simplex viruses (HSVs) are ubiquitous, extremely host-adapted pathogens
that can cause a wide variety of illnesses. Two types exist: type 1
(HSV-1) and type 2 (HSV-2). Both are closely related but differ in
epidemiology. HSV-1 is transmitted chiefly by contact with infected
saliva, whereas HSV-2 is transmitted sexually or from a mother’s genital
tract infection to her newborn.
Herpes simplex infections are asymptomatic in as many as 80% of
patients, but symptomatic infections may be characterized by significant
morbidity and recurrence. Moreover, infections can cause life-threatening
complications, particularly in immunocompromised hosts.
HSV infection appears to have increased in prevalence worldwide in the
last 2 decades, making it a major public health concern. The availability
of effective chemotherapy underscores that the prompt recognition of the
infection and early initiation of therapy are of utmost importance in the
management of the disease.
Pathophysiology: HSV, belonging to the family
Herpesviridae and to the subfamily Alphaherpesvirinae, is a
double-stranded DNA virus characterized by the following unique biological
- Neurovirulence (the capacity to invade and replicate in the nervous
- Latency (the establishment and maintenance of latent infection in
nerve cell ganglia): In HSV-1 infection, the trigeminal ganglia are
involved most commonly, while in HSV-2 the sacral nerve root ganglia
(S2-S5) are involved.
- Reactivation: The reactivation and replication of latent HSV can be
induced by a variety of stimuli (eg, fever, trauma, emotional stress,
sunlight, menstruation), resulting in overt or covert recurrent
infection and peripheral shedding of HSV. In immunocompetent patients
with equal chances of acquiring HSV-1 and HSV-2 both orally and
genitally, HSV-1 reactivates more frequently in the oral rather than the
genital region. Similarly, HSV-2 reactivates 8-10 times more frequently
in the genital region when compared to orolabial HSV-2. Reactivation is
more frequent and severe in immunocompromised patients.
Dissemination of infection occurs in people with impaired T-cell
immunity such as organ transplant recipients and individuals with
Distribution of HSV is worldwide. Humans are the only natural
reservoirs, and no vectors are involved in transmission. Because of latent
infection, periodic reactivation, and virus shedding, endemicity is easily
maintained in most human communities.
The mode of transmission is by close personal contact, and infection
occurs via inoculation of virus into susceptible mucosal surfaces (eg,
oropharynx, cervix, conjunctiva) or through small cracks in the skin. The
virus is readily inactivated at room temperature and by drying; hence,
aerosol and fomitic spread occur rarely.
- In the US: HSV is ubiquitous. Most individuals show
evidence of infection due to HSV. HSV-1 usually is acquired in childhood
by contact with oral secretions containing the virus. HSV-2 becomes an
issue when the individual becomes sexually mature. (The presence of
HSV-2 is an indirect measure of sexual activity.) Seroprevalence rates
do not reflect how many of these individuals have or will have
symptomatic episodes of HSV recurrence.
Seroprevalence: Antibodies to HSV-1 increase with age starting in
childhood and correlate with socioeconomic status. By age 30 years, 50%
of individuals in a high socioeconomic status and 80% in a lower
socioeconomic status are seropositive. Antibodies to HSV-2 begin to
emerge at puberty, correlating with the degree of sexual activity. The
lifetime seroprevalence can be 20-80%.
- Internationally: HSV is well distributed worldwide.
Mortality/Morbidity: Morbidity and mortality of HSV
infections are discussed in Complications.
Overall, the mortality associated with herpes simplex infections is
related to 3 situations: perinatal infection, encephalitis, and infection
in the immunoincompetent host.
Race: No clear evidence indicates that the risk of
infection with HSV relates directly to race.
Sex: Differences in frequency of genital HSV
infections relate to sex only because infection relates to sexual
activity, particularly without appropriate barrier protection.
Age: HSV-1 infections transmitted via saliva are
common in children, although such primary herpes gingivostomatitis can be
observed at any age. HSV-2 infections are clustered perinatally (from a
maternal episode at delivery) and primarily once sexual activity begins.
HSV-2 genital infections in children can be an indication of sexual abuse.
