Mycoplasma genitalium infection
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# Overview
Mycoplasma genitalium infection is caused by the bacteria Mycoplasma genitalium. It was first isolated from 2 men with urethritis in the early 1980s, but was not recognized as a sexually transmitted disease until the early 1990s, following the development of polymerase chain reaction (PCR). Co-infection of Mycoplasma genitalium with other STDs is not uncommon. However, an isolated infection with Mycoplasma genitalium must be differentiated from other STDs, which may have a similar presentation. Mycoplasma genitalium infection is more common than Neisseria gonorrhea, but less common than Chlamydia trachomatis. However, it is not recognized as a common STD, largely because the infection is mostly asymptomatic. Symptoms are related to the complications it may cause, such as PID and cervicitis in women, and urethritis and epididymitis in men. Prompt antibiotic treatment is needed to prevent complications. Mycoplasma genitalium infection is prevented by promoting safe sexual practice, as well as the use of condoms.

# Historical Perspective
- Mycoplasma genitalium is the 11th Mycoplasma species of human origin.
- In 1980, 13 men were tested for non-gonoccal urethritis (NGU). Mycoplasma genitalium was isolated from 2 of those 13 men.
- In the early 1990s, polymerase chain reaction (PCR) was developed, which allowed for diagnosis of Mycoplasma genitalium.
- Since 1993, the role of Mycoplasma genitalium as a cause of non-gonococcal urethritis has appeared in literature following the advances in polymerase chain reaction (PCR).

# Classification
Mycoplasma genitalium infection can be divided based on the clinical presentation into:
- Asymptomatic Mycoplasma genitalium infection
- Symptomatic Mycoplasma genitalium infection: symptoms are related to PID or cervicitis in women and urethritis or epididymitis in men

# Pathophysiology

## Pathogenesis

### Mode of Transmission
- Mycoplasma genitalium is recognized as a sexually transmitted disease (STD) with the mode of transmission being through direct genital-to-genital contact and subsequent inoculation of infected secretions. Transmission of Mycoplasma genitalium has also been implicated in penile-anal intercourse.
- Mycoplasma genitalium is less likely to be transmitted via oro-genital contact, as carriage in the oropharynx is low.
- Whether or not Mycoplasma genitalium is vertically transmitted from mother to newborn is yet to be studied. However, the bacterium has been isolated from the respiratory tract of newborns.

### Incubation Period
The incubation period of Mycoplasma genitalium is unknown yet.

### Infectious Dose
The infectious dose of Mycoplasma genitalium is unknown yet.

### Factors facilitating the pathogenesis of Mycoplasma genitalium
The following virulence factors have been implicated in the pathogenesis of Mycoplasma genitalium:
- Adhesion molecules: Mycoplasma genitalium has the ability to attach to different types of cells, including red blood cells, respiratory cells, fallopian tube cells, as well as sperm cells. It is believed that the attachment to sperm cells facilitates the spread of Mycoplasma genitalium to the female genital tract. MgPa, a major adhesion in attachment protein complex, facilitates not only adhesion to epithelial cells, but also the motility of Mycoplasma genitalium.
- Intracellular localization: Mycoplasma genitalium is a facultative intracellular organism and this allows for its survival both inside and outside of cells.
- Antigenic variation: Mycoplasma genitalium is able to generate surface lipoprotein with high frequency, which helps it evade the human immune system.
- Toxins: Mycoplasma genitalium has a calcium-dependent membrane associated nuclease known as MG-186. MG-186 is capable of degrading host cell nucleic acid, hence providing a source of nucleotides for the growth and pathogenesis of Mycoplasma genitalium.
- Enzymes: Glyceraldehyde 3-phosphate dehydrogenase (GADPH) acts as a ligand to the receptors mucin and fibronectin, found on vaginal and cervical epithelium.
- Immunological response: Mycoplasma genitalium possesses an immunogenic protein, MG-309, which secretes pro-inflammatory cytokines, such as IL-6 and IL-8. MG-309 exerts its effect via attaching to a toll-like receptor, hence activating nuclear factor kappa B (NF-kB)

## Genetics
There are no identified genetic factors associated with Mycoplasma genitalium infection.

## Associated Conditions
Mycoplasma genitalium infection is associated with co-infection with other sexually transmitted diseases, such as:
- Chlamydia trachomatis
- Neisseria gonorrhea
- Trichomonas vaginalis
- HIV: Studies have reported an increased risk for HIV infection among women with Mycoplasma genitalium, evidenced by noticing that HIV shedding occurs more frequently among individuals with Mycoplasma genitalium and HIV infection who are not being treated than among individuals without this infection.

