Frequent recurrences of herpes: recommendations for treatment. European guidelines for the management of patients with genital herpes (2010) Genital herpes recommendations for patients

Probably each of us faced in his life with such a phenomenon as herpes. Of course, the disease is extremely unpleasant, it manifests itself in the form of a rash of watery vesicles on the lips or in the genital area. A rash can instantly ruin all plans for the next week, because it significantly spoils the appearance and causes a lot of discomfort. Often the disease is called a cold on the lip. Why does the disease appear, why relapses can occur and how to deal with them, read on.

Herpes vulgaris

This disease is one of the viral infections. Like all viruses, the disease is extremely aggressive and is accompanied by specific symptoms. Once in the human body, the virus is embedded in the structure of the cell and begins to multiply along with cell division. The disease is dangerous during pregnancy, as it can infect the fetus. The disease is transmitted by household, airborne and sexual contact. The virus can also enter the body through a transfusion of infected blood.

The disease most often affects the mucous membranes of a person, a rash can appear on the lips, in the mouth, on the genitals. Less commonly, manifestations of the disease can be seen on the chest in the form of small watery bubbles. Without appropriate treatment, the acute phase of the disease can last up to 21 days. At the same time, symptoms such as itching, burning, pain are expressed.

Not everyone knows that a disease such as chicken pox, which most often manifests itself in childhood, is also caused by the penetration of a certain type of herpes virus. However, this virus is not so aggressive and the immune system, having developed protective antibodies, prevents re-infection with this disease. With the localization of rashes in the oral cavity, in order to prescribe the right treatment, it is necessary to exclude the diagnosis of stomatitis. For this, specialists use several diagnostic methods, among which are studies of the contents of the vesicles and scrapings from the site of erosion. As a result of the tests, the diagnosis of the virus is confirmed if there are multinucleated cells in the biological material.

Today, experts share three types of the virus:

1. Cytomegalovirus. Especially dangerous for pregnant women. Able to infect the fetus by penetrating the placenta. Often, with this disease, pregnancy ends in premature birth. In the absence of proper treatment, the fetus may be stillborn. This type of disease is extremely rare, but do not neglect the immediate trip to the clinic at the first sign of the disease.
2. Epstein-Barra. The virus masterfully disguises itself as a sore throat. The course of the disease is acute with high body temperature, chills, sore throat. It is distributed mainly through the household route. It is characterized by rashes of bubbles on the tonsils. Revealed during examination of the patient.
3. Zoster. The most common type of virus. It is this form of the disease that is characterized by rashes on the lips. The virus can also cause genital herpes.

Many people know that having appeared once, the disease can be renewed with enviable constancy. Frequent manifestations of the disease are the reason for consulting an immunologist.

Treatment of the disease depends on the type of virus, and mainly consists in taking antiviral and immunostimulating drugs for local and internal use.

chronic herpes

The disease develops against the background of a weakening of the protective functions of the body. The virus, which has entered the cells once, continues to live and develop, provoking relapses and affecting the internal organs and is manifested by periodic rashes on the mucous membranes. Any factor that reduces immunity, such as climate change, hypothermia, respiratory disease, diet, menstruation or pregnancy, can become an impetus for the activation of the virus.

The course of a chronic disease is characterized by less pronounced symptoms, the frequency of manifestations can be up to several times a year. Despite the seeming harmlessness, the chronic form of the disease is extremely dangerous and can last for years in a patient.

The most common form of this chronic disease is genital herpes. The disease is characterized by frequent watery rashes on the genitals. It is transmitted sexually and when using common household items (towels, washcloths, etc.), you can also become infected with the virus when visiting public baths and toilets. The danger of the disease lies in the more complex, with each subsequent time, treatment.

There are three types of genital herpes:

1. arrhythmic. This type of course of the disease is characterized by uncontrolled relapses of the disease. The main feature of the type is considered to be more pronounced rashes after a long remission. The disease is acute and requires special treatment, which involves the complete restoration of the immune system in several stages.
2. Monotone. The course of the disease in this type is characterized by frequent manifestations as a result of even minor hypothermia. In women, the genital type of the disease can manifest itself during each menstruation. This type of disease is difficult to treat and requires an integrated approach and a complete examination. With the ineffectiveness of traditional treatment, consultation with an immunologist is necessary.
3. Subsiding. This type of course of the disease is the most optimistic. Over time, with this type, the rest period has an increasing duration, and the symptoms are less pronounced each time. With proper treatment, experts predict a full recovery.

Manifestations of symptoms of genital herpes

Genital herpes can vary in severity depending on the form of the disease. At the primary stage of the disease, all symptoms are pronounced and often frightening.

• The genital form of the disease begins with a sharp rise in temperature to 38.5 degrees, weakness and general malaise.
• Further, itching joins the temperature in the genital area, where later, after 1-2 days, watery vesicles appear that are painful to the touch.
• After the bubbles open, crusts form in their place, which fall off when the wound heals.

People often confuse the primary stage of the disease with sexually transmitted diseases. At the first symptoms of the disease, you should immediately consult a doctor. Only a doctor can make a correct diagnosis and prescribe adequate treatment. Self-medication threatens the transition of the disease to the chronic stage.

The chronic form of the disease manifests itself less pronounced, the patient does not have a fever, the rashes are not so extensive and heal much faster. This type of disease is more dangerous. As a result of mild symptoms, many people do not seek the necessary treatment, continuing to infect their sexual partners. Despite the apparent safety, the disease often turns into serious complications.

The genital type of the disease is especially dangerous for pregnant women, since during childbirth the mother can infect the newborn.

In addition to the sexual route of distribution, the genital species can be transmitted by household means, using common hygiene products, things or bedding.

How to deal with a chronic illness

Due to the fact that the chronic form of the disease develops against the background of a weakening of the protective properties of the body, first of all, it is necessary to pay attention to increasing immunity. Experts note that in order to restore immune protection, it is first necessary to lead a healthy lifestyle. Raise immunity contribute to:

• Regular exercise;
• Complete, vitamin-rich nutrition;
• Rejection of bad habits;
• Healthy sleep;
• tempering procedures;
• Daily walks in the fresh air;
• Leisure.

With rashes, antiviral drugs should be used immediately. To prevent recurrence in the diagnosis of genital herpes, alternative medicine can also be used, but before using them, a specialist consultation is necessary.

