugby
(Herpes Rugbeiorum, or scrum pox)
HSV Encephalitis
Typically HSV-1
Most common cause of sporoadic viral encephalitis
Relatively rare (1000 cases/yr)
HSV Curriculum
Pathogenesis
• During the primary infection, HSV spreads locally and a shortlived viraemia occurs, whereby the virus is disseminated in the
body.
– Spread to the craniospinal ganglia.
• The virus then establishes latency in the craniospinal ganglia.
• The exact mechanism of latency is not known, it may be true
latency where there is no viral replication or viral persistence
where there is a low level of viral replication.
• Reactivation - It is well known that many triggers can provoke a
recurrence.
– These include physical or psychological stress, infection; especially
pneumococcal and meningococcal, fever, irradiation; including sunlight,
and menstruation.
HSV Curriculum
Pathogenesis
Pathology
• The re-activated virus may cause a cutaneous
outbreak of herpetic lesions or subclinical viral
shedding
• Up to 90% of persons seropositive for HSV-2
antibody have not been diagnosed with genital
herpes
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Lesson III: Clinical
Manifestations
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Clinical Manifestations
HSV is involved in a variety of clinical manifestations
which includes :
1. Acute gingivostomatitis
2. Herpes Labialis (cold sore)
3. Ocular Herpes
4. Herpes Genitalis
5. Other forms of cutaneous herpes
7. Meningitis
8. Encephalitis
9. Neonatal herpes
HSV Curriculum
Oral-facial Herpes
• Acute Gingivostomatitis
– Acute gingivostomatitis is the most common manifestation of primary herpetic
infection.
– The patient experiences pain and bleeding of the gums. 1 - 8 mm ulcers are
present. Neck glands are commonly enlarged accompanied by fever.
– Usually a self limiting disease which lasts around 13 days.
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Gingivostomatitis
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Gingivostomatitis
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Oral-facial Herpes
• Herpes labialis (cold sore)
– Following primary infection, 45% of orally infected individuals will
experience reactivation. The actual frequency of recurrences varies widely
between individuals.
– Herpes labialis (cold sore) is a recurrence of oral HSV.
– A prodrome of tingling, warmth or itching at the site usually heralds the
recurrence. About 12 hours later, redness appears followed by papules and
then vesicles.
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HSV-1 acute
herpetic
gingivostomatitis
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Herpes Simplex Type I
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Ocular Herpes
HSV causes a broad spectrum of ocular disease, ranging
from mild superficial lesions involving the external eye, to
severe sight-threatening diseases of the inner eye. Diseases
caused include the following:– Primary HSV keratitis – dendritic ulcers
– Recurrent HSV keratitis
– HSV conjunctivitis
– Iridocyclitis, chorioretinitis and cataract
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HSV-1 Ocular
HSV-1 Facial
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HSV Whitlow
HSV-1 Ear
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Herpes Simplex Encephalitis
• Herpes Simplex encephalitis is one of the most serious complications
of herpes simplex disease. There are two forms:
• Neonatal – there is global involvement and the brain is almost
liquefied. The mortality rate approaches 100%.
• Focal disease – the temporal lobe is most commonly affected. This
form of the disease appears in children and adults. It is possible that
many of these cases arise from reactivation of virus. The mortality rate
is high (70%) without treatment.
• It is of utmost importance to make a diagnosis of HSE early. It is
general practice that IV acyclovir is given in all cases of suspected
HSE before laboratory results are available.
HSV Curriculum
Neonatal Herpes Simplex (1)
• Incidence of neonatal HSV infection varies inexplicably from country
to country e.g. from 1 in 4,000 live births in the U.S. to 1 in 10,000
live births in the UK
• The baby is usually infected perinatally during passage through the
birth canal.
• Premature rupturing of the membranes is a well recognized risk factor.
• The risk of perinatal transmission is greatest when there is a florid
primary infection in the mother.
• There is an appreciably smaller risk from recurrent lesions in the
mother, probably because of the lower viral load and the presence of
specific antibody
• The baby may also be infected from other sources such as oral lesions
from the mother or a herpetic whitlow in a nurse.