## Gross Pathology
Gross pathology of Mycoplasma genitalium infection is related to the disease processes it may result: cervicitis, PID, urethritis, or epididymitis.

## Microscopic Pathology
Microscopic pathology of Mycoplasma genitalium infection is related to the disease processes it may result: cervicitis, PID, urethritis, or epididymitis.

# Causes
The cause of Mycoplasma genitalium infection is Mycoplasma genitalium.

# Differentiating Mycoplasma genitalium Infection from Other Diseases
Mycoplasma genitalium infection must be distinguished from other sexually transmitted diseases, which may have a similar presentation. These include:
- Chlamydia trachomatis
- Neisseria gonorrhea
- Trichomonas vaginalis
- Ureaplasma urealyticum
- Herpes simplex virus

# Epidemiology and Demographics
- The incidence and prevalence of Mycoplasma genitalium is not well established, because more than half of the women who tested positive were asymptomatic.
- In the United States, the prevalence of Mycoplasma genitalium was estimated as follows:
The prevalence of Mycoplasma genitalium in all females aged 14-70 years old is 16.3%.
The prevalence of Mycoplasma genitalium in all males aged 18-78 years old is 17.2%.
Infection in both males and females was more prevalent in those younger than 30 years of age.
The overall prevalence of Mycoplasma genitalium infection is 1%, which makes it more prevalent than Neisseria gonorrhea (0.4%), but less common than Chlamydia trachomatis (4.2%).
- The prevalence of Mycoplasma genitalium in all females aged 14-70 years old is 16.3%.
- The prevalence of Mycoplasma genitalium in all males aged 18-78 years old is 17.2%.
- Infection in both males and females was more prevalent in those younger than 30 years of age.
- The overall prevalence of Mycoplasma genitalium infection is 1%, which makes it more prevalent than Neisseria gonorrhea (0.4%), but less common than Chlamydia trachomatis (4.2%).
- Between the years 2002-2011, the prevalence of Mycoplasma genitalium worldwide ranged between 4%-42%.
- Mycoplasma genitalium is the cause of about 15%20% of nongonococcal urethritis and 40% of persistent or recurrent urethritis.
- Rectal infection with Mycoplasma genitalium was detected in 1%26% of men who had sex with men and among approximately 3% of women; however, rectal infections are usually asymptomatic.
- Macrolides resistance and treatment failure have been reported between 44% and 90% in the United States, Canada, Australia, and Western Europe due to frequent use of azithromycin as a single treatment for Mycoplasma genitalium.

# Risk Factors
There several risk factors that have been identified with Mycoplasma genitalium infection. These risk factors include:
- High risk sexual behavior, defined as having >3 new sexual partners in the past year
- Being engaged in sexual contact with persons with STDs, particularly Mycoplasma genitalium
- Non-white race
- Young age (<20 years old)
- Smoking
- Having less than high school education
- Having an annual income of less than $10,000
- Risk factors specific to females includes:
Frequent douching
Proliferative phase of the menstrual cycle
History of spontaneous miscarriage
Undergoing procedures that breach the cervical barrier
Use of Depo-Provera for contraception
- Frequent douching
- Proliferative phase of the menstrual cycle
- History of spontaneous miscarriage
- Undergoing procedures that breach the cervical barrier
- Use of Depo-Provera for contraception

# Screening
There are no recommendations for screening for Mycoplasma genitalium.

# Natural history, Complications and Prognosis

## Natural History
If left untreated, Mycoplasma genitalium infection can lead to persistent cervicitis, PID, or urethritis.

## Complications
The following complications may be the result of Mycoplasma genitalium infection:
- Complications in females include: cervicitis, endometritis, tubal factor infertility, pelvic inflammatory disease (PID), preterm labor as well as sexually active reactive arthritis (SARA).
- Complications in males include: epididymitis, urethritis, as well as sexually active reactive arthritis (SARA).

## Prognosis
The prognosis of Mycoplasma genitalium infection is generally excellent. Cure rates are almost 100% with the correct and prompt antibiotic treatment.

