Mycoplasma pneumoniae is an important cause of upper and lower respiratory tract infections, including pharyngitis, tracheobronchitis, and pneumonia, in children and adults of all ages. The organism eventually known as M. pneumoniae was first isolated from sputum of a patient with primary atypical pneumonia in 1944 [Eaton et al., 1944]. It was soon apparent that this organism, initially called the Eaton Agent, caused respiratory infections in humans, but it was not until the 1960’s that it was proven to be a Mycoplasma and not a virus. M. pneumoniae is a member of the family Mycoplasmataceae and order Mycoplasmatales.
Individual spindle-shaped cells of M. pneumoniae are 1–2 mm long and 0.1–0.2 mm wide. M. pneumoniae possesses a specialized tip structure, an attachment organelle, through which bacteria adhere to the surface of epithelial cells of upper and lower respiratory tract.
Factors that contribute to the disease state include localized damage to the respiratory epithelium and an immune response.
Infection is chronic in onset, developing gradually over a period of several days. It also has a relatively long incubation period of 2-3 weeks.
Whereas pneumonia may be the most severe type of M. pneumoniae infection, the most typical syndrome, especially in children, is tracheobronchitis, often accompanied by a variety of upper respiratory tract manifestations. The most typical symptom is persistent, hacking cough. Systemic symptoms of infection include fever, sore throat, and myalgia. In uncomplicated cases, the acute febrile period lasts about a week.
Approximately 7% of hospitalized patients with M. pneumoniae experience neurological complications of varying severity. Whereas neurological disorders may be the most severe extrapulmonary manifestations of M. pneumoniae infections, dermatological disorders, including erythematous rashes, are the most common complications, occurring in up to 25% of patients.
Transmission of infection occurs from person-to-person by airborne droplets.
Persons with active mycoplasmal infection carry the organisms in the secretions from nose, throat, trachea, and lung sputum.
Outbreaks of M.pneumoniae infections have a slight tendency to occur in the late summer or early autumn. Due to its lack of a cell wall, M. pneumoniae is extremely susceptible to desiccation, which explains the need for close contact for transmission of infection from person to person and relatively low transmission rate. Therefore, M. pneumoniae infections occur mostly in closed settings where large numbers of people dwell in close proximity.
Clinical isolates of M. pneumoniae are grouped into eight subtypes based on DNA sequences of P1 adhesin. There is no protective immunity even in the midst of a serological response thus making possible reinfection with another subtype.
M. pneumoniae infections occur worldwide in persons of all ages. M. pneumoniae infection accounts for between 1 and 10 out of every 50 cases of community-acquired pneumonia. 2 million estimated cases of M. pneumoniae infection occur each year in U.S.
M. pneumoniae specific IgM antibodies begin to appear within a week after the disease onset and their level increases steadily until peaking during the acute and/or early convalescent stage of infection, approximately 3 weeks after disease onset. IgM antibodies disappear by 2 to 3 months, but can persist for several months or longer. In cases of reinfection in adults, IgM response can be minimal or undetectable.
IgA antibodies are produced several days after appearance of symptoms, earlier than IgM, reach their maximum during the acute and/or early convalescent stage, and then decrease.
IgG antibodies appear 2 weeks after IgM antibody, during early convalescence, kept at a constant level during late convalescence, and then decrease gradually, remaining elevated for at least a year following infection.
M. pneumoniae possesses both protein and glycolipid antigens that elicit antibody responses in infected individuals. A surface protein, designated P1, has been well characterized as an attachment protein of M. pneumoniae to host cells, and most serum samples from patients with M. pneumoniae show an immune response to it. Assays using the P1 adhesin protein appear to be also the most specific.
Interestingly, immunodominant domains of the M. pneumoniae adhesins are not the highly conserved adherence-mediating domains. This could be a reason for the lack of protective immunity against reinfection.
Despite its ubiquity, M. pneumoniae may be one of the least frequently diagnosed respiratory pathogens in the clinical setting, primarily because of the lack of standardized, specific diagnostic tests helping to distinguish M. pneumoniae from several other microorganisms causing respiratory infections. Therefore, the therapy of M. pneumoniae infection is often empirical.
Despite its drawbacks for use with immunosuppressed persons who are unable to mount an antibody response, serological diagnosis of M. pneumoniae respiratory infections has long been the cornerstone of M. pneumoniae diagnosis and for epidemiological studies because of the relative lack of sensitivity and time-consuming nature of culture. Also, the carrier state that may occur in the absence of acute infection can potentially confound interpretation of PCR test results.
Historically, the first serological test was the cold-agglutinin test. Cold agglutinins are actually IgM antibodies that are produced 1 to 2 weeks after initial infection in about 50% of patients with M. pneumoniae and may persist for several weeks. However, cold agglutinins also occur in persons who have various bacterial and rickettsial infections as well as in those with influenza virus and adenovirus infections.
The complement fixation test is based on the glycolipid antigen. This test has also a limited value producing inconclusive results because it could measure antibodies deriving from earlier infections, and the glycolipid antigen which is not M. pneumoniae specific cross reacts with antigens of different origin such as other microorganism and body tissues .
Enzyme immunoassays have become the most widely used commercial methods for detection of M. pneumoniae. Reliable diagnosis of M. pneumoniae infection could not be made on the basis of single acute-phase sera; convalescent samples are necessary. The ‘‘gold standard’’ for serologic diagnosis is a 4-fold increase of M. pneumoniae-specific IgG titer 2 to 3 weeks after the initial measurement.