Genital herpes simplex virus infection: causes, symptoms, diagnosis, treatment

Genital herpes is a recurrent viral disease that does not heal completely. Two serotypes of the herpes simplex virus were identified . HSV-1 and HSV-2; the cause of most cases of recurrent genital herpes is HSV-2. According to serological studies, about 45 million people in the US are infected with HSV-2.

Most people infected with HSV-2 have no diagnosis of genital herpes; they have a mild or asymptomatic course of the disease, but nevertheless, from time to time, these individuals appear in the genital tract. In some cases, the first clinical episode of genital herpes is manifested as a serious illness requiring hospitalization. In most cases, the infection comes from people who do not know that they have a genital infection caused by HSV, or who have no symptoms at the time of sexual contact.

The use of antiviral drugs provides a partial control of the symptoms and signs of herpetic relapse, if used to treat the first clinical episode, recurrent episodes, or as daily suppressive therapy. However, these drugs do not destroy the latent virus and do not affect the risk, frequency and severity of relapses after discontinuation of treatment. Randomized studies show that there are three antiviral drugs that provide clinical well-being in genital herpes: acyclovir, valaciclovir and famciclovir. Valaciclovir is a valine ester of acyclovir with increased absorption after oral administration. Famciclovir, the precursor of penciclovir, also has high bioavailability when administered orally. Local therapy with acyclovir is much less effective than oral acyclovir, and its use is not recommended. In episodes of HSV infection, HIV-infected patients may require more aggressive therapy. In individuals with impaired immune status, episodes of the disease can be longer and more severe. Several of the following dosage regimens for acyclovir for both the first and repeated episodes are recommended, given the considerable clinical experience, the opinions of the specialists, and the dosages of the drugs approved by the FDA.

The first clinical episode of genital herpes

Management of patients with the first clinical episode of genital herpes includes the appointment of antiviral drugs and counseling about the characteristics of this infection, the possibilities of sexual and intrauterine transmission, as well as methods that reduce the risk of such transmission. 5 to 30% of the first episodes of genital herpes are caused by HSV-1, but the recurrent course is more typical of HSV-2 infection. Therefore, the identification of the type of herpetic infection is of prognostic value and can be useful in counseling the patient about this disease.

Recommended treatment regimens

Acyclovir 400 mg orally 3 times a day for 7-10 days,

Or Acyclovir 200 mg orally 5 times a day for 7-10 days,

Or Famciclovir 250 mg orally 3 times a day for 7-10 days,

Or Valaciclovir 1.0 g orally 2 times a day for 7-10 days.

NOTE: treatment can be continued if there is no complete healing after a 10-day treatment.

Higher dosages of acyclovir (400 mg orally 5 times a day) were used in studies of their effects in the treatment of the first episodes of herpetic proctitis and oral infection (stomatitis or pharyngitis). It is not clear whether these types of mucosal infection require higher dosages of acyclovir than those used in genital herpes. Valacyclovir and famciclovir are probably also effective in the treatment of acute herpetic proctitis or oral infection, but clinical experience with the use of these drugs is not yet sufficient.

Since genital herpes is a recurrent and incurable infection, counseling is an important part of the patient's management. Although counseling can be provided during the first visit, many patients use knowledge about the chronic aspects of the disease after the acute period of infection subsides.

Advising patients with genital herpes should include the following positions:

• Patients with genital herpes should be told about the natural course of the disease, highlighting the potential for the risk of repeated episodes, asymptomatic virus transmission and sexual transmission of the infection.
• Patients should be advised to refrain from having sex during the onset of herpetic eruptions or prodromal events and to encourage them to inform their sexual partners that they are infected with genital herpes. The use of condoms should be encouraged during all sexual intercourse with a new or uninfected sexual partner.
• Sexual transmission of HSV can occur during the asymptomatic period of the disease, when genital lesions are absent. Asymptomatic viral transport is most typical for patients infected with HSV-2 than HSV-1, as well as for patients with a disease duration of less than 12 months. Such patients should be counseled to prevent further spread of the infection.
• The risk of neonatal infection should be clarified to all patients, including men. Women of childbearing age who have genital herpes should be advised to inform their doctors who will observe them during pregnancy about their infection.
• Patients with the first episode of genital herpes should be informed that occasional antiviral relapse therapy can shorten the duration of herpetic lesions, and suppressive antiviral therapy can improve the course or prevent recurrent outbreaks.

