Clinical and Morphological Diagnosis and Treatment of Sexually Transmitted Diseases - Yakimova T. P. 2007

Genital herpes. Clinical features, morphological characteristics, and diagnostic criteria for genital herpes. Treatment of genital herpes

In the United States and Western Europe, herpesvirus infections became a major public health and social challenge more than 20 years ago. However, in our country, this group of infectious diseases remains largely unfamiliar to the vast majority of physicians. This is primarily due to the fact that patients suffering from herpesvirus infections seek care across various medical specialists: Skin and mucosal lesions are treated by dermatovenerologists and dentists; genital herpes is managed by urologists, gynecologists, and sexologists; neurological disorders are handled by neurologists; and involvement of the lymphoid system is addressed by hematologists, oncologists, and immunologists. Meanwhile, patients with visceral forms most frequently end up under the care of general practitioners and pediatricians, and specific clinical nosologies are routed to infectious disease specialists. In other words, herpesvirus infections in Ukraine are "everyone's and no one's responsibility." Consequently, approaches to examination, Diagnosis, Treatment, and Prevention of these conditions remain fragmented and inconsistent.

In real life, virtually every individual is infected with one or more human herpesvirus serotypes. Reinfection occurs quite frequently, exhibiting distinct Clinical Features depending on age and other contributing factors. Overall, herpesvirus infections are characterized by a marked polymorphism of Clinical presentation (A wide variety of clinical forms) and the lifelong persistence of the virus within The Human Body. Such latency is governed by The activity of specific viral genes and the interaction of the virus with host Cells of specific Tropisms.

The virus not only persists in the body for long periods but is also transmitted to daughter cells.

The clinical course and prognosis of herpesvirus infections are determined by the state of The Immune System. In the presence of immunodeficiency of any origin, Herpesviruses begin to replicate actively, the disease takes on a recurrent course, and systemic dissemination (generalization) frequently occurs. Eight antigenic serotypes of the herpes virus have been isolated: Herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and human herpesvirus types 7 and 8. It is estimated that 65 to 90% of the adult and pediatric population worldwide is infected with a herpes virus.

Herpes simplex virus type 1 typically causes lesions of the oral mucosa, whereas herpes simplex virus type 2 predominantly affects young people at the onset of their sexual activity. At the same time, both Viruses are capable of infecting any organ and system, causing localized and generalized, acute and chronic forms of infection. The disease is highly contagious; transmission occurs through genital, orogenital, and anal contact, during childbirth, and via contaminated personal hygiene items or personal belongings of the infected individual.

An infected person or carrier can spread the infection to other parts of their own body, such as the eyes, face, Lips, nasal alae, Oral Cavity, and genitals. Dentists and gynecologists may accidentally transfer the infection to their hands, making occupational transmission possible. In 15% of people, the herpes virus remains in a latent state.

The most common manifestation of herpetic infection is genital herpes—a recurrent sexually transmitted infection most frequently caused by genital herpes viruses, namely herpes simplex virus type 2, less commonly type 1, and cytomegalovirus infection. Recurrent forms of herpes are estimated to occur in 2 to 6% of the population, while genital herpes affects generally 0.5 to 2%, and up to 6% of the adult population in developed countries. Clinical and epidemiological studies have shown that genital herpes accounts for approximately 13% of all Sexually Transmitted Diseases in the United States. In developed countries, the incidence tends to increase by 10% annually, whereas herpetourological infections account for 0.9% of all Urinary Tract infections.

In 75% of patients infected with the herpes virus, lesions develop in the skin, mucous membranes, Internal Organs, and the Central Nervous system. HSV infection adversely affects the psychoemotional well-being of patients, triggering neurasthenia and depression, and can lead to meningitis, encephalitis, pharyngitis, immunodeficiency, and hematopoiesis disorders.

Genital herpes can cause Miscarriage, fetal and neonatal infection, developmental malformations, intellectual disability, and fetal or neonatal death. Therefore, screening young women for viral infections during family planning is of paramount importance. Some authors report that in 7–21% of cases, patients infected with herpes simplex virus are diagnosed with Cervical Cancer, although this virus is not traditionally considered a primary etiological factor in carcinogenesis at this site (Kozlova V.I. et al., 1995; Kruglikov V.T., 1998).

At the same time, certain authors consider herpes simplex virus type 2 to be the second most important etiological factor, following human papillomavirus, in The Development of cervical cancer.

Primary infection with herpes simplex virus is often accompanied by more pronounced symptoms compared to disease recurrences. Symptoms typically appear 2 to 14 days after exposure. Patients report general fatigue, irritability, and in some cases, fever and chills. Against this backdrop, characteristic erythema develops in various areas of the body, followed by fluid-filled papules and vesicles. The vesicles rupture, forming small, highly painful ulcers that tend to coalesce. The herpes virus can be successfully isolated from the patient During the first week of primary infection.

