Sexually Transmitted Diseases - I. I. Mavrov 2005

Genital Herpesvirus Infection

Genital herpes is a viral infection of the reproductive Organs. It is the most common form of herpetic infection, characterized by A wide variety of clinical symptoms and, in most cases, a prolonged recurrent course.

Etiology. The CAUSATIVE AGENT OF genital herpes belongs to the herpesvirus family (Herpesviridae). Currently, eight antigenic serotypes of the Herpes simplex virus (HSV) are known: HSV-1, HSV-2, HHV-5 (cytomegalovirus, CMV), HHV-6, HHV-7, HHV-8, the varicella-zoster virus (Varicella zoster), and the Epstein-Barr virus. Genital herpes is most commonly caused by HSV-2 and HHV-5 (CMV), and less frequently by HSV-1.

Herpesviruses contain linear double-stranded DNA, and their virions range in size from 120 to 150 nm. They replicate intracellularly, forming intranuclear inclusion bodies, and can be cultured in chick embryos and various tissue cultures. Herpesviruses are capable of infecting virtually all organs and systems of the host Organism, causing acute, latent, and chronic forms of infection.

Herpesviruses have a wide host range and can infect monkeys, rabbits, guinea pigs, mice, rats, and the chorioallantoic cavity of developing chick embryos. In experimental animals, vesicular rashes appear at the inoculation sites on the Skin, and viral penetration into the cornea leads to The Development of keratitis. Infection of rabbits with herpesviruses can result in dissemination and meningoencephalitis. In surviving animals, the virus can persist in a latent state, localized in the Brain and trigeminal ganglia. Intra-axonal transport of HSV is a characteristic feature of the Pathogenesis of herpetic infection.

HSVs are thermosensitive at isotonic concentrations of any salt, but become stable when diluted with distilled Water. They are inactivated by ether and photodynamic active Dyes (proflavin, neutral red) upon exposure to light.

Herpetic infections are caused by Viruses sharing the property of lifelong persistence in The Human Body and The ability to manifest in various forms under conditions of immunodeficiency. Approximately 80 members of this virus family are known, seven of which have been isolated from humans.

Infection with herpesviruses typically occurs during childhood via contact transmission, resulting in approximately 80% of children being infected by the age of 5–6 years. Like HIV, HSV penetrates the host Cell's genetic apparatus and remains there in an inactive state for life.

If viral Replication takes place within a cell, the newly formed virions damage The Cell and enter the Lymphatic vessels, and subsequently the bloodstream, where they are found in formed Blood elements (erythrocytes, lymphocytes, platelets). This leads to a decrease in their functional activity, ultimately resulting in immunosuppression.

In the presence of a normal Immune Response, the virus is eliminated from most organs and Tissues, with the exception of paravertebral sensory ganglia, where it persists in a latent state throughout life. Viral reactivation is associated with insufficient activity of macrophages, helper T lymphocytes (CD4+), cytotoxic lymphocytes, as well as reduced production of immune mediators, including interferon.

HSV penetrates Cells either by fusion with The cell membrane or via pinocytosis. This is followed by deproteinization, and the viral DNA becomes associated with the Cell Nucleus. As soon as viral replication begins, normal cellular DNA and Protein Synthesis ceases immediately.

The herpesvirus induces the synthesis of A number of Enzymes, among which it encodes thymidine kinase and DNA polymerase. Different herpesviruses differ serologically from one another and from the thymidine kinase they produce in uninfected cells. Substances such as phosphonoacetic acid specifically inhibit herpesvirus replication by suppressing viral DNA polymerase.

Suspensions of infected tissue cultures can be stored in a frozen state at -70 °C. Herpesviruses, long considered exclusively thermolabile, can be stabilized with a 1M $Na_2SO_4$ solution, after which they can withstand heating at +50 °C.

The chorioallantoic membrane of developing chick embryos is susceptible to herpesvirus infection. The resulting lesions appear as raised white plaques, each induced by a single plaque-forming unit. Plaques formed by HSV-2 are larger than the smaller plaques produced by HSV-1.

HHV-6 is capable not only of infecting and replicating in B lymphocytes, but also exhibits a tropism for T lymphocytes. Its ability to replicate in monocyte-macrophage cell lines has been demonstrated, along with the capacity to infect glial cells, fibroblasts, and epithelial cells.

The frequent detection of HHV-6, HHV-7, and HHV-8 in saliva and their ability to persist in the Salivary Glands suggest an airborne droplet route of transmission. Sexual transmission via semen is also not excluded, as is transmission through blood transfusions and organ transplantation.

The Significance of HHV-6, HHV-7, and HHV-8 in the development of human pathology continues to be intensively investigated. Their etiological role is now considered proven in generalized forms of infection, including Pneumonia, encephalitis, lymphadenopathy, hematological disorders in AIDS patients and organ transplant recipients, exanthema subitum, Chronic Fatigue Syndrome, Connective Tissue disorders, immunodeficiency states, and generalized Kaposi's Sarcoma.

HHV-5 (CMV) infects a wide range of organs and tissues, including cells of The Nervous system, Bone Marrow, Lymph Nodes, Liver, Lungs, gastrointestinal tract, and genitals. The virus is most frequently detected in monocytes, macrophages, fibroblasts, and endothelial cells, as these represent the primary cell populations infected by CMV.

The CMV genome is potentially capable of encoding over 200 Polypeptides. Certain polypeptides are known to undergo post-translational modification via proteolytic Cleavage, phosphorylation, and glycosylation. The host's Immune Response to these Proteins is crucial for the pathogenesis of CMV infection.

CMV can be reactivated in patients following blood transfusions and organ transplantation, during Pregnancy, and upon infection with other pathogens. The virus can also be transmitted vertically from mother to child—both intrauterinely and postnatally—even in the presence of high titers of maternal Antibodies.

CMV contains proteins with proteinase activity that influence the expression and activity of oncogene protein products. The expression of viral genes, and consequently the management of CMV infection, is determined not only by virus-associated factors but also by host cell factors. CMV regulates The activity of enzymes responsible for cellular proliferation and leads to an increased synthesis of host cell macromolecules in the early stages following infection.

The processes occurring in infected cells have been most thoroughly studied using the model of CMV infection in human fibroblasts, which are among the cells most sensitive to CMV. The overall impact of CMV infection on the human body remains poorly understood to date.

It has been established that HSV replication processes are more pronounced in the phagosomes of neutrophilic leukocytes than in macrophages; this is presumably related to lytic processes as well as the longer lifespan of the latter.

It has been noted that HSV possesses the ability not only to parasitize Blood Cells (neutrophils, macrophages) but also to adsorb onto The surface of microbes and subsequently penetrate their Cytoplasm. The localization of HSV within microorganisms protects them from the host's defense mechanisms. Furthermore, concurrent infection enhances the damaging impact of the herpetic process on organs and tissues. Such mixed associations of HSV with other microorganisms may also facilitate the spread of herpesvirus infection.

A significant body of data has accumulated demonstrating the tropism of HSV for immunocompetent cells, which reduces the body's resistance to other infectious agents, particularly in the presence of immune system suppression or immaturity (such as in newborns, pregnant women, etc.).

Recent studies have shown that in cases of intrauterine HSV infection, 10% of children present with symptomatic infection from the first hours of life, 30% of these infants die, and the majority of survivors exhibit severe neurological symptoms and develop deafness.

Herpes virus is isolated from the cervix and external genitalia in women, and from the Urethra, Prostate Gland, Seminal Vesicles, and semen in men.

Modes of transmission. The disease is highly contagious. Infection occurs primarily through close intimate contact, with sexual intercourse and kissing being the most common routes. The infection is spread via genital, orogenital, and anal intercourse, as well as during childbirth, when a newborn is infected by an infected mother. Cases of infection resulting from direct contact with infected bodily fluids via various objects have also been reported.