History: The clinical
course of the disease depends upon the age and immune status of the host,
the anatomic site of involvement, and the antigenic type of the virus.
While the primary infections caused by HSV-1 and HSV-2 are accompanied by
systemic signs, longer duration of symptoms, and higher rate of
complications, recurrent episodes are milder and shorter. Both HSV-1 and
HSV-2 can cause similar genital and orofacial primary infections after
contact with infectious secretions containing either HSV-1 (usually oral
secretions) or HSV-2 (usually genital secretions).
- Acute herpetic gingivostomatitis
- This manifestation of primary HSV-1 infection occurs in children
aged 6 months to 5 years.
- Infected saliva from an adult or another child is the mode of
infection. The incubation period is 3-6 days.
- Clinical features
- Abrupt onset
- High fever (102-104°F)
- Anorexia and listlessness
- Gingivitis is the most striking feature, with markedly swollen,
erythematous, friable gums.
- Vesicular lesions develop on the oral mucosa, tongue, and lips
and later rupture and coalesce, leaving ulcerated plaques.
- Tender regional lymphadenopathy
- Perioral skin also may be involved because of contamination with
- Course: Acute disease lasts 5-7 days, and the symptoms subside in
2 weeks. Viral shedding from the saliva may continue for 3 weeks or
more. Adults also may develop acute gingivostomatitis, but it is less
severe and is associated more often with a posterior
- Acute herpetic pharyngotonsillitis
- In adults, oropharyngeal HSV-1 causes pharyngitis and tonsillitis
more often than gingivostomatitis.
- Fever, malaise, headache, and sore throat are presenting features.
- The vesicles rupture to form ulcerative lesions with grayish
exudates on the tonsils and the posterior pharynx.
- Associated oral and labial lesions occur in fewer than 10% of
- HSV-2 can cause similar symptoms and is associated with orogenital
contact or can occur concurrently with genital herpes.
- This is the most common manifestation of recurrent HSV-1. A
prodrome of pain, burning, and tingling often occur at the site,
followed by the development of erythematous papules that rapidly
develop into tiny, thin-walled, intraepidermal vesicles that become
pustular and ulcerate. In most patients, fewer than 2 recurrences
manifest each year, but some individuals have monthly
- Maximum viral shedding is in the first 24 hours of the acute
illness but may last 5 days.
- Genital herpes: The severity and frequency of the disease and the
recurrence rate depend on a number of factors that include viral type,
prior immunity to autologous or heterologous virus, gender, and immune
status of the host.
- Primary genital herpes can be caused by both HSV-1 and HSV-2 and
is asymptomatic in most patients. The clinical features and course of
primary genital herpes caused by both HSV-1 and HSV-2 are
indistinguishable, but recurrences are more common with HSV-2.
- Primary genital herpes is characterized by severe and prolonged
systemic and local symptoms. The symptoms of persons with a first
episode of nonprimary HSV-2 infection are less severe and of shorter
- Preexisting antibodies to HSV-1 have an ameliorating effect on
disease severity caused by HSV-2.
- Prior orolabial HSV-1 protects against genital HSV-1 but not
- Women’s symptoms are more severe, and women have a higher rate of
complications than men.
- Clinical features: The incubation period is 3-7 days (range = 1 d
to 3 wk). Constitutional symptoms include fever, headache, malaise,
and myalgia (prominent in the first 3-4 d); local symptoms include
pain, itching, dysuria, vaginal and urethral discharge, and tender
- Clinical features in women: Herpetic vesicles appear on the
external genitalia, labia majora, labia minora, vaginal vestibule, and
introitus. In moist areas, the vesicles rupture, leaving exquisitely
tender ulcers. The vaginal mucosa is inflamed and edematous. The
cervix may be involved in 70-90% of patients and is characterized by
ulcerative or necrotic cervical mucosa. Cervicitis may be the sole
manifestation in some patients. Dysuria may be very severe and may
cause urinary retention. Dysuria is associated with urethritis, and
HSV can be isolated in the urine. HSV-1 causes urethritis more often
- Clinical features in men: Herpetic vesicles appear in the glans
penis, the prepuce, the shaft of the penis, and sometimes on the
scrotum, thighs, and buttocks. In dry areas, the lesions progress to
pustules and then crust. Herpetic urethritis occurs in 30-40% of
patients and is characterized by severe dysuria and mucoid discharge.
