Herpes simplex is a common viral infection that is characterized by small, fluid-filled blisters. Herpes simplex infections are contagious and are usually spread by direct contact. Most infections are quite mild.
There are two forms of the virus: HSV1 (herpes simplex virus, type 1) and HSV2 (herpes simplex virus, type 2). Most people are infected with HSV1 at some time in their lives, usually during childhood. HSV1 is usually associated with infections of the lips, mouth, and face; HSV2 is often associated with infections of the genitals and infections acquired by babies at birth. There is considerable overlap between the two types; sometimes, conditions usually due to HSV1 are caused by HSV2, and vice versa.
Type 1 virus
The initial infection may be symptomless; alternatively, it may cause a flu-like illness with mouth ulcers. Thereafter, the virus remains dormant in nerve cells in the facial area. In many people, the virus is periodically reactivated, causing cold sores that invariably erupt in the same site (usually around the lips). Sometimes the virus can infect a finger after touching a cold sore, causing a painful eruption called a herpetic whitlow. HSV1 may also produce eczema herpeticum (an extensive rash of skin blisters) in a person with a pre-existing skin disorder, such as eczema. Eczema herpeticum may require hospital admission. If the virus gets into an eye it may cause conjunctivitis, which usually lasts only a few days; more seriously, it may cause a corneal ulcer. Rarely, HSV1 spreads to the brain, leading to encephalitis. The virus may cause a potentially fatal generalized infection in a person with an immunodeficiency disorder or in someone taking immunosuppressant drugs.
Type 2 virus
HSV2 is the usual cause of sexually transmitted genital herpes (see herpes, genital), in which painful blisters erupt in the genital area. In some people, the blisters tend to recur.
Treatment of herpes simplex depends on its type, site, and severity of symptoms. Antiviral drugs, such as aciclovir, may be helpful, particularly if used early in an infection.
Herpes simplex viruses (HSV) - medical summary
These two alpha-herpesviruses infect epithelial cells and become latent in the central nervous system. (1) HSV-1—transmitted by direct contact with infected secretions from a carrier; predominantly causes orofacial infections; becomes latent in the trigeminal ganglion; reactivation may give rise to recurrent orolabial mucosal ulcers (‘cold sores’) on the lips or skin around the mouth; is the commonest identified cause of acute sporadic encephalitis occurring in immunocompetent subjects in Western countries. (2) HSV-2—usually acquired through sexual contact and is the predominant cause of genital HSV infection, which may also be recurrent.
Treatment of both HSV-1 and HSV-2 is with aciclovir, which is preferentially phosphorylated in HSV-infected cells, or other newer related drugs (famciclovir and valaciclovir). Oral treatment is used in immunocompetent patients, but intravenous therapy is indicated in severe infections, encephalitis and in immunosuppressed patients.
Herpes simplex virus infections in detail
‘Herpes’ derives from the Greek, meaning to creep or crawl, apparently used since antiquity to describe the evolution of the skin lesions caused by herpes simplex virus (HSV) and varicella–zoster virus. HSV was the first of the herpesviruses to be isolated, in the 1930s, although the transmission of infection to animals had been demonstrated in 1919. The serological distinction between the two types, HSV-1 and HSV-2, and the association of HSV-2 with genital herpes, was made in the 1960s. HSVs are now some of the most intensively studied human viruses.
HSV has a genome size of 150 kbp, and codes for about 80 proteins. The genomes of HSV-1 and HSV-2 are largely colinear, but have different restriction endonuclease sites. Gene expression occurs in three temporally regulated phases: immediate early, early, and late. Immediate-early proteins are largely regulatory proteins that prepare the cell to produce further virus. The early genes code particularly for enzymes involved in the replication of virus DNA, and the late genes for the structural proteins of the virion. Antigenic differences in the surface glycoprotein G are used to distinguish between HSV-1 and HSV-2. The release of progeny virus is normally accompanied by cell death, i.e. the infection is lytic. The virus infects a relatively wide range of cells in vitro, and can also infect experimental animals, allowing studies of its pathogenesis.
