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

Candidiasis: Clinical and Morphological Diagnosis, Course Features, and Treatment

Mycoses represent a large group of Human and Animal diseases caused by unicellular and multicellular Fungi. Over 500 species of parasitic fungi pathogenic to humans and animals have been described. Fungal infections are generally classified into contagious and opportunistic types. Contagious mycoses are frequently endemic.

The clinical and morphological manifestations of fungal diseases are exceptionally diverse, as some affect the Skin and mucous membranes of the Oral Cavity, respiratory tract, and gastrointestinal tract, while others involve deep-seated Tissues and Internal Organs. The majority of fungi that affect internal organs and cause deep visceral mycoses also involve the skin and mucous membranes.

The primary role in the Etiology of cutaneous fungal infections is played by three main groups of pathogens: dermatophytes, Yeasts and Yeast-like fungi, and Molds.

The Diagnosis of superficial mycoses is carried out by examining discharges, scrapings from the lesion site, fragments of nail plates, skin scales, and other biological specimens. Diagnosing deep mycoses is more complex and involves the investigation of any biomaterial: discharges from fistulous tracts, CEREBROSPINAL FLUID, puncture and biopsy material, feces, Bile, urine, sputum, and other specimens. Furthermore, detecting deep mycoses requires microscopic examination using light and fluorescence microscopes, Wood's lamp illumination, bacteriological and cultural examination of biomaterial, inoculation and infection of laboratory animals, as well as immunological and serological tests utilizing fungal Antigens. Nevertheless, the morphological method—cytological and histological examination—remains the most widespread and highly informative approach.

Of utmost importance in identifying deep mycoses is repeated microscopic examination of biomaterial, which shows an increasing quantity of fungi, alongside serological testing that reveals a rising antibody titer in the patients' Blood serum. Special Methods of Processing and staining biomaterial are employed for microscopic Diagnostics of fungi.

Biomaterial is examined in both native (unstained) and stained states. Skin scales, nail plates, and hairs are examined microscopically after incubation in a 10% sodium hydroxide solution, with gentle heating over a burner flame to achieve better maceration until crystals appear at the periphery of the preparation. However, precipitated crystals may interfere with the examination; therefore, clearing fluids are commonly used. These typically consist of a mixture containing 1 part alcohol, 2 parts glycerin, and 2 parts Water. Lugol's solution and physiological saline are also utilized. Fungi are stained using Gram's method, Romanowsky-Giemsa, Pappenheim's stain, methylene blue, and brilliant green Dyes.

When fungal lesions are localized in the respiratory tract, the most frequent biomaterial is sputum, which is collected in a sterile container after the oral cavity has been thoroughly cleansed beforehand. This requires brushing the Teeth and rinsing the Mouth three times with a 2% soda solution, a 2% borax solution, or a pink potassium permanganate solution.

When lesions affect the oral cavity, Tonsils, Vagina, Urethra, Nose, eye conjunctiva, or closed cavities, pus is obtained via aspiration, puncture, or scraping with sterile instruments into a sterile container.

Microscopic examination distinguishes between the body of the fungus—filaments or hyphae—and reproductive organs, known as spores.

The vegetative body of the fungus, the mycelium, consists of frequently branching filaments (hyphae) of varying length and width. In some classes of fungi, the mycelium is multicellular and septate, whereas in others it is unicellular and non-septate. The terminal Branches of the mycelium are significant for diagnosing the specific type of fungal lesion.

Parasitic fungi reproduce via spores located either inside the mycelium (endospores) or outside the mycelium (exospores). Various morphological variants of fungi are related to their habitat, aeration, humidity, Temperature, and nutrient medium. The appearance of cultures grown on nutrient media, as well as The Structure of the mycelium and fungal spores, are highly variable.