The perianal area and rectum can be involved in persons who engage in
anal intercourse, resulting in herpetic proctitis.
- In men and women, the ulcerative lesions persist from 4-15 days
until crusting and reepithelialization occur. New lesions can occur
during the course of the illness in 75% of patients, usually forming
in 4-10 days. The median duration of viral shedding is about 12
- The major morbidity of genital herpes is due to its frequent
reactivation rate. In one study, 90% of patients reactivated within
the first 12 months. For HSV-2 infection 38% had 6 recurrences in 1
year, and 20% had more than 10 recurrences in the first year.
- Both subclinical and symptomatic reactivation are more common with
HSV-2 compared to HSV-1. Sixty percent of patients with primary
genital HSV-2 experience recurrences in the first year.
- Patients who had severe primary genital herpes tend to have more
frequent recurrences of longer duration.
- Recurrent genital herpes is preceded by a prodrome of tenderness,
pain, and burning at the site of eruption that may last from 2 hours
to 2 days. In some patients, severe ipsilateral sacral neuralgia may
- In women, the vesicles are found on the labia majora, labia
minora, or perineum. The lesions are often very painful. Fever and
constitutional symptoms are uncommon. The lesions heal in 8-10 days
and viral shedding lasts an average 5 days. The symptoms are more
severe in women than men.
- In men, recurrent genital herpes presents as 1 or more patches of
grouped vesicles on the shaft of the penis, prepuce, or glans.
Urethritis is uncommon. Pain is mild, and lesions heal in 7-10 days.
The frequency and severity of recurrences decrease with
- Subclinical genital herpes
- The majority of primary genital HSV infections are asymptomatic,
and 70%-80% of seropositive individuals have no history of symptomatic
genital herpes. Nevertheless, they experience periodic subclinical
reactivation with virus shedding, thus making them a source of
- The rate of viral shedding may be 1-2% in immunocompetent persons
and may be as high as 6% in the first few months after acquiring the
infection. This fact is important in neonatal herpes because most
mothers have no signs and symptoms of genital herpes during
Physical: This section addresses the physical
examination of the herpetic lesion as it relates to primary and recurrent
lesions of cutaneous or mucosal HSV infection. This can be related to
either oral or genital infection.
- Primary mucocutaneous HSV infections
- Primary (first episode) infections present within several days of
exposure to secretions containing viable virus.
- Often painful, the lesions develop into vesicles quickly and can
continue to erupt over 1-2 weeks.
- The lesions are prominent and often are present internally on the
mucosal surface of the oral or genital area as well as on the
- Constitutional symptoms often are prominent with fever, malaise,
myalgias, and anorexia. Weight loss is not uncommon, either related to
illness or dysphagia (in primary gingivostomatitis).
- Individual vesicles on mucosal surfaces break down rapidly,
forming shallow painful ulcers (usually <8-10 mm in diameter). They
may be covered with a white exudate that can be confused with mucosal
candidosis. Those on cutaneous surfaces remain as vesicles longer,
only to develop into crusted ulcers that heal in 5-7 days.
- Recurrent mucocutaneous HSV infections
- Following the establishment of latency in the corresponding
sensory nerve ganglion cells, HSV can cause recurrent infection that
can be subclinical (manifest by viral excretion without lesions) or
overt (manifest by mucosal or cutaneous lesions with viral
- Oral recurrences often are triggered by recognizable stimuli such
as pyrexia (fever blisters and cold sores), stress, or sunburn.
Genital recurrences are more likely to be linked to stress and not
pyrexia. Females may relate a relationship to the menstrual
- Burning or paraesthesias at the point where the lesions are to
occur may herald recurrences. Unlike primary infection, constitutional
symptoms are minimal in most cases.
- Recurrences last 3-7 days and can occur numerous times per year or
once or twice in a lifetime. Overall, the number of yearly recurrences
tends to decrease over time.