Traditional medicine will reduce the frequency of relapses in herpes

Traditional medicine recipes for the treatment of chronic genital rashes involve the use of various fees and decoctions with a high content of vitamins and trace elements.

To strengthen the immune system, such decoctions as a decoction of rose hips, hawthorn, leaves and fruits of raspberries, currants, nettles, chamomile, St. John's wort are perfect.

Also, to prevent the recurrence of the disease, you need to eat honey, nuts, lemons, garlic, horseradish and other biologically active components that help our body fight various diseases and strengthen the protective functions of the body.
To quickly get rid of bubbles on the lips, you can use the following remedy: at the first symptoms, you need to take a tablet of acetylsalicylic acid, moisten it with water and apply it to the bubble on the lip for 5 minutes. After that, do not wipe the remnants of the tablet and do not wet the affected area. This recipe from traditional healers will quickly relieve you of a cold on your lip.

• Sometimes doctors recommend moistening the affected area of ​​the rash, but after that you need to dry it. You can do this with a terry towel or, in extreme cases, with a hair dryer. This is done to relieve itching, pain and discomfort during an outbreak of herpes.
• Try to keep the blisters clean. It is believed that well-groomed areas of the skin heal faster.
• Wear loose, breathable clothing during flare-ups. It can be cotton pajamas or other loose clothing. Remember, wearing synthetic, tight clothes will aggravate the course of the disease.
• If the pain is unbearable, consult your doctor and he will prescribe you a local antiseptic that relieves pain in a localized focus.

Medications for relapses

In pharmacy chains, you can find a huge variety of drugs that can cope with both the external manifestations of the disease and overcome the disease from the inside. Today, doctors most often prescribe drugs that include acyclovir and zovirax. These drugs have an antiviral effect and provide reliable protection of the body from the spread of a viral infection. Also, drugs can be prescribed to prevent the disease by direct contact with an infected person.

Depending on the stage and form of the disease, it is necessary to select individual treatment. This is especially true in chronic forms of the disease. Such treatment can only be prescribed by an experienced specialist, taking into account a comprehensive examination of the rash, biological tests and anamnesis of the disease.
Usually treatment occurs in several stages:

1. Suppression of external signs of the disease with the help of special ointments and creams.
2. Suppression of internal signs of the disease by taking antiviral drugs that block the growth of virus cells.
3. Restoration of the protective functions of the body by activating the immune system with the help of vitamins and immunostimulating drugs.

Virus vaccination

Vaccination against this virus is not common in our country, but a vaccine exists. Most often, it is recommended to be vaccinated in patients with a chronic form of the disease during the calm period of the disease. The vaccine helps to produce the necessary antibodies and strengthens the body's defenses.

Patients with genital herpes and their partners should be given education about the disease in order to help them overcome the infection and prevent sexual and perinatal transmission. Although patients receive advice during the first visit to the doctor, most of them prefer to learn after the rashes have been eliminated. Today, many sources of information can help patients, their partners, and healthcare professionals to gain knowledge about genital herpes.

Patients infected with the herpes simplex virus (HSV) often express concern about their disease, but for the most part it is not associated with a real understanding of its severity. HSV really significantly affects the human body, causing severe first manifestations, relapses of the disease, inconvenience in sexual relations, possible transmission of the virus to sexual partners, as well as significant difficulties and anxiety about the birth of healthy children.

Psychological problems that occur in patients with asymptomatic and latent genital herpes after they are informed of a laboratory diagnosis of HSV infection are usually not severe and transient.

Patients with genital HSV infection should be provided with the following important information:

• Emphasize the possibility of repeated episodes, asymptomatic shedding of the virus and the risk of sexual transmission.
• Recurrent recurring episodes can be prevented with effective and affordable suppressive therapy, and treatment of recurrent genital herpes is useful in reducing their duration. The scheme of suppressive therapy is given in the article " Treatment regimen for genital herpes»
• It is necessary to inform sexual partners (before sexual intercourse) about their infection.
• Sexual transmission of HSV is possible during the asymptomatic period. Asymptomatic viral shedding is more common with genital herpes simplex virus type 2 (HSV-2) infection than with HSV-1 and during the first 12 months after infection.
• All patients with genital herpes should abstain from sexual intercourse during the rash or in case of symptoms of the prodromal period.
• The risk of sexual transmission of HSV-2 can be reduced by taking valaciclovir daily.
• According to recent studies, the risk of transmission of genital herpes can be reduced by consistent and correct use of latex condoms.
• It is necessary to conduct special laboratory serological tests with the determination of the type of virus in the partners of persons infected with the genital herpes virus to determine the risk of acquiring HSV infection.
• Pregnant women and women of childbearing age with genital herpes should report their infection to midwifery workers and those caring for their newborn baby. Pregnant women not infected with HSV-2 should abstain from sexual intercourse with a husband with genital herpes during the third trimester of pregnancy. Pregnant women not infected with HSV-1 during the third trimester of pregnancy should abstain, for example, from oral sex with a partner with oral herpes, or from vaginal intercourse with a partner with genital herpes caused by HSV-1 infection.
• Asymptomatic individuals who are diagnosed with HSV-2 infection by laboratory serological testing should follow the same recommendations as those with symptomatic infection. In addition, such persons should be able to identify the clinical symptoms of genital herpes.

Management of sexual partners.

Symptomatic sexual partners should be evaluated and treated in the same way as patients with a genital rash. Asymptomatic sexual partners of patients with genital herpes should be asked about a history of genital rash and offered to undergo laboratory serological testing for the presence of HSV infection.

Genital herpes in our time is a common viral disease that. Statistics say that 90% of the world's population are carriers of HSV, and 20% of them have clinical symptoms.

A condom can't protect you from genital herpes

The cause of this common ailment is infection with the herpes virus, which occurs sexually. It is caused by two types of herpes simplex viruses: HSV type 1 and HSV type 2. In 80% of cases, the causative agent of the disease is the herpes simplex virus of the second type. The remaining 20% ​​of the incidence is associated with HSV type 1, which most often causes rashes on the lips.

When it enters the body of a healthy person, the virus invades nerve cells and integrates into their genetic apparatus, remaining in the body for life. According to statistics, the level of herpes infection of all people living on the planet is 90%.