HSV is a ubiquitous virus, widely distributed in populations throughout the world. Although animals can be infected experimentally, there are no natural animal hosts, and humans are the only reservoir. Transmission occurs when a susceptible person has direct contact with infected secretions from an HSV carrier, usually from oral, genital, or skin lesions, to mucous membranes or abraded skin of the recipient. HSV carriers can excrete virus asymptomatically, and 1 to 15% of adult carriers excrete HSV at any one time. Conventionally, the prevalence of infection is assessed by demonstrating antibody to HSV-1 or HSV-2. The prevalence of HSV-1 increases with age, although the time of acquisition of HSV-1 antibody varies depending on socioeconomic factors. Seroprevalence in early life is higher among lower socioeconomic groups, 70 to 90% of children having antibodies by the age of 10, whereas only about 30% of children in higher socioeconomic groups have antibodies by this time. By mid life, 80 to 90% of people are HSV-1 seropositive.
HSV-2 infection is usually acquired through sexual contact; consequently, seroconversion correlates with the onset of sexual activity, and a progressive increase in seroprevalence to HSV-2 begins in adolescence. The number of sexual contacts is a major risk factor for the acquisition of HSV-2. Cumulative seroprevalence rates in adults vary from 10 to 80%, depending on the population and risk factors.
HSV can be transmitted to neonates by infection (usually HSV-2) from maternal genital secretions at the time of delivery. The mothers are most often asymptomatic excretors of the virus who have no history of genital herpes.
HSV infects and replicates in epithelial cells at the site of inoculation onto mucous membranes or abraded skin, with an incubation period of 4 to 6 days before clinical lesions appear. There is a marked local inflammatory response, but viraemia and dissemination may occur in the immunocompromised host. Following local epithelial replication, HSV enters the peripheral sensory nerves innervating the site of replication, and ascends the axons by retrograde transport to reach the dorsal root ganglia, or the trigeminal ganglion in the case of oral or conjunctival inoculation. The virus then becomes latent in the sensory ganglia, but despite extensive study, the mechanism of virus latency remains uncertain.
Latent HSV DNA is in an inactive state, with minimal gene expression. RNA species called latency-associated transcripts are the only detectable transcripts. These have no detectable protein product, and their deletion from the genome does not prevent the establishment of latency, although reactivation is impaired. Latent HSV is carried for the lifetime of the host, but may be reactivated in response to certain stimuli, including stress, menstruation, ultraviolet light, and immunosuppression. Upon reactivation, infectious virus is produced, travels down the peripheral nerves by anterograde axonal transport, and replicates in the epithelial cells at the nerve ending.
The neuronal latency of HSV and varicella–zoster virus is an extremely effective method of virus persistence. Latent virus in neuronal cells appears to be inaccessible to the immune response, and as it does not replicate is not susceptible to the action of antiviral drugs. In normal HSV carriers, reactivation at local sites is thought to be controlled by a specific effector T-lymphocyte response. However, HSV DNA encodes proteins that interfere with antigen processing by the class I MHC pathway, and are presumed to help the virus evade the T-cell immune response. There is no good evidence that the immune response to HSV of people who have symptomatic reactivation episodes differs from that of asymptomatic carriers.
Primary infection with HSV is often asymptomatic; among sexually active subjects, only 60% of primary infections with HSV-1, and 40% with HSV-2, are symptomatic. HSV-1 is the predominant cause of orofacial infections, whereas HSV-2 is the usual cause of genital HSV infection, but the clinical manifestations overlap.
This is the most common clinical form of primary infection with HSV-1. It is most often seen in children, following an incubation period of 2 to 12 days. Primary infection may be associated with a considerable systemic reaction, involving fever, sore throat, pharyngeal oedema, and redness. Painful vesicles appear a few days later on the pharynx and oral mucosa, the lips, and the skin around the mouth. There may be cervical lymphadenopathy. Affected patients may have difficulty in eating, and the lesions last from 3 days to 2 weeks. The differential diagnosis includes other causes of pharyngitis, including bacterial pharyngitis and herpangina (from Coxsackie A virus infection). Anterior vesicles and ulceration affecting the lips and skin around the mouth are more suggestive of HSV infection. Stevens–Johnson syndrome and severe aphthous ulceration may appear similar, and staphylococcal impetigo affects the skin around the mouth, but is not associated with oral ulceration.
Reactivation of HSV may give rise to recurrent orolabial lesions, appearing as intraoral mucosal ulcers, but more frequently as the classical cold sore on the lips or skin around the mouth. A tingling sensation in the area of impending ulceration may precede the appearance of vesicles by 1 to 2 days. The lesions usually recur at the same site in individual patients. Around 25% of HSV-1 seropositive people develop recurrent orolabial lesions. The majority have only one or two reactivation episodes per year, although a minority (<10%) have more than one attack per month. The episodes are not associated with systemic symptoms, and diagnosis is usually straightforward.