- Although recurrent HSV may last much longer (>30 d) in
immunocompromised hosts, such as individuals with AIDS, frequent
recurrences are not necessarily a sign of an altered immune
- Because recurrences can be clinically unrecognizable, transmission
to susceptible individuals can occur without overt lesions being
present. In genital disease, this means barrier protection should be
used whether lesions are present or not, even if no history of genital
HSV is present.
- Vesicles occurring in a sacral dermatomal distribution
(zosteriform) can occur in recurrent genital HSV disease and be
confused with herpes zoster. A history of similar recurrences should
alert the clinician to this possibility.
- Sacral HSV recurrences also may present with signs and symptoms of
meningeal inflammation; and, in fact, an aseptic meningitis picture
can be found upon examination of the cerebrospinal fluid.
- The mode of transmission is by close personal contact.
- Infection occurs via inoculation of virus into susceptible mucosal
surfaces (eg, oropharynx, cervix, conjunctiva) or through small cracks
in the skin.
- The virus is inactivated readily at room temperature and by drying;
hence, aerosol and fomitic spread occur rarely.
- HSV-1 is transmitted chiefly by contact with infected saliva,
whereas HSV-2 is transmitted sexually or from a mother’s genital tract
infection to her newborn.
- HSV infection is best confirmed by isolation of virus in tissue
culture (the criterion standard for diagnosis).
- Rapid diagnosis is possible by the histological appearance of the
- Multinucleated giant cells and epithelial cells containing
eosinophilic intranuclear inclusion bodies distinguish the lesions of
- The characteristic cytologic changes induced by HSV can be
demonstrated in Tzank smears (see Procedures).
- Punch biopsy provides more reliable material for histological
examination, particularly when lesions are infected with bacteria and
- Rapid detection of HSV DNA in clinical specimens is now possible
with polymerase chain reaction (PCR) techniques.
- In HSV encephalitis, PCR using cerebrospinal fluid (CSF) provides
a rapid, noninvasive diagnostic technique that is as sensitive as
- PCR has detected HSV-2 as the cause of recurrent meningitis
(Mollaret) and has shown a strong association of HSV-1 with Bell
- PCR can detect asymptomatic viral shedding.
- Tissue culture for HSV often is positive within 48 hours of
- Characteristic cytopathic effect with ballooning of cells and cell
death are observed, and death of the entire monolayer of cells may be
- Immunofluorescent staining of the tissue culture cells can quickly
identify HSV and can distinguish between types 1 and 2.
- Antibody testing can demonstrate a primary seroconversion,
particularly with HSV-1 in childhood.
- Because of sero–cross-reactivity, HSV-1 and HSV-2 are not
generally distinguishable unless a glycoprotein G antibody assay is
- Antibody titer increases generally do not occur during recurrences
of HSV, which is in contradistinction to the situation in
varicella-zoster virus recurrence. Therefore, the test generally is
not used for the diagnosis of mucocutaneous HSV relapse.
- Brain imaging studies in simplex virus encephalitis generally
demonstrate focal localization in the temporal area that is associated
with edema and contrast enhancement.
- Typically, an intact vesicle is used from which the vesicular
fluid is aspirated by puncture with a sterile tuberculin syringe. This
fluid can be used for viral culture.
- Aspiration should facilitate complete collapse of the vesicle
because it is not multiloculated as cutaneous poxvirus infections can
- After aspiration, the vesicle should be unroofed
- Using a sterile instrument, the floor of the newly produced ulcer
can then be scraped. The obtained material can be spread on a glass
microscope slide and then dried and fixed for staining.
- Staining can be performed with a Papanicolaou smear stain. (In
actuality, whatever is available as Gram, Giemsa, or Wright stain will
- A positive result is the finding of multinucleate giant
- Using appropriate immunofluorescent antibody reagents, the smear
can distinguish different herpesviruses and nonherpesviruses that may
be present (eg, vaccinia, smallpox).
- Overall, medical treatment of HSV revolves around specific antiviral
- In situations in which constitutional effects such as fever occur,
symptomatic treatment can be used.
- Appropriate wound care is needed, and treatment for secondary
bacterial skin infections may be required.
