Frequent relapses 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 has encountered such a phenomenon as herpes in our lives. Of course, the disease is extremely unpleasant; it manifests itself in the form of a rash of watery blisters 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. The disease is often 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 classified as a viral infection. Like all viruses, the disease is extremely aggressive and is accompanied by specific symptoms. Once the virus enters the human body, it integrates into the cell structure and begins to multiply along with cell division. The disease is dangerous during pregnancy, as it can infect the fetus. The disease is transmitted through household, airborne and sexual contact. The virus can also enter the body through an infected blood transfusion.

The disease most often affects the mucous membranes of a person; a rash can appear on the lips, in the oral cavity, and on the genitals. Less commonly, manifestations of the disease can be seen on the chest in the form of small watery blisters. Without appropriate treatment, the acute phase of the disease can last up to 21 days. In this case, symptoms such as itching, burning, and pain are expressed.

Not everyone knows that a disease such as chickenpox, 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. When the rash is localized in the oral cavity, in order to prescribe the correct treatment, it is necessary to exclude the diagnosis of stomatitis. To do this, experts use several diagnostic methods, among which are studies of the contents of the bubbles and scraping 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 distinguish three types of the virus:

1. Cytomegalovirus. Particularly dangerous for pregnant women. Capable of infecting the fetus by penetrating the placenta. Often with this disease, pregnancy ends in premature birth. Without proper treatment, the fetus may be stillborn. This type of disease is extremely rare, but do not neglect to immediately go to the clinic at the first signs of the disease.
2. Epstein-Barr. The virus masterfully disguises itself as a sore throat. The course of the disease is acute with high body temperature, chills, and sore throat. It is spread mainly through household means. Characterized by rashes of blisters on the tonsils. Identified 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 recur with enviable regularity. Frequent manifestations of the disease are a reason to consult an immunologist.

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

Chronic herpes

The disease develops against the background of a weakening of the body's protective functions. The virus, having penetrated the cells once, continues to live and develop, causing relapses and affecting internal organs and manifests itself as periodic rashes on the mucous membranes. The trigger for the activation of the virus can be any factor that reduces immunity, such as climate change, hypothermia, respiratory disease, diet, menstruation or pregnancy.

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 its apparent harmlessness, the chronic form of the disease is extremely dangerous and can last for years in the 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 through sexual contact and through the use of common household items (towels, washcloths, etc.) and 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 disease course 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 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 occur during each menstruation. This type of disease is difficult to treat and requires an integrated approach and a complete examination. If traditional treatment is ineffective, consultation with an immunologist is necessary.
3. Fading. This type of disease course is the most optimistic. Over time, with this type, the rest period has an increasingly longer duration, and the symptoms are less severe each time. With proper treatment, experts predict a complete 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 type of the disease begins with a sharp increase in temperature to 38.5 degrees, weakness and general malaise.
• Next, the temperature is accompanied by itching in the genital area, where subsequently, after 1-2 days, watery blisters appear that are painful to the touch.
• After the blisters open, crusts form in their place, which fall off as 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 the 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 severely, the patient does not have a fever, the rashes are not as extensive and heal much faster. This type of disease is more dangerous. As a result of mild symptoms, many people do not seek necessary treatment and continue to infect their sexual partners. Despite its apparent safety, the disease often results in 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 spread, the genital species can be transmitted through household means, through the use of shared hygiene products, clothes or bedding.

How to cope with a chronic illness

Due to the fact that the chronic form of the disease develops against the background of a weakening of the body’s protective properties, it is first 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. Raising immunity helps:

• Regular exercise;
• Complete nutrition rich in vitamins;
• Rejection of bad habits;
• Healthy sleep;
• Hardening procedures;
• Daily walks in the fresh air;
• Leisure.

In case of rashes, antiviral drugs should be used immediately. To prevent recurrences when diagnosed with genital herpes, you can also use folk remedies, but before using them, you need to consult a specialist.

Traditional medicine will reduce the frequency of relapses in herpes

Traditional medicine recipes for the treatment of chronic genital rash involve the use of various mixtures and decoctions high in vitamins and microelements.

