Clinical and Morphological Diagnosis and Treatment of Sexually Transmitted Infections - Yakymova T. P. 2007

Chlamydia. Clinical and morphological criteria and features of the cellular structure of chlamydial infection. Treatment of chlamydia

Chlamydia represent a group of prokaryotic microorganisms characterized by highly heterogeneous, Gram-negative coccoid Morphology. These Obligate Intracellular Parasites exist in two distinct forms that differ biologically while sharing a common group antigen. The biphasic developmental cycle of chlamydia takes place within cytoplasmic vacuoles of the host Cell, where vegetative, large, non-infectious forms known as reticulate bodies emerge. The breakdown of these reticulate bodies subsequently yields small, spore-like elementary bodies, which serve as the infectious form of chlamydia. These two forms are adapted for intracellular and extracellular survival, respectively.

Elementary bodies exhibit low metabolic activity, are adapted for extracellular survival, and function as the infectious form of chlamydia. In contrast, reticulate bodies possess high metabolic activity but cannot survive extracellularly.

The developmental cycle of chlamydia spans 40 to 72 hours. The initial stage involves the adsorption of elementary bodies onto the host Cell Cytoplasm. Chlamydial entry into The Cell occurs via endocytosis, wherein the elementary body is internalized into a phagocytic vacuole. Elementary bodies inhibit the fusion of Lysosomes with the chlamydia-containing phagosome, thereby disrupting lysosomal activity and preventing the destruction of chlamydia within the host cell's phagosomal system. Phagocytosed elementary bodies then transform into Halberstaedter-Prowazek reticulate bodies via an intermediate transitional form.

Clinical manifestations of chlamydia in men share several common features alongside certain distinct differences.

Urogenital chlamydia in men manifests as chlamydial urethritis, paraurethritis, prostatitis, vesiculitis, epididymitis, or orchiepididymitis.

Chlamydial urethritis (urethritis chlamydialis). The most common signs of the disease include discomfort, itching, urethral pain, frequent urinary urgency, and various types of urethral discharge. The most typical symptom is mucous, or less frequently mucopurulent (and rarely purulent), discharge from the Urethra. In acute cases, the urethral discharge flows freely or can be expressed by pressing along the urethra.

In cases of chlamydial urethritis with mild subjective Complaints, discharge is typically very scant and presents as a "morning drop." Often, discharge appears after a prolonged period of urinary retention, sometimes during defecation or at the end of urination. Generally, when urethral discharge is minimal in chlamydial urethritis, both the First and Second portions of urine remain clear, containing only isolated mucous or occasionally multiple mucopurulent threads.

Chlamydial paraurethritis (parauretritis chlamydialis). Paraurethral ducts and glands serve as a reservoir for chlamydia, acting as a source of reinfection for the patient and infection for a healthy sexual partner. In the prostatic urethra, localized granulations and involvement of the seminal colliculus are frequently observed. The inflammatory process may also affect the Bulbourethral Glands. Chlamydial cowperitis is often asymptomatic, though patients occasionally report periodic pain in the perineal and thigh regions.

Chlamydial prostatitis (prostatitis chlamydialis) typically runs a chronic, torpid course with periodic exacerbations. Acute inflammation of the prostate is extremely rare. Patients usually complain of urethral discharge—sometimes occurring during defecation (defecatory prostatorrhea) or at the end of urination (micturitional prostatorrhea)—vague discomfort, itching in the urethra or rectum, and inconstant pain in the Perineum, Scrotum, inguinal region, suprapubic area, sacrum, or along the sciatic nerve. It is important to note that prostatitis may also result from mixed infections involving chlamydia alongside gonococci, Mycoplasmas, trichomonads, Viruses, or various Bacteria.

Chlamydial vesiculitis (vesiculitis chlamydialis) usually accompanies prostatitis or epididymitis. Patients report pelvic discomfort and pain, a sensation of fullness in the perineum, and dull pain radiating to the sacrum, groin, or testicle. Urination may be accompanied by discomfort, though frequency is not increased.