Infection at other cutaneous sites
HSV infection of the finger, herpetic whitlow, may complicate primary oral or genital herpes by autoinoculation of virus, or may occur through occupational exposure (e.g. in nursing, medical, and dental staff). There is oedema, erythema, and local tenderness of the infected finger. Lesions at the finger tip may be confused with pyogenic bacterial paronychias and incised, which is contraindicated for herpetic whitlow, and may even spread infection.
This is mucocutaneous HSV infection occurring by transmission of virus via skin trauma resulting from wrestling or other contact sports.
HSV infections of the skin are more severe in patients with pre-existing skin disease. In patients with eczema, burns, or other blistering skin diseases, HSV infection may become disseminated.
Cutaneous HSV infection can be confused with herpes zoster, although the latter is usually easy to diagnose by its unilateral dermatomal distribution.
About 15% of all cases of erythema multiforme are preceded by a symptomatic attack of recurrent herpes simplex, and in susceptible people the characteristic rash can be induced by the intradermal inoculation of inactivated herpes simplex virus antigen. The rash of erythema multiforme starts several days after the onset of the herpetic vesicles, and in severe cases can involve the mucous membranes (Stevens–Johnson syndrome). The frequency of these attacks can be reduced by aciclovir prophylaxis.
HSV keratitis is characterized by the acute onset of pain, blurred vision, conjunctival injection, and dendritic ulceration of the cornea. It can cause corneal blindness, and treatment is urgent. Topical aciclovir is the drug of choice; topical steroids may make the infection worse. HSV can also cause an acute necrotizing retinitis, usually only seen in immunosuppressed people, including those with HIV infection.
Primary genital HSV infection is sexually transmitted, and may be associated with systemic symptoms such as fever, headache, and myalgias. Symptoms tend to be more severe in women than men. There is local pain and itching, dysuria, vaginal discharge, and inguinal lymphadenopathy, with vesicles and ulcers on the vulva, perineum, vagina, and cervix, and sometimes on the skin of the buttocks. In males, primary HSV lesions are vesicles on the shaft or glans of the penis, and there may be associated urethritis. HSV-2 causes most genital infections, with a variable smaller proportion resulting from HSV-1. Only 40% of primary HSV-2 genital infections are symptomatic. In patients who have had prior HSV-1 infection, the symptoms of primary genital herpes tend to be less severe. HSV has been isolated from the urethra in 5% of women with urethral syndrome, in the absence of obvious genital lesions. Other manifestations of genital tract disease resulting from primary HSV infection are, rarely, endometritis and salpingitis in women, and prostatitis in men.
HSV proctitis may follow rectal intercourse. There is anorectal pain and discharge, with ulcerative lesions visible on sigmoidoscopy. Perianal lesions are seen in immunosuppressed patients, and spreading perianal HSV infection and HSV proctitis occur in HIV-infected patients.
Recurrent genital herpes is frequent in the first year after primary genital disease (90% for HSV-2 and 55% for HSV-1). Thereafter, the recurrence rate tends to decrease with time, to around three to four attacks per year for HSV-2, but fewer for HSV-1. Severe recurrent genital herpes is particularly troublesome to women.
The complications of primary genital HSV infection include sacral radiculomyelitis, with urinary retention and hyperaesthesia of the perineal area, which usually resolves over several weeks. Aseptic meningitis requiring admission to hospital occurs in up to 7% of women and 2% of men, although suggestive symptoms are more common. Occasionally, and more seriously, transverse myelitis may occur.
Encephalitis is the most serious type of disease produced by HSV in the immunocompetent host, and has an estimated annual incidence of two to three cases per million. It is the most commonly identified cause of acute sporadic encephalitis in Western countries. The great majority of cases are caused by HSV-1. A biphasic age incidence is reported, with higher rates between the ages of 5 and 30 years, and in those older than 50 years. The clinical features are of focal encephalitis, with acute onset of fever, confusion, and unusual behaviour, impaired consciousness, and possibly focal neurological abnormalities. However, there are no specific features, and the diagnosis of HSV should be considered in any patient with possible encephalitis.