Healthy immunity produces special antibodies and suppresses the clinical manifestations of the disease. Most people who are infected can go their entire lives without symptoms, being carriers and infecting others.

Activation of the virus occurs when the following risk factors occur:

• vitamin deficiency;
• decreased immunity;
• stress on the nervous system;
• violation of the regime of work and rest;
• the presence of sexually transmitted diseases;
• pregnancy.

The presence of the above factors can cause an active phase, which will manifest itself with its symptoms.

Transmission routes

transmission path

Treatment is based on The main task is to reduce the unpleasant manifestations of the disease. You can treat genital herpes at home only under the supervision of a doctor.

The success of therapy is manifested depending on the phase of the disease. When talking about how to quickly cure genital herpes and get rid of the accompanying symptoms, you need to understand that earlier treatment will lead to a speedy recovery.

If relapses occur more than 5 times a year, special preventive therapy is necessary. This is a long-term event that will significantly support immunity and reduce the frequency of relapses.

It is carried out very carefully to avoid harm to the fetus. A more gentle therapy is used, which is strictly controlled by the attending physician.

Medications

The main drugs used in traditional medicine in the treatment of genital herpes:

• Acyclovir;
• Famciclovir;
• Penciclovir;
• Valaciclovir.

They are produced in various forms of release, such as ointments, injections, creams. taken orally up to 5 times a day for 7 to 10 days. When using the drug Famciclovir, side effects such as headaches and allergic reactions are less common.

Interferon preparations, which include Arbidol and Amiksin, accelerate recovery and lengthen the period between relapses. Equally important in stimulating the work of immunity is the observance of a healthy lifestyle and a positive psychological background of the patient.

To get rid of skin rashes, ointments are used that are applied to the affected areas 5-6 times a day. For example, a well-established remedy is Poludon ointment.

As a rule, the doctor prescribes a complex of therapeutic measures, consisting of tablets and ointments.

An important addition is the intake of vitamin complexes, such as Vitrum, Complivit and others.

Of course, in the treatment of such an insidious disease, a pharmacological approach is needed with the use of specifically targeted drugs. However, the use of baths with essential oils of lemon or tea tree is not only not forbidden by medicine, but is even considered useful in alleviating the symptoms of the disease.

With all the variety of effective means, an infected person should remember that only a doctor can prescribe treatment.

When should I seek treatment and which doctor should I contact?

The diagnosis of "genital herpes" is made by a doctor on the basis of an examination, as it is obvious. If you have associated symptoms, you should immediately consult a doctor. Diagnosis and treatment of this disease are carried out by doctors of narrow specialization:

• dermatovenereologist;
• gynecologist;
• urologist.

With erased symptoms and infectious processes, the doctor prescribes laboratory tests. But such a diagnosis rarely reveals the activity of the disease and the duration of infection due to the high prevalence among the population. Therefore, for accurate diagnosis, a number of measures are taken:

• 1. Reveal the nature of the rashes on the mucous membranes of the genital organs;
• 2. The presence of a history of herpetic rash;
• 3. The state of the immune system;
• 4. Test results - PCR, antibodies to the herpes virus of the first and second types.

Only a specialist will be able to identify the disease and prescribe the appropriate treatment.

With the timely detection of genital herpes at the initial stage, there is a possibility of curing it with the help of modern effective pharmaceuticals. Advanced forms require immune support and drug therapy to alleviate symptoms. To prevent infection, it is necessary to use personal protective equipment and carefully observe hygiene.

Who said that curing herpes is difficult?

• Do you suffer from itching and burning in the places of rashes?
• The sight of blisters does not at all add to your self-confidence ...
• And somehow ashamed, especially if you suffer from genital herpes ...
• And for some reason, ointments and medicines recommended by doctors are not effective in your case ...
• In addition, constant relapses have already firmly entered your life ...
• And now you are ready to take advantage of any opportunity that will help you get rid of herpes!

There is an effective remedy for herpes. and find out how Elena Makarenko cured herself of genital herpes in 3 days!

Below we publish in Russian the European guidelines IUSTI (The International Union against Sexually Transmitted Infections) / WHO (World Health Organization) for the management of patients with genital herpes, 2010. The document describes the epidemiology, diagnosis, clinic, treatment and prevention of genital herpes virus infection. The Guidelines describe the management of pregnant patients, as well as immunocompromised and HIV-infected patients with genital herpes.

Search criteria

In compiling this guideline, a literature review was conducted using the following resources: Medline/Pubmed, Embase, Google, Cochran Library; and all related manuals published up to and including September 2008. When searching Medline/Pubmed, Embase databases, publications from January 1981 to September 2008 were taken into account. Keywords for search: HSV/herpes, erosive and ulcerative lesions of the genitals, HSV/herpes in pregnancy, HSV/herpes in newborns, treatment of HSV /herpes. Additional keywords were used where necessary to clarify individual recommendations. In September 2007, a search was conducted using the Google server, the phrase "HSV manual" was entered in the search bar. The first 150 documents found as a result of the search were analyzed. Searches in the Cochrane Library were made in the following sections: Database of systematic reviews, Database of summary reviews of the effectiveness of therapy, Centralized database of controlled clinical trials. The Guidelines for the Management of Genital Herpes 2001 served as the basis for this Guideline. In addition, a detailed analysis of the Guidelines for the Management of Patients with STIs 2006 (CDC, USA) and the National Guidelines for the Management of Genital Herpes 2007 (British Association for Reproductive Health and HIV).

Introduction

The primary episode of a herpes infection caused by herpes simplex virus type I (HSV-1) or type II (HSV-2) can be manifest with clinical manifestations localized at the site of entry of the virus into the human body (on the face or genitals). Clinical manifestations may not occur - in this case, the infection remains unrecognized. In addition, systemic manifestations characteristic of many viral infections can also be detected. Further, the virus enters a latent phase, being localized in the peripheral sensory nerve ganglia. In this case, the virus can cause the development of periodic exacerbations (lesions of the skin and mucous membranes), or the disease remains asymptomatic, which does not mean the impossibility of its transmission. Genital herpes can be caused by both HSV-1 (the causative agent of herpes labialis) and HSV-2. The clinical manifestations of the disease are identical for infections caused by HSV-1 and HSV-2. At the same time, the clinical manifestations of a particular episode in a particular patient may depend on the presence of a history of herpes (labial or genital), as well as the primary focus of infection. Exacerbations of genital herpes caused by HSV-2 occur more frequently than with HSV-1 infection.

