Mycoplasma Infection

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Introduction

Mycoplasmas are the smallest free-living microorganisms (R, R2).

They belong to the class of bacteria Mollicutes, meaning soft skin, because they have no cell wall (R).

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 (R).

Mycoplasmas have extremely small genome (all the DNA of the organism) (R).

Due to these features, mycoplasmas require specific conditions for their growth, and depend on the host for survival (R, R2).

The Role of Mycoplasma in Human Disease

More than 200 mycoplasma species have been identified in humans, animals, and plants (R).

16 mycoplasma species are found in humans but only a few have been proven to cause human disease (R).

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 (R).

Of the mycoplasma species known to infect man, M. pneumoniae is the best known cause of respiratory tract infections (R).

It can also infect organs other than lungs such as the nervous system, joints, skin, kidneys, heart, muscles, eyes and blood (R, R2, R3, R4).

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 (R).

1) Mycoplasma Causes Respiratory Disease

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M. pneumoniae

M. pneumoniae, initially known as Eaton’s agent, causes lung infection (R, R2, R3, R4).

Infection is most frequent in children from 5 years of age to young adults (R, R2).

The outbreaks occur in closed communities such as families, military bases, hospitals, and schools, because close contact is needed for spread of infection (R, R2).

Worldwide epidemics occur in children and adults every 3 to 5 years, most commonly in late summer or early fall (R, R2).

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” (R, R2).

It causes 15%-20% of all pneumonias, and up to 40% of community-acquired pneumonias (R, R2).

People who have walking pneumonia are rarely confined to bed or need to be hospitalized. Some may even feel well enough 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 (R).

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 (R).

Cough is initially dry but later small amounts of greenish sputum are coughed up.

Cough may also resemble pertussis, characterized by paroxysmal cough and vomiting, causing patients to complain of chest soreness from protracted coughing (R, R2).

Earache occurs in about 30% of patients, but inflammation of ear canal (otitis externa) and inner ear (otitis media and bullous myringitis) are rare (R, R2).

Children under 5 years of age are most likely to have symptoms of  common cold and wheezing (a whistling sound while breathing) (R).

Older children aged 5 to 15 years are more likely to develop pneumonia (R, R2).

Severe pneumonia, with multiple organ involvement and death, occurs in 0.5–2% of all M. pneumoniae pneumonia cases (R).

Children with impaired immune system have a greater risk of developing more severe pneumonia (R).

Studies suggest that severe disease can also occur in otherwise healthy children and adults of all ages (R, R2).

Almost 50% of the severe pneumonia cases occurred in patients aged 20–49 years, and 13.5% occurred in the elderly (age > 70 years) (R).

M. pneumoniae infection may play an important role in the occurrence of asthma.

It can precede the onset of asthma, worsen symptoms, and cause difficulties in controlling asthma (R, R2, R3).

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 (R).

Other Mycoplasmas

M. hominis and U. urealyticum have also been associated with pneumonia and respiratory distress syndrome in newborns (R, R2).

M. fermentans has been found in the throats of 16% of children with community-acquired pneumonia (R).

It has also been detected in previously healthy adults who presented with an influenza-like illness that sometimes progressed into respiratory distress syndrome (R).

2) Mycoplasma Causes Genital Tract Infections

Infections caused by M. hominis, M. genitalium, and U. urealyticum are sexually transmitted infections (R, R2).

According to the study, M. genitalium infection was more common in people who had at least 4 new sexual partners in the past year comparing to people who had 1 or less (R).

M. genitalium and U. urealyticum cause inflammation of urethra (urethritis) in men (R, R2, R3).

Men with infection experience burning, painful urination and discharge from the penis (R, R2, R3).

In women, M. genitalium is associated with cervical and urethral infection (R, R2).

40-75% of women with infection do not have any symptoms (R, R2).

Women experiencing symptoms have abnormal vaginal discharge, painful urination or urgency to urinate, and rarely, bleeding between menstrual periods or after sexual intercourse (R, R2, R3).

Genital mycoplasmas also cause:

3) Mycoplasma May Cause Arthritis

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Mycoplasmas occur in patients with arthritis, rheumatoid arthritis, and sexually transmitted reactive arthritis (R, R2, R3).

Bone, joint and muscle complications occur in approximately 14% of patients with acute M. pneumoniae infection (R).

U. urealyticum and M. hominis also caused septic arthritis in patients with compromised immune system (hypogammaglobulinemia) (R, R2, R3).

Canadian study showed an association between M. pneumoniae infections and juvenile rheumatoid arthritis in children (R).

4) Mycoplasma Causes Neurological Disease

0.1% of all patients with M. pneumoniae infection and 7% of hospitalized patients have neurological complications (R, R2, R3).

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 (R, R2).

Also, cranial nerve palsy, brachial plexus neuropathy, ataxia, choreoathetosis, and ascending paralysis (Guillain-Barre syndrome) have been described (R, R2, R3).