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

Also, to prevent relapses 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 body's protective functions.
To quickly get rid of blisters 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 blister on the lip for 5 minutes. After this, do not wipe off the remaining tablets 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. This can be done with a terry towel or, as a last resort, a hairdryer. This is done to relieve itching, pain and discomfort during a herpes outbreak.
• Try to keep blisters clean. It is believed that well-groomed areas of skin heal faster.
• During an exacerbation, wear loose, breathable clothing. This could be cotton pajamas or other loose clothing. Remember, wearing synthetic, tight clothes will aggravate the disease.
• If the pain is unbearable, consult your doctor and he will prescribe you a local antiseptic that relieves pain in a localized area.

Medicines 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 viral infection. Also, drugs can be prescribed to prevent the disease through 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 medical history.
Typically treatment occurs in several stages:

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

Vaccination against the virus

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

Patients with genital herpes and their partners need to be provided with education about the disease to help them overcome the infection and prevent sexual and perinatal transmission. Although patients receive advice during their first visit to the doctor, most of them prefer to study after the rashes have been eliminated. Today, many sources of information can help patients, their partners, and health care providers gain knowledge about genital herpes.

Patients infected with herpes simplex virus (HSV) often express anxiety about their illness, but much of this is not coupled with a real understanding of its severity. HSV really has a significant effect on the human body, causing severe initial manifestations, relapses of the disease, inconvenience in sexual relationships, possible transmission of the virus to sexual partners, as well as significant difficulties and anxiety about the birth of healthy children.

Psychological problems that arise in patients with asymptomatic and latent genital herpes after informing them of a laboratory diagnosis of HSV infection are, as a rule, not severe and transient.

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

• Emphasize the possibility of recurrent episodes, asymptomatic viral shedding, and the risk of sexual transmission.
• Recurrent recurrent episodes can be prevented with effective and affordable suppressive therapy, and treatment for recurrent genital herpes episodes is helpful in shortening their duration. The suppressive therapy regimen is given in the article “ Treatment regimen for genital herpes»
• It is necessary to inform sexual partners (before sexual intercourse) about your 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 the event of prodromal symptoms.
• The risk of sexual transmission of HSV-2 can be reduced by taking valacyclovir daily.
• According to recent research, the risk of transmitting genital herpes can be reduced by consistently and correctly using latex condoms.
• It is necessary to conduct special laboratory serological tests to determine the type of virus on partners of persons infected with the genital herpes virus to determine the risk of acquiring HSV infection.
• Pregnant and childbearing-age women with genital herpes should report the infection to obstetric providers and those who care for their newborn baby. Pregnant women who are not infected with HSV-2 should abstain from sex with a husband who has genital herpes during the third trimester of pregnancy. During the third trimester of pregnancy, pregnant women not infected with HSV-1 should abstain from, for example, oral sex with a partner who has oral herpes or vaginal intercourse with a partner who has genital herpes caused by HSV-1 infection.
• Asymptomatic individuals diagnosed with HSV-2 infection by laboratory serologic testing should follow the same recommendations as those with symptomatic infection. In addition, such individuals should be able to identify clinical symptoms of genital herpes.

Management of sexual partners.

Sexual partners with corresponding symptoms should be examined and treated in the same way as patients with a genital rash. Asymptomatic sexual partners of patients with genital herpes should be asked about their history of genital rashes and offered laboratory serological testing for the presence of HSV infection.

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

A condom will not protect you from genital herpes

The cause of this common disease is infection with the herpes virus, which occurs through sexual contact. 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 herpes simplex virus type 2. The remaining 20% ​​of the incidence is associated with HSV type 1, which most often causes rashes on the lips.

When the virus enters the body of a healthy person, it 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%.

A healthy immune system produces special antibodies and suppresses the clinical manifestations of the disease. Most infected people can live their entire lives without showing 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 work and rest schedules;
• presence of sexually transmitted diseases;
• pregnancy.

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

Transmission routes

transmission route

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

The success of therapy depends on the phase of the disease. When discussing how to quickly cure genital herpes and get rid of accompanying symptoms, you need to understand that earlier treatment will lead to a quick recovery.

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

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

Medicines

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

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

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

Interferon drugs, which include Arbidol and Amiksin, speed up recovery and lengthen the period between relapses. No less important in stimulating the functioning of the immune system is maintaining a healthy lifestyle and a positive psychological background for the patient.