Diet: A diet high in the amino acid lysine has been
suggested as useful in preventing recurrences of HSV. Although viral
yields in tissue culture are lower in a high lysine medium, replication
still occurs. No objective clinical evidence exists to support this
The goals of pharmacotherapy are to
reduce morbidity and to prevent complications.
Drug Category: Antivirals -- Nucleoside
analogs are phosphorylated initially by viral thymidine kinase to
eventually form a nucleoside triphosphate. These molecules inhibit HSV
polymerase with 30-50 times the potency of human alpha-DNA polymerase.
||Acyclovir (Zovirax) -- Synthetic
purine nucleoside analogue with activity against a number of
herpesviruses, including herpes simplex and varicella-zoster. Highly
selective for virus-infected cells because of its high affinity for
viral thymidine kinase enzyme. This effect serves to concentrate
acyclovir monophosphate into virus-infected cells. The monophosphate
then is metabolized into the triphosphate active form by cellular
Double dose is suggested for herpes simplex proctitis or
ocular infections. Ocular infections also can be treated with
topical acyclovir. Oral suspension available (40 mg/mL).
||First episode mucocutaneous herpes
simplex: 200 mg PO 5 times daily or 400 mg tid for 7-10 d or until
clinical resolution occurs|
Recurrent genital herpes: 200 mg
PO five times daily for 5 d
Chronic suppressive therapy: 400
mg bid or 200 mg 3-5 times daily; reevaluate after 1 y
simplex encephalitis: 10 mg/kg IV q8h for 10-14 d
infection in immunocompromised host: 5-10 mg/kg IV q8h for 5-10 d
||First episode mucocutaneous herpes
simplex: 20-30 mg/kg/d in 5 divided doses for 7-10 d|
infections in immunocompromised children: 10 mg/kg/d IV q8h for 7
Herpes encephalitis: 20 mg/kg IV q8h for 10-14 d
||Concomitant use of probenecid or
zidovudine prolongs half-life and increases CNS toxicity
||B - Usually safe but benefits must
outweigh the risks.
||Renal dysfunction (usually
reversible) can occur during high-dose IV administration (primarily
related to drug crystalluria); effect can be minimized by slow
infusion and adequate hydration;|
including lethargy, agitation, myoclonus, or seizures is observed in
<1% of patients; appears to be dose-related phenomenon with
increased risk with azotemia
||Valacyclovir (Valtrex) -- Prodrug
rapidly converted to the active drug acyclovir. More expensive but
has a more convenient dosing regimen than acyclovir.
||First episode herpes simplex: 1 g
bid for 10 d, preferably beginning within 48 h of
Recurrent episode herpes simplex: 500 mg bid for 5 d
beginning within 24 h of onset
Suppressive dosing for HSV:
500 mg to 1 g/d
||Probenecid, zidovudine, or
cimetidine coadministration prolongs half-life and increases CNS
toxicity of valacyclovir
||B - Usually safe but benefits must
outweigh the risks.
||Caution in renal failure and
coadministration of nephrotoxic drugs; associated with onset of
hemolytic uremic syndrome|
||Famciclovir (Famvir) -- Prodrug
that when biotransformed into active metabolite, penciclovir, may
inhibit viral DNA synthesis/replication. Used against herpes simplex
and varicella-zoster viruses.
||Recurrent genital HSV: 125 mg bid
for 5 d|
Recurrent genital HSV in HIV-infected patients: 500
mg bid for 7 d
Suppression of frequent recurrence of genital
HSV: 250 mg bid up to 12 mo
||Coadministration of probenecid or
cimetidine may increase toxicity; coadministration increases
bioavailability of digoxin
||B - Usually safe but benefits must
outweigh the risks.
||Caution in renal failure or
coadministration of nephrotoxic drugs; dosage adjustment in renal
impairment recommended (half-life prolonged by 5-6 times if CrCl
- Because of the ubiquitous and cosmopolitan nature of HSV, avoiding
contact with individuals who (often asymptomatically) are excreting the
virus in saliva or sexual secretions is difficult.
- Although not easily applicable to oral-oral contact, barrier
protection using latex condoms is recommended to minimize exposure to
genital HSV infections.