In North America, herpes simplex virus is the most common cause of sporadic fatal viral encephalitis, followed by the California encephalitis group, St Louis encephalitis virus, HZV, enteroviruses, mumps, measles, and, most recently, the West Nile virus. In the United States of America, herpes simplex encephalitis has an estimated incidence of 2.3 per million population each year; HSV-1 accounts for 95% of cases; HSV-2 causes encephalitis mainly in neonates and those who are immunosuppressed, such as transplant recipients, and those with HIV infection. In 1999 there was an outbreak of West Nile infection in the eastern United States of America with a cluster of cases of encephalitis in New York and 16 human deaths. West Nile virus is a mosquito-borne flavivirus closely related to JE. It has been known to cause encephalitis in Africa, the Middle East, and southern and eastern Europe, but this was the first appearance of this virus in the New World. In endemic areas, infection with West Nile virus is usually asymptomatic or associated with a mild flu-like illness. Only occasionally does it cause encephalitis, with a case fatality rate for patients admitted to hospital in New York of 12%. The virus has now become established in migrant bird populations across the United States of America and Central America, and in 2008 there were 1370 cases with 37 fatalities in the United States of America reported by the Centers for Disease Control (CDC), Atlanta.
Characteristic features of this condition are gross cerebral oedema and severe haemorrhagic and necrotizing encephalitis, which is often asymmetrically localized to the inferior and medial parts of the temporal lobe, the insula, and the orbital part of the frontal lobe. Histological sections show eosinophilic Cowdry type A intranuclear inclusions with margination of chromatin in neurons, oligodendrocytes, and astrocytes, inflammatory and haemorrhagic perivascular reactions, but no demyelination. Cowdry type A inclusions are also found in HZV and CMV encephalitides. The unique cerebral localization of herpes simplex encephalitis has not been satisfactorily explained, but is probably the result of viral spread along specific neural pathways rather than a differential susceptibility of particular cell populations. A popular idea is that HSV spreads along olfactory pathways to the base of the brain and temporal lobes, but it is also possible that virus may spread from the trigeminal ganglia through sensory fibres innervating the dura near these regions. This latter mechanism is consistent with the discovery of latent HSV-1 in the trigeminal, superior cervical, and vagal ganglia in a high proportion of normal individuals, irrespective of whether they have a history of mucocutaneous herpes infections (‘cold sores’). Latent HSV-1 might be reactivated by a variety of stimuli, such as sunlight, fever, trauma, and stress; however, the actual mechanisms underlying its latency and reactivation in the nervous system are not yet fully understood. If herpes simplex encephalitis is caused by the reactivation of latent virus, its rarity, despite ubiquitous asymptomatic infection in humans, is hard to explain.
The cerebrospinal fluid shows lymphocytic pleocytosis, although neutrophils and red cells may also be present, with a raised protein level. CT scans of the brain may show changes in the temporal lobe; MRI is a more sensitive method of detection. The electroencephalogram classically shows spike and slow-wave activity localized in the temporal lobes. The definitive way of establishing the diagnosis is brain biopsy. In the original trial of aciclovir for the treatment of HSV encephalitis, brain biopsy was an entry criterion, but confirmed the diagnosis in only 50% of clinically suspected cases. Since the advent of effective nontoxic chemotherapy for HSV, brain biopsy is very rarely used. There is good correlation between a positive polymerase chain reaction (PCR) test for HSV DNA in the cerebrospinal fluid, and a diagnosis of HSV encephalitis by brain biopsy and virus isolation. Evidence of intrathecal production of specific HSV antibody is also diagnostic, but as it usually not detectable until 1 week after onset, PCR-based diagnosis is more useful. Serum or cerebrospinal fluid titres of antibodies to HSV do not usually increase in the first week of the illness. In practice, the diagnosis is established by a compatible clinical picture, evidence of characteristic temporal lobe involvement on CT or MRI, and EEG, and by PCR-based detection of HSV DNA in the cerebrospinal fluid.
The pathogenesis of HSV encephalitis remains uncertain. Up to one-half of patients have primary infection, and in the rest the disease is presumed to result from reactivation. However, where HSV has been isolated from the brain and mouth simultaneously in the same patient, the two isolates differ by restriction endo nuclease analysis in about 30% of cases, suggesting a new exogenous virus infection in an already seropositive patient. HSV DNA can be detected at autopsy in the brains of normal virus carriers, and the factors precipitating HSV encephalitis are not known. Immunosuppression is not usually associated with encephalitis, which predominantly affects normal immunocompetent adults, and very rarely patients with advanced HIV infection. The pathological features are of focal haemorrhagic necrotizing encephalitis affecting the temporal lobes.