In men, herpetiform genital lesions are usually localized primarily on the Penis and the inner surface of the prepuce. In some cases, they are located on the Scrotum, Perineum, or within the Urethra. The condition is frequently accompanied by local pain and systemic symptoms such as fever, pharyngitis, myalgia, arthralgia, and inguinal lymphadenopathy. When lesions develop intraurethrally, patients exhibit signs of urethritis, including discomfort in the urethra and an abrupt onset of dysuria characterized by sharp pain, frequent painful urination, and urgency, sometimes in the absence of externally visible lesions.

Clinical signs and symptoms of genital herpes are more pronounced in women than in men. In virtually all cases of herpetic genital lesions in women, transmission occurs through sexual contact. Symptoms appear 2 to 14 days after exposure. Initially, patients experience systemic symptoms of infection: fever, malaise, and Muscle, HEAD, and joint pains. Within a few days, these systemic symptoms subside while local manifestations intensify—characteristic painful papules appear, followed by vesicular clusters that eventually rupture and ulcerate within a few days, causing severe pain. Such lesions are often accompanied by local lymphadenopathy and can be found on the vulva, inguinal folds, perineal skin, buttocks, thighs, and hip joint regions, as well as on the mucosa of the Vagina, urethra, and cervix. Redness of the genital skin and mucous membranes, tissue edema, and a sensation of heaviness and pressure in the perineal region are frequently observed; In addition to pain, women may experience spotting during sexual intercourse. Subsequently, the inflammatory process can spread to the Urinary Bladder and urethra. Herpetic lesions inside the bladder and urethra, as well as around the urethral and vaginal openings, cause acute and painful dysuria, which occasionally leads to Acute Urinary Retention. The complete cycle of herpetic eruptions lasts about 3 weeks, causing considerable suffering to patients.

Alongside clinically manifest forms of genital herpes, latent forms also occur. A significant proportion of patients exhibit minimal signs of the disease that may go unnoticed (such as nonspecific balanitis in men or vulvitis in women).

Various Methods are available to verify herpes simplex virus infection.

Serological methods for diagnosing herpes simplex virus are based on detecting Antibodies against viral Antigens. However, in patients with immune disorders, these tests may not always be reliable, and following Blood transfusions or the administration of IMMUNOGLOBULINS for prophylactic or therapeutic purposes, such assays lack diagnostic utility.

Diagnostic confirmation of the disease involves identifying herpes simplex virus in susceptible Cell cultures and chicken embryos, utilizing neutralization tests in mice, performing specific immunofluorescence staining of infected cells, or employing the Polymerase Chain Reaction (PCR). PCR is the most highly sensitive method, identifying specific fragments of the viral DNA molecule. While these methods are highly informative and specific, not all of them offer rapid turnaround times, and some are expensive or not universally available. The most accessible, technically straightforward, and rapidly reproducible method (taking 20–25 minutes) for any clinical diagnostic laboratory is cytological evaluation of morphological changes in cells infected with herpes simplex virus, performed on stained preparations—smears of biological material obtained from lesion sites.

The material for examination consists of cellular scrapings from herpetic lesions, secretions, and imprint smears. Thin smears are prepared on Glass slides, air-dried, fixed using an appropriate fixative, and stained with Pappenheim, Romanowsky-Giemsa, Unna, Papanicolaou, or other staining techniques containing azure and eosin. Vesicular fluid, urinary epithelial cell sediment, and, rarely, CEREBROSPINAL FLUID may also be examined.

In women, samples are collected from the urethra, cervix, and posterior vaginal fornix. In men, in addition to the sites mentioned above (see p. 70), material is collected from the urethral mucosa. Sample collection is performed using a disposable swab with high fluid absorption capacity, synthetic bristles, or a Volkmann spoon.

Cytological diagnosis of HSV infection.

Herpes simplex virus is a DNA virus that replicates intracellularly. Morphogenesis of infected cells primarily affects The Nucleus and, to a lesser extent, the Cytoplasm. The primary change in the affected cell is enlargement of the nucleus, driven by enhanced DNA Synthesis (color insert, figs. 36, 37). Herpes simplex virus may be detected concurrently with one or more other infections, such as Chlamydia or human papillomavirus (color insert, fig. 36).

As the virus accumulates within The Cell, its Structure changes, resulting in multinucleation, cellular enlargement, and cytoplasmic basophilia (color insert, figs. 38, 39). Subsequently, the nuclei progressively increase in size, accompanied by overall enlargement of the cells. The dimensions of both nuclei and cells increase moderately to very significantly (color insert, figs. 40–47).