HSV Curriculum
Neonatal Herpes
Courtesy of Dr. Félix Omeñaca Terés, Hospital Materno Infantil La Paz, Madrid, Spain
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Neonatal Herpes Simplex (2)
• The spectrum of neonatal HSV infection varies from a mild disease
localized to the skin to a fatal disseminated infection.
• Infection is particularly dangerous in premature infants.
• Where dissemination occurs, the organs most commonly involved are
the liver, adrenals and the brain.
• Where the brain is involved, the prognosis is particularly severe. The
encephalitis is global and of such severity that the brain may be
liquefied.
• A large proportion of survivors of neonatal HSV infection have
residual disabilities.
• Acyclovir should be promptly given in all suspected cases of neonatal
HSV infection.
• The only means of prevention is to offer caesarean section to mothers
with florid genital HSV lesions.
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Neonatal Herpes Simplex 2
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• Transmission:
– Genital herpes: penile-vaginal, oral-genital, oral-anal, or
genital-anal contact
– Oral herpes: through kissing, or oral-genital contact
– Herpes sores are highly contagious--need to avoid contact
between lesions and someone else’s body
– Can still transmit herpes even if no lesions are present
HSV Curriculum
Genital Herpes
• Genital lesions may be primary, recurrent or initial.
• Many sites can be involved which includes the penis, vagina, cervix,
anus, vulva, bladder, the sacral nerve routes, the spinal nerves and the
meninges.
– The lesions of genital herpes are particularly prone to secondary bacterial infection
eg. S.aureus, Streptococcus, Trichomonas and Candida Albicans.
• Dysuria is a common complaint, in severe cases, there may be urinary
retention.
• Local sensory nerves may be involved leading to the development of a
radiculitis.
– A mild meningitis may be present.
• 60% of patients with genital herpes will experience recurrences.
– Recurrent lesions in the perianal area tend to be more numerous and persists longer
than their oral HSV-1 counterparts.
HSV Curriculum
Clinical Manifestations
Definitions of Infection Types
First Clinical Episode
• Primary infection
– First infection ever with either HSV-1 or HSV-2
– No antibody present when symptoms appear
– Disease is more severe than recurrent disease
• Non-primary infection
– Newly acquired HSV-1 or HSV-2 infection in an
individual previously seropositive to the other virus
– Symptoms usually milder than primary infection
– Antibody to new infection may take several weeks
to a few months to appear
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Clinical Manifestations
Definitions of Infection Types
Recurrent symptomatic infection
• Antibody present when symptoms
appear
• Disease usually mild and short in
duration
Asymptomatic infection
• Serum antibody is present
• No known history of clinical outbreaks
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Clinical Manifestations
First Episode Primary
Infection without Treatment
• Characterized by multiple lesions that are more severe, last
longer, and have higher titers of virus than recurrent
infections
• Typical lesion progression:
– papules  vesicles  pustules  ulcers  crusts  healed
• Often associated with systemic symptoms including fever,
headache, malaise, and myalgia
• Illness lasts 2–4 weeks
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Clinical Manifestations
First Episode Primary Infection
without Treatment (continued)
• Numerous, bilateral painful genital lesions; last an average
of 11–12 days
• Local symptoms include pain, itching, dysuria, vaginal or
urethral discharge, and tender inguinal adenopathy
• Median duration of viral shedding detected by culture (from
the onset of lesions to the last positive culture) is ~12 days
• HSV cervicitis occurs in most primary HSV-2 (70-90%) and
primary HSV-1 (~70%) infections
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• Recurrence:
– After lesions heal, virus retreats up nerve fibers and stays
dormant in nerve cells in the spinal column
– Flare-ups occur when virus moves back down along fibers to
genitals or lips
– Triggered by wide variety of factors, such as: stress, anxiety,
depression, acidic food, UV light, fever, poor nutrition, fatigue
– Symptoms during recurrent attacks tend to be milder than
primary episode, heal more quickly