Infection can be acquired from an infected patient regardless of whether symptoms are present. Autoinfection occurs when patients transfer the virus themselves from the site of infection to unaffected PARTS OF THE body, such as the face, hands, eyes, Oral Cavity, or genitals. Self-infection is possible among medical professionals—particularly dentists through direct contact with a patient's saliva, as well as venereologists and obstetrician-gynecologists through contact with infected genital secretions.

Epidemiology and general pathology. Recurrent forms of genital herpes are estimated to affect 2–6% of the population. Clinical observations have shown that genital herpetic lesions account for approximately 13% of all Sexually Transmitted Infections (G. Corey, 1990).

The disease is diagnosed in young and middle-aged individuals and is more frequently registered among risk groups (such as sex workers and homosexual individuals), as well as those with multiple sexual partners. The high transmission rate of herpesviruses via sexual contact allows them to be considered among the most widespread causative agents of sexually transmitted infections, accompanied by The formation of single and multiple lesion foci with both active and latent disease forms.

Primary infection is often accompanied by more pronounced symptoms compared to recurrences. Signs of the disease appear 3–7 days after exposure. Patients report general fatigue, irritability, and, in some cases, fever and chills. Against this Background, characteristic erythema develops, followed by vesicles. These vesicles rupture, forming small erosions that tend to coalesce. The herpesvirus can be successfully isolated During the first week.

During primary infection, viral replication occurs at the site of invasion; the virus then travels along the nerve trunk and persists latently within nerve ganglion cells. In infected individuals, HSV-1 is harbored in the Trigeminal nerve ganglia, while HSV-2 resides in the sacral ganglia. The virus penetrates the ganglia via hematogenous or neurogenic pathways.

Recently, it has been established that the herpes virus can also persist in the skin in the complete absence of disease symptoms, and it has been isolated from the saliva, tear fluid, and genital secretions of individuals who reported no Complaints whatsoever.

In men, herpetic genital lesions typically develop on the Penis and the inner surface of the coronal sulcus, and occasionally on the Scrotum or Perineum. The condition is frequently accompanied by localized pain, nonspecific signs of fever, pharyngitis, myalgia, arthralgia, and inguinal lymphadenopathy. When lesions develop inside the urethra, patients exhibit signs of urethritis characterized by urethral discomfort and a sudden onset of dysuria, sometimes without externally visible lesions.

The clinical signs and symptoms of genital herpes are more pronounced in women than in men. Virtually all cases of infection occur through sexual contact. Symptoms appear 2–14 days after exposure. Initially, patients experience systemic symptoms (fever, malaise, Muscle aches, headaches, joint pain). After a few days, these signs subside while local symptoms intensify: characteristic painful vesicular lesions appear, coalescing into clusters before eventually disappearing. These lesions are frequently accompanied by local adenopathy and may manifest on the vulva, in the inguinal folds, on the skin of the perineum, buttocks, thighs, and around the hip joints, as well as on the mucous membranes of the Vagina, urethra, and cervix. Redness of the skin and genital mucosa, tissue edema, a feeling of heaviness and pressure in the perineal region, and pain or bleeding during sexual intercourse are frequently observed.

The inflammatory process may extend to the Urinary Bladder and urethra. Herpetic lesions inside the bladder and urethra, as well as around the urethral and vaginal orifices, cause dysuria, which sometimes leads to Acute Urinary Retention.

The intensity of local symptoms peaks during the first 7–10 days, vesicular elements persist for 6–8 days, viral shedding continues for up to 12 days, and complete epithelialization of ulcerative lesions occurs within 18–20 days. The complete cycle of a primary infection in women lasts 1–4 weeks. It is common to observe herpetic lesions at various Selection/3.html">Stages of development simultaneously.

Recurrences of genital herpes occur in 50–75% of cases. Special studies have shown that following a primary herpes infection caused by HSV-2, recurrences are noted in 80–90% of cases, on average after 50 days, whereas infection of the genitals with HSV-1 results in recurrences in 50% of cases with a significantly longer interval (averaging up to 1 year).

Clinical observations indicate that stress, emotional distress, and depression influence the frequency of genital herpes recurrences and determine their duration. A correlation has been revealed between signs of anxiety, nervous tension, depression, and immunocompetence.

In addition to clinically manifest forms of genital herpes, latent forms also exist. In a significant number of patients, the signs are so mild that they may go unnoticed (e.g., mild balanitis in men, vulvitis in women).

According to epidemiological data, HSV was detected in 16.4% of examined individuals who showed no herpetic lesions of the reproductive tract and had no history of infection. These individuals can be considered HSV carriers and, consequently, sources of infection spread. Latency—the virus's ability to persist in the infected host's body without manifesting disease symptoms—is the underlying cause of periodic flare-ups of genital herpes.

Subclinical or minimally symptomatic forms of the disease are more frequently observed in men than in women. The majority of asymptomatic patients act as virus carriers. Furthermore, genital herpes can develop within a strictly monogamous relationship (without third parties) with an incubation period of up to 24–26 weeks.

Research conducted at the Institute of Dermatology and Venereology of the Academy of Medical Sciences of Ukraine showed that among patients with genital herpes, urethritis was diagnosed in 31.2% of men and 17.6% of women. Prostatitis was noted in 16.1% of men, and vulvovaginitis in 38.7% of women. Endocervicitis is also quite frequently observed in women (30.9%).

Herpetic lesions in the perianal and anal areas developed following anal intercourse. Proctitis in such cases was diagnosed in 48.5% of women and 14.5% of men. Patients complained of rectal pain and mucous or bloody anal discharge. Some patients present with long-healing, painful herpetic ulcers in the anal region accompanied by autonomic neuropathy and concomitant inguinal lymphadenopathy.

Extragenital manifestations of the disease included keratitis in 7.3% of women and 1.6% of men, and encephalitis in 7.3% of women and 0.8% of men. Coccygeal reticulopathy was observed exclusively in 3.2% of women. Symptomatic pharyngitis occurred in 1.9% of men and 3.2% of women.

Sexual dysfunctions were reported by 14.5% of men, including erectile dysfunction in 6.4% and premature ejaculation in 8.1%. Infertility affected 7.3% of women and 1.6% of men. Meanwhile, 8.1% of women and 15.2% of men harboring the herpes infection reported no complaints.

Asymptomatic oropharyngeal herpes infection has been observed in children; the latter was also diagnosed in girls presenting with recurrent vulvovaginitis. The recurrence risk for genital lesions in children remains currently unknown.

In a number of cases, severe complications are associated with HSV-2, where exacerbations of the infectious process are accompanied by pronounced herpes manifestations.

Generalized herpetic infection is typically observed in various immunodeficient states. It should be noted that in such patients, herpes is characterized not only by generalized rashes on the skin and mucous membranes, but also by the involvement of Internal Organs and the nervous system. A predisposition to the dissemination of herpetic infection in pregnant women poses a particular hazard due to the potential development of congenital herpes and life-threatening risks to the mother.

The Theory of the pathogenesis of herpetic infection is not yet fully elucidated. However, analyzing scientific data on the clinical and epidemiological manifestations of known herpes variants, insights into the reactivity indices of the infected macroorganism, results from experimental animal models, and, finally, data concerning the biological characteristics of HSV enable us to outline the sequence and distinguish the key Developmental Stages of the pathological process.

A necessary condition for the initiation of an infectious process is the penetration and replication of HSV in susceptible host cells. The localization and replication of the virus are of great significance. Following viral replication at the site of invasion, the viruses travel along the nerve trunk and persist in a latent state within the cells of nerve ganglia (such as the trigeminal and sacral ganglia, among others).

