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International Journal of STD & AIDS 2001; 12 (Suppl.

3): 34 39

MANAGEMENT OF SPECIFIC INFECTIONS

European guideline for the management of


genital herpes
Herpes Simplex Virus Special Interest Group of the Medical
Society for the Study of Venereal Diseases, United Kingdom:
R Patel, S E Barton, D Brown , F M Cowan , G R Kinghorn,
P E Munday, A Scoular, D Timmins, M Whittaker
and P Woolley

INTRODUCTION patients can be highly variable4. The majority of


patients will suffer from atypical lesions where
First infection with either herpes simplex virus
signs may be easily confused with other genital
type 1 (HSV-1) or type 2 (HSV-2) is termed primary
infections or dermatoses. Clinical diagnoses alone
infection and results in either symptomatic disease
in atypical cases should, whenever possible, be
at the site of viral entry (i.e. around the mouth or
avoided.
around the genital area) or asymptomatic and
hence unrecognized disease. In addition there may
be systemic symptoms as with other acute viral Laboratory
illnesses. Following infection, the virus becomes Virus detection and characterization
latent in the local sensory ganglion, periodically The con rmation of the infection is essential and
reactivating to cause symptomatic lesions or characterization of its strain is recommended for
asymptomatic, but none the less infectious, viral diagnosis, prognosis-counselling and management.
shedding. Genital herpes can be caused by either Laboratory diagnosis is based on direct detection
HSV-1 (the usual cause of oro-labial herpes) or by of HSV from genital lesions which may be atypical
HSV-2. Infection with either virus can cause an (Table 1). The quality of samples is critical and
identical initial illness. However, subsequent re- specimens should be collected using swabs directly
currence frequency is greater for HSV-2 than HSV- from the base of the lesion. HSV is a labile virus
1 disease1. and successful virus culture depends on maintain-
ing the cool chain (48C), rapidly transporting
Transmission risk specimens to the laboratory and avoiding freeze
thaw cycles. Local factors (laboratory resources,
Risk of transmission appears to be greatest during
distance) should be considered in deciding on the
lesional recurrences or prodrome. Patients should be
testing strategy. The stage of the lesion will
advised to abstain from sexual contact during this
determine the success of virus detection5 7.
time. Transmission can occur in the absence of
Negative diagnostic tests do not exclude infection.
lesional recurrence as a result of subclinical viral
Patients may require reassessment on a number of
shedding. Ef cacy of condoms to prevent sexual
occasions for a de nitive diagnosis to be made.
transmission has not been formally assessed. Risk of
transmission is greater from men to women than vice
Serology
versa. Prior infection with HSV-1 reduces the HSV-2
Most currently available commercial tests for HSV
seroconversion risk in serodiscordant couples2,3.
antibodies are not type-speci c (e.g. complement-
xation test (CFT) and many enzyme immunoas-
DIAGNOSIS says (EIAs)). These tests are rarely of value in the
management of genital HSV. However, type-
Clinical
speci c commercial assays are becoming available
Although classical genital herpes can be recognized and are either EIAs based on glycoprotein G (gG1,
by the presence of typical papular lesions progres- gG2) or Western blot.
sing to blister and ulcer formation, associated with Type-speci c immune responses can take 8 12
local adenitis and in recurrent cases proceeded by weeks to fully develop following primary infection.
prodromal symptoms, the features in many Full serological assessment of genital HSV
requires access to both HSV-1 and 2 type-speci c
antibody assays, because of the high proportion of
Correspondence to: Dr R Patel, Department of Genito Urinary cases due to HSV-1 infection. HSV-1 type-speci c
Medicine, Royal South Hants Hospital, Brintons Terrace, assays are consistently less sensitive and speci c
Southampton SO14 0YG, UK than those for HSV-2.
34
Barton et al. Management of genital herpes 35

Table 1. Detection of HSV in lesions, available tests

Antigen detection (immuno-


uorescence on smears) Antigen Nucleic acid
Virus culture Tzanck test (e.g. EIA) (e.g. PCR)