# History and Symptoms
The presenting symptoms of Mycoplasma genitalium are related to the disease processes it may cause. Presenting symptoms can be divided based on gender:
- Females: 40-75% of women infected with Mycoplasma genitalium are asymptomatic. However, when symptoms are present, they are usually related to the disease process Mycoplasma genitalium resulted. These include:
Cervicitis: presents with vaginal discharge, vaginal itching, inter-menstrual, heavy or post-coital bleeding
PID: presents with pelvic discomfort or lower abdominal pain, painful sexual intercourse (dyspareunia), vaginal discharge, and/or bleeding
Urethritis: presents with pain on urination (dysuria) or urethral discharge
- Cervicitis: presents with vaginal discharge, vaginal itching, inter-menstrual, heavy or post-coital bleeding
- PID: presents with pelvic discomfort or lower abdominal pain, painful sexual intercourse (dyspareunia), vaginal discharge, and/or bleeding
- Urethritis: presents with pain on urination (dysuria) or urethral discharge
- Males: tend to be more symptomatic than females and present with symptoms of urethritis, which include urethral discharge and dysuria.

# Physical Examination
Physical examination findings in Mycoplasma genitalium are related to the disease processes it may cause. These findings can be divided based on the several disease pathologies in males and females.
- Females:
Cervicitis: findings include a purulent or mucopurulent cervical discharge, vaginal itching, inter-menstrual, heavy or post-coital bleeding
PID: signs include lower abdominal tenderness, rebound tenderness, cervical motion, uterine or adnexal tenderness, vaginal discharge and/or bleeding and decreased bowel sounds
- Cervicitis: findings include a purulent or mucopurulent cervical discharge, vaginal itching, inter-menstrual, heavy or post-coital bleeding
- PID: signs include lower abdominal tenderness, rebound tenderness, cervical motion, uterine or adnexal tenderness, vaginal discharge and/or bleeding and decreased bowel sounds
- Males:
Present with signs of urethritis, mainly urethral discharge. Urethral discharge may not be grossly evident hence, urethral milking or stripping may be needed. Other findings include balanitis (inflammation of the glans penis) or posthitis (inflammation of the foreskin).
- Present with signs of urethritis, mainly urethral discharge. Urethral discharge may not be grossly evident hence, urethral milking or stripping may be needed. Other findings include balanitis (inflammation of the glans penis) or posthitis (inflammation of the foreskin).

# Laboratory Findings
- Culture of Mycoplasma genitalium is not commonly used, as culture takes about 6 months to grow and is not widely available.
- Nucleic acid amplification test (NAAT) via polymerase chain reaction (PCR) or transcription-mediated amplification (TMA) is the preferred method for isolating Mycoplasma genitalium. Samples can be obtained from urine, urethral, vaginal or cervical swabs. However, first void urine sample is considered the best method for isolating the organism in both females and males.
- Males with recurrent nongonococcal urethritis as well as females with recurrent cervicitis or PID should be tested for Mycoplasma genitalium using NAAT. Resistance testing should be performed if available.

# Imaging Findings

## X Ray
There is no role for x ray in Mycoplasma genitalium infection.

## CT
CT scan may be used if Mycoplasma genitalium infection has been complicated by PID. These include thickened and fluid-filled tubes with or without free pelvic fluid.

## MRI
MRI may be used if Mycoplasma genitalium infection has been complicated by PID.

# Other Diagnostic Studies
There are no other diagnostic studies for Mycoplasma genitalium infection.

# Medical Therapy
Mycoplasma genitalium is intracellular and lacks the cell wall; hence, eradication of the organism is sometimes challenging. The antibiotic drug of choice and dosing depends on susceptibility of the Mycoplasma genitalium strain, and the availability of macrolides-resistance testing , as follows:

## Recommended Regimens if Mycoplasma genitalium Resistance Testing Is Available
- If macrolide sensitive: Doxycycline 100 mg orally 2 times/day for 7 days, followed by azithromycin 1 g orally initial dose, followed by 500 mg orally daily for 3 additional days (2.5 g total)
- If macrolide resistant: Doxycycline 100 mg orally 2 times/day for 7 days followed by moxifloxacin 400 mg orally once daily for 7 days

## Recommended Regimen if Mycoplasma genitalium Resistance Testing Is Not Available
Doxycycline 100 mg orally 2 times/day for 7 days, followed by moxifloxacin 400 mg orally once daily for 7 days

# Surgery
Surgical intervention is not recommended for the management of Mycoplasma genitalium infection.

# Primary Prevention
Since Mycoplasma genitalium infection is a sexually transmitted disease, prevention must target safe sexual practices. These include:
- Practicing safe sex with one partner and avoiding multiple sexual partners
- Using condoms and/or other barrier methods

# Secondary Prevention
Secondary prevention in Mycoplasma genitalium infection consists of the following measures:
- Prompt treatment with antibiotics to prevent complications of the infection
- Test of cure is not recommended for asymptomatic individuals
- Partner notification and evaluation: if partner does not attend evaluation for infection, then he/she can be offered the same treatment as the patient
- Screening and treatment for other sexually transmitted diseases