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

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

An important addition is taking vitamin complexes such as Vitrum, Complivit and others.

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

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

When should you resort to treatment and which doctor should you contact?

The diagnosis of “genital herpes” is made by a doctor based on examination, as they are obvious. If you notice accompanying symptoms, you should immediately consult a doctor. The diagnosis and treatment of this disease is carried out by highly specialized doctors:

• dermatovenerologist;
• gynecologist;
• urologist.

In case of erased symptoms and infectious processes, the doctor prescribes laboratory tests. But such diagnostics rarely reveal the activity of the disease and the duration of infection due to its widespread prevalence among the population. Therefore, for an accurate diagnosis, a number of measures are carried out:

• 1. Identify the nature of the rashes on the mucous membranes of the genital organs;
• 2.A history of herpetic rash;
• 3. State of the immune system;
• 4. Test results - PCR, antibodies to herpes virus types 1 and 2.

Only a specialist can identify the disease and prescribe appropriate treatment.

With timely detection of genital herpes at the initial stage, there is a possibility of its cure with the help of modern effective pharmaceuticals. In advanced forms, immune support and drug therapy are required 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 areas of the rash?
• The sight of blisters does not at all add to your self-confidence...
• And it’s somehow embarrassing, especially if you suffer from genital herpes...
• And for some reason, ointments and medications recommended by doctors are not effective in your case...
• In addition, constant relapses have already become a part of 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 IUSTI (The International Union against Sexually Transmitted Infections) / WHO (World Health Organization) guidelines for the management of patients with genital herpes, 2010. The document describes the epidemiology, diagnosis, clinical picture, treatment and prevention of genital herpesvirus infection. The Guidelines describe the management of pregnant patients, as well as immunocompromised and HIV-infected patients with genital herpes.

Search criteria

To compile this Guide, a literature review was conducted using the following resources: Medline/Pubmed, Embase, Google, Cochrane Libraries; as well as all related manuals published up to and including September 2008. When searching in the Medline/Pubmed, Embase databases, publications from January 1981 to September 2008 were taken into account. Search keywords: HSV/herpes, erosive and ulcerative lesions of the genitals, HSV/herpes during pregnancy, HSV/herpes in newborns, HSV treatment /herpes. Where necessary, additional keywords were used to clarify individual recommendations. In September 2007, a Google search was conducted using the phrase “HSV manual” in the search bar. The first 150 documents found as a result of the search were analyzed. The Cochrane Library was searched in the following sections: Database of Systematic Reviews, Database of Brief Reviews of Treatment Effectiveness, Central Database of Controlled Clinical Trials. These guidelines are based on the 2001 Guidelines for the Management of Genital Herpes. In addition, a detailed analysis of the 2006 Guidelines for the Management of STIs (CDC, USA) and the 2007 National Guidelines for the Management of Genital Herpes (British Association for Reproductive Health and Human Wellbeing) was carried out. HIV).

Introduction

The primary episode of herpes infection caused by herpes simplex virus type I (HSV-1) or type II (HSV-2) can occur manifestly 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. The virus then enters a latent phase, localizing 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 that it cannot be transmitted. Genital herpes can be caused by either HSV-1 (the causative agent of herpes labialis) or 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 herpes in the anamnesis (labial or genital), as well as the primary site of infection. Exacerbations of genital herpes caused by HSV-2 occur more often than with HSV-1 infection.

Risk of infection

The risk of virus transmission is greatest during exacerbations with lesions of the mucous membrane and/or skin, as well as during prodorma. For this reason, patients should be advised to abstain from sexual intercourse during these periods. In addition, transmission of the virus can occur in the absence of rash as a result of subclinical viral shedding. There is no definitive data on the effectiveness of using condoms to prevent transmission of the virus. However, indirect evidence from a failed HSV vaccination trial suggests the use of barrier methods of contraception (IIb B).

Diagnostics

Modern diagnostic methods are presented in Table 1.