Relapses of genital herpes

Most patients with the first episode of genital herpes will subsequently have repeated episodes of genital lesions. Episodic suppressive antiviral therapy can shorten the duration or improve the course of relapses. Because the effectiveness of antiviral therapy is quite high, the choice of treatment regimen should be discussed with all patients.

If treatment begins during the prodromal period or during the first day of the onset of lesions, it has a pronounced effect in many patients. If episodic therapy is chosen, the patient should be provided with antiviral medication or instruction, which indicates that it is necessary to start treatment at the first signs of a prodromal period or genital lesions.

Daily suppressive therapy reduces the incidence of recurrence of genital herpes in at least 75% of patients with frequent relapses (ie, 6 or more relapses per year). Safety and efficacy was confirmed in patients receiving daily acyclovir therapy for 6 years, and valaciclovir and famciclovir for one year. Suppressive therapy is not associated with the appearance of clinically significant resistance to acyclovir among immunocompetent patients. After 1 year of continuous suppressive therapy, it should be discussed with the patient the feasibility of interrupting treatment to assess the patient's psychological preparedness for manifestations of herpetic infection and the frequency of relapses, as with time it decreases in most patients. Given the inadequate experience with famciclovir and valaciclovir, it is not recommended to use these drugs for more than one year.

Suppressive therapy with acyclovir reduces, but does not prevent, the asymptomatic release of the virus. Therefore, it is not known to what extent suppressive therapy can prevent the transmission of HSV.

Recommended regimens for the treatment of recurrent infection

Acyclovir 400 mg orally 3 times a day for 5 days,

Or Acyclovir 200 mg orally 5 times a day for 5 days,

Or Acyclovir 800 mg orally 2 times a day for 5 days,

Or Famciclovir 125 mg orally 2 times a day for 5 days,

Or Valacyclovir 500 mg orally 2 times a day for 5 days.

Recommended regimens for daily suppressive therapy

Acyclovir 400 mg orally 2 times a day,

Or Famciclovir 250 mg orally 2 times a day,

Or Valacyclovir 250 mg orally once a day,

Or Valaciclovir 500 mg orally once a day,

Or Valaciclovir 1000 mg orally 1 time per day,

The use of valaciclovir in a daily dosage of 500 mg compared to its use in other dosages was less effective in patients with a very high relapse rate (more than 10 episodes per year). Several comparative studies of valaciclovir and famciclovir compared with acyclovir have demonstrated a relatively equal clinical efficacy of newer drugs and acyclovir. However, valaciclovir and famciclovir are more convenient to use, which is especially important for long-term treatment.

Severe course of the disease

The appointment of an intravenous method of treatment is recommended for patients with severe disease or complications requiring hospitalization (dysemptic infection, pneumonia, hepatitis) or with complications from the CNS (meningitis, encephalitis).

Recommended scheme

Acyclovir 5-10 mg / kg body weight IV every 8 hours for 5-7 days or until clinical symptoms resolve.

Management of sexual partners

Sexual partners of patients with genital herpes should be examined and advised. Sex partners with symptoms should be examined in the same way as any patient with genital lesions and prescribe appropriate treatment. However, in the majority of persons infected with HSV, a history of typical lesions; Such patients and their future sexual partners may benefit from screening and counseling. Thus, even asymptomatic partners need to know whether they have signs of typical and atypical genital lesions, advise them to conduct self-examination to detect such lesions in the future and, in the event of such lesions, seek medical help immediately.

Most currently available tests for the detection of antibodies to HSV do not allow the differentiation of antibodies to HSV-1 and HSV-2 and therefore their use is currently not recommended. The development and implementation of sensitive and type-specific commercial test systems for the detection of antibodies can help determine the further tactics of patient management.

Special Remarks

Allergies, intolerance and adverse reactions

Allergic or other adverse reactions to acyclovir, valaciclovir or famciclovir usually do not happen. Desensitization to acyclovir is described.

HIV infection

Persons with reduced immunity may have prolonged episodes of genital or perianal herpes with severe symptoms of the disease.

The lesions caused by HSV are fairly common among patients infected with HIV, they can be severe, painful and atypical. Periodic or suppressive therapy with oral antiviral agents is often successful.

