Anogenital herpes simplex virus infection: clinical guidelines

List of Abbreviations

IgM, G - immunoglobulins of classes M, G

HIV - human immunodeficiency virus

HSV - herpes simplex virus

DNA - deoxyribonucleic acid

STI — sexually transmitted infection

ICD — International Classification of Diseases

PCR — polymerase chain reaction

** - drug is included in the VED list

Terms and Definitions

Autoinoculation - mechanical transfer of an infectious agent from one body site to other body sites.

Abortive form - a form of the disease characterized by incomplete clinical symptoms or minimal severity of clinical symptoms of the infection.

Herpetic coinfection - simultaneous infection with herpes simplex virus types 2 and 1.

Latent herpetic infection is an inactive stage of the infection where the virus is not detected in biological materials but persists as a DNA-protein complex in nerve ganglia. Manifest herpetic infection is the active stage of the infection characterized by clinical symptoms.

Primary (first) episode of herpes refers to newly diagnosed clinical manifestations of herpetic infection.

Herpes recurrence refers to repeatedly registered clinical manifestations of herpetic infection.

Suppressive therapy for herpetic infection is the long-term, sometimes multi-year, continuous administration of low doses of nucleosides and nucleotides (excluding reverse transcriptase inhibitors) during disease remission. Episodic therapy for herpetic infection is the administration of nucleosides and nucleotides (excluding reverse transcriptase inhibitors) at the time of recurrence in therapeutic doses, maintaining the required frequency and duration of treatment.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Anogenital herpetic viral infection is a chronic recurrent viral disease transmitted predominantly sexually, caused by herpes simplex virus type 2 and/or type 1.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Anogenital herpetic viral infection (anogenital herpes) is caused by herpes simplex virus (HSV) types 1 and 2, with HSV type 2 being detected more frequently in anogenital lesions. Herpes simplex virus is a dermatoneurotropic DNA-containing virus belonging to the subfamily Alphaherpesvirinae of the family Herpesviridae.

At the inoculation site, HSV replicates in epithelial cells, after which the viruses enter the bloodstream and lymphatic system and invade nerve endings in the skin and mucous membranes. Moving centripetally along the axoplasm, the herpes simplex virus reaches the peripheral, and subsequently segmental and regional sensory ganglia of the central nervous system, where it persists for life within nerve cells (latently as non-enveloped L and PREP particles). The complete HSV reproduction cycle occurs exclusively in epithelial-type cells. Under the influence of trigger factors (stress, ultraviolet or radiation exposure, immunodeficiencies, etc.), viral reactivation and disease manifestation take place.

Infection of adults and adolescents occurs through any form of sexual contact with a person suffering from herpetic infection, both when clinical symptoms are present in the partner (the source of infection) and when they are absent, provided the virus is being shed (the risk of transmission is highest during disease manifestation and the prodromal period) [1-4]; infection via autoinoculation is also possible. In children, infection can occur via transplacental (rare), intranatal, sexual, or contact-household routes (due to poor personal hygiene and childcare practices), as well as through autoinoculation [96, 100, 101].

Most cases of neonatal herpes are associated with direct contact of the virus with the birth canal. In a primary episode of anogenital herpes in a pregnant woman close to delivery, the risk of transmission to the infant and neonatal infection is 30–40% [32, 81, 160]. This is facilitated by the child's exposure to high viral shedding combined with a lack of protective antibodies. Maternal immunoglobulins are produced as a result of the primary herpetic infection. IgM to IgG seroconversion occurs within 6–12 weeks, and since IgG crosses the placenta, the infant will be largely protected upon subsequent contact with the herpes virus [161]. Therefore, during a recurrence of anogenital herpes shortly before birth, the risk of neonatal infection is low: 0–2% [32, 81, 160, 161]. In pregnant women with a primary episode of anogenital herpes in the first and second trimesters, anti-HSV antibodies are produced by term and transmitted transplacentally to the fetus; the risk of neonatal infection at birth in these cases is estimated to be similar to that in pregnant women with recurrent anogenital herpes [162].

