ArticlePDF AvailableLiterature Review

Genital herpes and its management

Authors:

Abstract

Genital herpes is an important public health disease and is the leading cause of genital ulcer disease worldwide. We present the latest evidence based guidelines from the British Association for Sexual Health and HIV (BASHH), the Centers for Disease Control and Prevention (CDC), and other expert committees to provide an up to date account of genital infection with herpes simplex virus (HSV), its clinical features and diagnosis, and a practical approach to management of affected patients. Treatment regimens have largely been based on evidence obtained from randomised controlled trials, while certain new diagnostic tests are limited by lower levels of evidence obtained only from descriptive or case studies. #### Summary points We searched PubMed (1966-2006) for relevant studies using keywords and text terms for genital herpes. We accessed the WHO and Health Protection Agency (United Kingdom) website to assess the disease burden of genital herpes and consulted guidelines on genital herpes from the British Association for Sexual Health and HIV (2001) and the Centers for Disease Control and Prevention (CDC, 2006). Additional data and references were obtained from International Union against Sexually Transmitted Infections (IUSTI) meetings, BASHH meetings, the International Herpes Management Forum (IHMF), the World STI/HIV congress, and a personal archive of …
CLINICAL REVIEW
Genital herpes and its management
P Sen,
1
S E Barton
2
Genital herpes is an important public health disease
and is the leading cause of genital ulcer disease
worldwide. We present the latest evidence based
guidelines from the British Association for Sexual
Health and HIV (BASHH), the Centers for Disease
Control and Prevention (CDC), and other expert
committees to provide an up to date account of
genital infection with herpes simplex virus (HSV),
its clinical features and diagnosis, and a practical
approach to management of affected patients.
Treatment regimens have largely been based on
evidence obtained from randomised controlled
trials, while certain new diagnostic tests are limited
by lower levels of evidence obtained only from
descriptive or case studies.
Sources and selection criteria
We searched PubMed (1966-2006) for relevant
studies using keywords and text terms for genital
herpes. We accessed the WHO and Health Protection
Agency (United Kingdom) website to assess the
disease burden of genital herpes and consulted
guidelines on genital herpes from the British
Association for Sexual Health and HIV (2001) and
the Centers for Disease Control and Prevention
(CDC, 2006). Additional data and references were
obtained from International Union against Sexually
Transmitted Infections (IUSTI) meetings, BASHH
meetings, the International Herpes Management
Forum (IHMF), the World STI/HIV congress, and a
personal archive of references.
What causes genital herpes and how is infection
acquired?
Genital herpes is caused by infection with herpes
simplex virus (HSV), commonly by HSV type 2 and
now increasingly by type 1. Both HSV-1 and HSV-2
infections are acquired from contact with infectious
secretions on oral, genital, or anal mucosal surfaces.
Genital herpes can also be acquired from contact
with lesions from other anatomical sites such as the
eyes and non-mucosal surfaces such as herpetic
whitlow on fingers or from lesions on the buttocks
and trunk.
What is the prevalence of genital herpes in the UK and
worldwide?
In the UK, there was a 15% increase in the number of
diagnoses of first attack of genital herpes from 16 479
cases in 1995 to 19 180 cases in 2004.
1
In the United
States, an estimated 40-60 million people are infected
with HSV-2, with an incidence of 1-2 million infections
and 600 000-800 000 clinical cases a year.
2
The
prevalence of genital herpes in developing countries
varies from 2-74% according to the country. In some
African countries that are experiencing HIV
epidemics, HSV-2 is highly prevalent (70%), and
there is evidence that genital HSV increases the risk
of HIV infection and that people with both are more
likely to transmit HIV infection.
3
How do patients present?
First (initial) episode of genital herpes
The initial episode is the first episode of genital
infection with either HSV-1 or HSV-2 (box 1).
Primary genital herpes is the first episode in an
individual with no pre-existing antibodies to either
HSV type. A non-primary first episode is the first
infection in an individual with pre-existing antibodies
to the other HSV type.
45
Recurrent genital herpes
Groups of vesicles or ulcers develop in a single
anatomical site and heal within 10 days. For the first
two years patients may experience an average of five
clinical episodes a year, which may reduce in
frequency thereafter. Genital HSV caused by type 1
infection recurs less often, and thus typing of infection
may inform patient counselling.
Box 1
|
Presentation of first episode of genital herpes
Often severe
Multiple grouped vesicles that rupture easily leaving
painful erosions and ulcers
In men, the lesions occur mainly on the prepuce and
subpreputial areas of the penis
In women, the lesions occur on the vulva, vagina, and
cervix
There may be associated systemic symptoms such as
fever and myalgia
Healing of uncomplicated lesions takes two to four
weeks
Severe complications are rare but can include
autonomic neuropathy with urinary retention and
aseptic meningitis
1
National Skin Centre, 1 Mandalay
Road, Singapore 308205
2
Directorate of HIV and
GU Medicine, Chelsea and
Westminster Hospital Foundation
NHS Trust, London SW10 9NH
Correspondence to: S Barton
simon.barton@chelwest.nhs.uk
BMJ 2007;334:1048-52
doi: 10.1136/bmj.39189.504306.55
1048 BMJ |19 MAY 2007 |VOLUME 334
For the full versions of these articles see bmj.com
Asymptomatic HSV infection
Most people with HSV infection have mild unrecog-
nised or subclinical disease and are unaware of their
infection. They may shed the virus intermittently in the
genital tract and thus transmit the infection to their sexual
partners entirely unknowingly. Subclinical shedding
occurs most commonly in the first year of infection in
patients with genital HSV-2 infection and in individuals
with frequent symptomatic recurrences. Perianal shed-
ding is common in HIV negative, HSV-2 seropositive
men who have sex with men and are asymptomatic.
w1
Most infections of genital herpes are transmitted by
people who are unaware that they are infected or who
have no symptoms when transmission occurs.