Risk of infection

The risk of virus transmission is highest during exacerbations with mucosal and/or skin lesions, as well as during the prodorma period. For this reason, patients should be advised to have sexual abstinence during these periods. In addition, transmission of the virus can occur in the absence of rashes resulting from subclinical virus shedding. There is no precise data on the effectiveness of condom use in preventing transmission of the virus. However, circumstantial evidence from a failed HSV vaccination study suggests the use of barrier methods of contraception (IIb B) .

Diagnostics

Modern diagnostic methods are presented in Table 1.

Clinical diagnostics

The classic manifestations of genital herpes include: papular rashes, transforming into vesicles, and then into ulcers; regional lymphadenitis; in recurrent genital herpes, the rash is preceded by a period of prodrome. Although the clinical manifestations of herpes are well recognized, one should not forget that the manifestations can vary widely in individual patients. In many patients, lesions in the genital area may be mistaken for other genital dermatoses. For this reason, if possible, a diagnosis based solely on the clinical picture should be avoided, especially when atypical symptoms are detected.

Laboratory diagnostics

Virus detection

• Detection of the virus using direct diagnostic methods directly in the focus is recommended in all cases of detection of genital herpes. The material for the study is smears from the base of the rash (the tire is removed with a needle or scalpel). The probe with clinical material must be placed in a special transport medium in accordance with the instructions of the manufacturer of diagnostic systems (Ib A) .
• In all patients with a primary episode of genital herpes, virus typing, identifying HSV-1 and HSV-2, should be performed in order to choose the right approach for treatment, prevention and patient counseling (III B) .
• The study of samples from asymptomatic patients is not recommended, since the carriage of the virus in mucosal cells is intermittent, so it is almost impossible to confirm or refute the carriage in this way (Ib A) .
• For a long time, virus isolation in cell culture was considered the “gold standard” for diagnosing herpes infection. The advantages of the method include high specificity, the possibility of typing and determining sensitivity to antiviral drugs. At the same time, cultivation takes a rather long time (7–10 days to obtain a negative result), requires significant labor costs, and the sensitivity of the method is low. Viral load (which is significantly different at initial/relapse; early/late disease) has a significant impact on study sensitivity. In addition, the results of the study may be affected by a violation of the conditions of storage / transportation and the timing of material processing.
• Currently, detection of viral DNA using real-time PCR is the diagnostic method of choice, as it can increase the frequency of virus detection in skin and mucosal lesions by 11–71% compared to culture (Ib A) . Real-time PCR does not require harsh storage and transportation conditions, and allows rapid identification and typing of the virus. In addition, the risk of contamination with real-time PCR is significantly lower than with conventional PCR.
• Detection of the virus antigen is possible using direct immunofluorescence (DIF) of smears placed on a glass slide, using fluorescein-labeled monoclonal antibodies, as well as using enzyme-linked immunosorbent assay (ELISA). The sensitivity of these methods is 10-100 times lower than that of a culture study, and therefore they are not recommended for routine use (Ib A) . Despite this, ELISA can be used in conditions of limited laboratory capacity for patients with rashes, since in this case it allows a rapid study of the material with satisfactory sensitivity. ELISA does not have the ability to type the virus.
• Cytological examination (according to Tzank or Papanicolaou) is characterized by low sensitivity and specificity, and therefore cannot be recommended for diagnosis (Ib A).

Serological testing with virus typing

• Serological testing of blood serum is not recommended in asymptomatic patients (IV C). Serological studies are indicated for the following groups of patients.
• Recurrent genital herpes or herpes with atypical clinical presentation in the absence of a history of detection of the virus by direct methods (III B). The presence of antibodies to HSV-2 supports the diagnosis of genital herpes, while antibodies to HSV-1 do not differentiate between genital and oropharyngeal infections. When managing patients who test negative for HSV-2 IgG but positive for HSV-1 IgG, it is worth considering the fact that HSV-1, although rare, can cause recurrent genital disease.
• In a primary episode of genital herpes, to differentiate between primary or pre-existing infection for counseling and management purposes (III B). The absence of IgG to HSV of the type isolated from rashes in a symptomatic patient is in favor of primary infection. Seroconversion in this case is detected during further observation.
• When examining the sexual partners of patients with genital herpes, when questions arise about the possibility of infection transmission. With discordant results of serological studies in sexual partners, competent counseling of patients about the possibilities of reducing the risk of transmission of the virus (Ib A) is necessary. Routine serologic testing of asymptomatic pregnant women is not indicated, except in a history of genital herpes in a sexual partner (IIb B). HSV-1 and/or HSV-2 seronegative women should be counseled on ways to prevent primary infection with both types of virus during pregnancy.
• It is necessary to explain to carriers of HSV-2, belonging to a group of high-risk sexual behavior, that they are more likely to acquire HIV (Ia A) .
• Routine serologic testing for HSV in HIV-infected patients is not recommended (IV C). Although HSV-2 seropositivity increases the risk of HIV transmission, and frequent recurrences of genital herpes infection increase HIV replication, there is no evidence to date for the treatment of asymptomatic herpes infection in HIV-infected patients. In a small number of studies, HIV-infected women who are seropositive for HSV-2 have an increased risk of perinatal transmission of HIV. Because the evidence base is currently insufficient, routine testing for HSV in pregnant HIV-infected patients is not indicated (IV C) .
• When conducting serological studies, it is necessary to use diagnostic kits that allow the identification of antigenically unique glycoproteins gG1 and gG2. The information content of non-type-specific serological studies in the diagnosis and treatment of genital herpes is low.
• The “gold standard” for diagnosis is Western blotting (WB). The sensitivity and specificity of the method are > 97% and > 98%, respectively. However, this method is labor intensive, making it commercially unavailable.
• There are now a number of commercial ELISA kits (eg Focus HerpeSelect) and immunoblotting kits (eg Kalon HSV-2) as well as locally developed reagent kits with sensitivity greater than 95% and specificity quite high. It is worth noting that the specificity of these tests can vary widely in individual populations (from 40% to > 96%). False-positive results (FPR) are more common in the early period of infection, usually with repeated tests, a positive result is detected. DM has been noted in populations with a low prevalence of the virus, as well as in studies among some African peoples. In addition, rapid point-of-care tests have been developed with sensitivity and specificity greater than 92%. New tests continue to be developed.
• The positive predictive value (PPV) is influenced by such factors as the prevalence of HSV in the population, the presence of risk factors for HSV infection, and history data. These factors should be taken into account when prescribing an examination and interpreting laboratory data (III B) . Currently, studies are underway to assess the information content of various algorithms for interpreting ELISA results. Thus, when using Focus HSV-2 ELISA kits in heterogeneous or low-risk populations, a positive result should be taken as ≥ 3.5, not > 1.1 (IIa B). At the same time, one should not forget that this approach reduces the sensitivity of the method both in early and long-term infections. This means that samples with results between 1.1 and 3.5 should be retested using an alternative methodology, such as Biokit HSV-2 or Kalon ELISA (IIa B). When using the Kalon kit, it is necessary to set the lower cut-off at 1.5, which increases the specificity of the study (IIa B). Comparative studies have shown that Kalon's RP and DS are comparable or even exceed those of Focus HSV-2 ELISA. The coincidence of the results when using these two tests is 99% (with a cutoff of 3.5 for Focus).
• Before the detection of type-specific IgG to HSV from the onset of symptoms of the disease takes from 2 weeks to 3 months, so IgG is often not detected in the early stages of infection. When clinically indicated, repeat sampling should be performed for testing to demonstrate seroconversion (IIa B). The determination of IgM to HSV allows you to establish the presence of infection at an early stage before the appearance of IgG in sufficient quantities for detection (IIb B) . However, in routine practice, the determination of IgM is practically not used due to its low availability. In addition, IgM may be detected at reactivation of the infection or not at the initial episode of infection; determination of type-specific IgM is not possible. Due to these limitations, the use of this study in routine practice is not recommended.