Clinical diagnosis

The classic manifestations of genital herpes include: papular rashes that transform into vesicles and then into ulcers; regional lymphadenitis; with recurrent genital herpes, the rash is preceded by a prodrome period. Although the clinical manifestations of herpes are well recognized, it is important to remember that manifestations can vary widely among individual patients. In many patients, lesions in the genital area may be mistaken for other genital dermatoses. For this reason, if possible, you should avoid making a diagnosis based solely on the clinical picture, especially when identifying atypical symptoms.

Laboratory diagnostics

Virus detection

• Detection of the virus using direct diagnostic methods directly at the site is recommended in all cases of detection of genital herpes. The material for research is smears from the base of the rash (the covering 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 the diagnostic systems (Ib A).
• All patients with a primary episode of genital herpes should undergo viral typing, identifying HSV-1 and HSV-2, in order to select the appropriate approach to treatment, prevention and counseling of the patient (III B).
• Testing samples from asymptomatic patients is not recommended, since carriage of the virus in mucosal cells is intermittent, making it almost impossible to confirm or refute 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 quite a 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 differs significantly between initial/recurrent episodes; early/late disease) has a significant impact on the sensitivity of the test. In addition, the results of the study may be influenced by violation of storage/transportation conditions and timing of material processing.
• Currently, detection of viral DNA using real-time PCR is the preferred diagnostic method, as it can increase the detection rate of the virus in skin and mucosal lesions by 11–71% compared with culture (Ib A). Real-time PCR does not require strict storage and transportation conditions and allows for rapid identification and typing of the virus. In addition, the risk of contamination when using real-time PCR is significantly lower than that of traditional 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 an enzyme-linked immunosorbent assay (ELISA). The sensitivity of these methods is 10–100 times lower than that of culture, and therefore they are not recommended for use in routine practice (Ib A). Despite this, ELISA can be used in conditions of limited laboratory capacity for patients with rashes, since in this case it allows for rapid examination of the material with satisfactory sensitivity. ELISA does not have the ability to type the virus.
• Cytological examination (Tzanck or Papanicolaou) is characterized by low sensitivity and specificity, and therefore cannot be recommended for diagnosis (Ib A).

Serological studies with virus typing

• Serological testing of 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 an atypical clinical picture in the absence of detection of the virus by direct methods in the anamnesis (III B). The presence of antibodies to HSV-2 favors the diagnosis of genital herpes, while antibodies to HSV-1 do not differentiate between genital and oropharyngeal infection. When managing patients who test negative for IgG to HSV-2 but positive for IgG to HSV-1, it is worth considering the fact that HSV-1, although rare, can be a cause of recurrent genital disease.
• For a primary episode of genital herpes, to differentiate between primary or existing infection for the purpose of counseling and management of patients (III B). The absence of HSV-type IgG isolated from the rash of a symptomatic patient favors primary infection. Seroconversion in this case is detected during further observation.
• When examining sexual partners of patients with genital herpes, when questions arise about the possibility of transmission of infection. In case of discordant results of serological tests in sexual partners, it is necessary to competently counsel patients about the possibilities of reducing the risk of transmission of the virus (Ib A). Routine serological testing of asymptomatic pregnant women is not indicated, except in cases of a history of genital herpes in a sexual partner (IIb B). It is necessary to counsel women who are seronegative for HSV-1 and/or HSV-2 about ways to prevent primary infection with both types of virus during pregnancy.
• It is necessary to explain to carriers of HSV-2 who belong to the group of high-risk sexual behavior that their likelihood of becoming infected with HIV increases (Ia A).
• Routine serological 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 of the effectiveness of treatment for asymptomatic herpes infections in HIV-infected patients. A small number of studies suggest that HIV-infected women who are seropositive for HSV-2 are at 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 immunoblotting (Western blot, WB). The sensitivity and specificity of the method are >97% and >98%, respectively. However, this method is labor intensive, making it commercially unavailable.
• Currently, there are a number of commercial kits for research using ELISA (for example, Focus HerpeSelect) and immunoblotting (for example, Kalon HSV-2), as well as locally developed reagent kits, the sensitivity of which exceeds 95%, and the specificity is also quite high. It is worth noting that the specificity of such tests can vary widely in individual populations (from 40% to > 96%). False-positive results (FPR) are more common early in the infection, usually with repeated testing revealing a positive result. PPD was noted in populations with 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 exceeding 92%. New tests continue to be developed.
• The positive predictive value (PPV) is influenced by factors such as the prevalence of HSV in the population, the presence of risk factors for HSV infection, and medical history. These factors should be taken into account when ordering tests and interpreting laboratory data (III B). Currently, studies are being conducted to evaluate the information content of various algorithms for interpreting ELISA results. Thus, when using Focus HSV-2 ELISA kits in heterogeneous or low-risk populations, values ​​of ≥ 3.5 rather than > 1.1 should be considered positive (IIa B). At the same time, we should not forget that this approach reduces the sensitivity of the method both for early and long-term infection. This means that samples with results between 1.1 and 3.5 should be retested using an alternative assay such as the Biokit HSV-2 or Kalon ELISA (IIa B). When using the Kalon kit, a lower cutoff value of 1.5 must be set to increase the specificity of the test (IIa B). Comparative studies have shown that the DC and DC of Kalon are comparable or even higher than those of the Focus HSV-2 ELISA. The agreement between the two tests is 99% (using a cutoff of 3.5 for Focus).
• It takes from 2 weeks to 3 months before type-specific IgG to HSV is detected from the onset of symptoms of the disease, so IgG is often not detected in the early stages of infection. When clinically indicated, repeat testing specimens should be collected to demonstrate seroconversion (IIa B). Determination of IgM to HSV makes it possible to establish the presence of infection at an early stage before the appearance of IgG in sufficient quantities for determination (IIb B). However, in routine practice, IgM determination is practically not used due to its low availability. In addition, IgM may be detected during reactivation of the infection or not detectable during the primary episode of infection; determination of type-specific IgM is impossible. 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. Without treatment, many patients may develop local or generalized complications. It is during the initial episode that therapy is especially effective. In this regard, treatment of herpes with antiviral drugs should be prescribed at the first appointment, without waiting for laboratory confirmation.