Chlamydial epididymitis (epididymitis chlamydialis) most commonly develops against the backdrop of primary urethral involvement, as well as prostatitis and vesiculitis. Chlamydia reach the Epididymis via a canalicular route, infecting the epithelium lining the lumen of the vas deferens. Signs of deferentitis and funiculitis are sometimes detected. The inflamed vas deferens is palpable as a slightly tender cord. In funiculitis, the inflamed Spermatic Cord appears thickened and tender upon Palpation.

The inflammatory process may extend to the tunica vaginalis or engulf the entire testicle, leading to orchiepididymitis. Most frequently, Chlamydial infection in men manifests as widespread urogenital chlamydia, which requires comprehensive Diagnosis and pathogenetically targeted, sometimes prolonged, Treatment.

Urogenital chlamydia in women manifests as chlamydial vulvitis, bartholinitis, vaginitis, urethritis, paraurethritis, cervicitis, endometritis, salpingitis, salpingo-oophoritis, or Pelvioperitonitis.

Both men and women may develop Reiter's Syndrome, comprising chlamydial urethritis, Conjunctivitis, and Arthritis.

Chlamydial urethritis (urethritis chlamydialis) is frequently combined with concurrent involvement of the cervix and urethra. Notably, over 90% of women who test positive for chlamydia via endocervical or urethral cultures remain completely asymptomatic. Affected patients may experience urethral itching, pain at the onset of urination, and occasional urinary urgency. Mild irritation of the external urethral meatus is observed with no spontaneous discharge; however, scant, typically mucous, nearly colorless discharge can be obtained following urethral massage.

Chlamydial paraurethritis, vulvitis (parauretritis chlamydialis, vulvitis chlamydialis). Chlamydial urethritis is frequently accompanied by paraurethritis of the same Etiology. The vaginal vestibule may also be involved in the chlamydial inflammatory process, primarily localizing around the external urethral meatus or between the Clitoris and urethra. Subjective symptoms are usually mild, most commonly presenting as non-specific signs such as itching or burning in the external genitalia. Mucous discharge can be expressed from infected mucosal folds upon lateral pressure.

Chlamydial bartholinitis (bartholinitis chlamydialis). Symptoms in this condition are generally mild, characterized mostly by mucous or occasionally mucopurulent discharge, with patients reporting periodic itching in the area of the external genitalia.

Chlamydial vaginitis (vaginitis chlamydialis)

is a rare manifestation of chlamydial infection and virtually never occurs in women with a normal hormonal profile.

Chlamydial cervicitis (cervicitis chlamydialis).

Symptoms of chlamydial cervicitis are non-specific and mild. Patients occasionally report a sensation of increased vaginal moisture, a feeling of pelvic heaviness, and mild lower back pain during menstruation. Clinically, it manifests as slightly increased cervical discharge, observed in approximately 60% of cases.

Chlamydial endometritis, salpingitis (endometritis chlamydialis, salpingitis chlamydialis). Chlamydial infection can spread via an ascending pathway, infecting the endometrium and fallopian tubes. This can lead notably to late Postpartum Endometritis and subsequent Infertility.

Chlamydial salpingo-oophoritis (salpingo-oophoritis chlamydialis). The most common signs of the disease include aching pain in the lower abdomen and sacral region—which intensifies with abdominal Muscle strain—and intermenstrual bleeding. In some patients, body Temperature rises to low-grade fever levels (37–37.5°C). According to literature reports, apart from superficial ovarian lesions that lead to adhesions with surrounding Tissues and Organs, the chlamydial inflammatory process may also penetrate deeper into the Ovary, damaging its internal architecture.

Chlamydial pelvioperitonitis (pelvioperitonitis chlamydialis) is the most severe complication of urogenital chlamydia, developing secondary to salpingitis and salpingo-oophoritis. In addition to the Peritoneum covering the urogenital organs, other peritoneal areas may also be affected. In the acute stage of the disease, against a Background of symptoms typical of salpingitis, sharp pain suddenly arises, initially localized in the lower abdomen. Undoubtedly, chlamydial pelvioperitonitis is a frequent yet insufficiently studied complication of chlamydial salpingitis and salpingo-oophoritis that demands intensive and prolonged treatment—a fact that gynecologists and urologists must keep in mind.