• Prodromal symptoms: symptoms that warn of
an impending herpes outbreak
• Burning, throbbing, or tingling at sites of infection
• Sometimes includes pain in legs, thighs, groin, or buttocks
• Viral shedding is more common during prodromal symptoms than
beforehand--best to avoid contact w/infected area from first sign of
prodromal symptoms until sores have healed
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Clinical Manifestations
Recurrent Infection Without
Treatment
• Prodromal symptoms are common (localized
tingling, irritation) - begin 12–24 hours before
lesions
• Illness lasts 4–6 days
• Symptoms tend to be less severe than in primary
infection
• Usually no systemic symptoms
• HSV-2 primary infection more prone to recur than
HSV-1
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Clinical Manifestations
Genital Herpes: Primary Lesions
Source: Cincinnati STD/HIV Prevention Training Center
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Herpes Viruses
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Clinical Manifestations
Genital Herpes: Multiple Ulcers
Source: Cincinnati STD/HIV Prevention Training Center
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Clinical Manifestations
Genital Herpes: Recurrent Ulcer
Source: Cincinnati STD/HIV Prevention Training Center
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Clinical Manifestations
Genital Herpes: Periurethal Lesions
Source: Cincinnati STD/HIV Prevention Training Center
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Clinical Manifestations
Genital Herpes: Cervicitis
Source: Cincinnati STD/HIV Prevention Training Center
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Clinical Manifestations
Herpes on the Buttock
Source: Cincinnati STD/HIV Prevention Training Center
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Clinical Manifestations
Oral Herpes: Soft Palate
Source: Cincinnati STD/HIV Prevention Training Center
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Clinical Manifestations
Asymptomatic Viral Shedding
• Most HSV-2 is transmitted during asymptomatic
shedding
• Rates of asymptomatic shedding are greater in
HSV-2 than HSV-1
• Rates of asymptomatic shedding are highest in
new infections (<2 years) and gradually
decrease over time
• Asymptomatic shedding episodes are of shorter
duration than shedding during clinical
recurrences
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Clinical Manifestations
Asymptomatic Viral Shedding
(continued)
• Most common sites of asymptomatic
shedding are vulva and perianal areas
in women and penile skin and perianal
area in men
• Antiviral suppressive therapy
dramatically reduces, but does not
completely eliminate shedding
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Genital Herpes
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Herpes Simplex in Women with
AIDS
79
Credit: Jean R. Anderson, MD
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Clinical Manifestations
Complications of Genital Infection
• Aseptic meningitis
– More common in primary than recurrent
infection
– Generally no neurological sequelae
• Rare complications include:
– Stomatitis and pharyngitis
– Radicular pain, sacral parathesias
– Transverse myelitis
– Autonomic dysfunction
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• Other complications:
• Women:
– Increased incidence of cervical cancer--women with
herpes should get Pap smears every 6-12 months
– Newborn baby can be infected by passage through birth
canal--can cause severe damage or death
• C-section recommended for women w/active symptomatic
disease
• Both sexes:
– Ocular herpes infection can occur if virus is transferred
from a sore to the eye
• Must be treated quickly to avoid eye damage
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Lesson IV: HSV Diagnosis
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Diagnosis
HSV Diagnosis
• Clinical diagnosis is insensitive and
nonspecific
• Clinical diagnosis should be confirmed
by laboratory testing:
– Virologic tests
– Type-specific serologic tests
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Diagnosis
Virologic Tests
•
Viral culture (gold standard)
–
–
–
–
–
•
Preferred test if genital ulcers or other mucocutaneous lesions are
present
Highly specific (>99%)
Sensitivity depends on stage of lesion; declines rapidly as lesions
begin to heal
Positive more often in primary infection (80%–90%) than with
recurrences (30%)