These cellular changes vary across different cells. Consequently, alongside enlarged cells, very large and giant uni- and multinucleated cells measuring over 60–150 µm in diameter appear. Nucleus size varies; in multinucleated cells, nuclei may be arranged like "coins on a plate," overlapping one another. Alternatively, they can become massive and giant, occupying two-thirds of the Giant multinucleated cell. Crowding of nuclei and congruence of their surfaces are observed, with nuclei appearing to adapt to one another along their borders. The Chromatin Structure becomes blurred, homogeneous, or sometimes finely granular, resembling settled suspended particles. More frequently, however, the chromatin structure is uniform or pyknotic. Intranuclear oxyphilic inclusions occasionally appear within the nuclei (color insert, figs. 38, 44, 45).

The cytoplasm of the cells stains with extreme Variability, ranging from pale blue to violet-blue. Sometimes the cytoplasm appears pale blue with a dark blue peripheral rim. Frequently, a thin, uniformly wide clear ring or a broader halo is visible around the nucleus (color insert, figs. 37, 39, 40).

Pink inclusions in the form of small rounded droplets or large "lakes" may appear in the cytoplasm (color insert, figs. 44–47).

The cellular atypia caused by herpes simplex virus infection is so pronounced that these Cells must be carefully differentiated from malignant cells. A hallmark of such cells includes congruent surfaces in multinucleated cells, a uniform white rim around the nuclei, pink inclusion bodies resembling large “lakes,” finely dispersed or clumped chromatin of varying density within the nuclei, or distinct flaky nuclear “debris,” none of which are present in cancer cells (col. insert, Figs. 37-47).

In acute herpetic infection, smears reveal a significant number of neutrophilic granulocytes accompanied by secondary bacterial flora, such as streptococci, staphylococci, Fungi, or chlamydial coinfections. The association of the herpes simplex virus with other pathogens compromises the host's immune defense and enhances pathogen virulence, thereby complicating the efficacy of etiotropic therapy.

It should be noted that a limitation of the cytologic diagnostic method is its relatively low Specificity, as the presence of multinucleated cells and intranuclear inclusions—particularly in vesicular fluid—is pathognomonic not only for various types of herpes simplex virus, but also for other members of the *Herpesviridae* family.

TREATMENT OF HERPESVIRUS INFECTION

Managing herpes remains a challenging clinical task. A prolonged chronic course, characteristic of herpetic disease, induces significant immunological alterations: the development of secondary immunodeficiency, depression of non-specific host defenses, hypoglobulinemia, and sensitization to viral antigens. Nevertheless, Chemotherapy remains at the forefront of treating herpesvirus infections. For instance, tebrofen exhibits an inhibitory effect on both DNA- and Introduction/7.html">RNA-containing Viruses.

Poludan is employed in the treatment of viral and chlamydial genital infections. It is a biosynthetic, double-stranded polyribonucleotide complex composed of equimolar amounts of polyadenylic and polyuridylic acids. The drug acts as a potent interferon inducer, exhibiting pronounced antiviral activity by stimulating the patient's endogenous interferon production. Poludan is a white, odorless, and tasteless powder, highly hygroscopic, and completely soluble in room-Temperature Water within 30 seconds. It is administered intramuscularly as a solution prepared in sterile distilled water (2 mL) at a concentration of 200 mcg/mL, daily for 10 days.

Additionally, bonaphトン (bromnaphthoquinone) is used with favorable outcomes. It is an odorless and tasteless orange crystalline powder, insoluble in water, but soluble upon heating in alcohol, acetone, and benzene. Bonaphthon demonstrates high virucidal and potent virus-neutralizing activity against a range of viruses, including herpesviruses.

For the treatment of genital herpetic lesions, 0.25% and 0.5% ointments are recommended, applied topically to the affected areas 4 to 6 times daily. Bonaphthon is the first oral antiviral agent approved for the treatment and prevention of herpes and other viral infections. It is prescribed orally at a dose of 0.1 g (100 mg) 3 to 5 times daily, with a typical treatment course lasting 15 to 20 days. Oral administration of bonaphthon leads to a more frequent and sustained clearance of viremia.

Topical panthenol yields a high therapeutic efficacy in genital herpes when applied to lesions 4 to 6 times a day via aerosol spray from a distance of 10 cm. The product is supplied in pressurized 130 g aerosol containers, making it highly convenient, simple, and hygienic to use. Before application, the canister is shaken well, and the contents are sprayed directly onto the affected areas. The drug is readily absorbed, erosions undergo rapid epithelialization, and inflammatory signs resolve within 2 to 3 days. Treatment is continued for one week, twice daily (morning and evening).

