Patient may remain asymptomatic or present with following signs and symptoms:

• Non-productive cough
• Pharyngitis
• Low-grade fever
• Headache
• Malaise
• Erythema multiforme (rash characterized by a varied skin presentations like macules, papules, vesicles and bullae, and targetoid lesions).

Pneumonia caused by Mycoplasma Pneumoniae is sometimes called "walking pnemonia" because it is usually mild and, more often, does not require hospitalization.

Specific systemic clinical presentations may appear, some more common than others, but their appearance is unusual. These systemic findings may also be non-specific, such as diarrhoea, nausea, vomiting, abdominal pain, myalgias and arthralgias (in the form of polyarthritis). Since Mycoplasmas disturb body's immune system, aberrant immune responses may appear as tolerance to self-antigens is lost. This autoimmunity can manifest as hemolytic anemia (present in 60% of people), myocarditis, pericardial inflammation and effusions, hepatitis, aseptic meningitis, transverse myelitis or peripheral neuropathy. Specific cranial nerve palsies and cerebellar ataxia can also develop [7] [8]. A specific rash may appear in course of disease.

Most of these signs and symptoms are immune mediated but they may also result from direct invasion by Mycoplasma. In joint manifestations (arthralgia, polyarthritis), Mycoplasma can be isolated from joint fluid after aspiration. 

Respiratory examination is normal in most cases, unless severe symptoms or pneumonia develops. Wheeze (especially in children with a history of asthma) and scattered crepitations (crackles on examination with stethoscope), may be sometimes be heard in some patients.

Cold agglutinin are specific for Mycoplasma infection. Cold agglutinins are autoantibodies formed against red blood cells that agglutinate at low temperature. This results in Raynauds phenomenon (bluish discoloration of extremities at low temperature).

Disease may follow a complicated course in immuno-compromised, organ translplant patients, diabetics, patients on chemotherapy or cytotoxic drugs, in children and elderly people. Pneumonia is a common complication. Sometimes, complications that develop in other systems are far more severe than pneumonia, especially those involving vital organs.

Following specific diagnostic modalities can be employed for Mycoplasma infection:

• Polymerase chain reaction (PCR)
• Serological tests for Mycoplasma

Unlike other bacterial species, Gram stain cannot be performed to identify organism in microscopy because of lack of cell wall.

Polymerase chain reaction (PCR) is the most accurate method (sensitivity 78-100%) to detect pathogen within leukocytes. Human leukocytes are split open and Mycoplasma nucleic acid is amplified and analyzed in this procedure. This test may also be very useful for making a diagnosis in immunocompromised patients, in which serological tests or complete blood count (CBC) do not give specific findings. Enzyme-linked immunosorbent assay (ELISA) and gene tracking can also be performed.

Serlogical tests are useful as long as person's humoral immunity is viable to form antibodies against Mycoplasma. Sensitivity is less than PCR (50-66%). Serum IgG and IgM can be tested at 70-10 days and 3 weeks respectively and 1:32 titre is diagnostic. Serological tests can also be performed during active phase and convalescent phase (10 days to 3 weeks following infection), by which time patient's condition may be recovering or medical treatment started. Thus, serological tests are also not useful at the time of presentation in medical facility (definite diagnosis is made retrospectively). They may however be used when an epidemic is suspected. A four fold rise in titre during convalescent phase is diagnostic. In order to start prompt treatment, or to rule out the suspicion of other pathogens (bacterial/viral), nasopharyngeal swabs, blood or sputum cultures and Gram staining may be done [9] [10].

In severe cases, liver function tests (LFTs) may reveal an elevated level of liver enzymes in blood. Concurrence of hepatitis and pneumonia in patient should raise the suspicion of Mycoplasma infection. CBC often reveals leukocytosis, and reduced number of red blood cells (due to formation of autoantibodies). Blood urea nitrogen (BUN) may be raised in case of kidney damage. Blood oxygen saturation tests are done at the time patient presents in hospital with severe disease. ESR and CRP are also non-specific.

Chest X-rays give non-specific findings; unilateral or bilateral patchy consolidation and small amount of pleural infiltrates. These findings are common to various pneumonia caused by other organisms. Cold agglutinin test is very useful for making a differential diagnosis in patients. Isolation of organism can be done with media supplemented by serum, but cultures are rarely performed because Mycoplasma is a fastidious organism and there is a risk of spread.

Mycoplasma infection is treated on the basis of presentation of disease in patient. While a mild infection may require only a symptomatic treatment and antibiotics, treatment of complications and systemic involvement can be varied depending upon involvement of various organs.

Antibiotics

Antibiotics used against Mycoplasma Pneumonia infection are:

• Macrolides: Azithromycine, erythromycine, clarithromycine and roxithromycine
• Fluoroquinolones: levofoxacine, moxifloxacine
• Doxycycline

Penicillin and other beta-lactam antibiotics that act through cell wall of organism are not effective in this case. Clinical trials have shown maximum efficacy of azithromycine [11], and fluoroquinoles, levofloxacine [12], and moxifloxacine [13]. Studies have also shown azithromycine as the most effective drug in Mycoplasma Pneumoniae infection. Resistance to this drug did not develop despite multiple passages in the presence of azithromycine. Patients allergic to, or those who develop drug interactions or side effects of macrolides are given doxycycline and moxifloxacine.