Treatment with intravenous aciclovir should be started immediately if HSV encephalitis is clinically suspected, without waiting for confirmation of the diagnosis (in doses as below; see ‘CNS infections’). The untreated mortality from HSV encephalitis is more than 70%, and very few survivors make a full neurological recovery. Intravenous aciclovir was established to be more effective than the previous best therapy of vidarabine in a randomized trial reported in 1986. Mortality in the aciclovir-treated group was 28%, although a lower Glasgow coma score on entry carried a higher risk of mortality. However, only 38% of those who received aciclovir had fully recovered at 6 months. There is still a high incidence of permanent neurological sequelae, particularly seizures, defects of memory, and personality changes, and the prognosis of HSV encephalitis remains poor.
HSV can cause aseptic meningitis, which is quite independent of, and not associated with progression to, HSV encephalitis. It is most commonly associated with primary genital HSV-2 infection, in which the incidence of proven HSV meningitis is 7% in women and 2% in men. There is pleocytosis, usually lymphocytic, but neutrophils may predominate in early meningitis. HSV may be isolated from the cerebrospinal fluid by culture, but is now more reliably detected by PCR for HSV DNA. In a high proportion of patients with Mollaret’s meningitis (recurrent aseptic meningitis of unknown aetiology), HSV DNA is reported to be detectable in the cerebrospinal fluid by PCR. The role of HSV in this syndrome remains uncertain.
Neonatal HSV infection and pregnancy
The incidence of neonatal HSV infection is approximately 1 in 3500 deliveries per annum in the United States of America, but appears to be lower in the United Kingdom, at 1 in 6600 live births. About 70% of cases are caused by HSV-2, and result from fetal acquisition of HSV-2 from maternal genital secretions during delivery. Most infants with neonatal HSV are born to mothers without clinically evident HSV infection. The risk of transmission from women with symptomatic primary HSV or clinically evident recurrent HSV-2 infection is about 50 and 20%, respectively. A small proportion (c.10%) of infections is acquired postnatally through contact with people with active lesions.
Neonatal HSV infection may appear as lesions on the skin, eye, and mouth, or as encephalitis or disseminated visceral infection. Although initial superficial infection may progress to visceral infection, visceral infection can present without cutaneous lesions, and the diagnosis should be considered in severely ill neonates. Untreated, visceral infection has a high mortality (around 60%). Primary infection in early pregnancy can lead to congenital HSV infection, which is rare, but can produce serious congenital abnormalities.
HSV in immunosuppressed patients
HSV infections in immunosuppressed people are usually because of reactivation, rather than primary infection. They tend to be more severe, are more likely to progress, and take longer to heal than in the immunocompetent host. Clinical manifestations in patients with HIV infection include severe perineal, orofacial, and oesophageal infection. HSV pneumonitis, hepatitis, and colitis are also described in immunosuppressed patients.
The histological appearance of HSV infection remains the same, whether it is primary or recurrent. There is ballooning of infected cells, with condensed chromatin in the cell nuclei; intranuclear inclusion bodies (Cowdry type A bodies) may be seen; and multinucleated giant cells form. Varicella–zoster virus produces a similar appearance.
Definitive diagnosis is made by virus isolation. Swabs from vesicular fluid or other body fluids in virus transport medium can be inoculated into tissue culture, producing typical cytopathic effects. Electron microscopy of negatively stained vesicle fluid is rapid, but will not differentiate HSV from varicella–zoster virus. The use of PCR-based techniques to detect viral DNA is becoming more widespread. It is particularly applicable to the detection of HSV DNA in cerebrospinal fluid.
Serological tests for antibody to HSV are useful only for making a retrospective diagnosis. Seroconversion provides proof of primary infection, and the absence of antibody to HSV-1 or HSV-2 rules out a diagnosis of recurrent HSV infection. However, making a diagnosis of reactivation by demonstrating rising antibody titres is of limited value.
The introduction of aciclovir heralded a new era of specific antiviral drugs, and superseded the drugs previously used for the treatment of HSV infections, such as vidarabine and idoxuridine. Aciclovir is an acyclic nucleoside that is preferentially phosphorylated to the monophosphate in HSV-infected cells by the virus-encoded thymidine kinase. Cellular kinases then phosphorylate the monophosphate to the triphosphate, which is incorporated into nascent HSV DNA, where it acts as a chain terminator; aciclovir also directly inactivates the HSV DNA polymerase. Two newer, related drugs with the same mechanism of action are famciclovir, a prodrug of penciclovir, and valaciclovir, the valyl ester of aciclovir, which has greater bioavailability and less frequent dosage. All these drugs are relatively free of side effects, although intravenous aciclovir can crystallize in the renal parenchyma and produce renal impairment; it should be given by infusion over an hour, and patients should be adequately hydrated. The doses should be reduced in patients with renal impairment.
