Mycoplasma Infections

Definition

Mycoplasma organisms of the class Mollicutes are ubiquitous as pathogens and colonizing agents in the plant, animal, and insect kingdoms. They represent the smallest known free-living forms, but because they have fastidious growth requirements, they are difficult to culture. The presence of several species of Mycoplasma as commensals in animals and on human oral and genital mucosa frequently results in contamination of cell cultures. Such contamination led to the false implication of mycoplasmas as causative agents in many human diseases, both trivial and life-threatening. Of the human diseases that have proven to be due to mycoplasmas, pneumonia caused by Mycoplasma pneumoniae is by far the most clinically important. This infection constitutes a significant proportion of cases previously classified as atypical pneumonia ( Chapter 85 ), a nonspecific term for patchy pneumonias that generally do not respond to β-lactam antibiotics and have etiologic agents that are not easily cultured or visible on Gram stain. The term atypical pneumonia persists despite our increasing ability to identify specific etiologic agents, such as viruses, Legionella ( Chapter 290 ), and Chlamydophila ( Chapter 294 ).

Epidemiology

M. pneumoniae infection is spread person to person by respiratory droplets produced by coughing. Relatively close association with the index case appears to be required. The disease is usually introduced into families by a young child; in some studies, most of the infected adults were the parents of young children. As opposed to most viral respiratory infections, which are manifested 1 to 3 days after infection, Mycoplasma has an incubation period of 2 to 3 weeks. Therefore, a careful history showing several weeks between cases within a family may be an important clue to the mycoplasmal etiology. Organisms can be cultured from the sputum of infected individuals for weeks to months after effective treatment.

Most cases of Mycoplasma respiratory infection occur singly or as family outbreaks. However, in closed populations, such as military recruit camps and boarding schools, Mycoplasma can cause mini-epidemics and may be responsible for 25 to 75% of cases of pneumonia in such settings. Serologically based epidemiologic studies have documented the high incidence of Mycoplasma respiratory infection throughout the world. In the United States, it is estimated that each year at least one case of Mycoplasma pneumonia occurs for every 1000 persons, or more than 2 million cases annually. The incidence of Mycoplasma nonpneumonic respiratory infection may be 10 to 20 times greater. The highest attack rates are in individuals 5 to 20 years old, but M. pneumoniae infection can occur at any age.

As opposed to viral respiratory infections that peak in winter in temperate climates, a few studies have reported a peak incidence of M. pneumoniae outbreaks in the fall. Most surveys, however, show little or no seasonal predominance. Recurrent epidemic 4-year cycles have been described in several countries.

There is an age-related relationship of upper versus lower respiratory tract infection caused by M. pneumoniae . In children younger than 3 years, primarily upper respiratory tract infection develops, whereas bronchitis and pneumonia tend to occur in individuals ages 5 to 20 years. In older adults, pneumonia predominates.

Pathobiology

Inoculation onto animal tracheal organ cultures is followed by ciliary damage and desquamation of surface epithelium. This latter effect is probably responsible for the hacking cough in Mycoplasma respiratory infection.

Several characteristics of M. pneumoniae probably play a direct role in the respiratory pathogenicity of this organism. The first is the affinity of M. pneumoniae for respiratory epithelial cells. Attachment appears to be between a terminal organelle at one end of the filamentous organism and a sialylated glycoprotein (I-FI) on the surface of both respiratory epithelium and erythrocytes that acts as a receptor. M. pneumoniae attaches to ciliated epithelial cells at the base of cilia and appears to produce most of its physiologic and cytolytic changes while remaining extracellular. Hydrogen peroxide produced by M. pneumoniae (the only human mycoplasma to do so) may be responsible for some in vivo cell damage, as it is for the hemolysis seen when the organisms are grown on blood agar plates. Mycoplasma infection activates T and B cells and induces many pro-inflammatory and anti-inflammatory cytokines as well as chemokines that may play a role in inflammation-related cell destruction. M. pneumoniae also secretes a community-acquired respiratory distress syndrome toxin, which binds surfactant protein and dysregulates host adenosine diphosphate (ADP) ribosylation. High levels of this toxin are produced during infection, and inoculation of this toxin in an animal model induces many of the pathologic features of M. pneumoniae infection, including vacuolization, cilostasis, and inflammatory changes. ^, Strain-specific elaboration of biofilms probably plays a role in protecting the organism from host immune cells and may decrease antimicrobial penetration. Functional asplenia and its attendant opsonization deficiencies may contribute to overwhelming infection with M. pneumoniae , as they do with Streptococcus pneumoniae infection.