In addition, acute transverse myelitis and acute disseminated encephalomyelitis can result in some of the most severe complications associated with mycoplasma infection (R).

Studies also reported cases of neonatal meningitis and brain abscess caused by M. hominis (R, R2, R3, R4).

5) Mycoplasma Causes Skin Disease

Skin complications occur in approximately 25% of patients with M. pneumoniae infections (R).

Rashes (erythematous maculopapular, vesicular rashes), Stevens-Johnson syndrome, erythema nodosum, and ulcerative stomatitis commonly occur (R, R2, R3, R4).

In a study,  M. pneumoniae caused 42.1% of erythema multiforme cases (R).

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) (R, R2, R3).

Skin rashes can also be caused by antibiotics commonly used to treat M. pneumoniae respiratory infections (R).

6) Mycoplasma Plays a Role in Heart Disease

Heart complications associated with M. pneumoniae occur in 1 to 8.5% of persons with infection (R).

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) (R, R2, R3).

In addition, patients following heart surgery developed inflammation of the inner lining of the heart (endocarditis), including heart valves, caused by M. hominis (R, R2, R3).

Mycoplasma infection can also lead to a heart attack in rare cases (R).

7) Mycoplasma is Associated with Fatigue

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Mycoplasma infection has been detected in about 50% of patients with chronic fatigue syndrome (CFS) and/or fibromyalgia (R, R2).

In a European study, 68.6% 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 (R).

8) Mycoplasma May Cause Gulf War Illness

Gulf War Illness comprises symptoms found in veterans of the Persian Gulf War, including chronic fatigue, joint and muscle pain, headaches, and skin rashes (R).

Study suggested that mycoplasmas are responsible for a large number of cases among veterans (R).

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 (R).

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 (R).

9) Mycoplasma is Associated with Lyme Disease

Around 75% of chronic Lyme disease patients appear to have mycoplasma infections, and yet mycoplasma is often overlooked in the diagnosis and treatment of this condition (R).

Most symptoms that occur in Lyme disease such as fever, chills, headache, neck, muscle and joint pain, neurological symptoms, conjunctivitis, rash, and sleep problems, may be caused by mycoplasma (R).

10) Mycoplasma May Cause Kidney Disease

Kidney complications associated with M. pneumoniae are rare, and are usually presented as acute tubulointerstitial nephritis, kidney failure, and IgA nephropathy (R, R2, R3).

M. hominis is involved in approximately 5% of cases of acute pyelonephritis in humans (R, R2, R3).

U. urealyticum can induce the formation of kidney stones (R, R2).

11) Mycoplasma May be Associated with Gut Disease

12-44% of patients with M. pneumoniae pneumonia have poor appetite, nausea, vomiting, or diarrhea (R, R2).

Rarely, inflammation of the liver (hepatitis) and pancreas (pancreatitis) have been associated with respiratory infections (R, R2, R3).

Several epidemiologic studies showed an association of M. pneumoniae infections with exacerbation of Crohn’s disease and other chronic inflammatory bowel diseases (R).

12) Mycoplasma May be Linked to Blood Disease

M. pneumoniae can cause hemolytic and aplastic anemia, thrombotic thrombocytopenic purpura, arterial thrombosis, and Reynaud’s syndrome (R, R2).

Severe infection leading to fatal disseminated intravascular coagulation has also been reported (R).

13) Mycoplasma Causes 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 (R).

14) Mycoplasma Causes Infection in Patients with Compromised Immune System

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Patients with disorders of antibody production appear to be the most susceptible to mycoplasma infections (R, R2).

M. hominis causes suppurative arthritis in individuals with hypogammaglobulinemia (reduced number of antibodies in the blood) (R).

Also, patients who undergo organ transplantation or treatment of malignant diseases have an increased risk for mycoplasma infections (R, R2, R3).

Mycoplasmas cause deep wound infections that occurred shortly after kidney transplantation (R).

15) Mycoplasma is Linked to 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 (R).

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 (R, R2).

Mycoplasmas have also been detected in patients with amyotrophic lateral sclerosis, Alzheimer’s and Parkinson’s disease (R).

16) Mycoplasma May Exacerbate AIDS

M. fermentans, M. penetrans and M. pirum are the most common mycoplasmas associated with AIDS.

These microorganisms may accelerate the progression of HIV infection (R, R2).

A study showed that African women who are infected with M. genitalium are two times more likely to acquire HIV infection (R).

M. fermentans may also cause kidney and neurological complications in patients with AIDS (R, R2).

M. penetrans is linked to Kaposi’s sarcoma in homosexual men with AIDS (R).

17) Mycoplasmas May Play a Role in Cancer

Experimental studies showed that mycoplasmas cause changes in chromosomes and cells (R), potentially leading to cancer development.

The infection of mycoplasmas is associated with an increased risk of prostate cancer (R, R2, R3).

