What is Mycoplasma?
They belong to the class of bacteria Mollicutes, meaning soft skin because they have no cell wall .
Lacking a cell wall, they are able to change shapes, resist antibiotics that act on a cell wall, and they do not stain on a bacterial Gram stain .
Mycoplasmas have extremely small genome .
Due to these features, mycoplasmas require specific conditions for their growth and depend on the host for survival .
The Role of Mycoplasma in Human Disease
More than 200 mycoplasma species have been identified in humans, animals, and plants .
16 mycoplasma species are found in humans but only a few have been proven to cause human disease .
Several mycoplasma species including M. salivarium, M. orale, M. buccale, M. faucium, and M. lipophilum are normally found in the mouth and throat without causing disease .
Of the mycoplasma species known to infect man, M. pneumoniae is the best-known cause of respiratory tract infections .
These infections can be seen before, during, or after lung disease or can occur without respiratory illness.
Mycoplasma hominis, Mycoplasma genitalium, and Ureaplasma urealyticum, commonly found in the urinary and genital tracts, have also been proven to cause human disease .
1) Respiratory Disease
Approximately 20% of infected persons have no symptoms.
Around 75% have mild respiratory illnesses including chest cold (tracheobronchitis) and inflammation of the windpipe (tracheitis).
Only 3 – 10% of patients develop atypical pneumonia, also called “walking pneumonia” [22, 19].
People who have walking pneumonia are rarely confined to a bed or need to be hospitalized. Some may even feel well enough to go to work and carry on with other daily activities.
M. pneumoniae is spread through contaminated droplets from person to person by sneezing or coughing .
Symptoms include fever, headache, cough, sore throat, chills, muscle ache, and weakness. These symptoms develop slowly, over several days to a week, often persisting for weeks to months .
The cough is initially dry but later small amounts of greenish sputum are coughed up.
Children with an impaired immune system have a greater risk of developing more severe pneumonia .
Almost 50% of the severe pneumonia cases occurred in patients aged 20 – 49 years, and 13.5% occurred in the elderly (age > 70 years) .
M. pneumoniae infection may play an important role in the occurrence of asthma.
A study found that M. pneumoniae was the cause of asthma attacks in 50% of hospitalized children, and was a worsening factor in 20% of them .
M. fermentans has been found in the throats of 16% of children with community-acquired pneumonia .
2) Genital Tract Infections
According to the study, M. genitalium infection was more common in people who had at least 4 new sexual partners in the past year compared to people who had 1 or less .
Genital mycoplasmas also cause:
- Vaginal infection (bacterial vaginosis) 
- Pelvic inflammatory disease [54, 55, 56, 57]
- Infertility 
- Sexually acquired reactive arthritis [51, 59, 60]
- Preterm birth [61, 62]
- Spontaneous abortion 
- Postpartum (after childbirth) and postabortion fever [64, 65]
Bone, joint and muscle complications occur in approximately 14% of patients with acute M. pneumoniae infection .
4) Neurological Disease
Neurological complications include inflammation of the brain (encephalitis), spinal cord (myelitis), nerve roots (polyradiculitis), and membranes lining the brain and spinal cord (meningitis), psychosis, coma, and cerebellar syndrome [10, 75].
5) Skin Disease
Skin complications occur in approximately 25% of patients with M. pneumoniae infections .
Some studies suggest that 7% of cases of M. pneumoniae infection develop into Stevens-Johnson syndrome (characterized by severe rash, high fever, cold symptoms, and inflammation of mucosa) [88, 89, 84].
Skin rashes can also be caused by antibiotics commonly used to treat M. pneumoniae respiratory infections .
6) Heart Disease
Heart complications associated with M. pneumoniae occur in 1 to 8.5% of persons with infection .
The most frequent complications are inflammation of the heart (myocarditis) and a sac surrounding the heart (pericarditis), heart failure, and accumulation of fluid around the heart (pericardial effusion) [68, 91, 90].
Mycoplasma infection can also lead to a heart attack in rare cases .
In a European study, 68.6% of patients with CFS were infected with mycoplasma, compared to 5.6% healthy subjects (R).
Most patients recover after long-term antibiotic therapy, and the infection cannot be detected after recovery .
8) Gulf War Illness
A study suggested that mycoplasmas are responsible for a large number of cases among veterans .
In studies on hundreds of veterans, approximately 40-50% of Gulf War Illness patients show evidence of mycoplasmal infections compared to 6-9% in non-deployed, healthy subjects .
Gulf War Illness was also transmitted from veterans with Gulf War Illness to immediate family members.
77% of spouses and 65% of children had similar health complaints as the veterans .
9) Lyme Disease
Most symptoms that occur due to Lyme disease such as fever, chills, headache, neck, muscle and joint pain, neurological symptoms, conjunctivitis, rash, and sleep problems, may be caused by mycoplasma .
10) Kidney Disease
11) Gut Disease
12) Blood Disease
13) Eye Disease
Eye infections caused by mycoplasmas are occasionally seen in children, and include conjunctivitis, anterior uveitis, optic neuropathy, retinitis, iritis, and optic disk swelling, with or without permanent damage of vision .
14) Infection in Patients with Compromised Immune System
M. hominis causes suppurative arthritis in individuals with hypogammaglobulinemia Reduced number of antibodies in the blood) .