1.3 Epidemiology of the Disease or Condition

Anogenital herpetic viral infection is the most common erosive and ulcerative genital disease. Epidemiological studies indicate a ubiquitous distribution of herpetic infection. Approximately 500,000 people contract anogenital herpes annually. In the majority of cases, the infection remains undiagnosed due to frequent subclinical and atypical forms of the disease [30].

Asymptomatic viral shedding is of great importance in the epidemiology of anogenital herpes: up to 70% of HSV transmissions occur during the asymptomatic course of the infection in an infected individual [1-3].

In the Russian Federation, the incidence of anogenital herpetic viral infection in 2021 was 8.7 cases per 100,000 population [175].

1.4 Features of Coding the Disease or Condition

Anogenital herpetic viral infection [herpes simplex] (A60):

A60.0 - Herpesviral infections of genitalia and urogenital tract;

A60.1 - Herpesviral infection of perianal skin and rectum;

A60.9 - Anogenital herpesviral infection, unspecified

1.5 Classification of the disease or condition

In clinical practice, a distinction is made between: a primary clinical episode of anogenital herpes, recurrent anogenital herpes, and a primary episode of latently proceeding herpes simplex virus infection. The disease is also classified:

- by severity: mild (1–2 exacerbations per year), moderate (3–5 exacerbations per year), severe (6 or more exacerbations per year);

- by clinical presentation: typical and atypical anogenital herpes [97-99];

- by localization: herpetic urethritis, herpetic vaginitis, herpetic vulvitis, herpetic cervicitis, herpetic cystitis, herpetic infection of the perianal skin and rectum.

1.6 Clinical presentation of the disease or condition

The primary episode of the disease is characterized by pronounced clinical manifestations and may be accompanied by general malaise and a low-grade fever. The severity and duration of clinical symptoms in recurrences of anogenital herpes are generally less pronounced than during the initial episode of the disease.

Objective symptoms of manifest (typical) anogenital herpes:

- hyperemia and edema of the skin and mucous membranes in the affected area: in men — the penis, scrotum, pubic region, perineum, perianal area; in women — the vulva, clitoris, vagina, cervix, pubic region, perineum, perianal area;

- single or multiple vesicular elements of a polycyclic, scalloped shape with clear contents, often bilateral, on a hyperemic base, localized in the affected area;

- after the opening of the vesicular elements, superficial erosions covered with a grayish coating (2–4 mm in size, corresponding to the number of former vesicles) or a continuous erosion with a smooth base and non-undermined edges surrounded by a bright red halo are formed. When a secondary infection joins, purulent exudate appears;

- enlargement and tenderness of the inguinal lymph nodes.

Atypical forms of anogenital herpes may present with;

- erythema and edema without the development of rash elements (abortive form);

- a lesion in the form of an itchy spot of varying size with irregular outlines and indistinct pinkish borders (erythematous form);

- marked edema of the subcutaneous adipose tissue without vesicle formation (edematous form);

- recurrent fissures of the skin and mucous membrane of the genitals and/or perianal region accompanied by itching, which spontaneously epithelialize within 4–5 days (fissure form);

- small ulcers formed from vesicles, upon healing of which atrophic scars develop (erosive-ulcerative form);

- single or multiple vesicular elements with hemorrhagic contents (hemorrhagic form);

- prolonged non-healing ulcers transformed from erosions that developed after the rupture of vesicles (ulcerative-necrotic form);

- a single multilocular blister (bullous form).

Recurrences in HSV-2 infection occur earlier and more frequently than in HSV-1 infection and are accompanied by more pronounced clinical symptoms [5, 6, 31].

A rare complication of anogenital herpetic infection caused by HSV-2 is meningitis [177], characterized by headache, photophobia, fever, meningism, and cerebrospinal fluid lymphocytic pleocytosis accompanied by a moderately elevated protein level and normal glucose level [178]. It is important to differentiate this condition from HSV-2 encephalitis, as the latter represents a more severe infection with high neurological morbidity and mortality [179].

Another rare manifestation of disseminated herpetic infection in pregnant women in the second and third trimesters is hepatitis, characterized by a severe course and fulminant hepatic failure with high mortality (25%), fever, and often without concurrent genital or cutaneous herpetic lesions [180].