Antiviral drugs Patients who seek help within 5 days from the onset of clinical manifestations (or later, but in the presence of fresh elements of the rash) must be prescribed antiviral therapy. Acyclovir, valacyclovir and famciclovir are effective both in eliminating clinical manifestations and in reducing the duration of relapse (Ib A). However, 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 local use of acyclovir and the development of resistance to this drug. This means that topical medications are not recommended for the treatment of genital herpes (IV C). Parenteral drugs are administered only if it is impossible to swallow the drug or 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 valacyclovir 500 mg 2 times a day. The choice of a specific drug should be based on cost and the patient's likely adherence to treatment. In some patients, the relapse lasts more than 5 days. In case of prolonged exacerbations with persistent general symptoms, the appearance of new rashes and the development of complications, the course of treatment should be extended.

Symptomatic therapy When treating genital herpes, it is recommended to wash the eroded areas with saline solution; use painkillers. When using local anesthetics, the possibility of sensitization should be considered. Thus, 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, on the other hand, has a high potential for sensitization and should not be used (IV C).

Consulting It is necessary to explain to the patient that there is a high risk of viral transmission (including periods of subclinical viral shedding) even when using condoms and using antiviral drugs. Advice about telling a sexual partner about the presence of an infection should be practical and tailored to the patient's specific situation. The low impact on health 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, hearing the diagnosis for the first time 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 reaction of patients is difficult to assess in advance, so careful observation is necessary using more intensive methods of persuasion 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 unfavorable social conditions, hospitalization of the patient is necessary. When performing bladder catheterization (if necessary), it is worth considering the possibility of a suprapubic approach (if this will facilitate monitoring the condition of a particular patient). Superinfection of the rash is rare, but can occur in the second week of illness. Characterized by exacerbation of local symptoms. Fungi of the genus Candida are most often the etiological agent, and in these cases, diagnosis and treatment are not difficult.

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

There are currently no controlled studies on the treatment tactics of HIV-infected patients with a primary episode of genital herpes. Some doctors suggest a 10-day course of treatment with any antiviral drug (from those described above) at twice the standard dose (IV C).