Cultures should be typed
Polymerase Chain Reaction (PCR)
–
–
–
More sensitive than viral culture; has been increasingly used
instead of culture in many settings
May be a reasonable choice for diagnosing genital lesions; the
assays are FDA-cleared for use with anogenital specimens and
commercially available
84
Preferred test for detecting HSV in spinal fluid
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Diagnosis
Virologic Tests
(continued)
• Antigen detection (DFA or EIA)
– Moderately sensitive (>85%) in symptomatic
shedders
– Rapid (2–12 hours)
– May be better than culture for detecting HSV in
healing lesions
• Cytology (Tzanck or Pap)
– Insensitive and nonspecific and should not be
relied on for HSV diagnosis
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Diagnosis
Type-specific Serologic Tests
• Type-specific and nonspecific antibodies to
HSV develop during the first several weeks to
few months following infection and persist
indefinitely
• Presence of HSV-2 antibody indicates
anogenital infection
• Presence of HSV-1 does not distinguish
anogenital from orolabial infection
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Diagnosis
Uses of Type-specific
Serologic Tests
• Type-specific serologic assays might be
useful in the following scenarios:
– Recurrent or atypical genital symptoms with
negative HSV cultures
– A clinical diagnosis of genital herpes without
laboratory confirmation
– A sex partner with herpes
– As part of a comprehensive evaluation for STDs
among persons with multiple sex partners, HIV
infection, and among MSM at increased risk for
HIV acquisition
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Diagnosis
Evaluation of Genital, Anal or
Perianal Ulcer
• All patients with genital, anal or perianal
ulcers should be evaluated with a
serologic test for syphilis and a
diagnostic evaluation for genital herpes
• In settings where chancroid is prevalent,
a test for Haemophilus ducreyi should
also be performed
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Lesson V: Patient
Management
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Management
Principles of Management of
Genital Herpes
• Counseling should include natural history,
sexual and perinatal transmission, and
methods to reduce transmission
• Antiviral chemotherapy
– Partially controls symptoms of herpes
– Does not eradicate latent virus
– Does not affect risk, frequency or severity of
recurrences after drug is discontinued
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• Treatment:
• Reduce frequency of outbreaks
• Treat symptoms of outbreaks and speed healing
• Two types of therapies
– Suppressive therapy: medication taken daily to prevent
recurrent outbreaks; also reduces asymptomatic viral
shedding between outbreaks
– Episodic treatment: medication taken to treat outbreaks
when they occur
• Antiviral drugs-- reduce viral shedding and the
duration and severity of outbreaks
– Acyclovir (trade name Zovirax)
– Valacyclovir (trade name Valtrex)
– Famiclovir (trade name Famvir)
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Management
Antiviral Medications
• Systemic antiviral chemotherapy
includes 3 oral medications:
– Acyclovir
– Valacyclovir
– Famciclovir
• Topical antiviral treatment is not
recommended
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Management
Management of First Clinical
Episode of Genital Herpes
• Manifestations of first clinical episode may
become severe or prolonged
• Antiviral therapy should be used
– Dramatic effect, especially if symptoms <7
days and primary infection (no prior HSV-1)
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Management
CDC-Recommended Regimens
for First Clinical Episode
• Acyclovir 400 mg orally 3 times a day for 7–10 days,
or
• Acyclovir 200 mg orally 5 times a day for 7–10 days,
or
• Famciclovir 250 mg orally 3 times a day for 7–10
days,
or
• Valacyclovir 1 g orally twice a day for 7–10 days
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TREATMENT
Drug
Mode of Action
Administered
Form
Acyclovir
Disrupts the virusí ability to
reproduce. (replicate)
Capsules or Tablets.
Cream for use in oral
herpes Primary--> for 10
days
Recurrent-> for 5 days
Valacyclovir
Disrupts the virusí ability to
Capsules or Tablets
Primary--> w/in 48 hours
--> for 10 days
Recurrent -> w/in 24 hours
-> for 5 days
Famciclovir
Disrupts the virusí ability to
reproduce. (replicate
reproduce. (replicate
Capsules or Tablets.