- Because genital ulcers due to HSV may occur outside of areas covered
by the condom, transmission can occur in those areas.
- Herpetic whitlow can be avoided by the use of latex gloves when
health care workers insert their hands into the oral cavity of patients.
Transmission of genital virus to the hand, however, can occur during
unprotected finger-genital contact related to sexual exposures.
- Suppressive antiviral therapy is used for individuals with frequent
and/or particularly symptomatic relapses.
- Balanitis can occur in an uncircumcised male as a result of
bacterial infection of the herpetic ulcers.
- Candidal vaginitis has been described in as many as 10% of women
with primary genital herpes, particularly if they have diabetes. Care
should be taken to confirm the diagnosis of candidosis because
ulcerative herpetic disease can have whitish mucosal lesions that can
be confused with yeast infection.
- Ocular infections
- This complication is not uncommon in children as a result of
autoinoculation during acute herpetic gingivostomatosis or
asymptomatic oropharyngeal HSV infection.
- Ocular infection is caused primarily by HSV-1, except in neonates
in whom it may be caused by HSV-2, and manifests as unilateral
follicular conjunctivitis or as acute herpetic keratoconjuctivitis
with dendritic corneal ulcers.
- Recurrences can occur in as many as 25% of patients and can be
associated with progressive scarring of the cornea. HSV has been the
leading infectious cause of blindness in the US.
- Skin infections: Various cutaneous complications related to HSV can
- Eczema herpeticum: This occurs in individuals with underlying
dermatitis and may be localized (which can be confused with herpes
zoster) or disseminated. The process also can occur in patients with
extensive skin breakdown as with burns, pemphigus, or Sézary syndrome.
- Herpetic whitlow: HSV of the fingers of the hand occurs at or near
the cuticle or at other sites associated with trauma. When involving
the nail area, it has been confused with a bacterial felon and been
subjected, inappropriately, to incision and drainage. Herpetic whitlow
is associated with HSV-1 in health care workers and children related
to saliva exposure and with HSV-2 related to digital-genital exposure.
- Herpes gladiatorum: Scattered cutaneous HSV-1 lesions have been
observed in wrestlers who have had viral contact through exposure to
infectious saliva during a match.
- Visceral infections: HSV infection of the visceral organs usually
results from viremia, and multiple organ involvement is common. This may
occur during otherwise asymptomatic primary infections and sometimes in
seemingly immunologically normal hosts.
- In most cases of disseminated herpes, the lesions are confined to
the skin; however, fatal visceral dissemination can occur with or
without vesicular skin lesions. Multiple organs are involved, but
fulminant HSV hepatitis is usually clinically prominent.
- It is associated with leukopenia, thrombocytopenia, and
disseminated intravascular coagulation.
- Disseminated HSV-1 and HSV-2 infections also can result in
herpetic esophagitis, adrenal necrosis, interstitial HSV pneumonitis,
HSV cystitis, HSV arthritis, HSV meningitis, and HSV
- Central nervous system complications
- Aseptic meningitis: This condition is an acute, generally benign
lymphocytic meningitis. In 1 series, 36% of women and 13% of men with
primary genital HSV-2 had meningeal symptoms on 2 consecutive
examinations. It is more common with HSV-2 infection. Meningeal
symptoms usually start 3-12 days after the onset of genital lesions;
they reach a maximum 2-4 days into the illness and recede over 2-4
days. Signs and symptoms of encephalitis are unusual and neurological
sequelae are rare. HSV-1 also has been identified by PCR in the CSF of
patients with benign lymphocytic recurrent meningitis (Mollaret
meningitis), suggesting that HSV may be the cause of this so-called
- Ganglionitis and myelitis: Genital and anorectal HSV infections
may be complicated by urinary retention, sacral neuralgia, and sacral
anesthesia. This is due to associated ganglionitis and radiculitis.
The symptoms usually resolve in 1-2 weeks. Transverse myelitis rarely
- Herpes simplex encephalitis: This is an acute necrotizing viral
encephalitis that, beyond the neonatal period, is nearly always caused
by HSV-1. It accounts for 10-20% of all cases of encephalitis and is
the most common cause of sporadic acute necrotizing encephalitis in
the United States. Herpes simplex encephalitis occurs as a primary
infection in about 50% of cases and may be due to recurrent infection
or to reinfection with a different strain of HSV-1 in the remainder.