Patient Information When talking with the patient, it is necessary to explain the following aspects of herpesvirus infection:

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

Patient observation

Observation should be carried out until the symptoms of genital herpes are eliminated. Further observation is required if other causes of genital ulcers, which may occur as coinfections, are suspected. With repeated episodes of genital herpes, observation may be required in case of an atypical clinical picture and/or severe 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 what to do during subsequent exacerbations should be made together 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, treatment tactics may change over time as the frequency of exacerbations, the severity of the clinical picture, or the patient’s social status changes. For most patients, supportive care including saline irrigation and/or petrolatum jelly is appropriate.
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Episodic antiviral therapy Taking acyclovir, valacyclovir, or famciclovir by mouth effectively reduces the severity and duration of exacerbations of genital herpes. On average, the duration of an exacerbation is reduced by 1–2 days when taking any drug (Ib A). Direct comparative studies have not found any advantage of one drug over another, nor have 5-day courses of therapy been found to be superior to ultra-short treatment regimens. Prodrugs simplify dosing and are used 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 when treatment is started early. 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 (course of treatment 5 days):

• acyclovir 200 mg orally 5 times a day or
• acyclovir 400 mg orally 3 times a day for 3–5 days or
• valacyclovir 500 mg orally 2 times a day or
• famciclovir 125 mg orally 2 times a day.

Short treatment regimens:

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

Suppressive therapy A significant part of the studies examining suppressive therapy for herpes was conducted on patients with a frequency of exacerbations of 6 or more per year. In addition, recent studies have been conducted in patients with milder infections, including patients with exclusively serological evidence of infection. Studies have shown that the condition of patients in all groups improved with a decrease in the number of exacerbations throughout the year. When deciding whether to prescribe suppressive therapy, the key parameter is the minimum frequency of exacerbations at which such treatment tactics are justified. The relapse rate at which it makes sense to start suppressive therapy is a subjective concept. A balance must be struck between the frequency of relapses and the impact of the disease on the quality of life of the individual patient and balance this with the high cost and inconvenience associated with therapy. A reduction in relapse rates should be expected in all patients receiving suppressive antiviral therapy. However, we should not forget that rare clinically significant 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 development of resistance in the treatment process are obtained from observations during continuous use for more than 18 years. In some patients, from time to time it is worth assessing the advisability of further taking suppressive therapy, since changed living conditions can significantly affect the course of the infectious process. It is important to consider that many patients did not note a decrease in the frequency and/or severity of exacerbations after stopping suppressive therapy (even with a long previous course of taking the drug).

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

When comparing the effectiveness of taking valacyclovir (500 mg 1 time per day) and famciclovir (250 mg 2 times per day), no advantages were shown for any of the proposed treatment regimens (IV C). In case of insufficient clinical response to suppressive therapy, the dose of both valacyclovir and famciclovir may be doubled (IV C). Standard treatment regimens do not require dynamic testing of the patient's blood. When taking valacyclovir, adverse events such as mild headache or nausea may rarely occur. During suppressive therapy, the need for further medication use should be assessed 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 treatment tactics.

A small number of patients experience a reduction in the relapse rate after drug discontinuation compared with the relapse rate before suppressive therapy. Observation should be carried out for at least two consecutive exacerbations, which will allow assessing not only the frequency, but also the severity of relapses. Resumption of therapy after a break is justified 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 is worth considering that the suppressive effect is observed no earlier than 5 days from the start of taking the drugs.

Asymptomatic viral shedding and the possibility of viral transmission during suppressive therapy Subclinical viral shedding occurs in most patients infected with HSV-1 or HSV-2. Most often, viral shedding is observed in patients infected with HSV-2 less than a year ago, as well as in patients with frequent exacerbations. Acyclovir, valacyclovir and famciclovir effectively suppress both symptomatic and asymptomatic viral shedding. A partial reduction in viral shedding does not necessarily reduce the likelihood or frequency of viral transmission. At the same time, suppressive therapy with valacyclovir at a dose of 500 mg daily (with a relapse rate of 10 or less per year) reduced the frequency of HSV transmission in discordant couples by 50% (Ib A). Thus, valacyclovir can be used to prevent the transmission of HSV in combination with the use of barrier methods of contraception and abstinence from casual sexual intercourse.