Cream for use in oral herpes
Primary --> w/in 6 hours
--> for 5 days
HSV Curriculum
Management
Recurrent Episodes of
Genital Herpes
• Most patients with symptomatic, firstepisode genital HSV-2 experience
recurrent outbreaks
• Episodic and suppressive treatment
regimens are available
• Treatment options should be discussed
with ALL patients
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Management
Suppressive Therapy for
Recurrent Genital Herpes
• Reduces frequency of recurrences
– By 70%-80% in patients with > 6 recurrences per year
– Also effective in those with less frequent recurrences
• Reduces but does not eliminate subclinical viral
shedding
• Periodically (e.g., once a year), reassess need
for continued suppressive therapy
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HSV Curriculum
Management
CDC-Recommended Regimens
for Suppressive Therapy
•
•
•
•
Acyclovir 400 mg orally twice a day, or
Famciclovir 250 mg orally twice a day, or
Valacyclovir 500 mg orally once a day, or
Valacyclovir 1 g orally once a day
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HSV Curriculum
Management
Episodic Treatment for
Recurrent Genital Herpes
• Ameliorates or shortens duration of
lesions
• Requires initiation of therapy within 1
day of lesion onset
• Provide patient with a supply of drug or
a prescription and instructions to selfinitiate treatment immediately when
symptoms begin
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HSV Curriculum
Management
CDC-Recommended Regimens
for Episodic Therapy
• Acyclovir 400 mg orally 3 times a day for 5 days, or
• Acyclovir 800 mg orally twice a day for 5 days, or
• Acyclovir 800 mg orally 3 times a day for 2 days, or
• Famciclovir 125 mg orally twice a day for 5 days, or
• Famciclovir 1000 mg orally twice a day for 1 day, or
• Famciclovir 500 mg orally once, followed by 250 mg orally
twice daily for 2 days, or
• Valacyclovir 500 mg orally twice a day for 3 days, or
• Valacyclovir 1 g orally once a day for 5 days
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HSV Curriculum
Management
Severe Disease
• IV acyclovir should be provided for patients
with severe disease or complications requiring
hospitalization
• CDC-Recommended Regimen:
– Acyclovir 5-10 mg/kg IV every 8 hours for 2–7 days
or until clinical improvement
– Follow with oral antiviral therapy to complete at
least 10 days total therapy
– Acyclovir dose adjustment is recommended for
impaired renal function
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HSV Curriculum
Management
Allergy, Intolerance, and
Adverse Reactions
• Allergic and other adverse reactions to
acyclovir, valacyclovir, and famciclovir are rare
• Desensitization to acyclovir is described by
Henry RE, et al., Successful oral acyclovir
desensitization. Ann Allergy 1993; 70:386-8
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HSV Curriculum
Management
Herpes in HIV-Infected Persons
• HIV-infected persons may have prolonged, severe, or
atypical episodes of genital, perianal, or oral herpes
• HSV shedding is increased in HIV-infected persons
• Suppressive or episodic therapy with oral antiviral agents
is effective in decreasing the clinical manifestations of
HSV among HIV-positive persons.
• HSV type-specific serologies can be offered to HIVpositive persons during their initial evaluation, if infection
status is unknown, and suppressive antiviral therapy can
be considered in those who have HSV-2 infections. 103
HSV Curriculum
Management
CDC-Recommended Regimens for Daily
Suppressive Therapy in HIV-Infected Persons
• Acyclovir 400–800 mg orally twice a day
or three times a day, or
• Famciclovir 500 mg orally twice a day, or
• Valacyclovir 500 mg orally twice a day
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HSV Curriculum
Management
CDC-Recommended Regimens for
Episodic Infection in HIV-Infected Persons
• Acyclovir 400 mg orally 3 times a day for
5–10 days, or
• Famciclovir 500 mg orally twice a day for
5–10 days, or
• Valacyclovir 1 g orally twice a day for
5–10 days
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HSV Curriculum
Management
Genital Herpes in Pregnancy
• Majority of mothers of infants who acquire
neonatal herpes lack histories of clinically
evident genital herpes
• Risk for transmission to neonate is high (30%50%) among women who acquire genital herpes
near the time of delivery
• Risk is low (<1%) in women with histories of
recurrent herpes at term or who acquire genital
HSV during the first half of pregnancy
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HSV Curriculum
Management
Genital Herpes in Pregnancy
(continued)
• Prevention of neonatal herpes depends on:
✓ avoiding acquisition of HSV during late pregnancy
✓ avoiding exposure of the infant to herpetic lesions
during delivery
• All pregnant women should be asked whether
they have a history of genital herpes
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HSV Curriculum
Management
Genital Herpes in Pregnancy
(continued)
• At the onset of labor:
– All women should be questioned carefully about
symptoms of genital herpes, including prodromal
– All women should be examined carefully for
herpetic lesions
• Women without symptoms or signs of genital