How do I make a diagnosis of genital herpes?
The clinical diagnosis of genital HSV infection has a
low sensitivity and specificity; laboratory confirmation
of infection and typing of HSV is essential as it
influences the management, prognosis, and counsel-
ling of patients.
Detection of HSV in clinical lesions
Table 1 compares
the methods of detection. Take swabs from the base of
the lesion or fluid from a vesicle. For culture tests it is
essential that the cold chain (4ºC) is maintained and
appropriate media are used. Polymerase chain
reaction (PCR) is the most useful test as less meticulous
handling of specimens is required.
Serology
Commercial tests that use complement
fixation are not type specific. Seroconversion from a
zero baseline is usually diagnostic of a primary
infection. In the case of recurrent infection, an
immune response from a non-zero baseline may be
detected. These tests cannot distinguish between
initial and recurrent infections, however, and have
been replaced by sensitive tests such as enzyme linked
immunosorbent assay (ELISA) and radio-
immunoassay (RIA). Type specific serology tests
(TSSTs), which detect glycoprotein G2 specific to
HSV-2 and glycoprotein G1 specific to HSV-1
infection, are the only commercially available
diagnostic tools available to identify those with
asymptomatic HSV infection and can effectively
distinguish the two types with high sensitivity
(80-98%) and specificity (96%).
8
Case control studies
have shown that there are certain clinical settings
when these tests may help the diagnosis of HSV
infection
9 w2-w4
(boxes 2 and 3).
How do I manage patients with genital herpes?
First episode of genital herpes
General measures (evidence level IV, grade C, table 2)
for treating patients with a first episode include
cleaning affected areas with normal saline, giving
analgesia (systemic or local, such as lidocaine gel),
and treating any secondary bacterial infection.
Specific antiviral therapy
Aciclovir has a good record of safety and efficacy and is
available in generic formulations. Other drugs, such as
valaciclovir and famciclovir, have less frequent dosing
regimens compared with aciclovir (box 4) but are more
expensive. Randomised control trials have shown that
all three drugs reduce the severity and duration of
clinical attacks.
10 w5
None of these drugs eradicate the
infection or latent virus.
There is no evidence of benefit from courses of treat-
ment longer than five days. BASHH guidelines, how-
ever, recommend that treatment should be continued
beyond five days if new lesions continue to form, if
Table1
|
Comparisonof detection methods forHSV in clinical lesions
67
Tzanck smear Virus culture
Antigen detection
(DFA or EIA) PCR
Sensitivity Low High Low Highest
Specificity Low High High High
Viral typing No Yes No Yes
Comments Shows giant cells from lesions,
provides presumptive evidence
of infection
Ideal test. Sensitivity declines
as lesions heal
Low cost and rapid Rapid but expensive. Useful in late
clinical lesions. Test of choice in
examination of cerebrospinal fluid.
Used for research studies
DFA
=
direct fluorescent antigen; EIA
=
enzyme immunoassay; PCR=polymerase chain reaction.
Box 2
|
When type specificserology testing can be
useful
9w2-w4
The patient
s partner has genital herpes and patient
wants to know if he or she has been infected
The patient presents with recurrent genital or atypical
ulcers and results of culture or polymerase chain
reaction tests are negative
Screening of individuals at high risk of sexually
transmitted infections
Testing of pregnant women with undiagnosed genital
herpes
Box 3
|
When type specific serology testing is not useful
and should not be used
9w2-w4
To differentiate oral from genital HSV-1 infection
During the 2 to 12 weeks after infection as it is not
known how long after infection the test results remain
positive as antibody levels
serorevert
to normal over
time
In children aged <14 years as it has a low sensitivity
and specificity
In medicolegal cases as viral culture is the ideal test
for genital herpes
CLINICAL REVIEW
BMJ |19 MAY 2007 |VOLUME 334 1049
symptoms and signs are severe, or if the patient also has
HIV. The guidelines also state that combined oral and
topical treatment is of no additional benefit. Numerous
over the counter and internet based topical and oral
herbal curesare available. There is no scientific evi-
dence for the use of essential oils, plant extracts, zinc,
and L-lysine, and they have no place in the manage-
ment of genital herpes.
Our preferred treatment is aciclovir 400 mg orally
three times a day for seven days because it is effective,
low cost, and patients comply with treatment.
Recurrent genital herpes
Treatment of recurrent attacks includes supportive
therapy, episodic antiviral therapy, or suppressive
antiviral therapy. Most recurrent attacks are mild and
self limiting however, and can be managed with
supportive therapy only. General measures for treating
patients include cleaning the affected areas with norma
l saline, giving analgesia (systemic or local such as
lidocaine gel), and treating secondary bacterial
infection.
Supportive therapy
Supportive therapy includes
saline bathing, the use of analgesia, and counselling
of sexual behaviour and can be instituted when
recurrences are mild and self limiting.
Episodic antiviral therapy (1a, A)
Initiate episodic
antiviral therapy during the prodrome or early in an
attack (box 5).
w6
Oral aciclovir, valaciclovir,
11
and
famciclovir
w7
reduce the severity and duration by a
median of one to two days.
w6 w8 w9
Topical antiviral
therapy is less effective than systemic therapy.
4 w10
Randomised controlled trials have shown all these
regimens to be effective. Our preferred treatment is
aciclovir 400 mg orally three times a day for five days
because it is effective and low cost.