Special situations

Treatment of HSV in immunocompromised and HIV-infected patients

Treatment of a primary episode of genital herpes To date, there is 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 primary infection studies virtually impossible. Some clinical observations show that the primary episode of genital herpes in HIV-infected patients may have a longer and/or atypical course. If the local immune response is insufficient, 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 multiple dose increases may be required in immunocompromised patients. Such measures are not always required to treat HIV-infected patients, particularly those with normal CD4 cell counts. In patients with active HIV infection, treatment should begin with double the dose of the drug. If new rashes appear within 3–5 days from the start of therapy, the dose may be increased. In cases of fulminant 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);
• valacyclovir 500 mg – 1 g orally 2 times a day (IV C);
• famciclovir 250–500 mg orally 3 times daily (IV C).

The duration of treatment is 5–10 days. It is preferable to extend the course of treatment until complete reepithelialization 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, a 5-day course of treatment is advisable. However, 13–17% of patients with active HIV infection experience the appearance of new rashes on the 7th day of treatment. Shorter courses of treatment are reasonable in patients with a CD4 cell count of at least 500 (data from one study using famciclovir) (Ib B).

Antiviral drug dosage regimens Standard dosage regimens are effective in patients without signs of immunodeficiency (Ib A). In patients with immunosuppression, doubling the dose of the drug and prolonging the course of treatment are required (Ib B). There have been no studies on the use of ultra-short 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. Tests were conducted using three antiviral drugs (acyclovir, valacyclovir, famciclovir). Standard dosage regimens of acyclovir have been shown to be effective in immunocompromised patients. The effectiveness of valacyclovir is increased when taken 500 mg 2 times a day compared with 1 g 1 time a day. The effectiveness of a single 500 mg dose of valacyclovir has not been evaluated. Data from studies of the effectiveness of high doses of famciclovir are only available over 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)) assessed the use of high doses of acyclovir (400 mg 4 times a day), and a more recent study assessed 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. High-dose valacyclovir (2 g 4 times daily) has been evaluated in HIV-infected patients and bone marrow transplant patients. Recently, studies have been conducted on the effectiveness of suppressive therapy with acyclovir and valacyclovir, 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 valacyclovir 1 g once a day or 500 mg twice a day, leads to the development of a minimal 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 valacyclovir (8 g per day) can lead to the development of microangiopathic hemolytic-uremic syndrome.

Dosage regimens The best evidence for achieving suppression exists for valacyclovir 500 mg twice daily and acyclovir 400 mg twice daily, which effectively suppress viral replication (Ib A). If there is no effect of such treatment regimens, you should, first of all, double the dose of the drug used; if there is no effect, famciclovir 500 mg 2 times a day should be prescribed (IIa B). Treatment of persistent genital herpes in immunocompromised patients

In immunocompromised patients, cases of treatment resistance are rare, while in patients with severe immunodeficiency, including late stages of HIV infection, and patients with immune reconstitution inflammatory syndrome (IRIS) occurring after HAART, clinically apparent cases of genital herpes that cannot be treated can be a serious problem. The treatment algorithm for such patients is presented in Figure 1.

The effect of suppressive therapy on the progression of HIV infection Suppressive therapy with acyclovir and valacyclovir reduces the level of HIV viremia. The mechanism of this 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-scale RCT showed that in patients with early stage HIV infection (not taking HAART; CD4 > 250), the use of suppressive doses of acyclovir (400 mg 2 times a day) helps maintain a sufficient level of CD4 lymphocytes, resulting in After taking acyclovir, the number of patients requiring HAART decreased by 16% compared to 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 consultation. Partner notification during pregnancy is discussed in later sections of the guide. When counseling patients, emphasis should be placed on the following points:

• the use of barrier methods of contraception is necessary even in the case of suppressive therapy;
• asymptomatic viral shedding plays a significant role in the transmission of HSV;
• Notifying partners followed by serological testing helps identify both uninfected and asymptomatic patients;
• proper counseling leads to independent recognition of relapses of genital herpes in 50% of asymptomatic seropositive patients. Identification of clinically significant relapses in such patients leads to a reduction in the risk of HSV transmission;
• the risk of HSV transmission is reduced both when using barrier methods of contraception and when conducting 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 treatment regimens can be used. In the absence of a threat of premature birth, observational tactics for further pregnancy management are recommended; planning for vaginal delivery (IV C). Prescribing suppressive therapy (acyclovir 400 mg 3 times a day) from the 36th week of pregnancy reduces the risk of relapse at the time of the onset of labor and, accordingly, the frequency of births by cesarean section (Ib B). Infection in the third trimester of pregnancy (IV C)