Panthenol should be administered during the acute phase or at the very onset of a recurrence.

During the inter-recovurrency (inter-recurrence) period, herpetic vaccine therapy is indicated to stimulate specific antiviral cellular Immunity. The vaccine is administered as a series of intradermal injections. The initial injection simultaneously serves as an intradermal skin test for delayed-type hypersensitivity to the herpes simplex virus. This agent is used solely during periods of remission to prevent disease relapses, thereby achieving a sustained prophylactic effect. Antirecurrent vaccination is administered in courses (five 0.2 mL intradermal injections given every 2–3 days) at least twice a year.

Etiopathogenetic treatment is best achieved through the combined use of leukocyte interferon, endogenous interferon Inducers (such as IVS and poludan), antiviral agents, and the herpetic vaccine. Such a combination therapy exerts a more pronounced immunostimulatory effect than any single agent alone.

Optimal therapeutic outcomes are achieved through comprehensive treatment regimens that combine agents enhancing specific immunological reactivity and non-specific defense factors (polyvalent herpetic vaccine, immunoglobulins, interferon, and interferon inducers) with antiviral drugs such as bonaphthon, rimantadine, methisazone, riodoxol, alpizarin, megosin, and deoxyribonuclease.

In addition to the aforementioned agents, ribavirin (virazole) should be considered as a broad-spectrum antiviral drug with therapeutic efficacy against various herpetic manifestations, alongside cephalexin in 250 mg capsules. Concurrently, oral Virolex tablets are beneficial. Each tablet contains 200 mg of acyclovir, a potent antiviral agent highly active against herpes simplex virus types 1 and 2. Acyclovir acts as both an inhibitor and substrate for viral DNA polymerase, halting viral DNA synthesis without interfering with normal cellular processes. The recommended dosage is 200 mg every 4 hours. The drug is excreted from the body primarily unchanged via the Kidneys. The standard course of treatment is 5 to 7 days.

Recently, considerable attention has focused on interferon and its inducers. Synthetic and natural interferon inducers have demonstrated high therapeutic efficacy in the management of herpes. Administering interferon inducers during the acute phase ensures recovery in 60–70% of patients, whereas The Use of the immunomodulator levamisole (decaris) in chronic, indolent genital herpes with depressed cellular immunity helps restore cell-mediated immune responses, leading to recovery in nearly 50% of patients. In this context, Interlok (500,000 IU in lyophilized ampoules) should also be mentioned and administered via daily intramuscular injections for 2 weeks. Produced through Biosynthesis in donor blood leukocyte cultures, Interlok is a white powder containing no less than 50,000 IU of alpha-interferon, which suppresses the Replication of a wide spectrum of viruses, including herpesviruses, enteroviruses, and Adenoviruses. The antiviral action of alpha-interferon relies on blocking intracellular viral replication by activating protective enzymatic pathways in treated cells. Interlok is reconstituted in 1 mL of sterile water for injection; the resulting solution must be clear and colorless and should not be stored for more than 24 hours.

Megosin, a novel interferon inducer derived from cottonseed oil, has been successfully utilized in ointment form for the treatment of genital herpes.

These agents, particularly when used in combination, yield excellent therapeutic results. Endogenous interferon inducers include prodigiosan, cutizone, zymosan, and levamisole, all of which can be successfully employed in treating herpetic and chlamydial genital infections. In some cases, the limited therapeutic efficacy of levamisole (decaris) may be attributed to oral administration failing to achieve a therapeutically effective drug concentration at the pathological focus. Increasing the dosage, however, leads to undesirable side effects.

When recurrent viral and chlamydial genital infections are driven by immunopathological alterations—primarily T-cell immunity defects—Immunomodulatory therapy with tactivin (T-activin) is indicated. Tactivin is extracted from calf thymuses and Functions as an immunomodulatory agent. In immunodeficient states, it normalizes quantitative and functional parameters of the T-cell immune system, stimulates lymphocyte and interferon production, restores T-killer cell activity and the functional capacity of stem hematopoietic cells, and corrects various other markers of T-cell-mediated immunity. Tactivin is available as a 0.01% solution in 1 mL vials (100 mcg). It is administered subcutaneously into the upper third of the arm. A standard treatment course consists of 8 injections given at 1-day intervals, while topical Antiviral Therapy is continued concurrently. For the prophylaxis of refractory recurrent herpes, tactivin is administered every 3 to 6 months. The single dose during remission is 50 mcg, administered as a total of 5 subcutaneous injections every other day. Antiviral therapy combined with tactivin helps reduce the frequency of recurrences. In severe forms of genital herpes refractory to conventional drug therapy, tactivin demonstrates a marked therapeutic effect, ultimately leading to complete resolution of the herpetic lesions.