Mycoplasmas cause deep wound infections that occurred shortly after kidney transplantation .
15) Autoimmune Disease
The similarity between the mycoplasma and human cell membranes may cause the body to make autoantibodies that attack the host and produce autoimmune disease .
Mycoplasma infections have been linked to the progression of multiple sclerosis, Hashimoto’s disease, Graves’ disease, Sjögren’s syndrome, lupus, Kawasaki disease and other autoimmune diseases [124, 125].
16) May Exacerbate AIDS
M. fermentans, M. penetrans, and M. pirum are the most common mycoplasmas associated with AIDS.
A study showed that African women who are infected with M. genitalium are two times more likely to acquire HIV infection .
17) May Play a Role in Cancer
Experimental studies showed that mycoplasmas cause changes in chromosomes and cells , potentially leading to cancer development.
Mycoplasma was present in 55% of cases of gut carcinoma, including colon and gastric carcinoma .
Pathogenesis of Mycoplasmal Infections
Development of mycoplasma infection includes several factors:
Mycoplasma infection is caused by the close attachment of mycoplasma to host epithelial cells by structure present on the surface of bacteria (adhesins) .
Toxic Metabolic Products
M. pneumoniae produces a unique Community Acquired Respiratory Distress Syndrome (CARDS) toxin that is important in developing lung disease .
Immune System Changes
Mycoplasma can also avoid detection by the immune system by changing the composition of its cell membrane to imitate the host cell membrane .
Diagnosis of Mycoplasma Infections
Laboratory Diagnosis of Mycoplasmas
Culture of mycoplasmas is relatively simple for M. hominis and U. urealyticum, from specimens where they can be found easily, such as urogenital specimens (153).
Culture of M. pneumoniae from clinical samples such as nose and throat swabs or sputum was considered standard for diagnosis several years ago .
However, the organism usually takes 2 to 3 weeks to grow, it requires specialized and expensive growth media, and the sensitivity of cultures may be 60-70% .
Therefore, the culture method is rarely used for routine diagnosis of M. pneumoniae infections in specialized laboratories and should be done for epidemiological reasons .
Culture is rarely successful for M. genitalium (153).
Serologic tests are simple and very often used to diagnose M. pneumoniae respiratory infections .
Serologic tests for genital mycoplasma infections are not commercially available in Europe or the US, and are not recommended for routine diagnosis (R).
Serologic tests measure antibodies specific for M. pneumoniae to show the presence of infection .
In all serologic tests, two blood specimens are collected 2 – 4 weeks apart, one taken in the acute and one in the convalescent stage of the illness. A fourfold rise in antibody level (titer) indicates recent infection .
Serologic tests include:
- Complement fixation test:
Antibody levels do not peak until 4 – 6 weeks after infection. Since antibodies may persist for up to 1 year, a sustained high level of antibodies does not necessarily indicate a current infection .
- Cold agglutinin test is a test frequently used to confirm the diagnosis.
Approximately 30% – 60% of patients with M. pneumoniae infection develop cold agglutinins (IgM antibodies to the I antigen of red blood cells).
This test is not specific since positive results can be seen in infectious mononucleosis, influenza, cold agglutinin disease, and leukemia. However, if present in a patient with clinical signs of M. pneumoniae infection, a presumptive diagnosis can be made .
- ELISA (Enzyme Linked Immuno Assay) and IFA (immunofluorescence assays) for detection of IgM (shows the presence of acute infection) and IgG (shows prior exposure, remains positive for years) antibodies .
Antibodies can be detected after about 1 week of illness, and peeks at 3 – 6 weeks and then declines gradually.
Many studies have described the use of different molecular methods among which real-time PCR has both high sensitivity (true positive rate) and high specificity (true negative rate) .
Real-time PCR may detect mycoplasma in 60 – 100% of people with the infection, and show the absence of infection in 96.7 – 100% of healthy people .
The PCR technique is practically the only method for detection of M. genitalium .
Diagnosis is made only through nucleic acid amplification testing (NAAT), but there are no commercially available diagnostic tests .
Treatment of Mycoplasma Infections
It is important to emphasize that most antibiotics used in the treatment decrease mycoplasma growth but do not kill the bacteria (bacteriostatic).
This is one of the reasons why eradicating mycoplasmas is often slow and depends on the efficacy of the host immune system.
In the past, tetracyclines have been effective against both M. hominis and U. urealyticum, but the resistance had been increasing.
The optimal duration of antibiotic therapy is 10-14 days.
Prevention of Mycoplasma Infections
Like many respiratory diseases, M. pneumoniae infection may be prevented by taking simple precautions :
- Cover mouth and nose with a tissue when coughing or sneezing.
- Cough or sneeze into upper sleeve or elbow, instead of hands, if a tissue is not available.
- Wash hands often with warm water and soap for at least 20 seconds.
- Use an alcohol-based hand rub if soap and water are not available.
Several measures that can be taken in order to prevent genital infections include :
- Practice safe sex using condoms.
- No sex until you and your partner have completed antibiotic treatment.
- A follow-up test must be done to confirm that treatment has cleared the infection.
- All sexual partners need to be contacted, tested and, if needed, treated.