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

The patient should be informed that the likelihood of infection of the fetus or newborn with recurrent genital herpes is low. Exacerbations of genital herpes in the third trimester of pregnancy are characterized by a short duration; vaginal delivery is possible in the absence of rashes at the time of birth. Many patients will choose to deliver by cesarean section if they have rashes at the time of onset of labor. 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 a relapse at the time of the onset of labor and, accordingly, the frequency of births by cesarean section (Ia A).

If at the time of birth there are no rashes on the genitals, delivery by cesarean section for the purpose of preventing neonatal herpes is not indicated. A series of culture studies or PCR tests in late pregnancy is not indicated to predict the possibility of viral shedding at the time of delivery. The feasibility of conducting cultural studies or PCR during labor to detect asymptomatic viral shedding in women has not been proven. Treatment of recurrent genital herpes in early pregnancy

Despite the fact that there is insufficient data on the safety of acyclovir in pregnant women, 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 occasional use of antiviral drugs should be avoided. In some cases (severe and/or complicated course of genital herpes), it is impossible to avoid the prescription of antiviral drugs. In such situations, individual selection of a treatment regimen and careful monitoring are necessary. The use of the minimum effective dose of acyclovir is recommended; and newer antiviral drugs 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 in 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 a history of episodes of genital herpes (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 if there is a high risk of preterm birth (IV C). There is not yet sufficient evidence to recommend daily suppressive therapy to patients who have antibodies to HIV-1 and are seropositive for HSV-1 or -2, but do not have a history of genital herpes.

Treatment of patients with rashes at the time of onset of labor If there is a recurrence of genital herpes at the time of the onset of labor, delivery may be performed by cesarean section. When choosing a method of delivery, it is worth taking into account the low risk of neonatal herpes during vaginal birth in such cases, as well as the risk of surgical intervention in the woman in labor. Data from the Netherlands show that the conservative approach of vaginal delivery in the presence of anogenital rash does not increase the incidence of neonatal herpes (III B). This approach should only be used if supported by obstetricians and neonatologists and if it is consistent with local standards of care. Conducting cultural studies or PCR does not provide increased information for the diagnosis of both clinically significant relapses and asymptomatic viral shedding.

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

Prevention of infection (IV C) The risk of infection among pregnant women varies widely depending on geographic location. In this regard, the surveillance system must develop a prevention strategy for each region. Any prevention strategy must target both parents. At the first visit during pregnancy, it is necessary to find out whether the patient or her sexual partner has had episodes of genital herpes in the anamnesis. Patients who do not have a history of episodes of genital herpes, but whose sexual partners suffer from recurrent genital herpes, should be recommended a plan of preventive measures. 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 transmitting HSV to a seronegative partner. However, the effectiveness of male partner suppressive therapy as a method of preventing infection in a pregnant woman has not been evaluated, so at present such tactics 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, and therefore cannot be recommended for use in European countries. All patients, regardless of a history of herpetic infection, should be examined at the beginning of labor in order to identify herpetic rashes. If you have herpetic rashes on the face or herpetic whitlows (in the mother, employees of a medical institution, relatives/friends), contact of the affected area of ​​skin with the newborn should be avoided.

Treatment of newborns

Children born to mothers with a primary episode of genital herpes at birth

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

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

* Reviewer: Professor H. MOY. The authors would like to thank: S. BARTON, D. KINGHORN, H. LOTTERY. IUSTI/WHO editorial team: K. RADCLIFFE (editor-in-chief), M. VAN DER LAAR, M. JANIER, J.S. JENSEN, M. NEUMANN, R. PATEL, D. ROSS, W. VAN DER MUIDEN, P. VAN VOORST WADER, H. MOY. Estimated date for revision of the Guidelines: May 2013. Translation of the Guidelines 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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