herpes or its prodrome can deliver vaginally
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HSV Curriculum
Management
Genital Herpes in Pregnancy
(continued)
• Safety of acyclovir, valacyclovir, famciclovir in
pregnancy not definitively established, but no
clear evidence for increased birth defects
• Oral acyclovir may be given for first-episode
or severe recurrent herpes; IV acyclovir
should be used for severe infection
• Suppressive acyclovir late in pregnancy
reduces frequency of cesarean sections in
women with recurrent genital herpes; many
specialists recommend it
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HSV Curriculum
Lesson VI: Prevention
110
HSV Curriculum
• How to reduce risk of transmission:
– Herpes virus cannot pass through latex condoms
– During an outbreak (for most people, ~3 times/yr), best to
avoid sexual contact with the lesion area--condoms
should not be relied on when lesions are present
– Between outbreaks--safest strategy is to use condoms,
oral dams, etc. since there can sometimes be
asymptomatic viral shedding
• Condoms aren’t 100% effective at preventing transmission,
since they don’t cover entire genital area, but they reduce risk
significantly
– Medications are available that reduce the amount of
asymptomatic viral shedding that occurs between
outbreaks--can significantly reduce risk of transmission
HSV Curriculum
Prevention
Patient Counseling and Education
• Goals of counseling
– Help patients cope with the infection
– Prevent sexual and perinatal transmission
• Counsel initially at first visit
• Education on chronic aspects may be
beneficial after acute illness subsides
• HSV-infected persons may express anxiety
about genital herpes that does not reflect the
actual clinical severity of their disease
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HSV Curriculum
Prevention
Patient Counseling and Education
• Counseling should include:
–
–
–
–
Natural history of the infection
Treatment options
Transmission and prevention issues
Neonatal HSV prevention issues
• Emphasize potential for recurrent episodes,
asymptomatic viral shedding, and sexual
transmission
113
HSV Curriculum
Prevention
Counseling: Natural History
•
Recurrent episodes likely following a first
episode; with HSV-2 more than HSV-1
–
–
–
•
Frequency of outbreaks may decrease over time
Stressful events may trigger recurrences
Prodromal symptoms may precede outbreaks
Asymptomatic viral shedding is common
and HSV transmission can occur during
asymptomatic periods
114
HSV Curriculum
Prevention
Counseling:Treatment Options
• Suppressive therapy available and effective in
preventing symptomatic recurrences
• Episodic therapy sometimes useful in
shortening duration of recurrent episodes
• Explain when and how to take antiviral
medications
• Educate how to recognize prodromal
symptoms to determine when to begin
episodic therapy
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HSV Curriculum
Prevention
Counseling: Transmission and Prevention
• Inform current and future sex partners about
genital herpes diagnosis
• Abstain from sexual activity with uninfected
partners when lesions or prodrome present
• Correct and consistent use of latex condoms
might reduce the risk of HSV transmission
• Valacyclovir suppressive therapy decreases
HSV-2 transmission in heterosexual couples in
which source partner has recurrent herpes
116
HSV Curriculum
Prevention
Counseling: Neonatal Herpes
Prevention
• Risk of neonatal HSV infection should be
explained to all patients, including men
• Pregnant women should inform their
prenatal/perinatal providers that they have
genital herpes
• Pregnant women without HSV-2 infection
should avoid intercourse during third trimester
with men who have genital herpes
• Pregnant women without HSV-1 infection
should avoid oral sex from a partner with oral
herpes
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HSV Curriculum
Prevention
Counseling for Asymptomatic
Persons
• Give asymptomatic persons diagnosed
with HSV-2 infection the same
counseling messages as symptomatic
persons
• Teach the common manifestations of
genital herpes, as many patients will
become aware of them with time
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HSV Curriculum
Prevention
Partner Management
• Symptomatic sex partners
– Evaluate and treat in the same manner as
patients who have genital lesions
• Asymptomatic sex partners
– Ask about history of genital lesions
– Educate to recognize symptoms of herpes
– Offer type-specific serologic testing
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HSV Curriculum
Case Study
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HSV Curriculum
Case Study
Roberta Patterson: History
• 26-year-old woman, presents for her first prenatal visit
• Concerned for her baby because of her husband’s history
of genital herpes
• States that she is 6 weeks pregnant
• Has never had symptoms of vaginal or oral herpes
• Diagnosed and treated for chlamydia 7 years ago (age 19);
no other STD diagnoses reported
• Her 26-year-old husband had his first episode of genital
herpes 8 years ago; no other STD diagnoses reported. No
visible HSV lesions since they’ve been sexually active.