The doses of antiviral drugs required for HIV-infected patients have not yet been clarified, but clinical experience clearly shows that in patients with a weakened immune system, treatment is successful at higher doses of antiviral drugs. In this case, acyclovir is used at a dose of 400 mg orally 3-5 times a day, as in the treatment of other patients with reduced immunity. Treatment should continue until the resolution of clinical manifestations. The efficacy of famciclovir, 500 mg twice daily, was demonstrated in HIV-infected individuals, manifested in a decrease in the level of relapses and subclinical manifestations. In persons with immunodeficiency, valaciclovir, at a dose of 8 g per day, was sometimes associated with a syndrome similar to hemolytic uremic syndrome or thrombotic thrombocytopenic purpura. However, in the doses recommended for the treatment of genital herpes, valaciclovir, as well as acyclovir and famciclovir, are safe for immunodeficient patients. In severe forms of the disease, intravenous administration of aciculovir in a dose of 5 mg / kg every 8 hours may be required.

If, despite treatment with acyclovir, herpetic lesions in the patient persist, it should be assumed that the HSV strain that is available in this patient is resistant to acyclovir; such patients should be referred for consultation to specialists. In severe forms of the disease caused by strains with proven or suspected resistance to acyclovir, alternate treatment should be prescribed. All acyclovir-resistant strains are also resistant to valacyclovir and, in most cases, to famciclovir. For the treatment of acyclovir-resistant genital herpes, the appointment of foscarnet, 40 mg / kg body weight IV every 8 hours before the resolution of clinical manifestations, is often effective. The application of 1% cidofovir gel to herpetic lesions also appears to be effective in many patients.

Pregnancy

The safety of systemic therapy with acyclovir genital herpes in pregnant women has not been established. Glaxo Wellcome, along with CDC, continue to record individual cases of use of acyclovir during pregnancy to assess its effectiveness and adverse reactions. Women who receive acyclovir or valacyclovir during pregnancy are subject to registration.

To date, according to the registration data, there is no increase in the risk of serious birth defects or the consequences of acyclovir treatment compared with the general population. These data make it possible to convince counseled women who have received acyclovir during pregnancy, the safety of this drug. It is necessary to accumulate data in order to draw definite conclusions about the risk of using acyclovir for pregnant women and fetuses. The use of valaciclovir and famciclovir is too limited and does not allow conclusions about the safety of use of these drugs during pregnancy.

If the first episode of genital herpes occurred during pregnancy, you can prescribe oral acyclovir. In the presence of a dangerous course of HSV infection in a pregnant woman (for example, disseminated infection, encephalitis, pneumonia or hepatitis) is indicated in / in the administration of acyclovir. Data from studies on the use of acyclovir in pregnant women suggest that acyclovir, when used shortly before delivery, can reduce the number of deliveries by caesarean section in women with frequently recurrent or newly acquired genital herpes, as a result of a decrease in the incidence of active lesions. However, to date, it is not recommended routine administration of acyclovir to women during pregnancy, who have a history of recurrence of genital herpes.

Perinatal infection

Most mothers, whose children become infected with herpes during the newborn period, have no clinically significant episodes of genital herpes in their history. The risk of transmission of infection to a newborn from an infected mother is high (30-50%) if a woman has contracted genital herpes shortly before birth and is low in women who had genital herpes relapses during pregnancy and in women who contracted genital HSV in the first half of pregnancy (~ 3%). Therefore, in order to prevent neonatal herpes, it is important to prevent infection of a woman with HSV in later pregnancy. It should be recommended to pregnant women whose partners have manifestations of herpes on the genitals or in the oral cavity, to avoid unprotected genital or oral sex during late pregnancy. Cultural studies on the virus during pregnancy do not provide an opportunity to predict virus isolation during labor, so routine culture testing is not shown.

By the time of delivery, all women should be carefully interviewed regarding the symptoms of genital herpes and examined. Women without symptoms and signs of genital herpes (or prodromal signs) can give birth in a natural way. Cesarean delivery by birth does not completely eliminate the risk of HSV infection in a newborn.

Infants infected with HSV at birth (if confirmed by virus isolation in cell culture or detection of herpetic lesions) need careful follow-up. Some authoritative experts recommend that such a newborn culture be carried out from the surface of the mucous membranes to detect HSV infection before the development of clinical symptoms. The use of acyclovir in the routine order as a prophylaxis in asymptomatic newborns born through infected birth canals is not recommended. The risk of infection in most newborns is quite low. However, infants whose mothers have contracted genital herpes during pregnancy have a high risk of neonatal infection with HSV and some experts recommend the prophylactic treatment with acyclovir for such newborns. The management of such pregnant and newborns should be carried out in conjunction with a specialist consultant. All newborns with signs of neonatal herpes should be immediately examined and treated with systemic acyclovir. Recommended treatment regimen: acyclovir 30-60 mg / kg / day, for 10-21 days.

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