Treatment

Primary episode of genital herpes

Indications for treatment The course and management of initial episodes of genital herpes often determine the subsequent course of the infection. If left untreated, many patients may develop local or generalized complications. It is during the initial episode that therapy is especially effective. In this regard, it is necessary to prescribe the treatment of herpes with antiviral drugs already at the first appointment, without waiting for laboratory confirmation.

Antivirals Patients who seek help within 5 days from the onset of clinical manifestations (or later, but in the presence of fresh elements of rashes), should be prescribed antiviral therapy. Aciclovir, valaciclovir and famciclovir are effective both in eliminating clinical manifestations and in reducing the duration of relapse (Ib A). At the same time, none of the drugs prevents the further development of the infectious process.

In addition to the fact that local drugs are less effective than systemic ones, a relationship has been shown between topical use of acyclovir and the formation of resistance to this drug. This means that the use of topical preparations is not recommended for the treatment of genital herpes (IV C). Parenteral preparations are administered only if it is impossible to swallow the drug, with vomiting.

Recommended treatment regimens (treatment duration 5 days): acyclovir 200 mg 5 times a day, or acyclovir 400 mg 3 times a day, or famciclovir 250 mg 3 times a day, or valaciclovir 500 mg 2 times a day. The choice of a specific drug should be made taking into account the cost and the patient's likely adherence to treatment. In some patients, the duration of relapse is more than 5 days. With prolonged exacerbations with persistent general manifestations, the appearance of new rashes and the development of complications, the course of treatment should be extended.

Symptomatic therapy In the treatment of genital herpes, it is recommended to wash the eroded areas with saline; apply painkillers. When using local anesthetics, the possibility of sensitization should be considered. So, lignocaine rarely leads to sensitization, and therefore can be used in the treatment of genital herpes in the form of a gel or ointment. Benzocaine, in contrast, has a high potential for sensitization and should therefore not be used (IV C).

Consulting It is necessary to explain to the patient the existence of a high risk of transmission of the virus (including periods of subclinical viral shedding) even with the use of condoms and the use of antiviral drugs. Advice on reporting infection to a sexual partner should be practical and tailored to the individual patient's situation. The low health impact and the high prevalence of the virus in the population should be emphasized. Clear information about pregnancy is very important for both women and men. Typically, a first-time diagnosis causes a stress response that continues during exacerbations, but can be reduced with the use of antiviral drugs (Ib A). For many patients, 1-2 visits are enough to achieve the desired result, but the response of patients is difficult to assess in advance, therefore, careful observation using more intensive methods of persuasion is necessary if there is no effect within 3-6 months.

Treatment of complications With the development of urinary retention, meningism, generalization of the manifestations of the disease, as well as adverse social conditions, the patient must be hospitalized. When performing bladder catheterization (if necessary), it is worth considering the possibility of suprapubic access (if this will facilitate monitoring of the condition of a particular patient). Superinfection of the eruption is rare, but may occur in the second week of illness. It is characterized by exacerbation of local symptoms. Fungi of the genus Candida most often act as an etiological agent, and in these cases, diagnosis and treatment are not difficult.

Special cases. Primary episode of genital herpes in HIV-infected patients

Controlled studies on the tactics of treating HIV-infected patients with a primary episode of genital herpes have not yet been conducted. Some doctors suggest a 10-day course of treatment with any antiviral drug (as described above) at a dose twice the standard (IV C).

Information for patients When talking with the patient, it is necessary to explain the following aspects of herpes infection:

• possible variants of the course of infection, including asymptomatic viral shedding;
• therapy options;
• the risk of transmission to a sexual partner, as well as preventive measures that reduce this risk;
• the risk of intrapartum transmission of the virus - the patient should inform the obstetrician about the presence of herpes virus infection;
• the need to examine sexual partners and, if possible, to establish the source of infection.

Patient follow-up

Observation should be carried out until the symptoms of genital herpes are eliminated. Further observation is required if other causes of genital ulcers are suspected, which may occur as coinfection. With repeated episodes of genital herpes, observation may be required in case of an atypical clinical picture and / or a severe course of an exacerbation.