HSV can penetrate ganglia via hematogenous or neurogenic pathways. The latter involves axoplasmic or perineural spread. However, detecting the virus in ganglia 24–48 hours post-INFECTION AND ITS absence 24 hours after neurotomy suggests that the axoplasmic pathway is more likely. HSV may also localize in the skin and has been isolated from saliva, tears, and genital secretions.

Upon interacting with susceptible cells, the virus spreads from the inoculation site along peripheral nerves to the dorsal ROOT ganglia, where it remains "dormant" in a latent state. Subsequently, it can reactivate and migrate distally along the peripheral nerves.

When the virus reaches the surface of the skin or mucous membrane, it leads to either asymptomatic production or a clinically manifest recurrence. The latter can occur even against the background of high circulating antibody levels because the herpes virus, by moving intracellularly from one cell to another within neural tissue, avoids contact with virus-neutralizing antibodies.

In some patients, clinical manifestations of herpes present as a primary attack. At the same time, high titers of virus-neutralizing antibodies are found in the blood serum, indicating a prior infection of unknown localization, whether clinically apparent or subclinical. In such cases, it is difficult to determine whether these patients are suffering from a primary herpes infection or experiencing a recurrence of the disease.

If HSV retains the ability to replicate in macrophages, the infection can spread more extensively, leading to disseminated damage of organs and tissues. The virus's capacity for replication in macrophages often correlates with its virulence, whereas the ability of macrophages to suppress HSV replication correlates with their resistance to the viral infection. Increased resistance to viruses in such cases is associated with the inhibition of their replication within macrophages. Consequently, herpetic infection develops not only against the background of immunodeficiency, but HSV itself exerts an immunodepressive effect. By infecting leukocytes and disrupting their function, along with other factors, these viruses contribute to The breakdown of adaptive mechanisms.

HSV has been found inside microorganisms (gonococci), which serve as target cells for the viruses. As a result of their adsorption onto the phagosomal membranes—where they are found in an associative relationship with the capsules and nucleocapsids of gonococci—The Cell wall of the microbe detaches from the cytoplasmic membrane, causing the virus to integrate into the bacterial DNA genome.

The localization of the virus within gonococci, and potentially other microorganisms that may act as vectors, facilitates the spread of herpetic infection. Furthermore, localization inside gonococci protects the virus from therapeutic agents and the body's defense mechanisms. Coinfection involving these microorganisms may also occur.

Thus, as a result of pathogen replication and its pathogenic impact, a pathological process unfolds, dynamically reflecting the level of the body's local and systemic defense and compensatory reactions.

At the site of the primary lesion, edema and hyperemia of the mucous membrane develop, the integrity of the epithelial layer is disrupted with partial epithelial desquamation, leukocyte infiltration (predominantly neutrophilic, followed by lymphoid) is observed subepithelially and in deeper layers, an inflammatory exudate is formed, and functional impairments occur.

The localization, severity, and duration of these pathological manifestations, as well as their consequences, determine the clinical symptoms and reflect the form of the infectious process and The Nature of the disease course.

Herpetic infection is rarely restricted to the primary lesion site. For instance, HSV can cause not only the widely known skin and mucosal lesions, but also affect the nervous system, internal organs, and genital organs, leading to specific meningitis, encephalitis, esophagitis, hepatitis, pneumonia, disseminated lesions, and more.

It has been established that the cervical canal in women serves as a persistent reservoir of HSV, acting as a source of both sexually transmitted and perinatal infections. Newborns become infected during passage through the birth canal. HSV penetrates open Body Cavities, leading to infectious pathology. The conjunctival sac and nasopharynx are most frequently infected, resulting in diagnoses of Conjunctivitis and herpetic respiratory infection in newborns.

When examining the pathogenetic features of herpetic conjunctivitis in adults—which occurs when HSV enters the eyes—it should be noted that the pathogenesis of this form of the disease reflects the virulence of the pathogen and varying degrees of the macroorganism's immunobiological responses to repeated infection frequencies.

The Clinical presentation of herpetic pharyngitis can range from mild erythema to exudative and ulcerative lesions of the posterior pharyngeal wall, accompanied by cervical lymphadenopathy.

In discussing the pathogenesis of herpetic infection, it is essential to consider its persistent (latent) form, which is characterized by a clinically asymptomatic course. Latency is the ability of the virus to persist in the human body in the absence of viral replication and pathogenicity. The Mechanism of viral preservation within the cell, the conditions required for its transition into a latent state, and the activation of latent herpetic infection remain unknown. However, cell culture data suggest that cell death is the inevitable outcome of viral replication. If this holds true for Nerve Cells in vivo, it implies that the primary latent infection is not accompanied by a reproductive viral development cycle. It is highly probable that the transition of the virus into a latent state and the maintenance of its viability are regulated not by the virus itself, but by the host cell Gene machinery.

Reactivation of HSV—a process in which regulatory blockade is reduced and viral replication returns to baseline levels—triggers disease recurrence. With each exacerbation, the number of latent loci decreases on the one hand, which explains the gradual decline in recurrence frequency; on the other hand, it can be maintained via a closed-loop mechanism wherein the virus clinically migrates between the ganglion and the skin surface. In other words, intra-neuronal transport plays a specific role in the pathogenesis of both primary and recurrent HSV infections.

Thus, latency and neurovirulence are the most critical features of HSV that determine its pathogenesis. The virus's ability to persist in the body enables it to evade the host's immune response. Therefore, in addition to the discussed pathways of emergence and activation of latent herpetic infection, immune mechanisms must also play an active role.

In response to HSV infection, the macroorganism engages a series of humoral and cellular Immunity mechanisms while also utilizing non-specific defense factors. It should be borne in mind that by infecting erythrocytes, platelets, leukocytes, lymphocytes, and macrophages, HSV persists in the body for long periods, inducing non-sterile immunity.

The immune response formed during recurrent genital herpes is accompanied by alterations in METABOLISM, cellular cytochemical activity, and peripheral blood cell counts. However, immunological surveillance in this infection proves incapable of eliminating foreign Genetic information products. It is hypothesized that non-specific and specific cell-mediated immunity dictates the severity of the pathological process, while specific antibodies exert a stabilizing effect on the persistent virus in the body, which, however, does not prevent the development of recurrences.

Investigations of humoral immunity in patients with genital herpes during primary and recurrent herpetic infections have revealed a sequential synthesis of IMMUNOGLOBULINS M, G, and A. Specifically, antibodies represented by Class M immunoglobulins are detected within the first 1–3 weeks of a herpetic infection and typically disappear rapidly. The duration of type G antibody persistence depends on their Specificity. Type A antibodies are detected later and persist for a short time.

Following a disease relapse, a sharp increase in immunoglobulins M, G, and A is observed. In recurrent herpes, antibody titers are generally higher than in healthy individuals or patients with infrequent manifestations of herpetic infection.

In herpetic infection, Complement-dependent virus-neutralizing antibodies are represented by immunoglobulin classes M and G. They are detected during both primary infection and disease recurrences. Virus-neutralizing antibodies are more critical for developing anti-herpetic immunity than complement-fixing antibodies. The production of virus-neutralizing antibodies strongly correlates with the generation of antibodies against membrane Antigens of herpes virus-infected cells.

The mechanism of antibody action on infected cells is associated with the inhibition of viral egress into the extracellular environment. The phenomenon of immune-mediated suppression of viral release from cells plays a leading role in the immunological control of herpetic infection in patients by limiting viral spread to susceptible cells.