The most informative diagnostic Methods for chlamydia infection are considered to be serological, enzyme-linked immunosorbent assay (ELISA), direct immunofluorescence (DIF), and PCR. Cytological examination—though frequently underestimated by clinicians—also holds significant value, allowing the detection of chlamydia within epithelial Cells of the collected biological sample. According to the literature, the primary limitation of this method is its relatively low sensitivity, detecting only 10–30% of chlamydial infections whether asymptomatic or manifest. At the same time, cytological diagnosis can prove entirely reliable and even superior when identifying the pathogen is hampered by poor-quality Reagents and sera, procedural errors, or alterations in the biological Properties of the microorganism.

CYTOLOGICAL Diagnostics

The basis of the cytological diagnosis of chlamydial infection lies in the Structure and function of chlamydiae.

As stated above, chlamydial elementary bodies are infectious, small forms of the pathogen, ranging up to 300 nm in diameter. When stained using Pappenheim and Romanowsky-Giemsa methods, they stain pinkish-purple or reddish-purple. These small, reddish-purple, granular, coccoid structures are visible in the columnar epithelium of the cervical canal (col. insert, Fig. 26), the endometrium (col. insert, Fig. 31), and the fallopian tubes. Frequently, when There is a small number of elementary bodies within a cell and the phagosomes are small, we may not yet be able to see the reddish granular formations; however, at low magnification, we can identify columnar epithelial cells with diffusely stained pink cytoplasm showing dust-like granularity (col. insert, Fig. 27). This is not unexpected, as the secreting cell contains a vacuole with a light, whitish, translucent mucus vacuole against a background of moderately basophilic cytoplasm (col. insert, Fig. 28). When columnar epithelial cells of the endocervix or endometrium with pinkish cytoplasm are present, it is necessary to search for granular, coccoid forms of chlamydial infection. If these are absent, it is recommended to examine such patients using other, more informative methods, such as enzyme-linked immunosorbent assay (ELISA) or PCR. Thus, in this situation, the cytological method makes it possible to identify women with both overt and potential chlamydial infection, thereby forming a risk group for more complex and precise diagnostic examinations.

The CAUSATIVE AGENT OF chlamydial infection is typically located within cells at various STAGES OF REPRODUCTION, and intracellular vacuoles containing the pathogen vary in size, shape, staining properties, and their spatial relationship to the Cell Nucleus.

Within 4–6 hours after infection, the infectious form of chlamydia—elementary bodies—enters a productive developmental pathway and reorganizes into reticular bodies, which represent the vegetative form (col. insert, Figs. 26, 35). This is followed by the GROWTH AND DEVELOPMENT of elementary bodies and The formation of reticular bodies. Sometimes, both reticular and elementary bodies can be observed simultaneously within a cell (col. insert, Fig. 26). These inclusions were first described in 1907 by Lindner and may contain a mixture of small and large particles, as well as intermediate bodies, which are classified as a distinct form. Elementary bodies possess a higher electron density than nuclear material (col. insert, Figs. 29, 30).

Near the membrane bounding the elementary bodies, there may be a clear space containing specialized Antigens and peptidoglycans, which ensure the pathogen's rigidity against the Organism's protective-adaptive reactions and therapeutic agents.

Reticular bodies multiply by direct binary fission and, through a system of intermediate or transitional bodies, transform once again into elementary bodies of the new generation. Upon rupture of the Plasmalemma, these are released into the extracellular environment to infect new cells (col. insert, Fig. 30).

Reticular bodies are larger, ranging from 400 to 1000 nm, and occasionally up to 1200 nm. They appear as vacuoles that stain in various shades of blue within the cytoplasm of the host cell when using Papanicolaou or Romanowsky-Giemsa staining. Reticular bodies are distributed diffusely within cells, are usually highly variable in size, and exhibit heterochromia (col. insert, Figs. 32–34). They may resemble a blue vacuole or be sharply basophilic, with a round, oval, or nearly rectangular shape. Occasionally, the color of reticular bodies may closely approximate that of the Nucleus of the infected host cell. This applies particularly to those reticular bodies localized over the cell nucleus in the shape of a "cardinal's cap" (col. insert, Figs. 32–34).

Our studies have shown that during the exacerbation of the infectious process, reticular bodies are larger and exhibit more pronounced basophilia than during a latent infection; their localization is frequently perinuclear, or they are situated directly on The Nucleus itself in the form of a "cap," which can also vary in size. Such "caps" may be few in number. They can be located on an undeformed nucleus, or occasionally they form congruent surfaces with the nuclear karyolemma, indenting into the nuclear depression of corresponding structure and shape.