Antibiotics are not much beneficial in patients who develop cross-reacting antibodies in Mycoplasma infection, for example those presenting with hepatitis, or more importantly those with nervous system involvement (cranial nerve palsies, transverse myelitis, etc.).

Other therapies

1. Plasma exchange therapy (in case of immune-mediated reactions).
2. Plasmapheresis (to remove cross reacting antibodies)
3. Patients presenting with CNS symptoms may also be treated with steroids (glucocorticoids), diuretics and antiinflammatory drugs.
4. Cold agglutinin disease/hemolytic anemic patients may also be treated with plasmapheresis [14], glucocorticoids and warming.

Glucocorticoids are known to have an antiinflammatory action. Studies have shown an effective role of glucocorticoids in ameliorating condition of patients with CNS symptoms, particularly children [15].

The spectrum of disease varies from person to person depending upon virulence of organism, amount of infection and host factors (including immune system). A wide disseminated disease can cause serious complications of respiratory, neurological, muscular or gastrointestinal origin, and a protracted disease course in an immuno-compromised host. On the other hand, disease restricted to respiratory tract may resolve in a few days or weeks, or lung function may not improve before many months pass. Lower respiratory tract involvement can prolong the duration of illness in patients.

Primary and secondary complications are usually a bad prognostic sign. They must be mitigated or resolved as soon as possible. Some people may recover spontaneously.

Mycoplasma Pneumonia infection is a common cause of community acquired pneumonia throughout the world. Generally all the organisms within class Mollicutes are referred to as "Mycoplasma" organisms. Mycoplasma are rod-like and can reside inside cells of immune system to cause immune dysregulation in host.

Pathogenesis of following Mycoplasma species is well established in humans:

• Mycoplasma pneumonia
• Mycoplasma hominis
• Mycoplasma genitalium
• Ureaplasma urealyticum

Transmission of Mycoplasma pneumoniae in humans occurs through respiratory aerosols or respiratory droplets from nose and throat of an infected individual and hence, spread though coughing, sneezing, and during speech. Moreover, infection can also occur by:

• Contact with contaminated hands or skin surface
• Fomites and other contaminated surfaces
• Sexual contact (Ureaplama urealyticum, Mycoplasma hominis and Mycoplasma genitalium are genitourinary organisms)
• Tranplacental transmission from mother to child during pregnancy, is also reported.

Organism adheres to pseudostratified ciliated columnar lining of respiratory tract through a specialized organelle. It exhibits gliding motility on respiratory mucosal surface, another factor that may aid in its infection [2].

Immunocompromised people, such as patients of AIDS or diabetes, are at increased risk of acquiring an infection. Children, elderly people and pregnant women are also susceptible. A person may be infected with more than one species of Mycoplasma at a time.

Mycoplasma Pneumoniae is the cause of 20% cases of community acquired pneumonia. Epidemics occurs in people living in close community settings such as military camps, boarding schools and hostels. Hospital based epidemics can also occur. Incubation period is from one to three weeks and period of communicability of organisms is generally 20 days. Mode of transmission of organism is respiratory droplets and close contact with people infected with organism, and other routes mentioned above. Epidemics tend to occur at an interval of three to five years. There has been a relative increase in the incidence of infection in last summer or fall in some countries [3]. In New York city, no precise estimate for occurrence of disease is available because it is not a report-able disease.

The organism is associated with mucosal surfaces rarely invading submucosa, except in people with immunosuppression. Prevalence of genital infections is also higher among HIV patients [4]. Other species that reside in genital tract i.e, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, are the cause of 20% cases of non-gonococcal urithritis, post-pregnancy pelvic inflammatory disease (PID) and cervicitis. In other cases, organism does not cause an active infection in host.

Mycoplasmas are rod-like in shape and possess a special adherence protein with which they adhere to respiratory epithelium. Absence of a rigid cell wall aids the organism in gaining entry inside cells. In the cells of respiratory epithelium, this organism behaves much like a retrovirus. It utilizes cell's nutrients and induces the host cell to work as a machinery for the generation of its own proteins to carry out its own replication.

CD-4+ cells that get activated by (Mycoplasma protein binding) macrophages produce pro-inflammatory cytokines including Interleukin-1, Interleukin-6 and Tumor Necrosis Factor-alpha (TNF-a) [5]. These cytokines, in turn, take part in generating further immune response in body.