In addition to tactivin, leacadin—a novel immunostimulant presented as a white fine-crystalline powder—has been approved for medical use. Treatment with this agent reduces T-suppressor levels, normalizes the T-helper/T-suppressor ratio, and enhances the cytotoxicity of natural killer cells and monocytes.

Medical literature also reports the use of nucleic acid preparations, specifically sodium nucleinate, alongside the aforementioned immunostimulants. These agents enhance tissue repair capacity and accelerate wound healing. Sodium nucleinate is prescribed orally at a daily dose of 0.4–1 g divided into 3 to 5 doses, taken either daily or in 3-day cycles separated by 3-day rest periods. The duration of the course ranges from 10 to 30 days. Administered as a 3% solution or in tablet form, sodium nucleinate favorably influences the course of herpetic inflammation, increases T-lymphocyte counts, and achieves Clinical Recovery in the vast majority of patients (over 80%).

Thymoptin is structurally and functionally similar to tactivin. This polypeptide complex exerts immunomodulatory effects by inducing the proliferation and differentiation of T-lymphocyte precursors into mature immunocompetent cells, normalizing T- and B-lymphocyte interactions, activating neutrophil phagocytosis, and stimulating the megakaryocytic Lineage. Thymoptin is administered subcutaneously at a dose of 100 mcg per adult patient. The contents of a 100 mcg vial are dissolved in 1 mL of sterile isotonic sodium chloride solution. A course of 4 to 5 injections with a 4-day interval between doses is recommended. Treatment with thymoptin is monitored by assessing immune status parameters.

In recent years, Gevosh (epideoxyuridine / isopropyl-deoxyuridine), developed by Biogal (Hungary), has been introduced for the treatment of recurrent herpes, with isopropyl-deoxyuridine serving as its active pharmaceutical ingredient.

Currently, acyclovir, famciclovir (a prodrug of penciclovir), and inosine pranobex are established as effective agents in the management of primary genital herpes. Acyclovir is a specific antiherpetic drug that competitively inhibits viral thymidine kinase and suppresses DNA polymerase. According to various clinical trials, oral administration of this drug shortens viral shedding duration, alleviates clinical symptoms, and accelerates recovery in patients experiencing primary outbreaks of genital herpes. Unfortunately, it neither prevents recurrences nor reduces their frequency. Inosine pranobex is an immunomodulator that acts by stimulating host immune mechanisms rather than serving as a direct antiviral agent, although clinical studies indicate it can shorten viral shedding during convalescence.

The severity of herpetic infections depends heavily on the degree of host immune suppression—specifically, humoral and cellular immune deficits. The timing of antiviral therapy is also crucial in genital herpes. Early initiation of treatment is essential to achieve a significant antiviral effect, as host defense mechanisms soon become active, making the specific drug effect harder to isolate. By the time extensive tissue damage occurs, viral replication has often declined. Furthermore, tissue damage may be compounded by superinfections, other pathogens, or immune-mediated mechanisms, rendering subsequent antiviral therapy ineffective.

Viral infections are generally more resistant to chemotherapy than bacterial infections. However, recent advances have demonstrated that several pharmaceutical agents possess potent antiviral efficacy.

Viferon is a next-generation domestic recombinant interferon alpha-2a preparation. In addition to interferon, its formulation includes antioxidants: tocopherols (vitamin E acetate) and ascorbic acid (Vitamin C). It exhibits potent antiviral activity, serves as a highly effective treatment for genital herpes, and is fully compatible with baseline therapy. The treatment is free from side effects and complications. It normalizes the interferon-producing function of Blood Leukocytes and lymphocytes.

Interferons are natural factors of the body's non-specific defense and immune mediators (cytokines) characterized by the broadest spectrum of activity, including anti-infective and immunomodulating properties.

For the combination therapy of genital herpes, it is recommended to administer 2–3 courses of Viferon (500,000 IU) as suppositories (2 suppositories per day at 12-hour intervals, every other day, for a total of 10 suppositories per course). This is followed by a maintenance regimen of 2 suppositories per day at 12-hour intervals, 3 times a week, every other day, for 1 to 3 months.

During an acute flare-up of the disease, patients should receive antiviral drugs such as alpizarin, acyclovir, etc.