Recurrent genital herpes

Indications for therapy Exacerbations of genital herpes go away on their own and are accompanied by minimal symptoms. In this regard, the decision on how to deal with the next exacerbations should be made jointly with the patient. Possible treatment options: maintenance therapy, episodic antiviral therapy, suppressive antiviral therapy. For each patient, the approach must be selected individually, and, in addition, the tactics of therapy may change over time with changes in the frequency of exacerbations, the severity of the clinical picture, or the social status of the patient. Supportive care is appropriate for most patients, including rinsing with saline and/or Vaseline.
oil.

Episodic antiviral therapy Oral acyclovir, valaciclovir, or famciclovir is effective in reducing the severity and duration of genital herpes flare-ups. On average, the duration of an exacerbation is reduced by 1–2 days with any drug (Ib A). Head-to-head comparative studies found no advantage of one drug over others, nor did 5-day courses of therapy compare to ultrashort regimens. Prodrugs simplify dosing and are administered twice a day. Self-initiated treatment within the first 24 hours of an exacerbation is most likely to be successful. Almost a third of exacerbations take an abortive course with an early start of treatment. In order to ensure the most appropriate treatment, patients should be encouraged to carry small amounts of antiviral drugs with them at all times. Recommended treatment regimens (treatment course 5 days):

• acyclovir 200 mg orally 5 times a day or
• aciclovir 400 mg orally 3 times a day for 3 to 5 days or
• valaciclovir 500 mg orally twice a day or
• famciclovir 125 mg orally twice a day.

Short treatment regimens:

• aciclovir 800 mg orally 3 times a day for 2 days or
• famciclovir 1 g orally twice a day for 1 day or
• valaciclovir 500 mg orally twice a day for 3 days (Ib A) .

Suppressive therapy A significant part of the research devoted to the study of suppressive therapy of herpes has been carried out on patients with an exacerbation frequency of 6 or more per year. In addition, studies have recently been conducted in patients with a milder course of infection, including patients with exclusively serological signs of the infectious process. Studies have shown that the condition of patients of all groups improved with a decrease in the number of exacerbations during the year. When deciding on the appointment of suppressive therapy, the key parameter is the minimum frequency of exacerbations at which such a therapeutic tactic is justified. The frequency of relapses at which it makes sense to start suppressive therapy is a subjective concept. A balance should be struck between the frequency of relapses and the impact of the disease on the quality of life of a particular patient and correlate this with the high cost and inconvenience associated with therapy. A reduction in the relapse rate should be expected in all patients taking suppressive antiviral therapy. However, one should not forget that rare clinically pronounced relapses will still occur in most patients.

To date, the suppressive effect of acyclovir (Ib A) has been studied to the greatest extent. Data regarding patient safety and the formation of resistance during treatment are obtained from observations in the process of continuous use for more than 18 years. In a number of patients, from time to time it is worth evaluating the feasibility of further taking suppressive therapy, since changed living conditions can significantly affect the course of the infectious process. It is important to take into account that many patients did not notice a decrease in the frequency and / or severity of exacerbations after discontinuation of suppressive therapy (even with a long previous course of taking the drug).

Recommended treatment regimens The optimal suppressive regimen is considered to be 800 mg of acyclovir daily. To date, only one study has been published on the selection of the optimal dose of acyclovir for suppressive therapy, demonstrating that 200 mg orally 4 times a day is significantly more effective than 400 mg orally 2 times a day (p

When comparing the effectiveness of taking valaciclovir (500 mg 1 time per day) and famciclovir (250 mg 2 times a day), no advantages of any of the proposed regimens were shown (IV C). In case of insufficient clinical response to ongoing suppressive therapy, the dose of both valaciclovir and famciclovir may be doubled (IV C). Standard therapy regimens do not require a dynamic study of the patient's blood. When taking valaciclovir, such undesirable effects as a mild headache or nausea can rarely be observed. During suppressive therapy, the need for further medication should be evaluated at least once a year. At the request of the patient, it is possible to stop taking the drugs, which will allow re-evaluating the frequency of relapses and, possibly, reconsidering the tactics of treatment.

In a small number of patients, there is a decrease in the frequency of relapses after discontinuation of drugs compared with the frequency of relapses before the appointment of suppressive therapy. Follow-up should be carried out for at least two consecutive exacerbations, which will allow assessing not only the frequency, but also the severity of relapses. Resuming therapy after interruption is reasonable and safe in all patients whose disease severity warrants it (IV C). In some patients, it is possible to use short courses of suppressive therapy (for example, during vacations, exams, etc.). It should be borne in mind that the suppressive effect is observed no earlier than 5 days from the start of taking the drugs.

Asymptomatic Virus Shedding and Possibility of Virus Transmission During Suppressive Therapy Subclinical shedding occurs in most patients infected with HSV-1 or HSV-2. The most common viral shedding occurs in patients infected with HSV-2 less than a year ago, as well as in patients with frequent exacerbations. Aciclovir, valaciclovir and famciclovir effectively suppress both symptomatic and asymptomatic viral shedding. A partial reduction in viral shedding does not necessarily lead to a reduction in the likelihood and frequency of virus transmission. At the same time, suppressive therapy with valaciclovir at a dose of 500 mg daily (with a recurrence rate of 10 or less per year) reduced the frequency of HSV transmission in discordant couples by 50% (Ib A). Thus, valaciclovir can be used to prevent the transmission of HSV in combination with the use of barrier methods of contraception and abstinence from casual sex.

Special situations

Treatment of HSV in immunocompromised and HIV-infected patients

Treatment of a primary episode of genital herpes To date, there are no data on the treatment of a primary episode of genital herpes in HIV-infected patients. Most HIV-infected patients have serological evidence of HSV-1 and HSV-2, making it nearly impossible to conduct studies on primary infection. Separate clinical observations show that the primary episode of genital herpes in HIV-infected patients may have a longer and/or atypical course. With insufficient local immune response, severe systemic manifestations of the disease and / or chronic rashes on the skin and mucous membranes may occur. In the absence of controlled studies, it is believed that in immunocompromised patients, a multiple increase in the dose of the drug may be required. Such measures are not always required for the treatment of HIV-infected patients, in particular those with normal CD4 counts. In patients with active HIV infection, treatment should begin with a double dose of the drug. With the appearance of new rashes within 3-5 days from the start of therapy, the dose may be increased. With a fulminant course of infection, intravenous dosage regimens may be used. Recommended initial treatment regimens:

• acyclovir 200–400 mg orally 5 times a day or 400–800 mg orally 3 times a day (IV C);
• valaciclovir 500 mg - 1 g orally 2 times a day (IV C);
• famciclovir 250–500 mg orally 3 times a day (IV C).