Source Swabs/scraping Smear/tissue section Swabs/scraping Swabs/scrapin g


Sensitivity High, >90% from lesions Low 80% Highest
Speci city High High High Controls for cross-
contamination
important
Advantages Allows virus typing and antiviral Inexpensive Cost and speed Allows virus typing
sensitivity using monoclonal high sensitivity
antibodies testin g
Disadvantages Sample transport, labour-intensive, Insensitive Insensitive, no No commercial assay
expensive viral typing available , expensive

The value of screening all STD clinic attenders or . Valaciclovir 500 mg 2/day.
antenatal patients for HSV antibodies has not been
established. Choice should be made by individual clinicians
Tests should be fully evaluated for sensitivity, taking cost of therapy and likely compliance into
speci city, reproducibility against virus culture account.
and/or validated established tests (e.g. Western Supportive measures
blot) before being introduced into clinical practice. Saline bathing and the use of appropriate analgesia
The value of these tests for patient management is recommended. Caution should be exercised in
has not been fully assessed but they are likely to using topical anaesthetic agents because of the
contribute in cases with recurrent genital ulceration potential for sensitization.
of unknown cause, for counselling patients with
initial episodes of disease and the asymptomatic Counselling
partners of patients with HSV-2 infection 8. Counselling of patients with rst-episode genital
As adverse psychological sequelae may follow herpes should include a discussion of the following
the identi cation of an asymptomatic chronic topics: possible source(s) of infection, natural
infection, protocols for use of type-speci c anti- history including risk of subclinical viral shedding,
body of tests need to be developed in individual future treatment options, risk of transmission by
centres. sexual and other means, risks of transmission to the
foetus during pregnancy and the advisability of the
MANAGEMENT obstetrician and midwife being informed, sequelae
of infected men infecting their uninfected partners
First-episode genital herpes during pregnancy, the possibility of partner
Indications for therapy noti cation.
First episodes of genital herpes are frequently
associated with a prolonged disease course. Un- Management of complications
treated, many patients suffer general and local Hospitalization may be required for:
complications. Therapy can be highly effective and . Urinary retention
should be instigated on clinical suspicion alone. . Meningism
. Severe constitutional symptoms
Antivirals
. Adverse social circumstances.
Patients presenting within 5 days of the start of the
episode, or while new lesions are still forming, If catheterization is required, suprapubic catheter-
should be given oral antiviral drugs. Aciclovir, ization is preferred both on theoretical grounds (to
valaciclovir and famciclovir are all effective in prevent ascending infection) and practical grounds.
reducing the severity and duration of episode 9,10.
Topical agents are less effective than oral agents. Special situations HIV-positive patients with rst-
The only indication for the use of intravenous episode genital herpes
therapy is when the patient is unable to swallow or There are no controlled trials on duration and dose
tolerate oral medication because of vomiting. of treatment. Some clinicians advocate a 10-day
Intravenous therapy does not alter the natural course of treatment.
history of genital herpes infection 11.
The regimens recommended are (all for 5 days): Follow up
. Aciclovir 200 mg 5/day, or Patients are followed up until the episode has
. Famciclovir 250 mg 3/day, or resolved and counselling is considered complete.
36 International Journal of STD & AIDS Volume 12 Supplement 3 October 2001