Suppressive antiviral therapy (1a, A)
Meta-analyses of
randomised controlled trials have shown that
suppressive antiviral therapy can significantly reduce
(by 70 to 80%) the number of recurrences in patients
with frequently recurring (6 recurrences a year)
genital herpes.
12 w11
Box 6 shows the recommended
regimen. Patients should discontinue treatment after
12 months to assess the ongoing frequency of
recurrences. The timing of this should be agreed
with the patient, and recurrences should be treated.
How do I manage patients with asymptomatic HSV
infection?
A landmark study by Corey et al found that daily
suppressive treatment with valaciclovir can reduce
HSV-2 transmission among HSV-2 discordant
heterosexual couples by 75% for clinical disease and
reduce acquisition (measured by serology) by 48%.
13
Other antiviral drugs may be effective but have not been
investigated.
14
What are the important points to discuss when
counselling patients?
Counselling infected people and their sexual partners
is integral to the successful management of genital
Table 2
|
Details of gradeof recommendation and equivalent evidencelevel
Grades Requirement Equivalent evidence level
A At least one randomisedcontrolled trial as part of the body
of literature of overall good quality and consistency
addressing the specific recommendation
Ia
evidence obtained from meta-analysis of randomised
controlled trials;Ib
evidence obtained from at least one
randomised controlled trial
B Availability of well controlled clinical studies but no
randomised clinical trials on topic of recommendation
IIa
evidence obtained from at least one well designed
controlled study without randomisation; IIb
evidence
obtained from atleast one other type of well designed
quasi-experimental study;III
evidenceobtained from well
designed non-experimental descriptive studies, such as
comparative studies, correlation studies and case studies
C Evidence obtained from expert committed reports or
opinions or clinical experiences of respected authorities,
or both. Indicates absence of directly applicable clinical
studies of good quality
IV
evidence obtained from expert committee reports or
opinions and/or clinical experiences of respected
authorities
Box 4
|
Recommended regimens for firstepisode of
genital herpes (1b, A)
34
Aciclovir 200 mg orally five times a day for 5-10 days
or
Aciclovir 400 mg orally three times a day for 5-10 days
or
Valaciclovir 500 mg to 1 g orally twice a day for
5-10 days or
Famciclovir 250 mg orally three times a day for
5-10 days
Box 5
|
Recommended regimens for episodic therapy
(1a, A)
34
Aciclovir 200 mg orally five times a day for 5 days or
Aciclovir 400 mg orally three times a day for 5 days or
Aciclovir 800 mg orally twice a day for 5 days or
Aciclovir 800 mg orally three times a day for 2 days or
Valaciclovir 500 mg orally twice a day for 3-5 days or
Valaciclovir 1 g orally once a day for 5 days or
Famciclovir 125 mg orally twice a day for 5 days or
Famciclovir 1 g orally twice a day for 1 day
CLINICAL REVIEW
1050 BMJ |19 MAY 2007 |VOLUME 334
herpes.
w12
Physicians should provide counselling to
help patients cope with infection and prevent sexual
and perinatal transmission.
15
We have summarised the various points that
physicians need to consider and discuss when
counselling patients (box 7). This guide comes from
personal practices and guidance from the British
Association for Sexual Health and HIV (BASHH),
the Centers for Disease Control and Prevention
(CDC), and the International Herpes Management
Forum. Educational reading material
16
and access to
web based literature on genital herpes should be
provided as part of the counselling process.
How do I manage genital herpes in a pregnant woman?
Data from the aciclovir pregnancy registry on the use
of aciclovir in pregnancy does not show any increase in
the number of birth defects.
w13
First episode of genital herpes
For women who acquire the infection in the first and
second trimester treat with oral or intravenous
aciclovir in standard doses and plan for vaginal
delivery. For women in who vaginal delivery is
planned, continuous aciclovir in the last four weeks of
pregnancy will reduce the risk of clinical recurrence at
term delivery by caesarean section (1b, A).
17
All women presenting with the first episode of
genital herpes after 34 weeksgestation should be
delivered by caesarean section. If vaginal delivery
is unavoidable, treat the mother and baby with
aciclovir.
Recurrent genital herpes
In women with recurrent infection caesarean section
should not be performed if there are no genital lesions
at the time of delivery. Daily suppressive aciclovir in
the last four weeks of pregnancy might prevent
recurrences of genital herpes at term and might be cost
effective.
18 w14
If genital lesions are present at the onset
of labour, experts recommend delivery by caesarean
section.
19
What is the interaction between genital HSV-2 and HIV?
Both HSV and HIV have reached epidemic
proportions in certain developing countries. Genital
herpes caused by HSV-2 infection has been shown to
double the risk of becoming infected with HIV
through sexual transmission.
20
The ulcers and breaks
in the genital mucosa and skin caused by HSV-2
infection facilitate entry of the HIV virus. These lesions
contain large numbers of CD4 lymphocytes, which are
target cells for HIV. Transmission of HIV is more
likely from people who also have HSV-2,
w15
possibly
because of high titres of HIV in genital secretions
during HSV-2 reactivation.
w16
How do I manage genital herpes in HIV positive or
immunocompromised patients?
In patients with HIV or who are otherwise immuno-
compromised, episodes may be prolonged, more
severe, and require a longer duration of antiviral
treatment (box 8). A recent study found that treatment
with valaciclovir at 1 g a day significantly reduced HIV
RNA genital shedding as well as the plasma viral
load.
21
These data support the hypothesis that therapy
Box 7
|
Points to discuss during counselling
5-16
Information on the natural course of the disease, the potential for recurrent attacks,
and the role of asymptomatic shedding in sexual transmission. Patients should be
informed that asymptomatic viral shedding is more common in genital HSV-2 than
HSV-1 infection and is most frequent in the first 12 months after the infection is
acquired.