Step-by-step treatment for recurrent genital herpes is recommended as follows. During the acute phase, antiviral agents are prescribed: Virolex or acyclovir at 200 mg 5 times a day for 5 days, followed by 200 mg 3 times a day for 10 days; bonafton at 50 mg 3 times a day for 5 days (3 courses with a two-day break); alpizarin at 1 tablet 3–4 times a day for 14 to 30 days; along with immunomodulators: tactivin at 1.0 subcutaneous injection every other day for 10 doses, and anti-herpetic immunoglobulin at 3.0 ml intramuscularly once a week for 5 doses. Topical treatments include ointments: megasin (3%), gossypol (3%), gévizol, Viru-Merz 3–5 or more times a day; poludan tampons (10 Procedures); and DNAse compresses 2–3 times a day. In cases of immunodeficiency, phlaktozid is administered at 2 tablets 3 times a day for 7 days, followed by 1 tablet 3 times a day for another 7 days. Immunocorrectors include myelopid at 2.0 ml intramuscularly once every 3 days for 5 doses (repeat the course after 10 days), levamisole, and CNS stimulants (tincture of leuzea or eleutherococcus). Herpetic vaccine is administered intradermally at 0.2 ml once every 3 days for 5 doses, followed in 2 weeks by 0.3 ml intradermally once every 7–10 days for 5 doses; the course should be repeated after 6 months.

Genital herpes in immunosuppressed patients is accompanied by more severe mucosal ulceration than in individuals with a normal immune system.

Prior to treatment for recurrent genital herpes—both during remission and relapse—interferon production and natural killer cell activity decline while interferon levels remain normal; therefore, it is advisable to use interferon inducers for treatment, as they exert a pronounced effect on the antiviral immunity system.

As a treatment for genital herpes, the application of a beta-interferon cream as periodic Applications during the disease course for 6 months is also recommended.

It is known that the virus, while residing inside an infected cell, must synthesize DNA to produce its next generation, utilizing the nucleosides of the infected cell for this purpose. If a substitution is introduced during this period—that is, if the patient's body is saturated with pseudo-nucleosides—the latter will be incorporated into the building of the DNA-containing virus. In this case, the virions will prove non-viable, viral replication will be suppressed, and new Viral Particles will fail to form. Such is the MECHANISM OF ACTION of nucleoside drugs.

The first therapeutic synthetic nucleoside was acyclovir, which possesses high therapeutic activity and has long been considered the "gold standard" of anti-herpetic chemotherapy.

These principles form the foundation for the use of famciclovir and valacyclovir, which are highly specific. They also exhibit a high degree of selectivity in their anti-herpetic action.

Currently, clinical practice increasingly utilizes acyclic nucleosides—valacyclovir and famciclovir—which, compared to acyclovir, are readily absorbed in the gastrointestinal tract upon oral administration. The degree of bioavailability follows this descending order: famciclovir > valacyclovir > acyclovir. After absorption, valacyclovir is converted into acyclovir, whereas famciclovir yields a fundamentally new substance, penciclovir. This circumstance explains Famvir's activity against strains resistant to acyclovir and valacyclovir. Famciclovir stimulates thymidine kinase 75–100 times more actively than acyclovir (valacyclovir). Like valacyclovir, it accumulates exclusively within infected cells.

Famciclovir is available in 125 mg and 250 mg tablets. Its high bioavailability makes it possible to reduce the frequency of administration to 3 times daily for 7–10 days during an initial episode of genital herpes, and to twice daily during recurrences and daily suppressive therapy for 7–15 days.

RECOMMENDED TREATMENT REGIMENS FOR GENITAL HERPES

First episode of genital herpes. Daily suppressive therapy.

Acyclovir 400 mg 3 times daily for 7–10 days, or Acyclovir 200 mg 5 times daily for 7–10 days, or Famciclovir 250 mg 3 times daily for 7–10 days.

Valacyclovir 1 g twice daily for 7–10 days.

Acyclovir 400 mg 3 times daily for 5 days, or Acyclovir 200 mg 5 times daily for 5 days, or Acyclovir 800 mg twice daily for 5 days, or Famciclovir 125 mg twice daily for 5 days, or Valacyclovir 500 mg twice daily for 5 days.

Acyclovir 400 mg twice daily, or Famciclovir 250 mg twice daily, or Famciclovir 125 mg twice daily.

Valacyclovir 250 mg twice daily, or Valacyclovir 500 mg once daily, or Valacyclovir 1 g once daily.

Acyclovir is highly active, yet its oral bioavailability is very low (10–20%). Valacyclovir is a prodrug of acyclovir designed specifically to improve acyclovir's low bioavailability.