Reports having had no prodromal symptoms or symptoms
of active disease.
• No other sex partners other than her husband for the last
121
16 months
HSV Curriculum
Case Study
Physical Exam
• Vital signs: blood pressure 112/68, pulse 58,
respiration 13, temperature 38.5° C
• Cooperative, good historian
• Chest, heart, musculoskeletal, and abdominal
exams within normal limits
• Uterus consistent with a 6-week pregnancy
• Normal vaginal exam without signs of lesions
or discharge
• No lymphadenopathy
122
HSV Curriculum
Case Study
Questions
1. Which HSV general education messages
should be discussed with Roberta?
2. Given that Roberta’s husband Franklin has
a history of genital herpes, would it be
appropriate to test Roberta for genital
herpes using a type-specific serologic test?
3. What other STD screening should be
considered for Roberta?
123
HSV Curriculum
Case Study
Roberta’s Laboratory Results
•
•
•
•
•
•
HSV gG-based type-specific serologies: HSV-1
negative; HSV-2 positive
NAAT probe for Chlamydia trachomatis: negative
NAAT for Neisseria gonorrhoeae: negative
RPR: nonreactive
HIV antibody test: negative
Pregnancy test: positive
4. What would you tell Roberta about her HSV infection,
based on clinical manifestations and test results?
5. Would routine viral cultures during Roberta's
pregnancy be recommended?
124
HSV Curriculum
Case Study
Partner Management
Sex Partner and Exposure Information
• Franklin Patterson
• First sexual exposure: 16 months ago
Last sexual exposure: 1 month ago
• History of genital herpes infection; first episode 8
years ago. No HSV testing or treatment at time of first
episode or with subsequent episodes
• No history of other STDs; no sex partners other than
Roberta in past 16 months
6. Franklin reports genital lesions during Roberta's sixth
month of pregnancy. Which laboratory tests should be
performed on him?
125
HSV Curriculum
Case Study
Franklin’s Laboratory Results
• HSV cultures: HSV-1 negative; HSV-2
positive
7. What is an appropriate episodic
treatment for Franklin?
126
HSV Curriculum
Case Study
Follow-Up
• Roberta had no HSV symptoms during her
pregnancy
• Roberta discussed the use of acyclovir treatment in
late pregnancy with her certified nurse-midwife, but
decided against it because there are no data to
support the use of antiviral therapy among HSV
seropositive women without a history of clinical
genital herpes
• At onset of labor, she reported no prodromal or other
HSV symptoms and no lesions were found on
examination
• After a 14-hour labor, she vaginally delivered a
healthy 7.2 lb baby girl
127
HSV Curriculum
Case Study
Questions
8. What questions should be asked of
ALL women beginning labor?
9. If Roberta has genital herpetic lesions
at the onset of labor, should she
deliver vaginally or abdominally?
What is the risk to the infant?
128
HSV Curriculum
Case Study
Questions
10. Roberta is asymptomatic at the time of
delivery. Is it medically appropriate for her
to deliver vaginally?
11. If Roberta had acquired genital herpes
around the time of delivery, would she be
more or less likely to transmit genital herpes
to her baby during a vaginal delivery than if
she had a history of recurrent genital
herpes?
129