Patients with a first episode of genital herpes should be told that this does not
necessarily indicate recent infection and that genital symptoms may develop several
years after the infection is acquired.
Information on antiretroviral treatments available and their impact on infectivity.
Episodic as well as suppressive therapy should be discussed with patients in respect
to recurrent episodes of infection.
Patients in a stable long term relationship where one partner is not infected may
remain discordant for several years despite potential repeated exposure; they should
be told that the risk of sexual transmission of HSV-2 can be reduced by the daily use
of valaciclovir by the infected partner.
Abstention from sexual activity during prodromal symptoms or when lesions are
present.
Advice to inform current and new sexual partners before initiating a sexual
relationship.
Use of condoms with new or uninfected partners, particularly in the 12 months after
the first attack.
Sexual partners of infected patients should be advised that they may be infected
even if they have no symptoms. Type specific serological testing should be offered to
them to determine whether they are at risk of HSV acquisition.
Asymptomatic people who test positive for HSV-2 infection on type specific serology
testing should be counselled in the same way as those with symptoms and taught to
recognise the clinical manifestations of infection.
Women with a history of genital herpes or with male partners with a history of genital
herpes should inform their doctors early in any pregnancy to prevent the risk of
neonatal infections.
Pregnant women who are not infected with HSV-2 should avoid sexual intercourse
with their male infected partners during the third trimester. Pregnant women who are
not infected with HSV-1 should also avoid genital exposure to HSV-1 during the third
trimester (such as oral sex with a partner with oral herpes and vaginal intercourse
with a partner with genital HSV-1 infection).
Box 8
|
Recommended regimens for daily suppressive
therapy in peoplewith HIV (1b, A)
4
Aciclovir 400-800 mg orally two to three times a day or
Valaciclovir 500 mg orally twice a day or
Famciclovir 500 mg orally twice a day
Box6
|
Recommendedregimensforsuppressivetherapy
(1a, A)
34
Aciclovir 400 mg orally twice a day or
Valaciclovir 250 mg orally twice a day or
Valaciclovir 500 mg once daily or
Valaciclovir 1 g once daily or
Famciclovir 250 mg orally twice a day
CLINICAL REVIEW
BMJ |19 MAY 2007 |VOLUME 334 1051
for genital HSV infection in people with HIV reduces
the risk of their transmitting HIV and may affect the
natural progression of HIV infection. Further studies
to investigate this are ongoing.
What about a vaccine?
To date the development of effective vaccines has not
been promising. Difficulties arise because of the com-
plexity of the life cycle of the virus (latency) and the
current lack of understanding of the human mechan-
ism of control of primary and recurrent disease.
22
A
large scale study of a gD2-AS04 vaccine is being car-
ried out to further evaluate the protective effects in
women as initial studies have shown differential effects
in men and women.
Conclusions
Genital herpes is an important public health
disease that can cause substantial morbidity if it is
undiagnosed and untreated. Clinicians should
suspect HSV infection in all patients presenting
with ulcers in the genital area. Genital HSV infection
increases the risk of HIV infection and people with
both infections are more likely to transmit HIV to
their sexual partners.
Contributors: Both authors contributed equally to the manuscript.
Competing interests: None declared.
Provenance and peer review: Commissioned, peer reviewed.
1 UK Collaborative group for HIV and STI Surveillance. HIV and other
sexually transmitted infections in the United Kingdom: 2005. Part 2
other sexually transmitted infections. Genital herpes. www.hpa.
org.uk/publications/2005/hiv_sti_2005/herpes.htm
2 World Health Organization. Herpes simplex type 2. www.who.int/
vaccine_research/diseases/soa_std/en/index3.html.
3 Celum C, Levine R, Weaver M, Wald A. Genital herpes and human
immunodeficiency virus: double trouble. Bull World Health Organ
2004;82:447-53.
4 British Association for Sexual Health and HIV. National guideline for
the management of genital herpes. London: BASHH, 2001.
5 Centers for Disease Control and Prevention. Sexually transmitted
diseases treatment guidelines. Atlanta, GA: CDC, 2006.
6 Scoular A, Gillespie G, Carman WF. Polymerase chain reaction for
diagnosis of genital herpes in a genitourinary medicine clinic. Sex
Transm Infect 2002;78:21-5.
7 Ashley RL. Laboratory techniques in the diagnosis of herpes simplex
infection. Genitourin Med 1993;74:175-8.
8 Wald A, Ashley-Morrow R. Serological tests for herpes simplex virus
(HSV)-1 and HSV-2 infection. Clin Infect Dis
2002;35(suppl 2):S173-82.
9 Ashley RL. Sorting out the new HSV type specific antibody tests. Sex
Transm Infect 2001;77:232-7.
10 Fife KH, Barbarash RA, Rudolph T, Degregorio B, Roth R. Valaciclovir
versus acyclovir in the treatment of first-episode genital herpes
infection. Results of an international, multicenter, double-blind,
randomized clinical trial. Sex Transm Dis 1997;24:481-6.
11 Patel R, Bodsworth NJ, Woolley P, Peters B, Vejlsgaard G, Saari S,
et al. Valaciclovir for the suppression of recurrent genital HSV
infection: a placebo controlled study of once daily therapy.
Genitourin Med 1997;73:105-9.
12 Mertz GJ, Jones CC, Mills J, Fife KH, Lemon SM, Stapleton JT, et al.
Long-term acyclovir suppression of frequently recurring genital
herpes simplex virus infection. A multicenter double-blind trial. JAMA
1988;260:201-6.