2. Diagnostics, medical indications and contraindications for diagnostic methods

Diagnostic criteria

The diagnosis of anogenital herpetic viral infection is established based on the characteristic clinical presentation; if necessary (e.g., during a primary episode), it is confirmed by detecting herpes simplex virus type 2 and/or type 1 DNA in the studied biological material using molecular biological methods.

2.1 Complaints and Anamnesis

In primary episodes and recurrences of anogenital herpetic viral infection, the following subjective symptoms may occur: genital and/or perianal vesicles and/or erosions, tenderness in the rash area in the genital and/or perianal region; pruritus, pain, paresthesias in the anogenital region; pain during sexual intercourse (dyspareunia); painful inguinal lymphadenopathy; pruritus, burning, pain during urination (dysuria); in case of vaginal localization of the rash — mucopurulent vaginal discharge; general symptoms of intoxication (fever, chills, headache, nausea, malaise, myalgia, sleep disturbance), which occur more frequently during the first episode of the disease than during its recurrence [7-11].

Comments:

It is important to evaluate anamnestic data that support the diagnosis of genital herpes, such as a history of similar rashes, the appearance of elements in the same location, and the past efficacy of antiviral therapy.

2.2 Physical Examination

An examination of the skin and visible mucous membranes of the external genitalia and perianal region is performed; the condition of the mucous membrane of the external urethral meatus is evaluated, along with the presence and characteristics of free urethral discharge; palpation of the urethra and regional lymph nodes is performed to determine their tenderness and size [7, 9, 11].

In sexually active females, an examination of the vaginal vestibule, the mucous membranes of the vaginal walls and fornices, and the visible portion of the cervix is performed using gynaecological specula; the discharge in the posterior and posterolateral vaginal fornices is evaluated.

Comments:

Lymph node examination is performed bimanually and bilaterally, comparing the right and left areas of study. Examination of the lymph nodes provides information on the presence of an inflammatory process.

For objective clinical manifestations of the disease identified during physical examination, see the "Clinical Presentation" section.

2.3 Laboratory Diagnostics

Comments:

When collecting clinical material, the possibility of multi-site infection should be considered. Laboratory test results may be influenced by the severity of clinical manifestations, the quality of clinical material collection, storage conditions, transportation, and processing times [14-16, 19, 110].

To obtain reliable laboratory test results, it is advisable to comply with a number of requirements, which include:

- collecting clinical material from the urethra no earlier than 3 hours after the last urination; in the presence of abundant urethral discharge — 15-20 minutes after urination;

- collecting clinical material from the cervical canal and vagina before menstruation or 2 days after its cessation;

- collecting clinical material from the cervical canal and

vagina not earlier than 24–48 hours after transvaginal ultrasound of the uterus and appendages and expanded colposcopy;

- excluding vaginal douching on the eve of the examination and on the day it is performed;

- exclusion of genital hygiene procedures using intimate hygiene products on the day of the examination;

- excluding the use of fat-containing vaginal medicinal products (suppositories, creams, vaginal tablets) 3-5 days prior to the day of examination;

- collecting clinical material for molecular biological testing during the acute phase of anogenital herpes;

- collecting clinical material for molecular biological testing outside of antiviral therapy;

- compliance with the conditions for transporting clinical samples to the laboratory.

- in recurrent anogenital herpes or in anogenital herpes with an atypical clinical presentation and a history of negative HSV detection results by molecular biological methods [23];

GCR CLEL 5Grade of Recommendation C (Level of Evidence - 5)

- when examining sexual partners of patients with anogenital herpes [24-26];

LeR CLoE 4Level of Recommendation C (Level of Evidence — 4)

- upon the first manifestation of the disease during pregnancy to classify maternal infection as a primary clinical episode, a primary episode of latent infection, or recurrent anogenital herpes, since the mode of delivery depends on this [162].

GCR CLEL 5Grade of Recommendation C (Level of Evidence - 5)

Comments: it takes from 2 weeks to 3 months from the onset of clinical symptoms of the disease to the detection of type-specific IgG to herpes simplex virus [35-38].

The presence of antibodies to HSV type 2 supports the diagnosis of anogenital herpes, whereas the presence of antibodies to HSV type 1 does not allow differentiation between anogenital and orofacial infection; at the same time, HSV type 1 can be the cause of recurrent herpetic rashes in the anogenital region [1].

