SeminarGenital herpes
Introduction
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are large double-stranded DNA viruses of the Herpesviridae family.1 HSV-1 and HSV-2 share 83% sequence homology of their protein-coding regions and the structure of their genomes are alike, but can be distinguished serologically.2 These viruses are ubiquitous, affecting both urban and remote populations worldwide. Infections are lifelong with intermittent clinical and subclinical viral reactivation and shedding from mucosal surfaces. HSV infection is the major worldwide cause of sexually transmitted genital ulcers. This Seminar summarises the epidemiology and pathogenesis of HSV and the present approach for the assessment, treatment, and prevention of genital herpes.
Both HSV-1 and HSV-2 cause genital herpes and affect individual and public health. Immunocompetent people with genital HSV infection can have frequent, painful, and recurrent genital lesions associated with much psychosocial distress. Vertical transmission from an infected mother to her baby at delivery can result in disseminated infection, central nervous system complications, or death of the infant, even if treatment is started quickly.3 Over the past two decades, HSV-2 infection has also been linked to a three times higher risk of sexually acquired HIV.4 Mucosal disruption caused by genital ulcers favours HIV acquisition by providing a ready portal of entry.5 Moreover, HSV-2 reactivation results in mucosal infiltration with activated CD4-bearing lymphocytes, the target cells for HIV-1 attachment.6
HSV-1 mainly causes oral infections and is acquired during childhood with seroprevalence in adults reaching 70% in developed countries and 100% in developing countries.7 However, in the past decade, the USA, Canada, and several European countries have seen an upsurge in genital HSV-1 infections, which now account for at least half of first episodes of genital herpes.8, 9, 10, 11, 12 This increase probably results from a delay in acquisition of oral HSV-1 infection early in life in developing countries, and thus remaining susceptible to genital HSV-1 infection at initiation of sexual activity.13 The increase in genital HSV-1 is also in part attributable to an increase in oral sex in young adults, which is viewed as safer than intercourse and as a means of averting pregnancy.14 Although new genital HSV-1 infection is seen infrequently in people with HSV-1 antibodies, those with genital HSV-1 infection remain at risk of genital HSV-2 acquisition.15
HSV-2 is the main cause of genital herpes and is transmitted by sexual contact. The prevalence of HSV-2 rises with initiation of sexual activity in adolescence and steadily increases through adulthood.16 Women are more susceptible to HSV-2 infection than men.17, 18 The serological prevalence of HSV-2 varies from 7–40% in pregnant women19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 (figure 1A), to 60–95% in people infected with HIV and female sex workers26, 30, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48 in different regions of the world (figure 1B). HSV-2 shares risk factors with other sexually transmitted infections (STIs), such as high number of lifetime sexual partners, previous history of STIs, and early age of first sexual intercourse.16
Studies consistently show that only 10–25% of people with HSV-2 antibodies are aware that they have genital herpes.16, 49, 50 Consequently, most HSV transmission occurs from those who are not aware that they are infected.18 Recognition of HSV infection can be difficult because the full clinical range of manifestations is often not appreciated by patients and clinicians.51, 52, 53, 54 Additionally, the diagnosis might be missed because laboratory tests for HSV-2 are not done routinely, even in people tested for other STIs.
Section snippets
Pathophysiology
HSV infection is acquired through close contact with an infected person who is shedding virus from their skin or genital secretions.3 At initial infection, HSV enters the body through skin or mucosal surfaces and initiates cytolytic replication in epithelial cells at the site of entry (figure 2).55 Virions within epithelial cells are seen histologically as intranuclear inclusions, and HSV induces cells to fuse and form multinucleated giant cells. Cell damage in the skin causes epithelial cells
Natural history and diagnosis
The signs and symptoms of HSV infection are diverse and vary in frequency and severity between individuals. Several recognised host and viral factors affect the clinical course. First, the severity of symptoms is much greater for people with primary genital HSV infection (HSV-2 acquisition by a person without pre-existing HSV-1 immunity or HSV-1 acquisition by a seronegative person) than with initial non-primary HSV-2 infection (HSV-2 acquisition by a person with pre-existing HSV-1 immunity).68
Diagnosis and testing
A clinical diagnosis of genital herpes should be confirmed with laboratory tests.78 A definitive diagnosis of HSV guides the most appropriate choice of treatment and identification of the type of HSV provides important information for prognosis. Patients presenting with genital lesions should also be tested for other causes of genital ulcers such as Treponema pallidum and Haemophilus ducreyi, depending on local epidemiology.
A swab from the base of the genital lesion (vesicles should be unroofed
Psychosocial aspects
A diagnosis of genital herpes evokes many emotions including anger, disbelief, low self-esteem, fear of rejection by present and future sexual partners, and depression.90 Anger is usually directed at a present sexual partner, but often, the first diagnosed outbreak does not mean new acquisition.91 Typing of the virus also helps some couples to resolve issues about transmission—HSV-1 genital infection is frequently acquired by receiving oral sex in a monogamous relationship.8, 92, 93 Disbelief
Treatment
Management of genital herpes with antiviral drugs aims to abate the signs and symptoms of genital herpes. In randomised placebo-controlled trials, antiviral therapy resulted in faster symptom resolution and lesion healing, decreased viral shedding, and prevention of new lesions.98 Treatment also prevents complications such as urinary retention and aseptic meningitis.98 Antiviral agents cannot eradicate latent HSV infection and hence do not change the frequency or severity of recurrences, once
First clinical episode
Antiviral treatment for the first episode of genital herpes should be started before laboratory confirmation of diagnosis. Table 3 lists the choice of agents and recommended doses. Treatment duration is usually 7–10 days but should be extended if lesions are not adequately healed.78 Pain-relief measures like sitz baths, in which only the hips and buttocks are immersed, and analgesics can help to bridge the time until antiviral drugs take effect. Intravenous aciclovir (5–10 mg per kg bodyweight,
Conclusion
Genital herpes is a preventable chronic disease. Although most HSV infections are subclinical, clinical disease can be associated with substantial physical and psychosocial morbidity. The clinical manifestations are diverse; hence a suspected diagnosis of HSV should be confirmed by laboratory tests. The management of genital herpes should be tailored to the individual and should include counselling about the variable natural history appearance of lesions, education about prevention of
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