Ureaplasmosis – Symptoms and Treatment

Definition of the Disease. Causes of the Illness

Ureaplasmosis is a group of inflammatory and dysbiotic diseases associated with ureaplasmas (Ureaplasma species). Since 1995, two types of ureaplasma have been distinguished: Ureaplasma urealyticum and Ureaplasma parvum. The genome of U. urealyticum is significantly larger than that of U. parvum. Currently, it is impossible to assert that any of the species is an obvious pathogen or, conversely, a saprophyte. Ureaplasmas are conditionally pathogenic microorganisms that are often found on the mucous membranes of the urogenital organs, upper respiratory tract, and in the oral-nasopharynx.

In 2021, professional Russian communities ceased to develop official clinical recommendations for managing patients with Ureaplasma spp. and Mycoplasma hominis. According to the position of the International Union Against Sexually Transmitted Infections, active detection of these microorganisms and treatment causes more harm than good, as it leads to the development of antibiotic resistance in truly dangerous infections. Therefore, antibiotics should only be used when symptoms are present upon detection of these bacteria. Ureaplasmas were first isolated in the USA from a dark-skinned patient with non-gonococcal urethritis in 1954.

The initial introduction of ureaplasmas into the male urethra typically causes urethritis—inflammation of the urethra. There is evidence that in women, ureaplasmas are associated with acute inflammatory diseases of the organs of the small pelvis (AID), as well as bacterial vaginosis. The role of ureaplasmas in the development of bronchopulmonary diseases in newborns (bronchitis, pneumonia) and postpartum chorioamnionitis has been proven.

The role of ureaplasmas in human pathology has not been fully established. Research continues into the pathogenetic link of these microorganisms to a wide range of diseases from different spheres:

  1. Male urogenital diseases: infertility, prostatitis, vesiculitis, epididymo-orchitis;
  2. Urogenital pathology in women: AID, infertility, inflammation of the Bartholin’s gland;
  3. Newborn pathology. There is evidence that the presence of ureaplasmas leads to low birth weight and a decrease in the Apgar score;
  4. Maternal pathology: preterm labor, premature rupture of membranes, habitual miscarriage, missed abortion, etc.;
  5. Urolithiasis, cystitis. Ureaplasmas have been detected in stones removed from the kidneys in biopsies of the urinary bladder, and experiments infecting mice have led to the appearance of uric stones in the kidneys.

Ureaplasmas often make up the normal microflora of the urethra and vagina. The frequency of detection of ureaplasmas averages 40% in the urogenital organs of women and 5-15% in men. At the same time, U. parvum is detected much more often than U. urealyticum (38% versus 9%).

How Ureaplasma Is Transmitted

Ureaplasmas are spread through sexual contact. The more sexual partners one has throughout life, the more often colonization with ureaplasmas in the vagina or urethra occurs. Ureaplasmas are transmitted to newborns during passage through the birth canal. This leads to colonization of the vulvar and vaginal mucosa in girls and the nasopharynx in both sexes. The frequency of detecting ureaplasmas in newborns can reach 30% or higher, decreasing to a few percent by the first year of life. Subsequently, the frequency of colonization with ureaplasmas begins to increase from the onset of sexual activity (at 14-18 years old).

Attachment of ureaplasmas to the mucous membrane

Symptoms of Ureaplasmosis

Symptoms vary depending on the specific disease that develops.

Ureaplasmosis in Men:
In men, urethritis may occur, characterized by scanty discharge and burning sensation during urination, along with increased frequency of urination. Untreated urethritis tends to resolve on its own: symptoms subside, and the patient feels relieved. A history of urethritis increases the likelihood of developing prostatitis—inflammation of the prostate—in the future. Additionally, complications of urethritis may include epididymo-orchitis—inflammation of the testicle and its appendage, vesiculitis—inflammation of the seminal vesicle, and rarely, cooperitis—inflammation of the bulbourethral gland.

Ureaplasmosis in Women:

In women, under the influence of ureaplasmas, conditions such as salpingo-oophoritis, endometritis, and vaginosis may develop. Acute salpingo-oophoritis and endometritis may manifest as dragging pains in the lower abdomen, fever, weakness, and vaginal discharge. Inflammatory diseases of the pelvic organs in women are a predictable consequence of bacterial vaginosis, often observed when ureaplasmas are detected. The symptoms of the disease can worsen rapidly, often requiring hospitalization in a gynecological ward. In addition to inflammatory diseases, ureaplasmas, along with many other microorganisms, are associated with bacterial vaginosis. Bacterial vaginosis typically presents with discharge accompanied by an unpleasant odor, which worsens during sexual activity. The condition predisposes individuals to obstetric and gynecological complications such as preterm labor and low birth weight.

The author of the article shares the views of global experts in the field of urogenital pathology (Jenny Marazzo, Jorma Paavonen, Sharon Hillier, Gilbert Donders) on the lack of association between ureaplasmas and the development of cervicitis and vaginitis. It is important to note that the Russian guideline calls for the treatment of cervicitis and vaginitis based on the etiological role of ureaplasmas in these conditions, which is considered erroneous.

Ureaplasmosis in Children:

In most cases, ureaplasmas do not cause any diseases in girls, but rather healthy carriage is observed. Occasionally, inflammation of the vulva and/or vagina may develop. Newborn girls and boys are at increased risk of developing bronchopulmonary dysplasia.

Classification and Stages of Ureaplasmosis

Based on the duration of the disease, acute and chronic urethritis are distinguished. Acute urethritis lasts up to 2 months, while chronic urethritis lasts more than 2 months. In the latter case, recurrent and persistent urethritis are distinguished.