13 Corey L, Wald A, Patel R, Sacks SL, Tyring SK, Warren T, et al. Once-
daily valacyclovir to reduce the risk of transmission of genital herpes.
NEnglJMed2004;350:11-20.
14 Barton SE. Reducing the transmission of genital herpes. BMJ
2005;330:157-8.
15 PatelR,TyringS,StrandA,PriceMJ,GrantDM.Impactofsuppressive
therapy on the health related quality of life of patients with recurrent
genital herpes infection. Sex Transm Infect 1999;75:398-402.
16 International Herpes Management Forum. Patient information
leaflets. www.ihmf.org/Patient/PatientResources.asp
17 Scott LL, Sanchez PJ, Jackson GL, Zeray F, Wendel G Jr. Acyclovir
suppression to prevent caesarian section delivery after first-episode
genital herpes. Obstet Gynecol 1996;87:69-73.
18 Little SE, Caughey AB. Acyclovir prophylaxis for pregnant women with
a known history of herpes simplex virus: a cost-effectiveness
analysis. Am J Obstet Gynecol 2005;193:1274-9.
19 Catalano PM, Merritt AO, Mead PB. Incidence of genital herpes
simplex virus at the time of delivery in women with known risk
factors. Am J Obstet Gynecol 1991;164:1303-6.
20 Wald A, Link K. Risk of human immunodeficiency virus infection in
herpes simplex virus type 2 seropositive persons: a meta-analysis. J
Infect Dis 2002;185:45-52.
21 Nagot N, Ouedraogo A, Mayaud P, Konate I, Vergne L, Weiss H, et al.
Effect of HSV-2 suppressive therapy on HIV-1 genital shedding and
plasma viral load: a proof of concept randomized double-blind
placebo controlled trial (ANRS 1285 trial.) 13th Conference on
Retroviruses and Opportunistic Infections, Denver 2006 (abstract
33LB). www.retroconference.org/2006/.
22 Aurelian L. Herpes simplex virus type 2 vaccines: new ground for
optimism? Clin Diagn Lab Immunol 2004;11:437-45.
ADDITIONAL EDUCATIONAL RESOURCES
World Health Organization (www.who.int/topics/sexually_transmitted_infections/en/)
offers factsheets and latest publications and research on genital herpes
Centres for Disease Control And Prevention (www.cdc.gov/std/Herpes/default.htm)
offers factsheets on genital herpes
Sexually Transmitted Diseases Diagnostics Initiative (www.who.int/std_diagnostics)
Kimberlin DW, Rouse DJ. Genital herpes. N Engl J Med 2004;350:1970-7.
Jones CA, Cunningham AL. Vaccination strategies to prevent genital herpes and
neonatal herpes simplex virus (HSV) disease. Herpes 2004;11:12-7.
Information resources for patients
International Herpes Management Forum (www.ihmf.org/Patient/PatientResources.
asp)
this site offers information leaflets for patients on genital herpes; the materials
have been written in collaboration with people who have genital herpes to help others
with the condition. The International Herpes Alliance offers support and information to
those with genital herpes, those helping to manage the disease, and national patient
support groups around the world
Australian Forum (www.herpes.com.au)
Herpes Health (Canadian site) (www.herpeshealth.com)
Association Herp
è
s Actualit
é
s (French site) (www.herpes.asso.fr)
Herpes Informatie Organisatie (Dutch site) (www.hiso.nl)
New Zealand Herpes Management Forum (www.herpes.org.nz)
British Association for Sexual Health and HIV (www.bashh.org/guidelines/2002/
hsv_0601.pdf)
offers the latest UK management guidelines on genital herpes
Centers for Disease Control and Prevention (www.cdc.gov/std/Herpes/default.htm)
offers facts, statistics, treatment guidelines, and other resources on genital herpes
SUMMARY POINTS
Genital herpes is the leading cause of genital ulcer disease
worldwide
Most patients with genital herpes have no symptoms and
shed virus intermittently in the genital tract
Counselling of patients and their sexualpartners is critical in
the management of genital herpes
Caesarean section is recommended for all pregnant women
presenting with a first episode of genital herpes after
34 weeks
gestation
Genital herpes caused by HSV-2 infection has been shown
to double the risk of becoming infected with HIV through
sexual transmission
Suppressive antiviral therapy for genital herpes should be
routinely offered to people with both HSV and HIV
CLINICAL REVIEW
1052 BMJ |19 MAY 2007 |VOLUME 334
Chapter
Acute Care and Emergency Gynecology covers almost 100 common and uncommon gynecologic problems encountered in urgent and emergency settings. Problems are presented in a case-based approach, integrating relevant evidence-based major Society recommendations where available, and supplementing with carefully researched expert opinion for many common situations for which no guidelines apply. The emphasis in on management. Discussions are designed to be detailed enough to guide practice, but focused to where they can be read in the time available prior to seeing a patient. The book serves two goals: first, it is designed for the many providers who prefer case-based learning, particularly for continuing professional development purposes; secondly, it is designed for rapid reference for someone seeing a similar case in this setting. Essential reading for physicians, midwives, nurse practitioners, and physician assistants in the areas of gynecology, family medicine, and primary care who provide gynecologic care in the urgent and emergency setting.
Chapter
Acute Care and Emergency Gynecology covers almost 100 common and uncommon gynecologic problems encountered in urgent and emergency settings. Problems are presented in a case-based approach, integrating relevant evidence-based major Society recommendations where available, and supplementing with carefully researched expert opinion for many common situations for which no guidelines apply. The emphasis in on management. Discussions are designed to be detailed enough to guide practice, but focused to where they can be read in the time available prior to seeing a patient. The book serves two goals: first, it is designed for the many providers who prefer case-based learning, particularly for continuing professional development purposes; secondly, it is designed for rapid reference for someone seeing a similar case in this setting. Essential reading for physicians, midwives, nurse practitioners, and physician assistants in the areas of gynecology, family medicine, and primary care who provide gynecologic care in the urgent and emergency setting.