It has been established that herpetic infection involves the formation of antigen-antibody complexes characterized by diverse Functions. Their pathogenetic role is linked to the potential participation of immune complexes in the development of immunopathological tissue-damaging changes in patients and their regulatory effects on the functions of various effector cells.

Antigen-antibody complexes can bind to the receptors of infected or cytotoxic cells, leading to target cell lysis driven by the binding of antibodies to virus-specific antigen determinants localized on the cell surface of lymphocytes, macrophages, and polymorphonuclear leukocytes.

Thus, herpetic infection induces the synthesis of antibodies represented by immunoglobulins M, G, and A. A leading role in immunity is played by antibodies directed against viral membrane antigen envelopes and virus-specific antigens of infected cells. The neutralization of the virus by antibodies, or by antibodies and complement, prevents the spread of the infection through the extracellular space.

During herpetic infection, various cellular elements—including T-killers, T-effectors, macrophages, and polymorphonuclear leukocytes—are involved in shaping the immune response, independently of specific anti-herpetic antibodies. Cell-mediated immune reactions are directed against both the infected cells and the herpesvirus.

Patients with recurrent genital herpes exhibit immunological abnormalities manifested by the sensitization of lymphocytes to HSV, as well as alterations in the content and functional activity of immunocompetent cells. The impact on The Immune System is manifested by the suppression of T-cell-mediated immunity and an imbalance in immunoreactive subpopulations, driven by a decrease in the total number of lymphocytes and CD4-expressing lymphocytes (T-helper cells). Available data also indicate a reduction in T-suppressors.

Using the lymphocyte blastogenesis assay (LBA), the features of Primary and secondary immune responses were studied in rabbits. It was demonstrated that only the virus-specific antigen induces pronounced lymphocyte stimulation in immunized animals. Furthermore, the author revealed differences in the intensity and dynamics of the primary and secondary immune responses.

The Study of Cellular immunity in herpetic infection showed that lymphocytes from certain patients in the active stage of the disease are non-permissive to viral replication upon mitogenic stimulation. During this same period, the chemotactic activity of polymorphonuclear leukocytes is diminished. At the same time, the delayed-type hypersensitivity skin test for herpetic antigen is not suppressed in patients with recurrent herpes. In patients with severe recurrent herpes, a weakening of lymphocyte blast transformation is observed during the acute phase of the disease, whereas during remission, the opposite occurs—an enhancement.

Among female patients with urogenital herpetic infection, 71% exhibited alterations in T-cell-mediated immunity parameters, including a decrease in the total population of T-lymphocytes and a reduction in the counts of T-helper and T-suppressor cells. In atypical forms of genital herpes, the level of T-suppressors is significantly lower than in the typical course of herpetic infection.

Consequently, studies of cellular immunity in patients with genital herpes led to the Conclusion that cellular immunity is impaired in individuals infected with the herpes virus, including during the inter-recrudescence periods of the disease, reflecting a state of secondary immunodeficiency.

The development of immunodeficiency in herpetic infection is facilitated by prolonged persistence, accompanied by a productive herpetic infection, across virtually all types of cells in the immune system, resulting in their functional insufficiency. As emphasized by several researchers, the damage to immune system cells begins at the portal of entry—with the infection of Langerhans cells, which play a crucial role in maintaining the barrier function of the skin, as well as lymphocytes, macrophages, and BLOOD AND LYMPH node macrophages.

Thus, the portals of entry for herpetic infection can be viewed as involving viral damage not only to epithelial cells, but also to other cell types such as connective tissue cells (specifically pericytes and fibroblasts), endothelial cells, and lymphoid and myeloid cells drawn into the epithelial damage zone. However, the extent of this involvement clearly varies along a spectrum of transitions ranging from acute infection to the various states and processes characteristic of viral persistence.

In these cells, HSV either remains in a latent state, is passively transported, or undergoes a rapidly progressing reproductive cycle. This culminates in the colonization of regional nerve ganglia, while the compensatory Functions of the immune system remain unimpaired. Meanwhile, the epithelial Cells of the cornea, skin, or mucous membranes—acting simultaneously as both the portals of entry and target cells—determine the clinical manifestations of the herpetic infection.

A decrease or even suppression of certain immune system functions, which normally protect the entire organism, is not yet sufficient for a pathological process to arise in barrier organs—such as the Central Nervous System, which is protected by the blood-brain barrier and its own immune system. Conversely, as clinical observations have shown, a pathological process can develop in an organ shielded behind a barrier, such as herpesviral encephalitis, against a backdrop of robust immune defense functions.

Generalized herpetic infection is characterized by the suppression of defense mechanisms in both the biological barriers and the immune system as a whole. In this situation, the virus undergoes multiple re-orientations in its selection of target cells, which come to include various cells of the immune system, as well as lymphoid and myeloid cells. As a result of direct HSV-induced damage to these cells, an immunodeficiency state develops, creating favorable conditions for the systemic generalization of the infection in the patient.

Therefore, by replicating within the cells of various organs and systems, HSV affects virtually all cells of the immune system. This is likely responsible for the progressive nature of herpetic infection, which manifests in its most severe clinical form—the generalized form. It follows that herpes represents a secondary immunodeficiency and should be regarded as an infectious disease of the immune system.

The onset of clinical symptoms in herpetic infection is regulated at two hierarchical levels. The first level is cell infection, The regulatory mechanisms of which remain largely unclear and are realized through an enhancement of viral reactivity. As observations indicate, viral dissemination can occur even in the absence of overt clinical lesions; in other words, viral reactivation does not necessarily trigger the appearance of symptoms.

An intensification of viral reactivation stimulates The Emergence of effector reactions capable of suppressing infected cells, thereby delaying the cell-to-cell transmission of the virus. If this delay in reactivation is executed rapidly and efficiently, symptoms are either absent or present in a mild, subclinical form. Conversely, a delayed recruitment of Anamnesis-based effector reactions—for example, due to the selective elimination of T-helpers and a consequent increase in the suppressor cell population—leads to a temporary intensification of viral reactivation and visible tissue damage.

As both earlier and recently obtained data have demonstrated, the quantitative and functional parameters of the T- and B-cell immune systems serve as indicators of the disruption and restoration of the patient's immune status. Furthermore, assessing the helper, suppressor, and killer activities of lymphocytes offers a fresh perspective on immunotherapeutic interventions aimed at normalizing their impaired immune functions.

Thus, humoral, local, and cellular immunological mechanisms of the patient's organism play an active role as a consequence of the herpetic process. Their cooperation limits the spread of HSV, shapes the course of the viral infection, and helps prevent disease relapses. Therefore, determining the level and degree of immune deficiency in herpetic infection and providing timely correction pave the way for more effective Treatment of this condition.

Clinicians have long observed that certain herpes patients experience neurological and depressive states. These can sometimes reach alarming proportions, characterized by latent or overtly painful forms. As a rule, the clinical picture is dominated by negative emotions accompanied by a depletion of nervous energy, along with depressive and hypochondriacal disorders.

Recent studies have confirmed that emotional and psychological states in herpes patients generally correlate with immune impairments, with such patients experiencing more frequent and severe relapses. The Diagnosis of herpes itself exerts a profound psychological impact on the patient. Anxiety induces fear, keeps patients in a state of constant nervous tension, lowers the body's general reactivity, and weakens immune defense—which serves as the foundation for chronic fatigue syndrome.

Clinical manifestations. Lesions caused by herpes simplex virus can appear in a wide variety of body sites (see insert pl. XI, 1–3). Symptoms emerge 3–7 days after contact, beginning with local erythema followed by vesicles that subsequently rupture and form small erosions prone to coalescence. A crust forms over them, and the erosive surface heals within a few days without leaving a scar. Vesicles on mucous membranes do not develop crusts; instead, they become covered by a grayish-yellow film. Regional lymphadenopathy is frequently observed.