In the course of M. pneumoniae infection, several classes of antibody are produced. Some of these fulfill the desired role of antibody production (i.e., neutralization of the agent), and others appear to be autoantibodies. The latter include agglutinins to lung, brain, cardiolipins, and smooth muscle. The best studied of these autoagglutinins are the cold isohemagglutinins, which are capable of clumping erythrocytes at 4° C.

These oligoclonal M-type immunoglobulins (IgM) cross-react with I antigens, one of the blood group antigens common to almost all mature human erythrocytes. High titers of the cold reactive antibody may cause hemolysis (presumably as a result of complement-activated, Coombs-positive erythrocyte destruction). As with other IgM antibodies, the Mycoplasma -induced cold agglutinins ( Chapter 146 ) develop early in the disease (7 to 10 days) and are often present by the time the patient seeks medical attention. The titer of these agglutinins peaks at 2 to 3 weeks, and they persist for 2 to 3 months ( Fig. 293-1 ).

Clinical Manifestations

Although M. pneumoniae is predominantly an upper and lower respiratory tract infection, it can involve multiple organ systems.

Respiratory Infection

The majority of M. pneumoniae infections involve only the upper respiratory tract. After a 2- to 3-week incubation period, the disease has an insidious onset consisting of fever, malaise, headache, and cough (see Fig. 293-1 ). Cough is the clinical hallmark of M. pneumoniae infection. The frequency and severity of the cough increase during the next 1 to 2 days, and it may become debilitating. The gradual onset of symptoms is in contradistinction to the often fulminant manifestation of respiratory infection caused by influenza virus or adenovirus.

In 5 to 10% of patients, depending somewhat on age, the infection progresses to tracheobronchitis or pneumonia. In these cases, the initial manifestations persist, and the cough becomes more severe. Although the pneumonia is generally mild and self-limited, fulminant and severe cases can occur.

The cough is usually relatively nonproductive but may yield white or occasionally blood-flecked sputum. With continued cough, parasternal chest soreness may develop as a result of muscle strain, but true pleuritic pain is unusual. Fever is usually at the level of 101° to 102° F and may be associated with chills. As opposed to pneumonia caused by Streptococcus pneumoniae ( Chapter 268 ), that caused by M. pneumoniae rarely produces true shaking chills. In comparison to influenza ( Chapter 332 ), which also can be manifested as an atypical pneumonia syndrome, myalgias and gastrointestinal complaints of nausea and vomiting are unusual. Diarrhea, sometimes a concomitant of adenoviral ( Chapter 333 ) or Legionella ( Chapter 290 ) pneumonia, is uncommon in Mycoplasma infection. Unfortunately, no clinical signs or symptoms can reliably differentiate M. pneumoniae infections from other community-acquired pneumonias.

On physical examination, the patient usually does not appear to be severely ill. Mycoplasma is the paradigm of the term walking pneumonia . The pharynx may be injected and erythematous, usually without the marked cervical adenopathy seen with group A streptococcal pharyngitis. Pharyngitis is uncommon, and myringitis and otitis are rare.

Examination of the chest in patients with Mycoplasma pneumonia is often unrevealing, even in patients with severe, productive cough. There may be no auscultative or percussive findings, or only minimal rales (crackles) may be present. Although wheezing can occur, the wheezing isolation is more suggestive of viral respiratory pathogens, such as respiratory syncytial virus ( Chapter 330 ). M. pneumoniae is not a common pathogen in patients with preexisting chronic obstructive lung disease, and bacterial superinfection after M. pneumoniae respiratory infection is rare.

The radiographic finding of interstitial or patchy alveolar pneumonia does not differentiate M. pneumoniae from any of the other causes of atypical pneumonia, but the disparity between the physical findings and radiographic evidence of pneumonia in this condition may be the greatest of any of the atypical pneumonia syndromes ( Fig. 293-2 ).

Pleural effusion (usually small) occurs in 5 to 25% of patients. If effusion is present, thoracentesis reveals serous fluid that is exudative, with minimal inflammatory reaction. The cell differential count in the fluid is variable, and bloody effusions are rare. It is unusual to isolate M. pneumoniae from effusions when they do occur.