M. pneumoniae is the most common cause of pneumonia and tracheobronchitis in school-aged children and young adults treated in the outpatient setting. The average annual rate is approximately 5 in 1,000 school-aged children. M. pneumoniae is an uncommon cause of lower respiratory tract disease in infants and young children and usually does not result in hospitalization of children without chronic conditions. College students and military recruits may be confined to bed with M. pneumoniae pneumonia.

Epidemics of M. pneumoniae disease usually are long in duration and smoldering, and they may begin in the summer, with peak activity reached in autumn. Sporadic infections can occur throughout the year. In experimentally inoculated volunteers, the incubation period from the day of infection to the onset of pneumonia was approximately 14 days, but the average interval between the onset of an index case and the onset of a secondary case in the same household ranges from 3 weeks to as long as 3 months. The longer interval may be explained by the fact that pharyngeal carriage may persist, even in patients who have been treated with appropriate antibiotics.

When growing on human respiratory epithelium, the organism is a small, filamentous structure, approximately 0.1 to 2.0 μm. Infection of a susceptible person probably occurs through contact with M. pneumoniae-containing droplet nuclei that are coughed into the environment. Dissemination by aerosol has been demonstrated experimentally and deduced from descriptions of remarkable outbreaks occurring in closed populations. Human infection by aerosol may be accomplished by as little as one colony-forming unit (CFU), whereas approximately 100 CFUs are needed to infect volunteers by nose drops. The concentration of organisms in sputum specimens from patients with pneumonia has ranged from 10² to 10⁶ CFU/mL.

The organism attaches to ciliated respiratory epithelial cells by a specialized tip. The attachment protein has been isolated, and specific antibodies have been demonstrated in serum and respiratory secretions of immune subjects. These antibodies apparently block attachment and thereby prevent acquisition of infection. Uninhibited attachment of M. pneumoniae to ciliated cells leads to ciliostasis, then loss of cilia, and, eventually, the desquamation of epithelial cells. Mononuclear cells infiltrate the submucosa of affected bronchi and bronchioles. An exudate consisting of debris from the desquamated cells, polymorphonuclear leukocytes, macrophages, and mucus develops as the disease progresses and may lead to a productive cough.

The main clinical features of M. pneumoniae disease are fever, malaise, sore throat, and a dry, hacking cough. The onset usually is gradual, developing over the course of several days. The affected school-aged child may not appear particularly ill, and the examiner may be surprised when chest auscultation reveals rales and rhonchi. The chest roentgenogram may show peribronchial thickening and infiltration of one or both lower lobes, with some subsegmental atelectasis. Pleural effusion is not a prominent finding. The peripheral white blood cell count usually is in the normal range. The severity of the illness may be exaggerated in children with sickle cell disease. These children appear toxic, with prolonged high fever and peripheral white blood cell counts greater than 25,000 cells/μL, and they require hospitalization. Chest roentgenography may reveal dense infiltrates involving more than one lobe and prominent pleural effusion.

The progress of the infection may be aborted in some children who have fever and pharyngitis. A larger proportion of children will have a prominent cough and rhonchi in the larger airways on auscultation; in these children, a diagnosis of tracheobronchitis is warranted.

Some children not known to wheeze previously may have expiratory wheezing on examination. A nondescript rash may accompany the infection. A few children present with acute otitis media or bullous myringitis. The total course of the illness with or without treatment may encompass 2 weeks, with a bothersome night cough persisting even longer.