The most frequent causative agents of genital tract mycoses are yeast-like fungi of the genus Candida, particularly Candida albicans, which cause candidiasis. This fungus is widespread in the human environment and exists on fruits, vegetables, the skin and mucous membranes of the oral cavity in humans and animals, the gastrointestinal tract, and the vagina. Fungi of the genus Candida cause both superficial and deep mycoses, which typically present as localized, and less frequently generalized or systemic, infections. People of all ages fall ill, though the elderly, children, and newborns in maternity hospitals are affected most often. Over the past decade, the incidence of candidiasis in newborns has increased 5-7 fold due to fungi of the genus Candida, with C. albicans accounting for an especially high proportion at 75–94%. Other fungal species, such as C. tropicalis, C. parapsilosis, and C. lusitaniae, are encountered in only 8–10% of cases. Outbreaks of candidiasis are noted within families, childcare facilities, among workers and visitors at swimming pools, and among employees at canning, vegetable, and confectionery factories.

Deep candidiasis leads to lesions of the Urinary Tract, Kidneys, respiratory tract and gastrointestinal tract, Brain and Meninges, Muscles, bones, Heart Valves, and Spleen. Fungal Sepsis may also develop.

The disease has an acute and, more frequently, a chronic course. Infected individuals and recovered carriers can transmit the infection to others via household items, food products, water, air, clothing, and even handshakes. In clinical settings, transmission can occur through patients' linens, waterproof sheets, and bedpans. Factors predisposing to The Development of candidiasis include Pregnancy, Diabetes Mellitus, immunodeficiency states, leukemias, HIV infection, viral diseases, prolonged Treatment for chlamydia, and chronic infections.

Clinically, localized candidiasis of the skin and mucous membranes manifests as redness, followed by fluid-filled vesicles covered with whitish membranes. Once ruptured, these leave behind ulcers covered with whitish-brownish deposits composed of intertwined pseudomycelial threads, yeast-like Cells, neutrophil granulocytes, and desquamated surface epithelial cells. When the fungus penetrates deep into the skin and mucous membranes, necrotic processes develop, and vascular invasion leads to hematogenous dissemination to various organs and potentially to fungal sepsis. As the process becomes chronic, inflammatory granulomas form around the mycotic focus, consisting of macrophages, lymphocytes, plasma cells, and multinucleated "foreign body" giant cells containing fragments of pseudomycelium and budding fungal forms. In cases of fungal sepsis, fungi are detected within neutrophil and eosinophil granulocytes, in body cavity effusion fluids, and in peripheral blood.

The success of the morphological diagnosis of fungal infections depends on proper specimen collection. Several weeks or days prior to gathering pathological material, all treatment must be discontinued, excluding even indifferent agents and disinfecting solutions. Material should be taken from fresh yet fully developed lesions. Skin scales must be scraped from the periphery of the lesions, where fungi occur in the form of mycelium and spores. Skin scales are removed with a scalpel, while crusts are removed with epilating forceps. Alongside the scales, a small amount of outwardly healthy skin adjacent to the lesion should be collected, as a high concentration of fungal elements can often be found in these seemingly healthy areas. If pustules and vesicles are present, the analysis should utilize the fluid, the vesicular roofs, and large scales at the border of the lesion that detach with difficulty.

When stained using Gram's method, fully or unevenly stained dark violet Candida cells may be found interspersed among sparse Gram-negative pink specimens. When stained with Romanowsky-Giemsa or Pappenheim, yeast-like cells acquire a pinkish-violet hue, occasionally displaying red Chromatin material or dark violet volutin granules. Frequently, yeast-like cells exhibit a uniform purple coloration. Young cells are round or oval, with a diameter of 0.5–5 µm, occurring singly or in clusters resembling bunches of grapes. Mature cells have an elongated shape. True mycelium is not formed by Candida; instead, elongating cells form a pseudomycelium 12–16 µm in length, appearing as thin, curved or straight, short and long filaments, sometimes bearing daughter buds (color insert, fig. 20).