Following the Treatment of Chlamydial infection according to standardized regimens, complete morphological cure is not always achieved, despite Clinical Recovery and the disappearance of clinical signs of the disease. In such cases, smears reveal altered reticular bodies that vary in shape, size, and stainability, appearing as intracytoplasmic vacuoles. They decrease in size and number, become weakly basophilic, and shift away from the nucleus toward the peripheral Regions of the cell. Chlamydial inclusions in squamous epithelial cells are also detectable in native (unstained) material. In this case, chlamydial inclusions appear as rounded formations that glow brightly in a brightfield Microscope, predominantly within the squamous epithelium of the uterine cervix, Vagina, or Pharynx. When examining urine in native preparations, chlamydial inclusions can likewise be observed within the epithelial cells of the urethra, cervix, or external genitalia; however, they must subsequently be confirmed in stained smears. To this end, smears should be prepared from the urine sediment, and the physician should be recommended to screen the patients for chlamydial infection using enzyme immunoassay (EIA), PCR, or other informative methods.

Under METABOLISM/18.html">The Influence of medicinal products and adverse developmental conditions, abnormal forms of chlamydia emerge, and an L-form-like transformation of chlamydia is possible, which impedes the maturation of reticular bodies. Such a transformation leads to the persistence of chlamydia and the appearance of atypical, large-sized reticular bodies. Continued growth of chlamydia without division and Differentiation of the Halberstädter-Prowazek bodies results in the formation of large, edematous chlamydial structures in the form of sparse cytoplasmic inclusions. Alterations in the biological properties of chlamydia affect their biochemical and antigenic characteristics, thereby complicating the immunodiagnostics of the infection. In such instances, morphological examination serves as the most informative, significant, and objective diagnostic method. Occasionally, low antibody titers in ELISA lead to the assumption that the patient has been completely cleared of the infection, whereas cytological examination reveals chlamydial cellular inclusions. In such cases, repeated parallel investigations are necessary.

COMPREHENSIVE THERAPY OF CHLAMYDIAL INFECTION

The treatment of chlamydial infection must be comprehensive and individualized, depending on the stage of the process. Since chlamidiosis is a bacterial infection, Antibiotics form the basis of its therapy.

The rational use of antibacterial agents is one of the primary conditions in the comprehensive treatment of patients with chlamydial infections. Given that chlamydiae are intracellular pathogens, the management of diseases caused by them involves ANTIBIOTICS AND CHEMOTHERAPEUTIC agents that effectively penetrate the cell. Antibacterial agents intended for the treatment of patients with Sexually Transmitted Infections (including Urogenital Chlamydiosis) must possess the following properties:

1) high efficacy (at least 95%);

2) good tolerability and low toxicity;

3) accessibility to broad segments of the population;

4) The ability to ensure maximum effect with a single administration;

5) ease of use (oral administration);

6) no adverse effects on fetal development in pregnant women;

7) absence of rapid development of resistance by the pathogen.

The treatment of chlamydiosis must begin with immunocorrective therapy and/or the enhancement of the body's nonspecific resistance. To this end, the following medications and methods should be employed:

✵ Tactivin 0.01% 1 ml (100 mcg) subcutaneously, Thymalin 10 mg (dissolved in 1 ml of saline) intramuscularly, Thymoptin 100 mcg (dissolved in 1 ml of saline) subcutaneously, Thymogen 0.01% 1 ml (100 mcg) intramuscularly daily for 10 days;

✵ Diaphenylsulfone (Diucifon)—course dose 1.2 g (0.1 g orally twice daily for 2 days, followed by 0.05 g twice daily on all subsequent days);

✵ Cycloferon 0.25 g intramuscularly on days 1, 2, 4, 6, and 8 of treatment;

✵ leukinferon 10 thousand IU on days 1, 3, 6, 9, and 12 of therapy;

✵ reaferon 1 million IU (1 dose) 1–2 times a day i.m. for 7–10 days;

✵ neovir 0.25 g i.m. with a 48-hour interval, 5–7 injections;

✵ in the absence of contraindications, ultraviolet Blood irradiation (UVBI) therapy is performed, with the number of Procedures ranging from 5 to 7;

✵ low-level helium-neon laser blood irradiation may be performed (wavelength 0.638 µm with an output power of 5–10 mW).