The duration of treatment is 5-10 days. It is preferable to extend the course of treatment until complete re-epithelialization of the lesions, which often requires more than 10 days, in contrast to HIV-negative patients.

Treatment of recurrent infection

A number of studies have been conducted on the use of antiviral therapy in immunocompromised patients.

Duration of treatment For most patients, it is reasonable to prescribe a 5-day course of treatment. However, in 13–17% of patients with active HIV infection, new lesions appear on the 7th day of treatment. Shorter courses of treatment are warranted in patients with a CD4 count of at least 500 (data from one study using famciclovir) (Ib B).

Dosage regimens for antivirals Standard dosing regimens are effective in patients without evidence of immunodeficiency (Ib A). In immunosuppressed patients, doubling the dose of the drug and prolonging the course of treatment is required (Ib B). There have been no studies on the use of ultrashort regimens in immunocompromised patients, so such regimens should be used with caution.

Suppressive therapy Suppressive therapy for HSV is quite effective and well tolerated by patients. Trials were carried out using three antiviral drugs (acyclovir, valaciclovir, famciclovir). Standard dosing regimens of acyclovir have been shown to be effective in immunocompromised patients. The effectiveness of valaciclovir is increased when taking 500 mg 2 times a day compared to 1 g 1 time per day. Evaluation of the effectiveness of a single dose of 500 mg of valaciclovir has not been conducted. Data on the efficacy of high doses of famciclovir are only available for a very short period.

A sufficient amount of data has been accumulated on the safety of the use of antiviral drugs in immunocompromised patients. Two early studies (before the introduction of highly active antiretroviral therapy (HAART)) evaluated the use of high doses of acyclovir (400 mg 4 times a day), in a recent study, the use of standard doses of acyclovir. A number of studies have been conducted on the effectiveness of valacyclovir to prevent exacerbations of genital herpes. The use of high doses of valacyclovir (2 g 4 times a day) has been evaluated in HIV-infected patients, as well as in patients after bone marrow transplantation. Recently, studies have been conducted on the effectiveness of suppressive therapy with acyclovir and valaciclovir, as well as the effect of these drugs on HIV transmission. The results of these studies indicate that the use of standard doses of acyclovir, as well as valaciclovir 1 g 1 time per day or 500 mg 2 times a day, leads to the development of a minimum number of adverse events, in addition, the toxicity of the drug does not exceed that for HIV-negative patients. . The use of high doses of valaciclovir (8 g per day) can lead to the development of microangiopathic hemolytic uremic syndrome.

Dosage regimens The best evidence base for achieving suppression exists for valaciclovir 500 mg twice daily and acyclovir 400 mg twice daily, which effectively suppress viral replication (Ib A). In the absence of the effect of such treatment regimens, it is necessary, first of all, to double the dose of the drug used; if there is no effect, famciclovir 500 mg twice daily should be given (IIa B). Treatment of genital herpes with persistent course in immunocompromised patients

In immunocompromised patients, cases of resistance to therapy are rare, while in patients with severe immunodeficiency, including advanced stages of HIV infection, and patients with immune reconstitution inflammatory syndrome (IRIS, IRIS) that occurs after HAART, symptomatic cases of genital herpes , not amenable to treatment, can be a serious problem. The treatment algorithm for such patients is shown in Figure 1.

Impact of suppressive therapy on the progression of HIV infection Suppressive therapy with acyclovir and valaciclovir lowers the level of HIV viremia. The mechanism of such action is not fully understood. The use of these drugs makes a significant contribution to the course of HIV infection, especially in patients not taking HAART. A large RCT showed that in patients with early HIV infection (not on HAART; CD4 > 250), suppressive doses of aciclovir (400 mg twice daily) help maintain adequate CD4 counts, resulting in 2 years taking acyclovir, the number of patients requiring HAART decreased by 16% compared with the control group.

Treatment of sexual partners There is no evidence base to support recommendations for notifying sexual partners. In some cases, it is possible to invite partners to an appointment for joint counseling. Partner notification during pregnancy is discussed in later sections of the manual. When counseling patients, the following points should be emphasized:

• the use of barrier methods of contraception is necessary even in the case of suppressive therapy;
• asymptomatic shedding of viruses plays a significant role in the transmission of HSV;
• notification of partners followed by serological testing helps to identify both uninfected and asymptomatic patients;
• proper counseling leads to self-recognition of recurrent genital herpes in 50% of asymptomatic seropositive patients. Identification of clinically significant relapses in such patients leads to a decrease in the risk of transmission of HSV;
• The risk of HSV transmission is reduced both with the use of barrier methods of contraception and with suppressive therapy.

Treatment of pregnant women with a primary episode of genital herpes Infection in the first and second trimester of pregnancy Treatment should be carried out in accordance with the clinical picture of the disease. Both oral and parenteral regimens can be used. In the absence of a threat of preterm birth, observational tactics for further management of pregnancy is recommended; planning for vaginal delivery (IV C). The administration of suppressive therapy (acyclovir 400 mg 3 times a day) from the 36th week of pregnancy reduces the risk of recurrence by the time of the onset of labor and, accordingly, the frequency of delivery by caesarean section (Ib B) . Infection in the third trimester of pregnancy (IV C)

For all pregnant women in this group, delivery by caesarean section is preferable, especially with the development of symptoms of the disease 6 or less weeks before delivery. This is due to the high risk of viral shedding in these patients (Ib B). The appointment of suppressive therapy (acyclovir 400 mg 3 times a day) from the 36th week of pregnancy reduces the risk of relapse by the time of the onset of labor. If there is a need for vaginal delivery, a long anhydrous period should be avoided whenever possible, as well as the use of invasive procedures. It is possible to use acyclovir intravenously for both the woman in labor and the newborn. Such tactics should be coordinated with neonatologists. Treatment of recurrent genital herpes in pregnancy (III B)

The patient should be informed that the likelihood of infection of the fetus or newborn with recurrent genital herpes is low. For exacerbations of genital herpes in the third trimester of pregnancy, a short duration is characteristic; childbirth through the natural birth canal is possible in the absence of rashes at the time of childbirth. Many patients will opt for delivery by caesarean section if there is a rash by the time labor begins. In such cases, it is possible to prescribe acyclovir 400 mg 3 times a day from the 36th week of pregnancy in order to reduce the likelihood of recurrence by the time of the onset of labor and, accordingly, the frequency of delivery by caesarean section (Ia A) .