In case of discordant serological test results in sexual partners, patients are counselled on ways to reduce the risk of HSV transmission [26].

Comments: For differential diagnosis, patients with erosive and ulcerative rashes in the genital and perianal regions should undergo laboratory tests for syphilis: determination of antibodies to Treponema pallidum in non-treponemal tests (RPR, VDRL) (qualitative and semi-quantitative assay) in blood serum and/or determination of antibodies to Treponema pallidum by enzyme immunoassay (EIA) in blood. Due to common routes of transmission of STIs, HIV infection, and hepatitis B and C, patients with a primary episode of anogenital herpes should undergo:

- laboratory tests for syphilis (determination of antibodies to Treponema pallidum in non-treponemal tests (RPR, VDRL) (qualitative and semi-quantitative assay) in blood serum and/or determination of antibodies to Treponema pallidum by enzyme immunoassay (EIA) in blood);

- determination of antibodies of classes M and G (IgM, IgG) to human immunodeficiency virus HIV-1 in blood. Determination of antibodies of classes M and G (IgM, IgG) to human immunodeficiency virus HIV-2 in blood;

- determination of hepatitis B virus surface antigen (HBsAg) in blood and determination of total antibodies of classes M and G (anti-HCV IgG and anti-HCV IgM) to hepatitis C virus in blood;

- for individuals with an unidentified source of infection: repeat testing for syphilis (determination of antibodies to Treponema pallidum using non-treponemal tests (RPR, VDRL) (qualitative and semi-quantitative assay) in blood serum and/or determination of antibodies to Treponema pallidum by enzyme immunoassay (EIA) in blood) after 3 months; repeat determination of immunoglobulin M and G (IgM, IgG) antibodies to human immunodeficiency virus HIV-1 in blood; determination of immunoglobulin M and G (IgM, IgG) antibodies to human immunodeficiency virus HIV-2 in blood; determination of hepatitis B virus surface antigen (HBsAg) in blood and determination of total classes M and G antibodies (anti-HCV IgG and anti-HCV IgM) to hepatitis C virus in blood after 3–6–9 months.

2.4 Instrumental Diagnostics

Not applicable.

2.5 Other Procedures

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

In patients with manifest primary anogenital herpes or disease recurrence, systemic antiviral therapy with nucleoside and nucleotide analogues (excluding reverse transcriptase inhibitors) is recommended to suppress viral replication, minimize the risk of complications, reduce the severity and shorten the duration of the primary episode or recurrence, and lower the risk of subsequent disease relapses [43-49].

Treatment strategy selection takes into account disease severity, recurrence frequency, infection phase (primary episode or recurrence), as well as the presence and nature of complications [51].

3.1. Conservative management

aciclovir** for children aged 3 years and older and adults: 200 mg 5 times daily orally for 5 days; treatment duration may be extended in severe primary infections [43-45, 114, 182]

LeveL of Recommendation BGrade of Evidence 2LeveL of Recommendation B (Grade of Evidence - 2)

or

valaciclovir for children aged 12 years and older and adults: 500 mg twice daily for 7–10 days [181]

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

or

famciclovir for adults [50, 57, 167]

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

Comments: for adults, 250 mg 3 times daily for 5 days

aciclovir** [47, 182]

GCR BLEL 2Grade of Recommendation B (Level of Evidence - 2)

Comments: for children aged 3 years and older and adults, 200 mg 5 times daily for 5 days

or

valaciclovir [167]

GCR CLEL 5Grade of Recommendation C (Level of Evidence - 5)

Comments: for children aged 12 years and older and adults, 500 mg twice daily for 3 days

or

famciclovir for adults: 125 mg twice daily for 5 days [55, 62, 167]

GCR ALeE 2Grade of Recommendation A (Level of Evidence - 2)

or

famciclovir for adults [167]

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

Comments: for adults, 500 mg once daily, followed by three doses of 250 mg every 12 hours, with a total dose of 750 mg.

famciclovir for adults: 1.0 g twice daily for 1 day [59, 60, 167]

GCR BLEL 2Grade of Recommendation B (Level of Evidence - 2)

Comments:

Both in primary episodes and recurrences of genital herpes, therapy may be prescribed for a shorter or longer number of days depending on the duration and severity of the disease. None of the drugs has a proven advantage in efficacy regarding the disease course [14, 43-49, 121].