In men, herpetic genital lesions typically develop on the penis and the inner surface of the corona glandis. In some cases, they are located on the scrotum, urethra, or perineum. The vesicles rupture, forming erosions surrounded by a red inflammatory border.

The process is frequently accompanied by local pain, fever, inguinal lymphadenopathy, and occasionally dysuria. Relapses of the disease may be preceded by paresthesias (tingling or burning sensations).

Although herpetic genital lesions in women are most commonly caused by HSV-2, in certain populations (accounting for up to 40% of cases) the disease may also be caused by HSV-1 (M. McCaughtry et al., 1982). Virtually all cases of genital herpes in women result from sexual contact. The incubation period ranges from 3 to 14 days, presenting with pain, local irritation, dysuria, and discharge.

Primary infections may also feature systemic symptoms such as fever, malaise, headache, and myalgia. After a few days, these systemic symptoms subside while local symptoms intensify. Within 3–4 days, small, painful vesicles appear at the lesion site, coalescing into clusters. They are frequently accompanied by local adenopathy and may occur on the vulva, inguinal folds, perineal skin, buttocks, thighs, and hip regions, as well as on the mucosa of the vagina, urethra, and cervix. Later, these vesicles rupture and become covered with erosions. Eventually, the erosions crust over and disappear, with the exception of those located on mucosal surfaces, which undergo a deeper ulceration phase before healing. The complete cycle of a primary infection lasts up to 3 weeks; it is not uncommon for lesions to appear simultaneously at various stages of development.

Patients with genital herpes infections most commonly complain of pain and itching. In 30–50% of cases, patients experience one to several recurrent flare-ups of the disease. Diagnosing recurrences can be challenging because the febrile period is very brief and signs of extrogenital discomfort may be absent. However, some patients report tingling and paresthesia at the site of the primary lesion 6–12 hours before the appearance of a rash.

Extragenital manifestations of the disease include the development of vesicles on the perineal skin, proctitis (in homosexual individuals and following anal intercourse), symptomatic pharyngitis, herpetic whitlow, aseptic meningitis, and keratitis.

Herpetic keratitis, which frequently results from autoinoculation, leads to blindness in the majority of cases. The condition begins as acute follicular conjunctivitis, typically unilateral. Fever and malaise may be accompanied by preauricular lymphadenopathy. When the involvement is confined to the conjunctiva, it generally resolves within a few days. Photophobia, tearing, and blurred Vision are symptoms indicating that the disease is becoming complicated. Branching ulcers may appear along the edges of the cornea; these often run a severe course and are slow to heal. Following the scarring of these ulcers, visual acuity deteriorates, and blindness may ensue.

In most cases, central nervous system (CNS) herpes infections follow a benign course, manifesting as mild diffuse encephalitis, meningitis, or minor/subclinical forms, such as "CEREBROSPINAL FLUID" meningitis. Their diagnosis relies entirely on specialized virological and immunological studies. In some instances, CNS herpes lesions—particularly those resulting from the reactivation of herpes infections of various localizations—lead to psychopathological disorders presenting as hypochondria, phobias, and other conditions.

Occasionally, the disease presents as severe encephalitis. Three forms of herpetic encephalitis can be distinguished: 1) diffuse meningoencephalitis, which develops primarily in newborns and is also encountered in individuals with congenital or acquired immunodeficiency, such as transplant recipients or other patients receiving immunosuppressive or Radiation therapy (with the latter usually developing against the background of generalized primary herpes infection); 2) acute comatose encephalitis in children; and 3) focal CNS lesions in adults.

According to various authors, herpetic meningoencephalitis accounts for 10% to 86% of all viral meningoencephalitides. This discrepancy in data is likely due to the lack of uniform diagnostic criteria and methodological approaches for determining etiology. The absence of a systematic registry for CNS herpes infections also plays a significant role.

Recently, most researchers have noted that the incidence of herpetic meningoencephalitis is steadily rising. This trend is particularly evident in the results of pathomorphological Diagnostics.

The predilection of HSV-1 and HSV-2 viruses for specific body sites may simply reflect the situations with the highest probability of viral contact. For example, herpetic whitlow is caused with equal frequency by both HSV-1 and HSV-2. Such infections are commonly seen in dental professionals who have direct contact with the saliva of infected patients.

Similar lesions may occur in children with herpetic stomatitis and gingivostomatitis who have a habit of thumb-sucking (J. Mintz, 1976). Children with genital lesions exhibit asymptomatic oropharyngeal herpes infection, and girls with recurrent vulvovaginitis are found to harbor the herpesvirus infection. The risk of recurrent genital lesions during childhood remains unknown.

Genital herpes in mothers is associated with Spontaneous Abortion, premature birth, and, rarely, congenital anomalies.

Newborns exposed to the herpes simplex virus do not always avoid infection when passing through the infected birth canal of the mother. The rate of infection—which does not coincide with the rate of clinically apparent disease in newborns whose mothers shed the herpes virus late in pregnancy—ranges from 40 to 60%.

The risk of neonatal infection is higher when the mother is diagnosed with primary genital herpes—due to higher viral replication rates compared to recurrences—and when viremia (the presence of virus in the blood) may occur while the fetus is in utero, as well as in cases of prolonged labor following early rupture of the amniotic membranes.

Symptoms in newborns typically appear during the first month of life. The onset of localized nervous system involvement generally occurs within the first 11 days, whereas disseminated infections typically manifest within the first 16 days.

Vesicular rashes are observed in only a fraction of neonatal herpes cases. Progression of the primary infection can occur in approximately 70% of infected neonates, with ocular involvement—manifesting as dendritic corneal ulceration or chorioretinitis—frequently accompanying the process. When the infection is widely disseminated, the brain is frequently affected (meningoencephalitis), though lesions in most other organs may also occur.

Signs of disseminated infection include irritability, lethargy, coma, respiratory distress, a bleeding tendency, liver dysfunction, CNS abnormalities, and eye lesions. Notably, the primary diagnostic marker—the herpetiform rash—is present in only one-third of patients. The mortality rate for disseminated neonatal infection is approximately 50%, and half of the survivors suffer from severe ocular or neurological sequelae.

Diagnosis

The majority of herpetic infections are diagnosed on The basis of clinical findings. Certain infectious or non-infectious conditions can mimic the herpetic process.

Primary herpetic lesions are so distinct that they are difficult to mistake for anything else. Contact dermatitis or drug eruptions are generally less painful, resolve more quickly, and are unaccompanied by systemic symptoms. Isolated recurrent genital herpes lesions must be differentiated from Scabies, Molluscum Contagiosum, and other sexually transmitted infections characterized by ulcerative presentations. A history of recurrent herpes infections, prodromal pain or paresthesias, and a typical clinical picture point toward a recurrent herpetoviral infection.

Laboratory Diagnostics. Laboratory testing is of paramount importance for detecting occult or asymptomatic infections—particularly in lesions of the penis, cervix, conjunctiva, and CNS, as well as in severe local and disseminated forms of the disease. The diagnosis of viral urogenital herpes relies on the detection of multinucleated giant cells and inclusion bodies in scrapings or smears taken from the base of fresh skin or mucosal lesions of the urethra, cervical canal, and eyes, as well as on the Isolation of the pathogen in developing chicken embryos and tissue cultures. Cytological Methods, virus isolation and identification, enzyme-linked immunosorbent assay (ELISA) for viral antigen detection, serological testing, and the Polymerase Chain Reaction (PCR) are widely utilized.

