In addition to the general features of Mycoplasma, M pneumoniae has a terminal organelle which is a membrane-bound protrusion of the cytoplasm capped by a button. This structure contains a number of proteins (P1, P30) which are involved in attachment to cell surfaces. It also mediates a form of movement called gliding motility in which the organism advances over smooth surfaces in the direction of the protrusion. Mycoplasma pneumoniae also produces an ADP-ribosylating toxin called the Community Associated Respiratory Distress Syndrome (CARDS) toxin. In the laboratory, colonies of M pneumoniae bind red blood cells (RBCs) onto the surface of agar plate cultures (hemadsorption). This is due to binding by the mycoplasma to sialic acid-containing oligosaccharides present on the RBC surface.
Terminal organelle mediates attachment and gliding motility
CARDS toxin is ADP-ribosylating
RBCs adsorb to colonies
Mycoplasma pneumoniae produces a common form of pneumonia, which tends to occur in any season and has a predilection for younger persons. The illness is characterized by a nonproductive cough, fever, and headache, with radiologic and clinical evidence of scattered areas of pneumonia. The course is almost always benign, but improvement is accelerated by treatment with non–cell wall–active antimicrobials.
Mycoplasma pneumoniae accounts for approximately 10% of all cases of pneumonia. Infection is acquired by droplet spread. Experimental challenges indicate that the human infectious dose is very low, possibly less than 100 organisms. Infections with M pneumoniae occur worldwide, but they are especially prominent in temperate climates. Epidemics at 4- to 6-year intervals have been noted in both civilian and military populations. The most common age range for symptomatic M pneumoniae infection is between 5 and 15 years, and the disease accounts for more than one-third of all cases of pneumonia in teenagers (but is also seen in older persons). Infections in children younger than 6 months are uncommon. The disease often appears as a sporadic, endemic illness in families or closed communities because its incubation period is relatively long (2-3 weeks) and because prolonged shedding in nasopharyngeal secretions may cause infections to be spread over time. In families, attack rates in susceptible persons approach 60%. Asymptomatic infections occur, but most studies have suggested that more than two-thirds of infected cases develop some evidence of respiratory tract illness.
Infecting dose is very low
Found worldwide most often in teenagers
Outbreaks occur in families and closed communities
Mycoplasma pneumoniae infection involves the trachea, bronchi, bronchioles, and peribronchial tissues and may extend to the alveoli and alveolar walls. The organism appears to thrive on the phospholipids present in lung epithelia. Initially, M pneumoniae attaches to the cilia and microvilli of the cells lining the bronchial epithelium. This attachment is mediated by protrusion-associated proteins (P1, P30) which bind to complex oligosaccharides containing sialic acid found in the apical regions of bronchial epithelial cells (Figure 38–2). The oligosaccharide receptors are chemically similar to antigens on the surface of erythrocytes and are not found on the nonciliated goblet cells or mucus, to which M pneumoniae does not bind. Other proteins bind to elements of the extracellular matrix like fibronectin. The CARDS toxin interferes with ciliary action and causes nuclear vacuolization and fragmentation of tracheal epithelial cells. This leads to inflammation and desquamation of the involved mucosa (Figure 38–3). The inflammatory response is most pronounced in the bronchial and peribronchial tissue and is composed of lymphocytes, plasma cells, and macrophages, which may infiltrate and thicken the walls of the bronchioles and alveoli. Organisms are shed in upper respiratory secretions for 2 to 8 days before the onset of symptoms, and shedding continues for as long as 14 weeks after infection.
Mycoplasma pneumoniae infecting respiratory epithelium. Transmission electron micrograph. Note the distinctive appearance of the tips of the mycoplasmas adjacent to the host epithelium. The tips probably represent a site on the microorganism that is specialized for attachment. (Reproduced with permission from Nester EW: Microbiology: A Human Perspective, 6th edition. 2009.)
Mycoplasma pneumoniae bronchiolitis. This lung section shows destruction of the bronchiolar wall and mucosal ulceration. (Reproduced with permission from Connor DH, Chandler FW, Schwartz DQ, et al: Pathology of Infectious Diseases. Stamford CT: Appleton & Lange, 1997.)