Primary mucocutaneous infection
In primary oral and genital infection, aciclovir 200 mg 5 times daily given orally for 10 to 14 days from the onset reduces the severity of infection, the duration of symptoms, and the duration of viral shedding. There is little evidence that the treatment of primary infection reduces the incidence of subsequent symptomatic reactivation episodes. If swallowing is difficult, intravenous aciclovir (5 mg/kg 8 hourly) may need to be given. Famciclovir 250 mg 3 times daily or valaciclovir 500 mg twice daily are alternatives.
Symptomatic reactivation of mucocutaneous infection
The treatment of recurrent infections in immunocompetent hosts is often unnecessary, as the symptoms are usually very mild. However, aciclovir can shorten the duration of symptoms if it is given very early in the course of the recurrence, preferably during the prodrome before vesicles appear. Oral aciclovir is effective, and anecdotal reports suggest that topical aciclovir is effective symptomatically. The same dosage as above for primary infection can be given for 5 days. Patient-initiated courses of single-day famciclovir (1 g twice daily) or 3-day valaciclovir (500 mg twice daily) have been shown to be effective for recurrent genital HSV.
Long-term suppressive therapy
This can be considered in immunocompetent patients with genital herpes who have frequent reactivation episodes. Trials of aciclovir in recurrent genital herpes have shown that a dose of 400 mg twice daily significantly reduces the frequency of attacks. However, patients may be able to find a lower effective dose, and in some, 200 mg daily prevents attacks. Because there is some evidence that resistant virus is a problem in this population, it is advisable to stop treatment for a month every 6 to 12 months. Valaciclovir 500 mg daily or famciclovir 250 mg twice daily are alternatives.
For HSV encephalitis, intravenous aciclovir (10 mg/kg 8 hourly for 10–14 days) should be given to any patient in whom the diagnosis is clinically suspected (see ‘HSV encephalitis’ above). For HSV meningitis, intravenous aciclovir 5 mg/kg 8 hourly can be used, with conversion to oral valaciclovir 1 g twice daily when improvement occurs, for a total of 10 days.
Systemic infection in the immunosuppressed
Oral treatment, as for primary HSV, can be used for mild mucocutaneous infection, but for more severe and for visceral involvement, intravenous aciclovir 5 mg/kg 8 hourly should be used. After resolution, continued prophylaxis is usually necessary until immunocompetence is restored, particularly in patients with HIV.
Resistance of HSV to aciclovir develops readily in vitro, but is clinically rare; it results from mutations in the HSV thymidine kinase or DNA polymerase genes. It is seen almost exclusively in immunocompromised patients who have received prolonged aciclovir prophylaxis, especially those with HIV infection, and is manifest as unresponsive or worsening HSV disease despite treatment with aciclovir. There is usually crossresistance to famciclovir and valaciclovir, and intravenous foscarnet is the most useful alternative drug in severe infection caused by resistant HSV, although it is more usually used for human cytomegalovirus (see ‘Human cytomegalovirus’ below).
Prevention and control
No vaccine is licenced for HSV, although a gD (glycoprotein D) based vaccine reduced new HSV2 infection in seronegative women, and other candidates are approaching phase III trials. There is particular interest in the use of vaccines for postinfective immunization to reduce the frequency of recurrent genital HSV attacks. This has proved possible in guinea pigs.
Special problems in pregnant women
Prevention of neonatal HSV infection is best achieved by preventing genital HSV infection late in pregnancy. There is no reason to give aciclovir prophylactically to women with a history of recurrent genital herpes who are asymptomatic, as the incidence of neonatal HSV infection is low in their children. However, women with clinically apparent genital herpes in the last trimester (and probably at any other time in pregnancy) can be treated with aciclovir, although the drug is not licensed for treatment in pregnancy. Women with no clinical lesions may have a vaginal delivery, but the presence of active lesions at the time of labour is an indication for Caesarean section. Babies born to mothers with clinically apparent genital HSV infection, or with a history of recurrent genital HSV infection, should be screened for HSV by cultures from the nasopharynx and eyes after birth.
Proven neonatal HSV infection should be treated with high-dose intravenous aciclovir (20 mg/kg per day every 8 h for 21 days).