On days 3–5 from THE START OF Immunomodulatory therapy, it is necessary to prescribe etiopathogenetic therapy with one of the following drugs:

✵ tetracycline 0.5 g 4 times a day for 7 days;

✵ doxycycline (Unidox) 0.1 g twice a day for 7 days;

✵ ericycline 0.5 g 4 times a day for 7 days;

✵ erythromycin 0.5 g 4 times a day for 7 days;

✵ erythromycin acistrate (eracin) 0.4 g 3 times a day for 7 days;

✵ azithromycin (Sumamed) 0.5 g twice a day for 3–5 days;

✵ azithromycin (Sumamed) 1 g as a single dose on day 1 and 0.5 g on day 2 (for uncomplicated forms of the disease);

✵ clarithromycin (Klacid) 0.5 g twice a day for 7 days;

✵ roxithromycin (Rulid) 0.15 g twice a day for 5–7 days;

✵ ofloxacin (Tarivid) 0.2 g twice a day for 7 days;

✵ pefloxacin (Abactal) 0.4 g twice a day for 7 days;

✵ ciprofloxacin (Quintor, Cyprinol, Ciprolet) 0.5 g twice a day for 7 days;

✵ lomefloxacin hydrochloride (Maxaquin) 0.4 g twice a day for 7 days.

If *Trichomonas vaginalis*, *Gardnerella*, or bacterial vaginosis is detected, it is necessary to prescribe metronidazole 0.5 g twice a day for 7–10 days, starting 2–3 days prior to etiotropic drug therapy.

When using antibacterial drugs, all patients should be prescribed antifungal agents (fluconazole, Diflucan, Diflazon, Difluzol, etc.), local treatment (2% clindamycin vaginal cream, Polygynax, clotrimazole, Pimafucin, Betadine, Gyno-Travogen), and eubiotics. Preparations such as lactobacterin, acilact, etc., perform a dual function:

✵ occupy the niche of the eliminated pathogenic flora;

✵ restore the disrupted mucosal biocenosis.

To potentiate the action of antibiotics and improve their penetration into the inflammation focus—especially in patients with chronic inflammatory processes and pelvic adhesions in women—it is necessary to prescribe Proteolytic Enzymes:

✵ lidase 64 IU i.m. (dissolved in 1 ml of 0.5% novocaine solution) for 10 days;

✵ crystalline Trypsin 10 mg 1–2 times a day for 10 days.

These preparations, as well as terrilytin (200 PU), can be used for Electrophoresis.

In the absence of contraindications, nonsteroidal anti-inflammatory drugs should be included in the complex therapy of chlamydiosis:

✵ indomethacin (metindol) 0.05 g 2–3 times a day;

✵ ibuprofen (brufen) 0.2 g 3–4 times a day

✵ diclofenac sodium (voltaren, diclomax) 0.05 g 2–3 times a day;

✵ naproxen (naprosyn) 0.5–0.75 g twice a day.

Nonsteroidal anti-inflammatory drugs should be taken after meals for 2–3 weeks. Treatment should be initiated concurrently with immunomodulatory therapy, i.e., prior to antibacterial therapy.

To correct Lipid Peroxidation during and after antibacterial therapy, antioxidant therapy is administered. The following agents are used for this purpose:

✵ tocopherol acetate 0.2 g 1–2 times a day for 14 days;

✵ unitiol 0.5 g twice a day (5% – 5 ml i.m.) for 10–14 days;

✵ sodium thiosulfate 30% 5–10 ml i.v. for 10–14 days.

Simultaneous administration of antioxidant synergists—ascorbic acid, glutamic acid, and multivitamin preparations—is indicated at standard dosages for 15–30 days.

Treatment must be administered concurrently to both partners. To achieve clinical and etiological cure, 2–3 courses of treatment (or potentially more) should be performed with an interval of 2–3 weeks. When switching between courses, changing the antibiotics is desirable, though not always feasible due to the high cost of the latest generations of macrolides and certain fluoroquinolones.