Clinical features include the following:
- Nonspecific findings common to all forms of encephalitis, which
include headache, signs of meningeal irritation, altered mental
status, and generalized seizures
- Changes referable to focal necrosis of the orbitofrontal and
temporal cortex and the limbic system, including anosmia, memory
loss, olfactory and gustatory hallucinations, and focal seizures
- Rapid development of hemiparesis and coma may occur. In some
patients, the clinical picture may be protracted, mimicking acute
psychosis or delirium tremens.
- The CSF has moderate pleocytosis with mixed mononuclear cells
and polymorphonuclear cells, moderate RBCs, and mildly elevated
protein with normal glucose.
- MRI is the most sensitive imaging procedure.
- The most sensitive noninvasive method of diagnosis is the
demonstration of HSV DNA by PCR.
- The mortality rate is high (70%) in untreated patients. Even
with treatment, a high incidence of neurological sequelae
- Genital herpes and pregnancy
- Recurrent genital herpes is similar in pregnant and nonpregnant
women, although an increase in the number of recurrences in the course
of pregnancy may occur.
- Recurrent genital herpes accounts for 1-2% of all cases of
neonatal herpes. Considering the fact that a high serological evidence
of herpes and low incidence of neonatal herpes exists, recurrent
herpes is not an important risk factor. Hence, cesarean delivery is
recommended only in mothers who have active genital lesions during
- First-episode infections have more severe consequences to the
mother and infant. Thus, identification of women at risk for primary
infection (seronegative for HSV-2) is of paramount importance.
- Serological discordance between partners may be 15-20%, so that
the risk of a seronegative mother becoming infected from the father
during pregnancy is 10-15%.
- Pregnant women may have widely disseminated infection with a high
mortality rate of 50%.
- Infection in the third trimester of pregnancy is associated with
neonatal HSV infections, intrauterine growth retardation, and
- Neonatal HSV disease
- Ninety percent of infections are acquired perinatally, 5-8% are
acquired congenitally, and a few are acquired postnatally.
- Neonatal infection is caused by contact with infected genital
- In 70% of mothers, the infection is asymptomatic. The risk of
transmission from a mother with primary infection is about 50%.
- Neonates and infants (aged <6 wk) have a very high frequency of
visceral and CNS infections. Without therapy, the mortality rate is
65%, and a high degree of neurological sequelae
- The disease may be confined to the skin, eyes, or mouth, or it may
manifest as encephalitis or disseminated visceral disease involving
the lungs, liver, heart, adrenals, and skin.
- Suits over sexual transmission
- Legal actions have been taken over transmission of HSV through
unprotected sexual activity.
- Demonstration that both partners are infected with the same type
of HSV is not adequate to prove that one partner infected the
- The use of restriction endonucleases, which lyse DNA at very
specific base sequences, can strongly suggest an epidemiologic link
between 2 isolates but does not indicate the direction of the
- The presence of genital HSV-2 infection in young children can be
an indicator of sexual abuse in parallel to gonococcal infections but
is not necessarily the case.
- Recognition of HSV encephalitis
- Because prompt treatment of HSV encephalitis appears to minimize
residual neurologic damage and death, considering this diagnosis early
is important in appropriate cases. Perform necessary diagnostic tests,
and institute early, usually empirical, antiviral therapy.
- Unsatisfactory outcomes can occur, however, even with the early
use of antiviral treatment.
- Development of antiviral drug resistance
- Antiviral resistance of HSV can be selected for both in vitro and
- Once these isolates are present, commonly representing thymidine
kinase–negative mutants, the usual treatments are not likely to be
effective, and alternate modalities of therapy must be
- The use of prolonged suppressive therapy for HSV no doubt
contributes substantially to the risk of developing
- Because of the possibility of developing resistance, the decision
to use chronic suppression (or patient-driven relapse treatment) must
be made while carefully balancing the positive effect of suppression
or any likely minimal effect of therapy on an already overt
mucocutaneous relapse against the potential for
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