Episodic treatment of recurrent herpes is most effective when initiated within the first 24 hours of disease onset or during the prodromal period; therefore, patients should be advised to keep a supply of medication on hand to start treatment immediately upon the first symptoms [167].

valaciclovir [46, 183, 187]

GoR BLoE 2Grade of Recommendation B (Level of Evidence - 2) – adults

GoR CLoE 5Grade of Recommendation C (Level of Evidence - 5) – children

Comments: for children aged 3 years and older and adults, 500 mg once daily

or

famciclovir for adults: 250 mg twice daily [184]

GCR BLEL 2Grade of Recommendation B (Level of Evidence - 2)

or

aciclovir** [65, 67, 185, 187]

GoR BLoE 2Grade of Recommendation B (Level of Evidence - 2) – adults

GoR CLoE 5Grade of Recommendation C (Level of Evidence - 5) – children

Comments: for children aged 3 years and older and adults, 200 mg 5 times daily. Indications for suppressive therapy include: severe, frequently recurring (more than 6 times a year), complicated disease course; severe prodromal symptoms; marked immunosuppression; impaired psychoemotional state due to the potential transmission of herpes simplex virus. The duration of suppressive therapy is determined individually. Upon achieving sustained improvement, suppressive therapy may be discontinued. The efficacy of suppressive therapy is evaluated after at least two recurrences. If the disease course worsens thereafter, a decision to resume suppressive therapy may be made.

aciclovir*[1] 200 mg 5 times daily [68, 69, 113]

or

valaciclovir 500 mg twice daily [69, 113]

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

Comments: The drug should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus.

Comments: Pregnant women with a primary episode of anogenital herpes in the first or second trimester, or with recurrent herpes episodes regardless of gestational age, are recommended to have a vaginal delivery because the risk of neonatal herpes is low [162]. With recurrent anogenital herpes during vaginal delivery, the risk of transmission to the infant is 0–3% [81, 117, 160, 161, 164]. Cesarean section does not completely eliminate the risk of neonatal herpes and entails anesthetic and surgical risks for the mother [117, 165].

aciclovir** 200 mg 5 times daily for 5–10 days [113]

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

or

valaciclovir 500 mg twice daily for 5–10 days [166, 167, 113]

LoR CGoE 5Level of Recommendation C (Grade of Evidence - 5)

Comments:

Aciclovir** is the drug of choice for the treatment of pregnant women and is considered safe for use in all trimesters [168–170]. Valaciclovir is an alternative agent, but data on its use during pregnancy are limited [168]. The National Birth Defects Prevention Study in the USA showed a 4.7-fold increase in the odds of gastroschisis among women who took aciclovir and valaciclovir between one month before conception and the third month of pregnancy [171]. An increased risk of gastroschisis was also observed among women who did not receive antiviral therapy but self-reported a history of genital herpes. Aciclovir** belongs to pregnancy safety category B; the expected benefit to the mother and potential risk to the fetus should be weighed [163, 167]. The use of aciclovir** and valaciclovir is not a contraindication to breastfeeding, provided there are no herpetic lesions on the breasts [LactMed as of March 1, 2013].

Comments: Preparations containing human recombinant interferon alfa-2b** or human recombinant interferon gamma** are used [72-77, 86-89, 103, 107-109, 156-159] in accordance with the instructions for use. Topical acyclovir (D06BB03 – Acyclovir) and/or certain antiseptic preparations (D08A Antiseptics and disinfectants) [127-130] may also be used in accordance with the instructions for use.

Recommendations for the management of neonatal herpes are beyond the scope of these clinical guidelines.

3.2. Surgical treatment

Not applicable.

3.3. Other treatment

Diet therapy is not used.

Pain management is not used.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comments: The diagnosis leads to the development of various psychosomatic conditions. Initial diagnosis of anogenital herpes and recurrences are typically accompanied by high levels of stress, which can be mitigated by the use of systemic antiviral drugs.