Cytological Methods. Urethral and cervical scrapings are obtained using a Volkmann spoon. The cervix is first washed with a hydrogen peroxide solution, dried with a sterile cotton swab, and, in the case of heavy discharge, wiped with a swab soaked in antibiotic solutions (ristomycin and monomycin at 100 IU/mL each). Smears from the eyes of newborns are collected using a sterile cotton swab according to standard Procedures.

The scraping material is spread onto clean Glass slides and fixed with methyl alcohol or Nikiforov's fixative. Smears are stained using the Romanowsky-Giemsa or Macchiavello method and examined under a Light Microscope with an immersion system. Typically, smears are stained with a ready-to-use Romanowsky-Giemsa staining solution (2–3 drops per 1 mL of phosphate buffer at pH 7.2 or distilled water) for 1–2 hours at room Temperature, or with a boiling solution of the same stain (5–10 drops per 1 mL of distilled water) for 5–8 minutes. After staining, the specimen is rinsed with distilled water, fixed in 96% alcohol for 1–2 seconds, air-dried, and examined under a Light microscope Using an immersion oil lens. Macchiavello's staining is performed as follows: scrapings spread onto degreased glass slides are fixed over a burner flame and stained with a 0.25% basic fuchsin solution for 5 minutes. The stain is then rinsed off with running water, and the slide is immersed in a 0.5% citric acid solution for a few seconds, rinsed again with running water, and counterstained with a 1% methylene blue solution for 20–30 seconds.

Immunofluorescence Assay. Clinical specimens are placed onto glass slides, fixed in cold acetone for 10 minutes, rinsed with physiological saline (pH 7.4) for 20 minutes, and treated with a specific anti-herpetic fluorescent serum in a humid chamber at 37 °C for 30 minutes. The preparation is then washed in physiological saline for 15 minutes and examined under a fluorescence microscope equipped with FS-1-2, BS-8-2, SZS 7-2, and ZhS-18 light filters. In the presence of the herpes virus, polymorphic, rounded, yellow-green fluorescent structures are revealed within the nuclei of infected cells.

Virus Isolation. The virus can be isolated from sites of infection (skin, mucous membranes, cornea). It may be detected in the urethra, cervix, Larynx, saliva, and feces during both the primary infection and the asymptomatic phase of the disease. Therefore, virus isolation alone does not constitute definitive proof that it is the causative agent of the specific clinical presentation under investigation.

Virus isolation is generally accomplished through the inoculation of tissue cultures. The appearance of a characteristic cytopathic effect and intranuclear inclusion bodies in the culture indicates the presence of the herpes virus. Identification of the isolated agent is carried out by neutralization with a specific anti-herpes serum or by specific immunofluorescence staining of the infected cells. Tissue culture techniques can yield a provisional diagnosis within 24 hours of specimen receipt.

Serological Testing. Antibodies can be quantified by titration using pH determination in tissue cultures or the epithelial cells of chicken embryo yolk sac membranes. During the Cytology/cytology/16.html">Early stages of the primary immune response, virus-neutralizing antibodies can be detected in the presence of fresh complement. These antibodies are subsequently replaced by other neutralizing antibodies capable of functioning without complement, although their titers can be increased 4- to 8-fold by adding complement to the virus-antibody mixture.

Since successful treatment of urogenital herpesvirus infections depends on the earliest possible diagnosis, rapid diagnostic methods must be employed. Currently, immunofluorescence and immunoenzymatic staining of prepared smear scrapings using specific and Monoclonal Antibodies are readily available and highly advantageous in this field.

The presence of passive hemagglutinating antibodies in the cerebrospinal fluid is a more reliable indicator of infectious virus than the presence of serum antibodies. In the indirect hemagglutination assay (IHA), the herpes virus is fixed to tannin-sensitized erythrocytes. If the serum or cerebrospinal fluid contains antibodies against the herpes virus, the sheep erythrocytes will agglutinate. Results are obtained within a few hours.

The soluble complement-fixing antigen is significantly smaller than the virus and can be prepared from infected chorioallantoic membranes or tissue cultures. This soluble herpes antigen can be used to detect skin sensitivity in previously infected individuals. There is a good correlation between skin hypersensitivity and the presence of antibodies in blood serum.

Neutralizing and complement-fixing antibodies appear by the 4th to 7th day after primary infection, peak in 2-3 weeks, and may persist for life (likely as a result of latent or recurrent infection). Because an antibody titer rise is crucial for establishing a diagnosis, their presence in a single serum sample proves nothing—most adults always have antibodies in their blood.

During a primary HSV-1 infection, IgM class virus-neutralizing antibodies are type-specific, whereas in a primary HSV-2 infection, the generated IgMs neutralize both types of herpes virus. Following a recurrent disease associated with HSV-1, patients retain IgG class antibodies to both HSV-1 and HSV-2 for a prolonged period. In patients with primary HSV-1 infection who experience a superinfection with HSV-2, the detectable antibody rise may be directed against HSV-1. Primary infection with type 2 virus leads to the production of both type 2 and type 1 antibody titers.

Most serological assays yield cross-reactions between HSV-1 and HSV-2, making it difficult to differentiate between primary and secondary infections.

A certain degree of cross-stimulation is also observed between herpes simplex virus and varicella-zoster virus antigens in patients with pre-existing antibodies to either virus.

Modern molecular-biological methods (such as PCR and dot Hybridization) hold great promise for diagnosing the entire herpesvirus group. However, each of these diagnostic methods has its drawbacks. For instance, the culture method, which boasts 80-100% sensitivity and 100% specificity, cannot be widely applied in practical healthcare for numerous reasons. Detecting antigens alone is insufficient because transient viral shedding can occur without affecting the organism. PCR is a highly sensitive (95%) and specific (90-100%) method, but false results cannot be ruled out due to Interference by Nucleases, blood, suboptimal primer-template ratios, or contamination with foreign DNA.

Serological tests cannot detect active infection (up to 80% of the population may carry antibodies to HSV), but the absence of antibodies rules out a viral infection diagnosis. The detection of IgG antibodies indicates that the organism has previously encountered this type of virus. The determination of IgM antibodies may point to an acute infectious process, but they either disappear rapidly or, conversely, persist for a long time.

If no antibodies to HSV are detected in blood samples taken during the acute phase of a herpetic infection, but they appear 2-3 weeks later, a primary infection can be diagnosed. Only a rising IgG titer or the appearance of IgMs indicates a recurrence of the herpetic process. Antibody titers in recurrent forms of viral infection tend to be lower.

Most frequently, multiple methods are used simultaneously: detection of viral antigens via immunofluorescence, enzyme immunoassay, or immunoperoxidase staining; detection of the viral genome (PCR, dot hybridization); and cytologic, electron microscopic, and serological diagnostic methods.

Treatment and Prevention

Treating herpetic lesions is exceptionally challenging because, firstly, the infection can remain latent, and secondly, the virus can "evade" immune system control. Consequently, modern combination therapy does not always prevent relapses and complications of the disease.

Successful treatment of herpetic lesions is possible only through The Use of targeted antiviral medications.

Several antiherpetic drugs have been evaluated in clinical practice, and some have proven effective. Antiviral Therapy incorporating acyclovir (Zovirax) and valacyclovir (Valtrex) provides quite successful treatment. Observations have confirmed the efficacy of these drugs in reducing viral shedding and the severity of clinical symptoms in primary genital infections.

Zovirax is administered orally, intravenously, and topically (3-5% acyclovir ointment). It exerts a pronounced effect in the local treatment of herpetic keratitis, though it does not reduce the frequency of recurrences.

Zovirax penetrates cells easily, exhibits minimal toxicity, acts selectively, does not induce drug dependence, and does not accumulate in the body, allowing for prolonged administration.