Further follow up may be required to exclude other tance data on patients on long-term therapy now
causes of genital ulceration that may be co-existent. extends to over 11 years of continuous surveillance.
Patients should be invited to reattend should
recurrences be problematic. Recommended regimens
The optimal daily dose of suppressive aciclovir
Recurrent genital herpes therapy is 800 mg. The only published clinical
dose-ranging study concluded that a dose of
Indications for therapy 200 mg 4 times a day was clinically superior to
Genital herpes recurrences are self-limiting and 400 mg twice daily. However, ability to comply
generally cause minor symptoms. Decisions about with a 4 times a day regimen should determine
how best to manage clinical recurrences should be prescribing decisions for individual patients.
made in partnership with the patient. Managemen t Suppressive therapy using famciclovir (250 mg
strategies include supportive therapy only, episo- twice daily) has only been compared with placebo
dic antiviral treatments and suppressive antiviral and not against the current standard of care17.
therapy. The most appropriate strategy for mana- Twice-daily valaciclovir (250 mg twice daily) has
ging an individual patient may vary over time been shown to be as effective as twice-daily
according to recurrence frequency, symptom aciclovir (400 mg twice daily)15 in all patients.
severity and relationship status. For most patients Patients with less frequent recurrences (<10 per
management will need to be supportive only, with annum) may be adequately suppressed on once-
simple local measures such as saline bathing or daily valaciclovir (500 mg once daily). Patients with
topical petroleum jelly being adequate. more frequent disease (>10 attacks per year)
require higher doses of once-daily valaciclovir to
Episodic antiviral treatment maintain control (1000 mg once daily). Once-daily
Oral aciclovir, valaciclovir and famciclovir are aciclovir does not suppress genital herpes recur-
effective at reducing the duration and severity of rences.
recurrent genital herpes. The reduction in duration Therapy should be discontinued after a max-
is a median of 1 2 days for most patients12 14. imum of a year of continuous antiviral therapy to
Valaciclovir is no more or less effective than reassess recurrence frequency. Twenty per cent of
aciclovir15. Famciclovir has not been compared patients will experience a reduction in recurrence
with aciclovir. Famciclovir and valaciclovir have frequency compared with pre-suppression sympto-
not been compared. Both famciclovir and valaci- matic levels. The minimum period of assessment
clovir have a twice-a-day dosing regimen which is should include two recurrences. It is safe and
easier to take than a 5-a-day regime. It is likely that reasonable to restart treatment in patients who
patient-initiated treatment started early in an continue to have an unacceptably high rate of
episode is most likely to be effective. Valaciclovir recurrence.
aborted one in 10 lesional recurrences when Short courses of suppressive therapy to prevent
initiated by patients early in the course of an clinical symptoms may be helpful for some patients
episode13. (e.g. for holidays, exams, etc.).
The recommended regimens are all for 5 days:
Viral shedding and transmission on suppressive therapy
. Aciclovir 200 mg 5 a day or
Subclinical shedding of infectious virus occurs in
. Valaciclovir 500 mg twice daily, or
some individuals with genital HSV-1 and/or HSV-
. Famciclovir 125 mg twice daily, plus suppor-
2. Viral shedding is more likely to occur in patients
tive measures including saline bathing, petro-
with genital HSV-2 infection, in the rst year after
leum jelly.
infection or in individuals with frequent sympto-
Suppressive therapy matic recurrences. In one study, aciclovir 400 mg
All trials of suppressive therapy have been done in twice daily substantially reduced both the number
patients with a recurrence rate equivalent to 56 of women with subclinical viral shedding and the
recurrences/annum. However, it is likely that number of days on which viral shedding oc-
patients with a lower rate of recurrence will also curred18,19. The evidence in men is awaited. The
reduce their rate of recurrence with treatment. The effect of antiviral drugs on rate of sexual transmis-
frequency of recurrence at which it is worth sion has not been established.
starting suppressive therapy is a subjective issue
and needs to balance the frequency of recurrence SPECIAL SITUATIONS
against the cost and inconvenience of treatment.
Management of herpes in immunocompromised
Patients with culture-proven genital herpes who
individuals
have a recurrence rate equivalent to 56 episodes of
genital herpes annually are highly likely to Although rare in immunocompetent individuals,
experience a substantial reduction in recurrence clinically refractory lesions due to genital HSV are
frequency on suppressive antiviral therapy. a major problem in patients with severe immuno-
Experience with suppressive antiviral therapy is de ciency, including late-stage HIV diseases. The
most extensive with aciclovir16. Safety and resis- algorithms in Figure 1 is modi ed from a paper
Barton et al. Management of genital herpes 37