Studies suggest a possible role of mycoplasma infection in childhood leukemia, kidney, ovarian, and breast cancer (R, R2, R3, R4, R5).

Mycoplasma was present in 55% cases of gut carcinoma, including colon and gastric carcinoma (R).

Pathogenesis of Mycoplasmal Infections

Development of mycoplasma infection include several factors:

Adherence factors

Mycoplasma infection is caused by the close attachment of mycoplasma to host epithelial cells by structure present on the surface of bacteria (adhesins) (R).

The main adhesin P1 of M. pneumoniae and  the MgPa adhesin of M. genitalium are the best studied adhesins in mycoplasma (R, R2).

This close attachment prevents bacteria from being removed by the normal clearance mechanisms of host’s respiratory and genitourinary tract (R, R2).

Toxic Metabolic Products

The close association of the mycoplasma and the host cells increases production of toxic products (hydrogen peroxide and superoxide) that damages host tissues (R).

Mycoplasmas also inhibit host cell enzyme catalase, further increasing the peroxide concentrations (R).

M. pneumoniae produces a unique Community Acquired Respiratory Distress Syndrome (CARDS) toxin that is important in developing lung disease (R).

Immune System Changes

Mycoplasmas can activate macrophages, B-cell differentiation and antibody production (R, R2, R3).

They can cause white blood cells to produce cytokines IL-1, IL-2, IL-4, IL-6 , and TNF-alpha, which leads to either increased or decreased function of the immune system (R, R2, R3).

Mycoplasma can also avoid detection by immune system by changing the composition of its cell membrane to imitate the host cell membrane (R).

The similarity between the mycoplasma and human cell membranes may cause the body to make autoantibodies that attack the host and produce autoimmune disease (R).

Diagnosis of Mycoplasma Infections

Patient symptoms, physical examination, radiology procedures and laboratory findings along with additional serologic and culture tests lead to an accurate diagnosis (R, R2).

Laboratory Diagnosis of Mycoplasmas

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Culture

Culture of mycoplasmas is relatively simple for M. hominis and U. urealyticum, from specimens where they can be found easily, such as urogenital specimens (R).

Culture of M. pneumoniae from clinical samples such as nose and throat swabs or sputum was considered standard for diagnosis several years ago (R).

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% (R).

Therefore, culture method is rarely used for routine diagnosis of M. pneumoniae infections in specialized laboratories, and should be done for epidemiological reasons (R).

Culture is rarely successful for M. genitalium (R).

Serology

Serologic tests are simple and very often used to diagnose M. pneumoniae respiratory infections (R).

Serologic tests for genital mycoplasma infections are not commercially available in Europe or US, and are not recommended for routine diagnosis (R).

Serologic tests measure antibodies specific for M. pneumoniae to show the presence of infection (R).

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 (R).

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 (R).

  • 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 (R).

  • ELISA (Enzyme Linked Immuno Assay) and IFA (immunofluorescence assays) for detection of IgM (shows presence of acute infection) and IgG (shows prior exposure, remains positive for years) antibodies (R).

Antibody can be detected after about 1 week of illness, and peeks at 3–6 weeks and then declines gradually.

Molecular methods

Development of molecular methods such as polymerase chain reaction (PCR) assays improved diagnosis of mycoplasma infection in pediatric and adult patients (R, R2).

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) (R).

Real-time PCR may detect mycoplasma in 60-100% of people with the infection, and show absence of infection in 96.7-100% of healthy people (R).

The PCR technique is practically the only method for detection of M. genitalium (R).

Diagnosis is made only through nucleic acid amplification testing (NAAT), but there are no commercially available diagnostic tests (R).

Treatment of Mycoplasma Infections

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Mycoplasma infection is treated with antibiotics.

All mycoplasmas lack a cell wall and, therefore, they are not susceptible to penicillins and other antibiotics that act on this structure (R).

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.

Macrolides, such as erythromycin, clarithromycin and azithromycin, are the treatment of choice for M. pneumoniae infections in both adults and children (R, R2, R3).

Resistance to macrolides has been emerging and increasing in M. pneumoniae since 2000, especially in Asia (R, R2).

Several Japanese studies have reported that 20-40% of strains are resistant to macrolides (R, R2).

Tetracyclines, fluoroquinolones (levofloxacin) and ketolides are also effective in treating mycoplasma infection (R, R2, R3).

In the past, tetracyclines have been effective against both M. hominis and U. urealyticum, but the resistance had been increasing.

Clindamycin is an alternative to the tetracyclines (R).

The optimal duration of antibiotic therapy is 10-14 days.

Prevention of Mycoplasma Infections

Different types of vaccines against mycoplasmas have been tested but none are presently available (R).

Like many respiratory diseases, M. pneumoniae infection may be prevented by taking simple precautions (R):

  • 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 (R):

  • 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.

 

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