Orally, the drug is prescribed in the form of tablets and suspensions. Tablets are available in 200, 400, and 800 mg strengths. Patients are typically advised to take one of these doses 5 times a day, roughly every 4 hours, excluding the night dose. Treatment should continue for 5 days, but in complicated herpetic lesions, the course may be extended. The 200 mg/ml and 400 mg/ml suspensions contain 200 and 400 mg of acyclovir per 5 ml, respectively.

Oral formulations of Zovirax are indicated for treating herpetic lesions of the skin and mucous membranes. They are used to prevent recurrences and for prophylaxis of herpetic infection in immunocompromised patients. Clinical observations have demonstrated that oral administration of Zovirax in the early Stages of the disease provides significant pain relief and reduces the incidence of postherpetic neuralgias, such as those associated with shingles (herpes zoster).

For treating HSV infections in children under 2 years of age, half of the adult Zovirax dose is recommended; older children are prescribed adult dosages. To treat chickenpox in children over 6 years old, 800 mg of Zovirax 4 times daily can be recommended. Children under 2 years of age may take 200 mg of Zovirax 4 times daily. A more precise dosage is calculated as follows: 20 mg of Zovirax per 1 kg of body weight (not exceeding 800 mg) 4 times a day. Treatment lasts for 5 days, though clinically indicated, it can be extended to 7-10 days.

For treating HSV-induced infections, Zovirax at a dose of 200 mg is prescribed 5 times daily for 5 days, but in cases of primary infection with prominent clinical manifestations, the therapeutic course is 7-10 days. For patients with severe immunodeficiency, the single dose of Zovirax is increased to 400 mg (or even up to 800 mg), or intravenous administration is considered. Treatment should be initiated as early as possible after the first manifestations of herpetic lesions.

Valtrex is prescribed at 500 mg twice daily for 5 days. The drug has demonstrated high efficacy at doses of 250 mg 3 times daily for treating primary herpesvirus infections and 125 mg twice daily for treating recurrent herpes. When taken orally, the bioavailability of Valtrex is 3 to 5 times higher than that of Zovirax.

Topical corticosteroids should be avoided as they may facilitate the spread of infection. In all cases of genital herpetic lesions, hygienic measures and topical anesthetics can provide some relief.

To treat herpetic infection and prevent its recurrences, antiherpetic Vaccines (administered in courses of intradermal injections) are used in combination with interferon Inducers (pyrogenal, levamisole, poludan).

Herpes simplex virus infections present a wide range of clinical challenges. Existing treatments only suppress disease relapses rather than eradicate the herpetic infection. This necessitates the search for more effective methods of Chemotherapy, Chemoprophylaxis, and specific immunoprophylaxis of this infection. To date, there is no consensus regarding the positive impact of vaccines. Antibodies generated in naturally infected individuals do not prevent recurrences, and it remains unknown whether vaccine-induced antibodies will be effective against primary and/or secondary infections.

Until specific treatments for herpetic infections are found, limiting their spread is of utmost importance. It is essential to recognize the symptoms of the disease and study the factors that trigger recurrences of herpesvirus infections. Above all, health education efforts should be targeted at adolescents and young adults who, being sexually active, frequently serve as a potential source of infection. They are capable not only of transmitting the infection to others but also, upon reaching childbearing age, of infecting newborns, thereby perpetuating the infection cycle.

Currently, controlling herpes simplex virus infection depends primarily on the patient's own level of awareness. Because the infection spreads through direct contact with an infected individual, they should avoid sexual or other intimate contact with others during flare-ups. Personal hygiene remains a reliable method of prevention.

Disease exacerbations are triggered by various factors, notably excessive ultraviolet radiation from prolonged sun exposure, drafts, severe cooling, fatigue, menstruation, and stress factors that cause emotional and physiological imbalances.

Herpesvirus Infection and Pregnancy

Herpetic infection in pregnant women is one of the most common Sexually Transmitted Diseases encountered in obstetric populations. According to serological studies, the prevalence of HSV-2 among pregnant women is 20% in Ukraine, up to 36% in the USA, and 35% in Russia. In European countries, 45% of women are seropositive for CMV in early pregnancy.

Most often, herpetic infection in pregnant women proceeds latently. Specific antibodies to HSV-2 are detected in 20–30% of pregnant women, and to CMV in 33–77% in cases of obstetric pathology. Herpesviruses typically persist in the body without manifesting clinical signs of the disease.

However, the presence of HSV antibodies does not prevent virus reactivation. Specific titers in the asymptomatic form of the infection are lower than those during clinical manifestations. Maternal immunity is unable to prevent the reactivation of a latent infection during pregnancy or the transmission of HSV to the fetus. At the same time, the higher the seropositivity rate in the population, the lower the risk of primary herpetic infection during pregnancy and vertical transmission of HSV.

Pregnancy complications, even in the latent form of herpetic infection, include Miscarriage, prolonged threat of termination, early toxicosis, Hypoxia, fetal growth restriction, premature birth and its anomalies, chorioamnionitis, and endometritis.

In the presence of autoimmune and endocrine disorders in pregnant women, herpetic infection takes a severe course, manifesting as blistering rashes with pronounced itching in a herpetiform arrangement. The symptoms typically develop In the second half of pregnancy, more frequently in young women with multiple sexual partners.

Polymorphic rashes are observed—vesicular, papulourticaria, and bullous lesions on erythematous areas, less commonly on clinically healthy skin. Spanning large areas of the trunk and limbs, the rashes are usually accompanied by intense itching, leading to excoriations and bloody crusts. The patients' general condition is very severe. The disease regresses after childbirth, but it may recur in subsequent pregnancies.

It has been established that manifest forms of herpetic infection in pregnant women generally play a significant role in fetal and neonatal pathology. However, adverse pregnancy outcomes may be associated not only with manifest but also with asymptomatic forms of maternal herpetic infection. Without causing marked health disorders, HSV can penetrate the Placenta, embryo, or fetus, causing severe fetal and neonatal damage. Therefore, some of the most serious complications of herpes in pregnant women include intrauterine fetal infection and the infection of newborns during passage through the mother's infected birth canal, leading to clinical lesions in the postnatal period. Maternal genital herpes can cause spontaneous abortions, premature birth, missed miscarriage, Congenital Malformations, and congenital neonatal and postnatal infections.

It is believed that infection of the fetus and newborn at the time of delivery occurs in 20–50% of cases involving primary genital herpes, primarily affecting the cervix. Typically, in such cases, a significant viral load accumulates in the cervix, while maternal virus-neutralizing antibodies are absent. During recurrences, vertical transmission of the virus to the fetus and infection of newborns occur much less frequently (up to 8% of cases).

The lower rate of infection during a recurrent course of herpetic infection is explained by the low viral load in the lesion site in the presence of maternal anti-herpetic antibodies transmitted to the fetus. The risk of newborn infection with the herpes virus is higher in cases of prolonged labor following early rupture of membranes.

The clinical manifestations of herpetic infection in the fetus depend on the gestational age at the time of infection, the infectious dose, virulence, and the routes of viral entry. Adverse pregnancy outcomes for the fetus in viral and certain bacterial infections are mainly associated with the hematogenous (transplacental) route of disease transmission.

Symptoms of the disease in newborns typically appear during the first month of life. The onset of localized nervous system involvement generally occurs within the first 10–12 days, and in cases of disseminated disease, within the first 14–16 days. Affected newborns develop fever, progressive jaundice, hepatosplenomegaly, cerebral symptoms, vesicular rash, and frequently stomatitis and keratoconjunctivitis.

Skin manifestations alone at the onset of the disease are observed in 60–70% of cases. Disease progression may occur in approximately 70% of infected newborns, with involvement of the eyes, manifested as dendritic corneal ulceration or chorioretinitis. In cases of severe disseminated infection, the brain is frequently affected (meningoencephalitis), along with herpetic lesions in most other organs.