Chapter
Acute Care and Emergency Gynecology covers almost 100 common and uncommon gynecologic problems encountered in urgent and emergency settings. Problems are presented in a case-based approach, integrating relevant evidence-based major Society recommendations where available, and supplementing with carefully researched expert opinion for many common situations for which no guidelines apply. The emphasis in on management. Discussions are designed to be detailed enough to guide practice, but focused to where they can be read in the time available prior to seeing a patient. The book serves two goals: first, it is designed for the many providers who prefer case-based learning, particularly for continuing professional development purposes; secondly, it is designed for rapid reference for someone seeing a similar case in this setting. Essential reading for physicians, midwives, nurse practitioners, and physician assistants in the areas of gynecology, family medicine, and primary care who provide gynecologic care in the urgent and emergency setting.
Chapter
Acute Care and Emergency Gynecology covers almost 100 common and uncommon gynecologic problems encountered in urgent and emergency settings. Problems are presented in a case-based approach, integrating relevant evidence-based major Society recommendations where available, and supplementing with carefully researched expert opinion for many common situations for which no guidelines apply. The emphasis in on management. Discussions are designed to be detailed enough to guide practice, but focused to where they can be read in the time available prior to seeing a patient. The book serves two goals: first, it is designed for the many providers who prefer case-based learning, particularly for continuing professional development purposes; secondly, it is designed for rapid reference for someone seeing a similar case in this setting. Essential reading for physicians, midwives, nurse practitioners, and physician assistants in the areas of gynecology, family medicine, and primary care who provide gynecologic care in the urgent and emergency setting.
Chapter
Acute Care and Emergency Gynecology covers almost 100 common and uncommon gynecologic problems encountered in urgent and emergency settings. Problems are presented in a case-based approach, integrating relevant evidence-based major Society recommendations where available, and supplementing with carefully researched expert opinion for many common situations for which no guidelines apply. The emphasis in on management. Discussions are designed to be detailed enough to guide practice, but focused to where they can be read in the time available prior to seeing a patient. The book serves two goals: first, it is designed for the many providers who prefer case-based learning, particularly for continuing professional development purposes; secondly, it is designed for rapid reference for someone seeing a similar case in this setting. Essential reading for physicians, midwives, nurse practitioners, and physician assistants in the areas of gynecology, family medicine, and primary care who provide gynecologic care in the urgent and emergency setting.
Chapter
Acute Care and Emergency Gynecology covers almost 100 common and uncommon gynecologic problems encountered in urgent and emergency settings. Problems are presented in a case-based approach, integrating relevant evidence-based major Society recommendations where available, and supplementing with carefully researched expert opinion for many common situations for which no guidelines apply. The emphasis in on management. Discussions are designed to be detailed enough to guide practice, but focused to where they can be read in the time available prior to seeing a patient. The book serves two goals: first, it is designed for the many providers who prefer case-based learning, particularly for continuing professional development purposes; secondly, it is designed for rapid reference for someone seeing a similar case in this setting. Essential reading for physicians, midwives, nurse practitioners, and physician assistants in the areas of gynecology, family medicine, and primary care who provide gynecologic care in the urgent and emergency setting.
Chapter
Acute Care and Emergency Gynecology covers almost 100 common and uncommon gynecologic problems encountered in urgent and emergency settings. Problems are presented in a case-based approach, integrating relevant evidence-based major Society recommendations where available, and supplementing with carefully researched expert opinion for many common situations for which no guidelines apply. The emphasis in on management. Discussions are designed to be detailed enough to guide practice, but focused to where they can be read in the time available prior to seeing a patient. The book serves two goals: first, it is designed for the many providers who prefer case-based learning, particularly for continuing professional development purposes; secondly, it is designed for rapid reference for someone seeing a similar case in this setting. Essential reading for physicians, midwives, nurse practitioners, and physician assistants in the areas of gynecology, family medicine, and primary care who provide gynecologic care in the urgent and emergency setting.
Chapter
Acute Care and Emergency Gynecology covers almost 100 common and uncommon gynecologic problems encountered in urgent and emergency settings. Problems are presented in a case-based approach, integrating relevant evidence-based major Society recommendations where available, and supplementing with carefully researched expert opinion for many common situations for which no guidelines apply. The emphasis in on management. Discussions are designed to be detailed enough to guide practice, but focused to where they can be read in the time available prior to seeing a patient. The book serves two goals: first, it is designed for the many providers who prefer case-based learning, particularly for continuing professional development purposes; secondly, it is designed for rapid reference for someone seeing a similar case in this setting. Essential reading for physicians, midwives, nurse practitioners, and physician assistants in the areas of gynecology, family medicine, and primary care who provide gynecologic care in the urgent and emergency setting.
Chapter
Acute Care and Emergency Gynecology covers almost 100 common and uncommon gynecologic problems encountered in urgent and emergency settings. Problems are presented in a case-based approach, integrating relevant evidence-based major Society recommendations where available, and supplementing with carefully researched expert opinion for many common situations for which no guidelines apply. The emphasis in on management. Discussions are designed to be detailed enough to guide practice, but focused to where they can be read in the time available prior to seeing a patient. The book serves two goals: first, it is designed for the many providers who prefer case-based learning, particularly for continuing professional development purposes; secondly, it is designed for rapid reference for someone seeing a similar case in this setting. Essential reading for physicians, midwives, nurse practitioners, and physician assistants in the areas of gynecology, family medicine, and primary care who provide gynecologic care in the urgent and emergency setting.