Chronic recurrent urethritis is considered a condition in which leukocytes in the urethra return to normal levels by the end of treatment, but after 3 months, there is a rise again, exceeding 5 in the field of view (at a magnification of x1000). Chronic persistent urethritis occurs when elevated leukocyte levels are observed at the end of treatment and persist after 3 months.

AID implies the involvement of the fallopian tubes, ovaries, and their ligaments. Inflammation of the appendages can be unilateral or bilateral, acute or chronic. The main symptoms include lower abdominal pain, lumbar pain, genital discharge, and a temperature of 38°C and above.

Complications of Ureaplasmosis

In men, complications of urethritis include balanoposthitis—inflammation of the glans penis and foreskin. Prostatitis is also possible, less commonly epididymo-orchitis and seminal vesicle cystitis. Ureaplasmas are not considered an independent agent causing inflammation of the prostate. It is likely that this chain of complications arises through posterior urethritis and is realized through urethroprostatic reflux, i.e., the reflux of content from the posterior urethra into the prostatic acini and ejaculatory ducts.

In women, AID can be complicated by tubo-ovarian abscess, and occasionally peritonitis and sepsis may occur. In the long term, serious complications with social consequences may occur, including chronic pelvic pain, ectopic pregnancy, and infertility.

It is unlikely that the presence of ureaplasmas alone in the vaginal microbiota will lead to such complications. These microorganisms realize their pathogenic potential in conjunction with other microorganisms leading to dysbiotic changes—bacterial vaginosis.

Diagnosis of Ureaplasmosis

Indications for conducting tests to detect ureaplasmas are clinical and/or laboratory signs of inflammatory processes: urethritis, AID. Routine testing should not be conducted for all patients, including those without signs of any disease.

Only direct detection methods are used to detect ureaplasmas: bacteriological and molecular-genetic. Determining antibodies: IgG, IgA, IgM is not informative. Materials for research can include secretions from the urogenital organs, urine, vaginal secretions, etc.

  • Bacteriological examination (bacterial culture) allows the determination of microorganism concentration but does not differentiate between Ureaplasma urealyticum and Ureaplasma parvum species. In the case of a positive result, it will be indicated: “Growth of Ureaplasma urealyticum at a concentration of 10^ CFU/ml,” which may indicate both U. urealyticum and U. parvum.
  • Molecular-genetic examination (polymerase chain reaction, PCR) determines ureaplasmas to the species level. Moreover, more modern quantitative real-time PCR determines microorganism concentration in “genome equivalents per milliliter,” which is one logarithm higher than traditional CFU/ml.
  • Flora analysis – there are commercial panels based on quantitative molecular-genetic methods (“Florocenosis,” “Inbioflor,” “Femoflor”), which determine the diagnosis of “bacterial vaginosis.”

Direct immunofluorescence (DIF) and immunofluorescent analysis (IFA) are less informative for ureaplasmosis compared to molecular-genetic and bacteriological studies. They are used only in the absence of the latter.

Bacterial vaginosis is verified using Amsel’s criteria:

  1. Milky discharge on the walls of the vagina with an unpleasant odor;
  2. Positive amine test (intensification of the “fishy” odor when adding 10% KOH to vaginal secretions);
  3. Increase in vaginal pH above 4.5;
  4. Presence of clue cells upon microscopic examination of vaginal secretions.

With the presence of any 3 out of the 4 criteria, the diagnosis is established. However, due to the complexity of implementation and the inability to measure pH, the assessment of Amsel’s criteria is difficult.

Treatment of Ureaplasmosis

Treatment of ureaplasmosis is indicated only in cases where examination results reveal an obvious association between ureaplasmas and inflammatory processes. Treatment is not indicated for healthy carriers of ureaplasmas. It is erroneous to prescribe therapy to all individuals with detected ureaplasmas.

Treatment is recommended for sperm donors and in cases of infertility when no other causes are identified.

Recent bacteriological studies have shown high activity against ureaplasmas for Doxycycline, Josamycin, and several other antimicrobial agents.

Treatment Regimen for Ureaplasmosis

According to clinical recommendations of Dermatovenereologists, for uncomplicated urethritis, a 10-day course of ureaplasmosis treatment is conducted:

  • Doxycycline monohydrate 100 mg, 1 tablet twice daily; or
  • Josamycin 500 mg, 1 tablet three times a day.

In case of persistent inflammatory processes, the course of ureaplasmosis treatment may be extended to 14 days.

In cases of bacterial vaginosis, vaginal preparations are prescribed:

  • Metronidazole vaginal gel 0.75%, applied nightly for 5 grams for 5 days; or
  • Clindamycin cream 2%, applied nightly for 7 days.

It is important to note that the goal of treatment is not to “cure ureaplasmas”; complete eradication of these microorganisms is not required. The main objective is to treat the disease: urethritis, bacterial vaginosis, AID. In most cases, treatment of ureaplasmosis in sexual partners is not necessary.

Special Considerations for Treating Ureaplasmosis During Pregnancy

During pregnancy, under a doctor’s prescription, drugs from the macrolide and azalide groups (Josamycin, Azithromycin) can be used.

Prognosis. Prevention

Limiting the number of sexual partners and using barrier methods of contraception reduce ureaplasma colonization. In cases where ureaplasma carriage already exists, preventive examination and consultation with specialists are necessary before:

  • Planning pregnancy;
  • Scheduled surgical interventions on the urogenital organs;
  • Sperm donation.