Signs of disseminated infection include hyperexcitability, lethargy, coma, respiratory symptoms, a tendency toward bleeding, eye damage, and impaired liver and CNS functions. The primary diagnostic sign—herpetiform rash—is noted in only a third of patients. Mortality from disseminated infection in newborns is about 50%, and half of the survivors suffer from pronounced ocular or neurological sequelae.

With transplacental infection up to 20 weeks of gestation, spontaneous miscarriage occurs in 34% of cases; when infected between 20–34 weeks, premature birth occurs in 30% of cases. It has been established that infection in the first trimester leads to microhydrocephalus, Heart defects, gastrointestinal and urogenital tract anomalies, skeletal malformations, cataracts, and deafness in the fetus. Infection in the second and third trimesters causes fetal pneumonia, meningoencephalitis, Sepsis, anemia, hepatosplenomegaly, jaundice, and growth restriction. Sepsis is a frequent cause of antenatal death.

Miscarriage (early and late spontaneous abortions, missed miscarriages) is noted in 25–30% of women infected with HSV-2. Data have been obtained indicating The Role of herpetic lesions of the uterine appendages in pregnancy loss. However, 70% of mothers whose children were born with generalized intrauterine herpes showed no signs of genital herpes during delivery, and 52% had no history of it whatsoever. Meanwhile, approximately 30% of these women (or their partners) had clinical manifestations of genital and extragenital herpes during pregnancy.

The urgency of Structure/149.html">The problem of herpetic infection in the genesis of fetal developmental disorders is determined by the fact that the fetus, with its intensive Cell Division and High Metabolic Rate, provides an ideal environment for viral replication and their destructive action on tissues and organs.

The following pathways of HSV entry into the embryo and fetus are distinguished:

1) ascending or transcervical, where herpesviruses from the external genitalia or cervical canal penetrate through the fetal membranes into the Amniotic Fluid due to decreased Protective Functions of cervical mucus or as a result of medical procedures; 2) hematogenous or transplacental, where HSV reaches the fetus via the placenta and umbilical vein; 3) transovarian, in which viruses travel from the Abdominal cavity through the fallopian tubes.

The consequences of herpes in pregnant women depend primarily on the virulence of the pathogen, the route of entry, and the gestational age of the fetus. Severe disseminated lesions of the fetoplacental complex, brain, liver, and lungs of the fetus are observed with the hematogenous route of HSV transmission.

Primary herpes during pregnancy is associated with intrauterine fetal infection in 5% of cases. Reaching the fetoplacental system as a result of maternal viremia, HSV can cause miscarriages in the First and Second trimesters, premature birth, antenatal fetal death, intrauterine growth restriction, and periprecipital/periplacental hematoma.

Vertical transmission of HSV is observed in primary, recurrent infection, and asymptomatic carriage. Postnatal infection is also possible, but intrauterine fetal infection is rare, which is presumably due to the protective role of the placenta.

HSV infection of the fetus in the first trimester of pregnancy causes micro- or Hydrocephalus, microphthalmia, cataracts, deafness, intracranial calcification, and developmental abnormalities. Herpes infection in the second and third trimesters leads to hepatosplenomegaly, anemia, jaundice, chorioretinitis, growth restriction, meningoencephalitis, and sepsis.

Manifestations of intrauterine herpesvirus infection may include birth asphyxia, respiratory distress syndrome, congenital pneumonia, hyaline membrane disease, and hemorrhages. Intrauterine herpetic infection is an uncontrollable cause of perinatal mortality and childhood disability (cerebral palsy, Epilepsy, blindness, deafness, etc.).

Management of Pregnant Women with Herpetic Infection

Analysis of epidemiological features, clinical findings, and laboratory data regarding herpetic infection in pregnant women, fetuses, and newborns has enabled the development of rational management tactics for labor. These are based on the causal relationship between miscarriage and herpetic infection, neonatal herpes and maternal genital herpes (including asymptomatic cases).

First, the medical history of both the pregnant woman and her sexual partner is assessed to identify episodes of herpetic infection. Clinical and laboratory examinations are performed to detect HSV. The progression of pregnancy, the condition of the fetoplacental complex, and the immune and other Regulatory Systems of the body are closely monitored.

In cases of asymptomatic viral carriage, general health-improving therapy is recommended. Its core principle is the early prevention of placental insufficiency. To treat pregnant women, suppress viral replication in the maternal organism, and prevent neonatal infection, acyclovir (Zovirax) and valacyclovir (Valtrex) are used. Zovirax is administered intravenously as an infusion to pregnant women over the course of an hour at a dose of 250 mg, 3 times a day with an 8-hour interval, for a course of 5-10 days. Caution should be exercised when administering Zovirax intravenously to patients with renal impairment.

Valtrex is prescribed orally at 500 mg twice daily for 5-10 days. The drug has demonstrated high efficacy at a dose of 250 mg three times a day during active primary herpesvirus infection.

In newborns (aged 0-3 months), the intravenous dose of Zovirax is determined based on body weight at 10 mg/kg. The drug is administered via intravenous infusion over the course of an hour every 8 hours.

To prevent fetal infection during delivery, pregnant women with an active primary herpetic infection that has developed by the time of labor undergo a Cesarean Section. Treatment with Zovirax and Valtrex is administered to both the mother and the newborn.

Women with a history of genital herpes are evaluated more thoroughly in the second half of pregnancy to confirm the diagnosis. Testing for the herpesvirus is also performed on the eve of the due date. At the onset of labor, smears from the cervical mucosa must be taken for cytological and immunofluorescence studies, as well as for HSV detection via polymerase chain reaction. If clinical and laboratory signs of herpetic infection are absent, vaginal delivery may be performed.

Pregnant women with primary herpetic infection in the first and second trimesters (over 30 weeks) are subject to etiotropic treatment with Zovirax. For term labor in cases of primary infection during the second trimester, most authors recommend a cesarean section. However, some specialists suggest vaginal delivery if the pregnancy was uncomplicated and no genital lesions appeared by the time of labor. In such cases, preventive measures are implemented: instrumental interventions must be avoided, swabs taken to detect the virus, and prophylactic Treatment of the newborn administered using Zovirax.

For pregnant women at 30 to 34 weeks of gestation, the management approach is the same. From 34 weeks until delivery, treatment with Zovirax is administered, and a cesarean section is mandatory.

Prevention of herpetic infection is challenging due to the ability of HSV to persist in the human body, particularly within cells of the nervous system.

Currently, controlling HSV infection depends primarily on the patient's own level of awareness. Since the infection spreads through direct contact with infected individuals, the patient should avoid intimate contact with others during outbreaks. Personal hygiene remains a reliable means of prevention.

Exacerbation of the disease is promoted by various factors (excessive ultraviolet radiation from prolonged sun exposure, drafts, overcooling, fatigue, menstruation, and stress factors causing emotional and physiological imbalance).

It should be borne in mind that postnatal infection of children is possible in the presence of herpetic lesions on the skin not only of the mother, but also of relatives, close contacts, and medical staff. Therefore, midwives and nurses working in neonatal wards who exhibit herpetic rashes must be suspended from caring for other pregnant women, postpartum women, and newborns.

Women who have experienced herpes during pregnancy are placed on outpatient dispensary follow-up. Monitoring must be conducted with extreme care during any subsequent pregnancy. At the first symptoms of the disease, examinations are performed, and treatment is administered when indicated.

When planning pregnancy, patients with a confirmed herpetic infection are recommended to undergo suppressive therapy with Zovirax (Valtrex) for one month.