Adherence mediated by protrusion-associated proteins
CARDS toxin interferes with ciliary action and leads to desquamation
Both T- and B-cell–mediated immune responses occur, and generally appear to be effective in preventing reinfection. Complement-fixing serum antibody titers reach a peak 2 to 4 weeks after infection and gradually disappear over 6 to 12 months. Also, nonspecific immune responses to the glycolipids of the outer membrane of the organism often develop, which can be detrimental to the host. For example, cold hemagglutinins are IgM antibodies that react with an altered antigen on human RBCs and are seen in about two-thirds of symptomatic patients infected with M pneumoniae.
Complement-fixing antibody titers peak at 2 to 4 weeks
Cold agglutinins are IgM
Immunity is not complete, and reinfection with M pneumoniae may occur. Clinical disease appears to be more severe in older than in younger children, which has led to the suggestion that many of the clinical manifestations of disease are the result of immune responses rather than invasion by the organism. High titers of cold agglutinins may be associated with hemolysis and Raynaud phenomena.
Immunity is incomplete, and reinfection may occur
MYCOPLASMAL PNEUMONIA: CLINICAL ASPECTS
A mild tracheobronchitis with fever, cough, headache, and malaise is the most common syndrome associated with acute M pneumoniae infection. The pneumonia is typically less severe than other bacterial pneumonias. It has been described as “walking” pneumonia because most cases do not require hospitalization. The disease is of insidious onset, with fever, headache, and malaise for 2 to 4 days before the onset of respiratory symptoms. Pulmonary symptoms are generally limited to a non- or minimally productive cough. X-rays reveal a unilateral or patchy pneumonia, usually in a lower lobe, although multiple lobes are sometimes involved. Small pleural effusions are seen in up to 25% of cases. The average duration of untreated illness is 3 weeks. The severity of pulmonary involvement is particularly great in patients with immune deficiencies, sickle cell disease, or Down syndrome. The reason for the latter is not understood.
“Walking” pneumonia has insidious onset
Cough is usual
Pharyngitis with fever and sore throat may also occur. Nonpurulent otitis media or myringitis may occur concomitantly in up to 15% of patients with M pneumoniae pneumonitis, but bullous myringitis is rare. A variety of other extrapulmonary complications have been described, involving skin (erythema multiforme), peripheral vasospasm (Raynaud phenomenon), central nervous system (encephalitis, myelitis), joints (arthralgias), and other sites.
Pharyngitis and otitis common
Other extrapulmonary complications sometimes occur
Clinical diagnosis of M pneumoniae infection may be difficult because the manifestations overlap with those of other respiratory infections. Gram-stained sputum usually shows some mononuclear cells, but because it lacks a cell wall, M pneumoniae is not seen. The absence of bacteria suggests a viral or Mycoplasma etiology. The organism can be isolated from throat swabs or sputum of infected patients using special culture media and methods, but because of its slow growth, isolation usually requires incubation for a week or longer. Thus, serologic tests rather than cultures are more commonly used for specific diagnosis. A fourfold rise of serum antibody titer or seroconversion in acute and convalescent sera indicates M pneumoniae infection. The most widely used serologic method is complement fixation. With the relatively long incubation period and insidious onset of the disease, many patients already have high antibody titers at the time they are first seen. In these situations, a single high titer, such as a complement fixation titer greater than 1:128 or IgM-specific antibody (measured by enzyme immunoassay or immunofluorescence), indicates recent or current infection because these antibodies are generally of short duration.
Diagnosis is usually serologic
Single high CF or IgM-specific antibody titer supports diagnosis
Because more than two-thirds of patients with symptomatic lower respiratory M pneumoniae infection develop high titers of cold hemagglutinins, their demonstration can be useful in some clinical situations. It must be remembered that cold hemagglutinins are nonspecific and have been observed in adenovirus infections, infectious mononucleosis, and some other illnesses. The test is simple, however, and can be performed rapidly in any clinical laboratory or even at the bedside. Nucleic acid amplification (NAA) tests have been developed and offer the best hope for rapid and specific diagnosis. The sensitivity and specificity of NAA methods are now acceptable, but practical issues (cost) impede their wide implementation.
Cold agglutinins are nonspecific, but helpful if present
NAA tests rapid and specific
Macrolides (azithromycin, clarithromycin, erythromycin) or doxycycline are the usual agents used for treatment of M pneumoniae pneumonia. Fluoroquinolones are effective alternatives. β-Lactams are ineffective as M pneumoniae lacks a cell wall. Almost all patients with M pneumoniae pneumonia recover, but treatment markedly shortens the course of illness.
Macrolides and fluoroquinolones are effective