Famciclovir belongs to a different Class of antiviral medications and serves as a prodrug of penciclovir. Following oral administration, famciclovir ensures high bioavailability of penciclovir (77%). Acyclovir and penciclovir are phosphorylated by viral thymidine kinase, and in this form, they inhibit the activity of viral DNA polymerase. The half-life of penciclovir triphosphate within the cell is significantly longer than that of acyclovir triphosphate (10–20 hours versus less than 1 hour, respectively). Compared to acyclovir, penciclovir exhibits a higher affinity for viral thymidine kinase, but a lower affinity for viral DNA polymerase. Penciclovir and acyclovir inhibit herpes simplex virus replication in vitro with equal potency. However, compared to valacyclovir, famciclovir more effectively suppresses

the replication of the herpes virus during the acute phase of INFECTION AND ITS reactivation during the latent phase. The antiviral effect of famciclovir is preserved even when administered at later stages following infection.

A different treatment regimen is employed for the so-called suppressive therapy of genital herpes. This therapy is necessary to maintain stable remission with the aim of eliminating recurrences of genital herpes.

New antiviral drugs—famciclovir, valacyclovir, and acyclovir—provide more convenient treatment regimens, thereby simplifying patient management and the administration of long-term suppressive therapy.

When famvir is prescribed at the recommended dosages, sustained remission is achieved in 72% of cases within 11 months, whereas the standard acyclovir and valacyclovir regimen provides remission in 40 - 50% of cases within 8 months.

Vectavir cream, containing 10 mg of penciclovir per 1 g of cream, is intended for topical use and should be applied to the affected areas every 2 hours for 4 days. This is an original, first-in-class antiviral agent with no direct analogs, distinguished by its high selectivity of action. Unlike acyclovir, it penetrates deeply into the skin and virus-infected cells, effectively blocking further viral replication.

Liquorice ROOT derivatives also exhibit antiherpetic activity: lakrinate, administered orally as 1 tablet every 12 hours, and herpinate balm, applied topically to the affected lesions.

Cycloferon (manufactured in Russia) exhibits a similar therapeutic effect, acting as an interferon inducer and immunomodulator. It is available in 2 ml ampoules or as a lyophilized powder in vials containing 0.25 g of the active substance. Cycloferon is administered intramuscularly once daily for 7–10 days. A repeat course is prescribed after 6–12 months. Cycloferon is well tolerated by patients, with no adverse effects reported.

This outlook may change with the advent of antiherpetic Vaccines. These vaccines can be utilized for suppressive therapy (immunotherapy) in patients with genital herpes, preventing transmission to seronegative partners, as well as for vaccinating seronegative individuals. Vaccination stimulates The production of significant titers of virus-neutralizing antibodies (detectable by ELISA) and induces lymphocyte transformation in response to the vaccine. Furthermore, it leads to a reduction in the frequency of genital herpes recurrences in patients at 3 and 6 months post-vaccination, as well as an overall decrease in recurrence rates in patients of both sexes.

Thus, therapeutic immunization can significantly influence the clinical manifestations of latent genital infection caused by herpes simplex virus. The use of antiherpetic vaccines holds great promise as a primary method for the prevention and immunotherapy of genital herpes, potentially curbing the spread of this infection to a substantial degree.

To prevent recurrent genital herpes, the herpes vaccine should be administered intradermally at a dose of 0.2 ml every 2–3 days, for a total of 5 injections. Booster vaccinations are recommended at least twice a year. Immune status largely determines the clinical outcome and course of the disease.

Antibiotics AND CHEMOTHERAPEUTIC agents are traditionally used to treat infectious and Inflammatory Diseases, but such therapy proves ineffective in A number of cases. On the one hand, this is due to the widespread RESISTANCE OF MICROORGANISMS to drugs, The Emergence of new resistant strains, and the persistence of infection. On the other hand, antibiotic therapy can induce secondary immune deficiency syndrome. Nevertheless, the efficacy of etiotropic therapy can be significantly enhanced by stimulating the immune system using immunomodulators.

Against the Background of primary treatment for genital herpes, patients exhibiting compromised immunity can benefit from a novel and potent immune system stimulant—the antiviral drug Likopid. It is administered sublingually at a dose of 2 tablets (1 mg) three times a day, or 1 tablet (10 mg) 1–2 times a day for 10 days.

For the treatment and prevention of recurrent genital herpes, the antiviral medication Epigen (manufactured in Spain) is prescribed, supplied in a 125 ml spray bottle. Its active substance, derived from liquorice root (glycyrrhizic acid), inhibits DNA and RNA viruses, including mutant strains resistant to acyclovir and dioxyuridine. Epigen exerts anti-inflammatory, analgesic, and healing effects. The preparation is sprayed onto the affected areas from a distance of 4–5 cm by depressing the valve 4–5 times for several seconds, over a course of 5–6 days.