Yeast-like fungal cells can transform into rounded, thick-walled resting blastospores.

At The Cell junctions, lateral budding results in The formation of whorls or verticils. Along the course of the pseudomycelium, glomeruli—rounded clusters composed of numerous yeast-like cells—may develop. Pseudomycelium differs from true mycelium by the absence of a common sheath and septa. It is composed of thin, elongated cells touching at their bases with intervals remaining between them.

Microscopy of cultured Candida albicans reveals pseudomycelial threads and double-walled chlamydospores. Chlamydospores are fungal spores possessing a double wall. They are typically identified when examining smears from fungal colonies grown on nutrient media during bacteriological testing, but they are also detected in biomaterial obtained directly from the lesion site (color insert, fig. 21). In fungi of the genus Candida, the transition from budding to hyphal growth indicates an increase in pathogenicity.

TREATMENT

Therapy for patients with urogenital candidiasis must be comprehensive and staged, encompassing not only etiotropic treatment but also the elimination of predisposing factors and the management of concurrent diseases. A multidisciplinary approach achieves both the cure of the urogenital candidiasis episode and a reduction in The rate of disease recurrences. Managing coexisting conditions is of great importance in treating urogenital candidiasis. One of the primary requirements during the treatment period is, wherever possible, the discontinuation of corticosteroids, cytotoxics, hormonal estrogen-progestin preparations, and Antibiotics, alongside the cessation of harmful habits.

Local treatment is generally employed for acute forms of the disease.

ACUTE UROGENITAL CANDIDIASIS

Imidazole group drugs — Miconazole:

✵ gyno-dactanol 0.2 g (vaginal tablets);

✵ gyno-daktarin 0.1 g (vaginal suppositories). The tablets or suppositories are inserted into the posterior vaginal fornix in the supine position;

✵ gyno-peварил 50 (cream 1%, granules 0.05 g; vaginal suppositories 0.15 g). The drug is administered into the posterior vaginal fornix once daily at bedtime for 2 weeks;

✵ gyno-peварил 150 (vaginal suppositories 0.15 g). The suppositories are inserted into the vagina once daily at bedtime for 3 days;

✵ gyno-travogen 0.6 g (vaginal suppositories). The drug is inserted into the posterior vaginal fornix at bedtime;

✵ travogen 0.01 g (cream). Applied to the affected areas once daily until symptoms disappear;

✵ kanesten (vaginal tablets 0.1 g; ointment 1%);

✵ kanesten 1 (vaginal tablets 0.5 g; ointment 10%);

✵ kanesten 3 (vaginal tablets 0.2 g; ointment 2%). The treatment course with kanesten is 6 days;

✵ clotrimazole (vaginal tablets 0.1 and 0.2 g; cream 1%, ointment 1%, solution 1%, vaginal cream 2%). Cream, ointment, and solution are applied in a thin layer to the affected areas of the skin and mucous membranes 2-3 times daily and rubbed in gently. The average course of treatment is 14 days. Vaginal cream is administered into the posterior vaginal fornix at a dose of 0.5 g once daily at bedtime for 3 days. Vaginal tablets are inserted 1–2 times daily for 6 days (it is advisable to combine their use with treatment using cream, ointment, and solution);

✵ butoconazole: 2% cream, 5.0 g intravaginally at bedtime for 3 days;

✵ tioconazole: 5% ointment, 5.0 g intravaginally at bedtime as a single dose;

✵ terconazole: vaginal tablets 80 mg at bedtime once daily for 3 days or 0.4% cream (5.0 g) once daily at bedtime for 7 days.