Mycoplasmas mostly remain extracellular, restricted to mucosal surfaces and rarely a systemic involvement occurs; although the main mechanism by which Mycoplasmas cause damage to body organs is through dysregulation of immune system. When Mycoplasmas break out of cells they had infected, they take host cell membrane fragment with them. Immune system, thus starts recognizing self-proteins as foreign and an abnormal, auto-immune response is generated against body's own proteins, causing damage to various organs. Antibodies produced against glycolipids antigens of Mycoplasma pneumonia may act as cross-reactive antibodies and attack red blood cells, heart, brain, skin or liver cells. Cold agglutinins are cross reactive antibodies against red blood cells. These cross-reactive antibodies are specific (and diagnostic) for Mycoplasmas infection and some other diseases. Autoimmunity against joint cells causes arthritis. When they develop against TSH receptors of thyroid, they can cause Hashimoto's thyroiditis or Graves disease). Similarly myalgias, meningitis, transverse myelitis and hepatitis can be produced when these cross-reactive antibodies react against cellular proteins of muscle, brain, spinal cord and liver respectively.

Mycoplasmas can both, stimulate or depress the activity of B and T cells. They can also evade immune response, as they can reside inside certain cells of immune system such as Natural Killer cells (NK-cells). Infection of NK-cells reduces their number and weaken the innate immune mechanism of body against viral (e.g, HHV-6; Human Herpes virus-6) and other pathogens. Since organism resides inside cells, conventional serological techniques may not be useful for detection [6]. In order to confirm the presence of microorganism, leukocytes are split open and analyzed using PCR (Polymerase Chain Reaction). Otherwise, disease can go undetected in human body for many years.

Chronic Fatigue Syndrome (CFS), Chronic Fatigue and Immune Dysfunction Syndrome (CFID), Fibromyalgia Syndrome (FMS) and Multiple Chemical Sensitivity (MCS) are a group of overlapping disorders that share some common symptoms and often occur together. Mycoplasma pathogenesis is likely to be involved in the causation of these syndromes. Mycoplasmas can cause an increased production of cytokines, reduce the amount of Natural Killer cells (NK-cells), cross the blood brain barrier, invade central or peripheral nervous system and trigger an autoimmunity that damages cells of limbic system and other brain areas, causing symptoms that are associated with above mentioned disorders. Neurological symptoms are caused by:

• Increased production of inflammatory cytokines (through the stimulation CD-4+ cells)
• Activation of pituitary-hypothalamic axis
• Damage to cells of limbic system.

Mycoplasma infection spread through respiratory aerosols, contact with contaminated articles, and less commonly, through sexual contact. There is no vaccine for Mycoplasma pneumoniae infection. Following preventive measures can be adopted in order to prevent infection or a serious pneumonia epidemic in close communities.

• Maintaining personal hygiene (frequent hand-washing, using handkerchief while sneezing, coughing)
• Isolation of diagnosed case
• Chemoprophylaxis: Azithromycine or doxycycline are used for prevention in close contacts and health care personnel [16].

Mycoplasma species are wall-less, bacteria-like organisms that have been known as smallest free-living organisms. They can survive in aerobic as well as in anaerobic condition. Mycoplasma infection generally refers to an infection from any of the organisms belonging to class Mollicutes that includes 120 named species of Mycoplasma. Thirteen Mycoplasma species, two Ureaplasma species and two Acholeplasma species have been isolated from humans. Ureaplasma urealyticym, Mycoplasma hominis and Mycoplasma Genitalium also cause known infections in humans. These organisms are often involved in non-gonococcal urithrits, cervicitis or pelvic inflammatory disease, more commonly in women. Genital Mycoplasmas occur in 80% of sexually active women.

Lack of cell wall imparts this species some special properties:

• They cannot be visualized by Gram staining [1].
• Penicillin and other Beta-lactam drugs have no effect on them.

Infection more commonly manifests as respiratory tract symptoms, although rarely there may be a multi-system involvement, if dissemination occurs, as in immunocompromised hosts, or after instrumentation.

Mycoplasma infection refers to an infection from any of the organisms belonging to class Mollicutes that includes 120 named species of Mycoplasma. Mycoplasma pnemoniae is an important cause of community-acquired pneumonia.

Transmission

• Respiratory droplets from infected person, released during coughing, sneezing or talking.
• Contact with contaminated articles and surfaces.
• Direct transmission through sexual contact.

Disease is most common in close-community setting (boarding schools, camps).

Clinical features

• Fever
• Cough
• Sore throat
• Headache
• Malaise
• Muscle and joint pain
• Pneumonia (mild, hence called "walking pneumonia")
• Rash

Other clinical features are nausea, vomiting, abdominal pain, diarrhoea, meningitis, nerve palsies, hepatitis.

Diagnosis

Diagnosis of infection is made through:

• Clinical features
• Polymerase chain reaction (PCR)
• Serological tests (antibody IgM and IgG)
• ELISA

Treatment

Antibiotics treatment comprising of azithromycine, erythromycine, doxycycline, moxifloxacine and levofloxacine. In rare cases, patients may require plasmapheresis or plasma exchange therapy. Glucocorticoids, antiinflammatory drugs and diuretics are sometimes included in regimen to alleviate systemic symptoms.

Prevention

• Avoid contact with an infected person
• Chemoprophylaxis (azithromycine, doxycycline)

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