Article
Full-text available
To investigate whether suppressive antiviral therapy improves health related quality of life in patients with recurrent genital herpes. Health related quality of life was measured using the disease specific recurrent genital herpes quality of life questionnaire (RGHQoL) as part of a randomized, double blind, 52 week, placebo controlled, dose ranging study of once and twice daily valaciclovir or aciclovir for the suppression of recurrent genital herpes in patients with six or more recurrences per year. Of 1479 participants, 1349 patients completed the baseline questionnaire. There were no significant baseline differences in RGHQoL score between any of the treatment groups. After 3 months there were significantly greater improvements in mean RGHQoL scores for all active treatment groups compared with placebo (p < 0.05). Mean RGHQoL score improvements from baseline remained significantly higher in the active treatment groups than in the placebo group after 6 and 12 months, indicating that the improved health related quality of life in patients receiving suppressive antiviral therapy was sustained over a prolonged period of time. Suppressive antiviral therapy is an effective strategy for improving the quality of life of patients with recurrent genital herpes. These improvements in quality of life are sustained over time, thus enhancing the clinical benefit in the long term management of this condition.
Article
Full-text available
This review will delineate performance characteristics and limitations, as far as they are known, of the new glycoprotein G based, type specific HSV serologies. Several of these tests have been FDA approved in the United States for use in adults. With the departure of Gull/Meridian from the HSV serology market, it is important for clinicians to understand the sources and claims of the remaining type specific tests. Moreover, inaccurate tests using crude antigen preparations remain on the market. These tests are identified based on product insert information provided by company representatives.
Article
Background and Objectives:: Valaciclovir, the L‐valine ester prodrug of acyclovir, is much better absorbed than acyclovir and produces acyclovir exposures three to five times those attainable with the parent drug. Goals:: To determine whether the improved bioavailability of valaciclovir and a more convenient, less frequent dose regimen can maintain the clinical efficacy previously demonstrated for acyclovir. Study Design:: This was an international, multicenter, randomized, double‐blind clinical trial comparing 10‐day regimens of valaciclovir (1000 mg, twice daily) and acyclovir (200 mg, 5 times daily) in the treatment of 643 otherwise healthy adults (≥18 years of age) with first‐episode genital herpes. Patients were evaluated clinically and lesions were staged and cultured on days 1, 2, 3, 5, 7, 10, 14, and then twice weekly until healed. Blood for herpes serology tests was obtained on days 1 and 14; hematology and chemistry toxicity screening was done on days 1 and 7. Results:: Valaciclovir and acyclovir did not differ significantly in efficacy with respect to duration of viral shedding (hazard ratio, 1.00; 95% confidence interval [CI], 0.84–1.18), time to healing (hazard ratio, 1.08; 95% CI, 0.92–1.27), duration of pain (hazard ratio, 1.0; 95% CI, 0.85–1.18), and time to loss of all symptoms (hazard ratio, 1.02; 95% CI, 0.85–1.22). Patients with primary genital herpes (no preexisting antibody to either herpes simplex virus type at enrollment with seroconversion at day 14) had longer times to healing and longer duration of viral shedding and pain than patients with nonprimary first genital episodes. Adverse experiences were generally infrequent and mild and were comparable in the two treatment groups. Conclusions:: Twice‐daily valaciclovir proved as effective and well tolerated in the treatment of first‐episode genital herpes as five‐times‐daily acyclovir. Valaciclovir provides a useful alternative to acyclovir with the advantage of a more convenient dosing regimen and the potential for improved compliance.
Article
A total of 143 women with known risk factors for genital herpes simplex virus had cultures performed at the time of delivery. A total of 123 were without symptoms, of which three (2.4%) had positive herpes simplex virus cultures at the time of delivery. Fifteen women had lesions clinically consistent with genital herpes simplex virus at the time of delivery and five (33.3%) were culture positive. Five women had only prodromal symptoms of genital herpes simplex virus, but two of these (40%) had positive herpes simplex virus cultures from the site of previous lesions. Of the 10 women with positive herpes simplex virus cultures in this group of 143, no infant was delivered with evidence of neonatal herpes simplex virus infection, including two who had vaginal deliveries. The results of this study support the recommendations that in women without symptoms but with known risk factors for genital herpes simplex virus, a trial of vaginal delivery be allowed and that in women with either a lesion clinically consistent with genital herpes simplex virus or prodromal symptoms of genital herpes simplex virus a cesarean section be the mode of delivery.
Article
Normal adults with six or more episodes of genital herpes in the previous year were enrolled in a one-year, multicenter, double-blind trial comparing placebo with 400 mg of acyclovir administered orally twice daily. Patients with episodes during the study were offered 200 mg of acyclovir administered orally five times daily for five days; this allowed comparison of suppressive and episodic treatment. After one year, 227 (44%) of 519 patients receiving suppressive treatment and seven (2%) of 431 receiving placebo (episodic) treatment remained free of recurrences, and the mean numbers of recurrences per year were 1.8 and 11.4, respectively. Among 67 patients who had received suppressive therapy for one year, the mean duration of lesions in the first episode following the discontinuation of treatment was 9.3 days compared with 7.3 days among 45 patients who had received episodic therapy for one year. Treatment was well tolerated, and no changes were noted in the in vitro susceptibility to acyclovir of herpes simplex virus cultured during or after the one-year trial. Continuous or episodic oral acyclovir therapy for one year remained safe and effective.