Other antiviral agents that can be used to treat genital herpes include: alpizarin, flacosid, helepin, and gelpin at a dose of 1 tablet (0.1 g) 3–4 times daily, or ribamidil (virazole, ribavirin), as well as metisazone at a dose of 1 tablet (0.2 g) 2–3 times daily, taken 1 hour after meals for 7–15 days.

During the prodromal period and the development of recurrence up to the erosion stage, ointment applications should be employed: acyclovir cream (5%), panthenol aerosol, megosin ointment (3%), gossypol liniment (3%), hevizosh ointment (Hungary), oxolin (0.25–3%), riodoxol (0.25–1%), tebrofen (0.5–2%), and alpizarin (2–5%). These topical agents are applied to the affected areas 3–5 times a day for 5–12 days. In the presence of erosions or severe edema, compresses with a 0.5% deoxyribonuclease solution, poludan, or a 0.5% zinc sulfate solution, among others, are recommended.

Various combinations of these methods can be integrated into a comprehensive treatment plan tailored to each individual case, taking into account the clinical manifestations and course of the disease, prior treatments, their efficacy and tolerability, as well as the patient's general health status and concomitant conditions.

An important factor aggravating the course of urogenital herpetic lesions is the minimal involvement of this tissue in the overall process of immunogenesis. Another critical circumstance is the resistance of the herpes virus to broad-spectrum antibiotics and other pharmacological agents.

In light of the above, the critical importance of early administration of effective etiotropic therapy becomes evident. Certainly, a comprehensive approach combining the aforementioned medications with clinical expertise is fully justified, aimed at both specific treatment and the enhancement of the patient's immunobiological defense mechanisms.

When treating patients with recurrent genital herpes, The addition of Amiksin to standard therapy enhances treatment efficacy. Amiksin is prescribed at 0.25 g daily for 2 days, followed by 0.125 g every 48 hours for 1 month. It prolongs the recurrence-free interval more than threefold. At therapeutic doses, it is non-toxic and well tolerated; it activates the interferon system across various organs, increases the sensitivity of target cells to endogenous interferon, combines effectively with antibiotics and chemotherapeutic agents, suppresses herpes virus replication, crosses the blood-Brain barrier, and provides a prolonged therapeutic effect.

Recently, a staged treatment regimen for genital herpes has been recommended as follows:

Stage 1: acyclovir 200 mg 5 times daily for 5–10 days, concurrently with oral Amiksin at 250 mg once daily for 2 days, followed by 125 mg every other day for 2 weeks;

Stage 2: Amiksin 125 mg once a week for 2 months;

Stage 3: polyvalent herpes vaccine intradermally at 0.2 ml every 2–3 days (5 injections), followed by another 5 injections at 10-day intervals;

Stage 4: every 6 months, patients are prescribed Amiksin 125 mg once a week for 2 months and the polyvalent vaccine at 0.2 ml subcutaneously every 10 days (a course of 5 injections).

For sluggish (torpid) recurrent genital herpes accompanied by ulceration, autologous blood combined with poludan—namely cytokine therapy—is successfully utilized. This approach accelerates epithelisation and exerts an anti-relapse effect due to the presence of high titers of antiherpetic antibodies, autofibronectin, and cytokines generated upon the contact of poludan with the blood in the patients' autologous blood.

Treatment Procedure: 5 ml of blood drawn from the patient's vein is mixed with 1 ml of poludan solution (at a dose of 2000 mcg) diluted in 0.5% novocaine and administered intramuscularly twice a week. The full course consists of 4–5 injections.

The polyvalent herpes vaccine is used in combination with poludan for relapse prevention. Treatment is initiated 1–1.5 months after the resolution of acute inflammatory symptoms, administering 0.1 ml subcutaneously for 2 weeks. The full course comprises 5 injections. Booster vaccinations are repeated every six months for 2–3 years.

Furthermore, immunomodulators in combination with poludan are also successfully employed for torpid forms of genital herpes.

Intramuscular injections of Poludan (200 mcg each) are alternated daily with intramuscular injections of Thymolin (20 mg), Tactivin (100 mg), or subcutaneous injections of Thymoptin (100 mg). The course of treatment consists of 10 injections of each drug over a period of 20 days.

Genital herpes causes severe psychological and psychosexual disorders. Most commonly, patients experience depression, emotional pain, anger, loss of self-esteem, and hostility toward the suspected source of infection. It was previously believed that stressful life events could trigger the recurrence of genital herpes. However, recent studies show that in patients with frequent recurrences, emotional stress is rather a consequence than a cause affecting a person's personality. Therefore, physicians should improve psychological support for patients undergoing long-term specific treatment for recurrent genital herpes. Patients must be reassured that effective antiviral treatment and continuous medical supervision will be available to them.