5. Prevention and Dispensary Observation

- informing the public about the transmission routes of anogenital herpes;

- avoiding casual sexual contacts;

- using barrier methods of contraception during all types of sexual intercourse [21, 78, 79]

LeveL of Recommendation BGrade of Evidence 3LeveL of Recommendation B (Grade of Evidence - 3)

Comments:

Preventive counseling is provided when patients seek medical care.

- abstain from sexual intercourse during a recurrence of herpetic infection [83-85]

GCR CLEL 5Grade of Recommendation C (Level of Evidence - 5)

- for adults with regular sexual intercourse, use valacyclovir [29, 80]

LoE CGoE 2Level of Evidence C (Level of Data Reliability - 2)

Comments: adults 500 mg orally once daily for 12 months

- use barrier methods of contraception during all types of sexual intercourse [85, 122]

GCR CLEL 5Grade of Recommendation C (Level of Evidence - 5)

Follow-up medical observation is not carried out.

6. Organization of Medical Care

Treatment of patients with anogenital herpes is carried out on an outpatient basis.

In the event of complications such as urinary retention, hospitalization in a specialized urology inpatient facility is indicated; in the event of complications characterized by neurological symptoms, hospitalization in a specialized neurology inpatient facility is indicated.

Upon the initial diagnosis of anogenital herpetic viral infection in a patient, dermatovenereologists, obstetricians-gynecologists, coloproctologists, urologists, and physicians of other specialties shall complete form No. 089u/kv "Notice of a patient with a newly established diagnosis of: syphilis, gonococcal infection, chlamydial infections, trichomoniasis, anogenital herpetic viral infection, anogenital (venereal) warts, mycosis, scabies" in the manner established by the letter of the Russian Ministry of Health dated March 2, 2015, No. 13-2/25.

7. Additional Information

Factors negatively affecting the course of anogenital herpes include:

1. Refusal to use systemic antiviral drugs when indicated.

2. Presence of factors promoting the reactivation of herpes simplex virus types 1 and 2 (psychoemotional stress, somatic pathology, ultraviolet radiation, menstruation, alcohol consumption).

3. Co-infection.

4. Development of infectious complications [92-97].

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Alexey Alexeevich Kubanov - Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Director of the State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, President of the Russian Society of Dermatovenereologists and Cosmetologists.

2. Margarita Rafikovna Rakhmatulina - Doctor of Medical Sciences, Professor, Deputy Director for Organizational and Analytical Work at the State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Chair of the Executive Committee of the Russian Society of Dermatovenereologists and Cosmetologists.

3. Inna Anatolyevna Apolikhina - Doctor of Medical Sciences, Professor, Head of the Department of Aesthetic Gynecology and Rehabilitation at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Member of the Russian Society of Obstetricians and Gynecologists.

4. Mikhail Alexandrovich Gomberg - Doctor of Medical Sciences, Professor, Chief Researcher at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology of the Moscow Healthcare Department, Member of the National Alliance of Dermatovenereologists and Cosmetologists Union.

5. Elena Alexeevna Gorbunova - Obstetrician-Gynecologist, Researcher at the Department of Aesthetic Gynecology and Rehabilitation, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Member of the Russian Society of Obstetricians and Gynecologists.

6. Natalia Vitalievna Dolgushina - Doctor of Medical Sciences, Professor, Deputy Director for Research at the Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Member of the Russian Society of Obstetricians and Gynecologists.

7. Ziganshin Oleg Raisovich - Doctor of Medical Sciences, Professor, Chief Physician of the State Budgetary Healthcare Institution "Chelyabinsk Regional Clinical Dermatovenereological Dispensary", member of the Russian Society of Dermatovenereologists and Cosmetologists.

8. Georgy Leonidovich Katunin - Candidate of Medical Sciences, Dermatovenereologist at the State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, Member of the Russian Society of Dermatovenereologists and Cosmetologists.

9. Nechaeva Irina Anatolyevna - Candidate of Medical Sciences, Dermatovenerologist, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, member of the Russian Society of Dermatovenerologists and Cosmetologists.