Antifungal antibiotics:

✵ natamycin (pimafucin): vaginal tablets 0.025 g; vaginal suppositories 0.1 g; solution in 20.0 ml vials (1 ml of solution contains 0.025 g of natamycin), cream in 30 g tubes (1 g of cream contains 0.02 g of natamycin). Cream and solution are applied to the affected surface 1–4 times daily. Vaginal tablets are used daily at bedtime or 1 tablet twice daily for 10 days;

✵ nystatin: ointment 100,000 IU. Applied to the affected surface twice daily. The course of treatment ranges from 1 to 2–4 weeks. Vaginal and rectal suppositories: used twice daily for 7 days;

✵ levorin: ointment 500,000 IU. Used twice daily for 1–4 weeks;

✵ amphotericin; ointment. Used 2–3 times daily for 1–2 weeks.

Oral therapy for acute vulvovaginal candidiasis in non-pregnant women:

✵ itraconazole: orungal orally 200 mg once daily for 3 days;

✵ nizoral orally 200 mg twice daily for 5 days;

✵ fluconazole, diflucan 150 mg orally, as a single dose.

CHRONIC UROGENITAL CANDIDIASIS

Along with local treatment, one of the systemic agents is used.

Imidazole derivatives:

✵ itraconazole: Orungal (0.1 g capsules), 0.2 g orally as a single dose or 0.2 g daily for 3 days;

✵ ketoconazole: Nizoral, Oronazol (0.2 g tablets). 1 tablet twice daily with meals for 10 days;

✵ fluconazole: Diflucan (0.05 g, 0.15 g, 0.1 g, 0.2 g capsules; intravenous solution). Administered as a single 150 mg dose.

Antifungal antibiotics:

✵ natamycin: Pimafucin 0.1 g (enteric-coated tablets). 1 tablet 4 times daily for 7–12 days. The tablets should be combined with a single topical application of Pimafucin formulations;

✵ nystatin: 250,000 IU, 500,000 IU tablets. 500,000 to 1,000,000 IU 3–4 times daily;

✵ leворин (levorin): 500,000 IU tablets. Administered at 500,000 IU 3–4 times daily for 14 days;

✵ amphoglucamine: 100,000 IU tablets. Administered at 200,000 IU twice daily, 30–40 minutes after meals, for 10–14 days.

Concurrently with etiotropic therapy for urogenital candidiasis, Treatment of the underlying condition should be carried out and, where indicated, agents that stimulate the body's resistance should be added.

UROGENITAL CANDIDIASIS IN PREGNANT WOMEN

Topical therapy is preferred for treating pregnant women. Recommended agents include clotrimazole, miconazole, isoconazole, and natamycin.

Patients with chronic candidiasis are advised to undergo Pathogenetic Therapy tailored to identified disorders in their gynecological, endocrine, and immune status:

✵ vitamin therapy (Vitamins C, B₆, Folic acid);

✵ anti-anemic agents (Ferroplex, Ferramide);

✵ agents regulating gastrointestinal function and secretion (Pepsidil, Pancreatin, Festal);

✵ Immunomodulatory therapy is performed using Tactivin (100 mcg subcutaneously daily for 10 days), Decaris, methyluracil, or Placenta extract according to standard regimens under the monitoring of immunological parameters;

Numerous unconventional methods exist for treating vulvovaginal candidiasis. Such alternative treatment methods include:

✵ The Use of yogurt containing Lactobacillus spp;

✵ oral administration of capsules containing Ribosomes of Candida albicans serotypes (as an attempt to stimulate Immunity).

Each of the listed treatment methods provides significant clinical improvement in recurrent vulvovaginal candidiasis.

The criteria for cure in urogenital candidiasis are the disappearance of clinical symptoms and negative microbiological test results. The follow-up period is determined individually, depending on the duration, nature of clinical manifestations, and extent of urogenital candidiasis. Account should be taken of the potential for a chronic recurrent course of the disease, reinfection, Candida carriage, and the persistence of factors contributing to the Development of the disease. Patients with urogenital candidiasis should be informed that their sexual partners are recommended to undergo examination and, if necessary, treatment. Patients are advised to abstain from sexual intercourse until cured or to use Barrier methods of Contraception.