If there is no rash on the genitals by the time of delivery, delivery by caesarean section to prevent neonatal herpes is not indicated. It is not indicated to conduct a series of culture studies or PCR in late pregnancy in order to predict the possibility of virus shedding at the time of delivery. The feasibility of performing culture studies or PCR in childbirth in order to detect asymptomatic viral shedding in women has not been proven. Treatment of recurrent genital herpes in early pregnancy

Despite the fact that data on the safety of acyclovir in pregnant women is not enough, the use of the drug in cases of probable infection has a sufficient number of supporters. In the case of recurrent herpes, this approach is not applicable. In the early stages, both long-term and episodic administration of antiviral drugs should be avoided. In some cases (severe and / or complicated course of genital herpes), it is impossible to avoid the appointment of antiviral drugs. In such situations, an individual selection of a therapy regimen and careful monitoring are necessary. The use of the minimum effective dose of acyclovir is recommended; and the use of newer antivirals should be avoided.

Treatment of recurrent genital herpes in HIV-infected patients (IV C) There is some evidence, independent of other factors, indicating that the risk of HIV transmission is higher from HIV-infected patients with erosive and ulcerative manifestations of genital herpes during pregnancy. However, such observations are not confirmed by all authors. It is necessary to prescribe suppressive therapy to HIV-infected women with episodes of genital herpes in history (acyclovir 400 mg 3 times a day from the 32nd week of gestation). This tactic reduces the likelihood of HIV-1 transmission, especially when planning a physiological birth. Early initiation of suppressive therapy is possible with a high likelihood of preterm birth (IV C). There is not yet sufficient evidence to recommend daily suppressive therapy for patients who have HIV-1 antibodies and are HSV-1 or -2 seropositive but do not have a history of genital herpes.

Treatment of patients in the presence of rashes at the time of the onset of labor If there is a recurrence of genital herpes by the time of the onset of labor, it is possible to perform delivery by caesarean section. When choosing a method of delivery, it is worth considering the low risk of neonatal herpes during vaginal delivery in such cases, as well as the risk of surgical intervention in a woman in labor. Data from the Netherlands show that a conservative approach, in which vaginal delivery in the presence of an anogenital rash, does not lead to an increase in the incidence of neonatal herpes (III B) . This approach can only be used if supported by obstetricians and neonatologists, and if it does not conflict with local standards of care. Carrying out cultural studies or PCR does not provide an increase in the information content for the diagnosis of both clinically pronounced relapses and asymptomatic viral shedding.

Attention! None of the antiviral drugs are recommended for use during pregnancy. At the same time, when using acyclovir, there were no significant adverse events in relation to the course of pregnancy or the condition of the fetus / newborn, with the exception of transient neutropenia. Safety data for acyclovir can be extrapolated to late pregnancy and valaciclovir, which is its valine ester, but experience with valaciclovir is much less. Famciclovir should not be used during pregnancy.

Infection Prevention (IV C) The risk of infection in pregnant women varies widely by geographic location. In this regard, the surveillance system should develop a prevention strategy for each region. Any prevention strategy should target both parents. At the first visit for pregnancy, it is necessary to find out whether there were episodes of genital herpes in the anamnesis of the patient or her sexual partner. Patients who have not had a history of genital herpes episodes, but whose sexual partners suffer from recurrent genital herpes, should be recommended a preventive plan. Such measures include the use of barrier methods of contraception, sexual abstinence during exacerbations, as well as in the last 6 weeks of pregnancy. Daily suppressive treatment has been shown to significantly reduce the risk of HSV transmission to a seronegative partner. However, the effectiveness of male partner suppression therapy as a method of preventing infection in a pregnant woman has not been evaluated, so at present this tactic should be used with caution.

It is necessary to warn the patient about the possibility of HSV-1 infection through orogenital contact. Particular attention should be paid to this in the third trimester of pregnancy. Identification of women susceptible to infection using type-specific serological tests is not economically justified, therefore, it cannot be recommended for use in European countries. All patients, regardless of the presence of a herpes infection in history, should be examined at the beginning of labor in order to identify herpetic eruptions. In the presence of herpetic eruptions on the face or herpetic felons (in the mother, employees of a medical institution, relatives / friends), contact of the affected skin area with the newborn should be avoided.

Treatment of newborns

Children born to mothers with a primary episode of genital herpes at the time of delivery

• Neonatologists should be informed about the infection in the mother.
• For the purpose of early detection of infection, a PCR study of urine, feces, smears from the oropharynx, from the conjunctiva and skin of the newborn should be carried out.
• It is possible to start intravenous administration of acyclovir before receiving the results of a PCR study.
• If antiviral therapy is not carried out, careful monitoring of the newborn is necessary in order to detect signs of infection (lethargy, fever, refusal to feed, rashes).

Children born to mothers with recurrence of genital herpes at the time of delivery Although many clinicians feel that taking samples for culture after delivery may help in early detection of infection, there is no evidence base to justify this practice. At the same time, health care workers and parents should be advised to take into account the possibility of HSV infection in the differential diagnosis if the child, especially in the first 2 weeks of life, has any signs of infection or lesions on the skin, mucous membranes or conjunctiva.

* Reviewer: Prof. H. MOY. The authors are grateful to: S. BARTON, D. KINGHORN, H. LOTERI. IUSTI/WHO Editorial Team: C. RADCLIFF (Editor-in-Chief), M. VAN DER LAAR, M. JANIE, J.S. JENSEN, M. NEWMANN, R. PATEL, D. ROSS, W. VAN DER MUIDEN, P. VAN VOORST WADER, H. MOY. Estimated date for the revision of the Guidelines: May 2013. The Guidelines were translated by T.A. Ivanova, edited by M.A. Gomberg.

• KEY WORDS: herpes virus, herpes, genital herpes, urogenital infections, infectology, virology, infectious diseases

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