Figure 1. Algorithm for the treatment of herpes in immunocompromised patients

published following a consensus symposium on It is worth bearing in mind the following points
the management of resistant herpes simplex20. when counselling patients.
In addition there is evidence from a randomized,
. Asymptomatic shedding plays a major role in
double blind, placebo-controlled trial that cidofovir
the transmission of HSV infection
gel (0.1% or 0.3% applied once daily for 5 days),
. Partner noti cation is an effective way of
achieves complete healing or >50% decrease in
detecting asymptomatic individuals when
lesional area in up to 50% of patients. However combined with type-speci c antibody testing22
cidofovir has only been compared with placebo
. Up to 50% of asymptomatic HSV-2 seroposi-
and not against current standard of care (foscarnet
tive women can be taught to recognize genital
or tri uridine)21. herpes recurrences after counselling. It may be
possible to prevent transmission by educating
patients to recognize symptomatic recur-
Suppressive antiviral therapy rences23
There is no evidence to suggest that immunocom- . Although there is no de nitive evidence that
promised patients on suppressive therapy for either antiviral treatment or patient educa-
frequently recurring genital herpes need other than tion/counselling alters transmission rates of
the standard regimen. HSV at a population level, it seems logical to
increase awareness of the diagnosis in patients
when appropriate, with the aim of preventing
Management of partners further onward transmission.
There is no evidence on which to base recommen-
Management of pregnant women with rst-
dations for partner noti cation. On an individual
episode genital herpes
basis it may be appropriate to offer to see partners
to help with the counselling process. Partner First and second trimester acquisition
noti cation in relation to pregnancy is discussed . Management of the woman should be in line
below. with her clinical condition and will often
38 International Journal of STD & AIDS Volume 12 Supplement 3 October 2001

involve the use of either oral or intravenous . Pregnant women should be advised of the risk
aciclovir in standard doses of acquiring HSV-1 as a result of orogenital
. Providing that delivery does not ensue, the contact
pregnancy should be managed expectantly . Identical susceptible women by means of type-
and vaginal delivery anticipated speci c antibody testing has not been evalu-
. Continuous aciclovir in the last 4 weeks of ated in terms of costs and bene ts
pregnancy may prevent recurrence at term . All women, not just those with a history of
and hence the need for delivery by Caesarean genital herpes, should undergo careful vulval
section24. inspection at the onset of labour to look for
clinical signs of herpes infection
Third trimester acquisition . Mothers, staff and other relatives/friends with
. Caesarean section should be considered for all active oral lesions should be advised about the
women, particularly those developing symp- risk of postnatal transmission.
toms within 6 weeks of delivery, as the risk of
viral shedding in labour is very high Management of the neonate
. If vaginal delivery is unavoidable, aciclovir
treatment of mother and baby may be in- Babies born to mothers with rst-episode genital herpes
dicated. at the onset of labour
. HSV culture of urine and stool, from the
Management of pregnant women with recurrent oropharynx, eyes and surface sites to allow
genital herpes early identi cation of infected babies
. The potential bene ts and risks of starting
. Sequential cultures during late gestation to intravenous aciclovir without waiting for the
predict viral shedding at term are not results of these cultures should be discussed
indicated25 . If aciclovir is not started immediately the
. Caesarean section to prevent neonatal herpes neonate should be closely monitored for signs
should not be performed in women who do of lethargy, fever, poor feeding or lesions.
not have genital lesions at delivery
. Symptomatic recurrences of genital herpes Babies born to mothers with recurrent genital herpes at
during the third trimester will be brief; vaginal the onset of labour
delivery is appropriate if no lesions are present . One set of specimens for viral culture collected
at delivery after delivery may help with early identi ca-
. The bene ts of obtaining specimens for culture tion of infection
at delivery, in order to identify women who . Parents should be advised to report early any
are asymptomatically shedding HSV, are signs of infection (lethargy, fever, poor feeding
unproven. or lesions).

Management of women with genital lesions at References


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