Article
To determine if suppressive acyclovir therapy given to term gravidas experiencing a first episode of genital herpes simplex virus (HSV)-infection during pregnancy decreases the need for cesarean delivery for that indication. Forty-six pregnant women with first episodes of genital herpes during pregnancy were randomly assigned to receive oral acyclovir 400 mg or placebo, three times per day, from 36 weeks' gestation until delivery as part of a prospective, double-blind trial. Herpes simplex virus cultures were obtained when patients presented for delivery. Vaginal delivery was permitted if no clinical recurrence was present; otherwise, a cesarean was performed. Neonatal HSV cultures were obtained and infants were followed-up clinically. None of the 21 patients treated with acyclovir and nine of 25 (36%) treated with placebo had clinical evidence of recurrent genital herpes at delivery (odds ratio [OR] 0.04, 95% confidence interval [CI] 0.002-0.745; P = .002). No woman treated with acyclovir had a cesarean for herpes, compared with nine of 25 (36%) of those treated with placebo (OR 0.04, CI 0.002-0.745; P = .002). No patient in either treatment group experienced asymptomatic genital viral shedding at delivery. No neonate had evidence of herpes infection or adverse effects from acyclovir. Suppressive acyclovir therapy reduced the need for cesarean for recurrent herpes in women whose first clinical episode of genital HSV occurred during pregnancy. Suppressive acyclovir treatment did not increase asymptomatic viral shedding and was not harmful to the term fetus.
Article
To determine the efficacy and safety of once daily valaciclovir for the suppression of recurrent genital herpes simplex virus (HSV) infection in immunocompetent patients. 382 otherwise healthy patients with a history of frequently recurring genital HSV infection (eight recurrences per year) were randomly allocated to receive either oral valaciclovir (500 mg once daily) or placebo (3:1 ratio) for 16 weeks or until the first genital HSV recurrence, whichever occurred first. Patients were clinically assessed at regular intervals and also if they experienced a recurrence. Safety was evaluated through adverse experience reporting and monitoring of haematology and biochemistry variables. On completion of the double blind phase, patients were eligible for follow up to a maximum of 48 weeks' treatment with open label valaciclovir (500 mg once daily) for further safety monitoring. The results from the double blind phase of the study are reported here. A significant difference was detected between valaciclovir and placebo in the time to first recurrence of genital HSV infection. The hazard ratio [95% confidence interval] for valaciclovir v placebo was 0.155 [0.112, 0.214], p < 0.0001. Valaciclovir prevented or delayed 85% of the recurrences that would have occurred with placebo. After 16 weeks (day 112) with treatment, 69% of patients receiving valaciclovir were recurrence free compared with only 9.5% of patients assigned to placebo. The safety profiles of valaciclovir and placebo were comparable, with adverse experiences being infrequent and generally mild. This study has demonstrated that once daily valaciclovir (500 mg), is highly effective and well tolerated for the suppression of recurrent genital HSV infection. Once daily dosing with valaciclovir provides a more convenient dosing regimen than the more frequent aciclovir regimens.
Article
Valaciclovir, the L-valine ester prodrug of acyclovir, is much better absorbed than acyclovir and produces acyclovir exposures three to five times those attainable with the parent drug. To determine whether the improved bioavailability of valaciclovir and a more convenient, less frequent dose regimen can maintain the clinical efficacy previously demonstrated for acyclovir. This was an international, multicenter, randomized, double-blind clinical trial comparing 10-day regimens of valaciclovir (1000 mg, twice daily) and acyclovir (200 mg, 5 times daily) in the treatment of 643 otherwise healthy adults (> or = 18 years of age) with first-episode genital herpes. Patients were evaluated clinically and lesions were staged and cultured on days 1, 2, 3, 5, 7, 10, 14, and then twice weekly until healed. Blood for herpes serology tests was obtained on days 1 and 14; hematology and chemistry toxicity screening was done on days 1 and 7. Valaciclovir and acyclovir did not differ significantly in efficacy with respect to duration of viral shedding (hazard ratio, 1.00; 95% confidence interval [CI], 0.84-1.18), time to healing (hazard ratio, 1.08; 95% CI, 0.92-1.27), duration of pain (hazard ratio, 1.0; 95% CI, 0.85-1.18), and time to loss of all symptoms (hazard ratio, 1.02; 95% CI, 0.85-1.22). Patients with primary genital herpes (no preexisting antibody to either herpes simplex virus type at enrollment with seroconversion at day 14) had longer times to healing and longer duration of viral shedding and pain than patients with nonprimary first genital episodes. Adverse experiences were generally infrequent and mild and were comparable in the two treatment groups. Twice-daily valaciclovir proved as effective and well tolerated in the treatment of first-episode genital herpes as five-times-daily acyclovir. Valaciclovir provides a useful alternative to acyclovir with the advantage of a more convenient dosing regimen and the potential for improved compliance.
Article
To determine the contribution of herpes simplex type 2 (HSV-2) infection to the risk of human immunodeficiency virus (HIV) acquisition, a systematic review of literature and data synthesis were done. Thirty-one studies addressed the risk of HIV infection in HSV-2–seropositive persons. For 9 cohort and nested case-control studies that documented HSV-2 infection before HIV acquisition, the risk estimate was 2.1 (95% confidence interval, 1.4–3.2). Thus, the attributable risk percentage of HIV to HSV-2 was 52%, and the population attributable risk percentage was 19% in populations with 22% HSV-2 prevalence but increased to 47% in populations with 80% HSV-2 prevalence. For 22 case-control and cross-sectional studies, the risk estimate was 3.9 (95% confidence interval, 3.1–5.1), but the temporal sequence of the 2 infections cannot be documented. Control strategies for HSV-2 need to be incorporated into control of sexually transmitted infections as a strategy for HIV prevention