10. Onipchenko Viktoriya Viktorovna - Candidate of Medical Sciences, Chief Physician of the State Budgetary Healthcare Institution of the Novosibirsk Region "Novosibirsk Regional Clinical Dermatovenereological Dispensary", Chief Specialist in Dermatovenereology and Cosmetology of the Novosibirsk Region, member of the Russian Society of Dermatovenereologists and Cosmetologists.

11. Perlamutrov Yury Nikolaevich - Doctor of Medical Sciences, Professor, Head of the Department of Skin and Venereal Diseases, A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Russian Ministry of Health, member of the Russian Society of Dermatovenerologists and Cosmetologists.

12. Plakhova Ksenia Ilyinichna - Doctor of Medical Sciences, Scientific Secretary, Acting Head of the STI Department, State Research Center of Dermatovenereology and Cosmetology of the Russian Ministry of Health, member of the Russian Society of Dermatovenerologists and Cosmetologists.

13. Potekaev Nikolay Nikolaevich - Doctor of Medical Sciences, Professor, Director of the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology of the Moscow Healthcare Department, Chief freelance specialist in dermatovenereology and cosmetology of the Russian Ministry of Health, President of the National Alliance of Dermatovenerologists and Cosmetologists Union.

14. Priputnevich Tatyana Valeryevna - Corresponding Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Director of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, member of the Russian Society of Obstetricians and Gynecologists.

15. Khaldin Alexey Anatolyevich - Doctor of Medical Sciences, Professor, Chief Researcher at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology of the Moscow City Health Department, member of the Union "National Alliance of Dermatovenereologists and Cosmetologists".

Conflict of interest:

The authors declare no conflict of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

• Medical specialists: dermatovenereologists, obstetrician-gynecologists, coloproctologists, urologists, pediatricians, infectious disease specialists.

• Residents and trainees of continuing professional education programs in the specified specialty.

Table 1. Scale for assessing levels of evidence (LE) for diagnostic methods (diagnostic interventions)

Table 2. Scale for assessing levels of evidence (LE) for prevention, treatment and rehabilitation methods (preventive, therapeutic, rehabilitation interventions)

Table 3. Scale for assessing levels of recommendation evidence (LRE) for prevention, diagnosis, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, rehabilitation interventions)

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their

systematic updating at least once every three years, as well as upon the emergence of new data from the perspective of evidence-based medicine regarding the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

No information available.

Appendix B. Physician Action Algorithms

Flowchart 1. Algorithm for managing a patient with suspected anogenital herpes (excluding pregnant women)

Flowchart 2. Algorithm for managing a pregnant woman with anogenital herpes [162].

Appendix C. Patient Information

1. Anogenital herpesvirus infection is a chronic recurrent disease characterized by lifelong persistence of the herpes simplex virus in the body.

2. For the prevention of anogenital herpesvirus infection transmission, it is necessary to:

   - use condoms or abstain from all forms of casual sexual contact (oral, vaginal, anal);

   - abstinence from all forms of sexual contact with individuals showing symptoms of sexually transmitted infections (unpleasant-colored and odorous genital discharge, rashes, or ulcerations on the external genitalia).

3. During an episode of anogenital herpes recurrence and throughout treatment, sexual contact should be avoided.

4. Transmission of the infection can occur in the absence of clinical manifestations due to asymptomatic viral shedding.

5. Consistent and correct use of condoms helps reduce the risk of infecting a sexual partner.

6. Screening for other sexually transmitted infections, HIV infection, and hepatitis B and C is recommended.

7. The indication for the treatment of anogenital herpes is the presence of clinical manifestations of the disease. The presence of specific anti-herpetic antibodies circulating in the blood serum or other biological fluids and secretions of the patient is not an indication for prescribing therapy.

8. None of the drugs has a superiority in efficacy regarding the course of the disease.

9. Treatment does not lead to the eradication (elimination) of the herpes simplex virus and does not always affect the frequency and severity of subsequent recurrences.

10. Parents and caregivers with active lesions of anogenital and labial herpes who care for an infant, regardless of the lesion localization, must exercise caution when handling the infant: lesions must be covered and hands washed before touching the child. From 5% to 15% of neonatal herpes cases are acquired postnatally from a family member [174].

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Not used.