Although more than 200 species in the genus Mycoplasma are now recognized, relatively few are pathogenic in humans. The best known and most intensely studied of these species is Mycoplasma pneumoniae. The initial descriptions of M. pneumoniae as a human pathogen, realization that it was not a virus, characterization of clinical manifestations of mycoplasmal respiratory disease, mode and extent of transmission, and development of serological assays began more than 40 years ago. However, very little was known at that time about how this mycoplasma interacts with and damages host cells, affects the immune system, and the extent to which it may mediate illness outside of the respiratory tract.
Progress in understanding the biological properties of M. pneumoniae and its true role as a human pathogen have been hindered significantly over the years by its very slow replication rate (∼6 h), fastidious demands for successful laboratory cultivation and the relatively low sensitivity and specificity of the earliest complement fixation serological tests, which were much better suited for less antigenically complex viral pathogens. Until recent years, as more sophisticated laboratory techniques have become available, dependence on nonstandardized sero-logical tests performed in reference laboratories requiring measurement of antibodies in acute and convalescent sera meant that laboratory confirmation of mycoplasmal infection was seldom sought. Physicians could not easily distinguish mycoplasmal respiratory infection from clinically similar illnesses caused by several other bacteria including Chlamydophila pneumoniae and various respiratory viruses, and therefore did not appreciate how often it occurred in their patient populations. A frequent, but incorrect assumption was that mycoplasmal respiratory infection was uncommon, rarely significant from a clinical standpoint and limited to select age groups. Primary-care physicians seldom considered a mycoplasmal etiology when patients presented with a more severe respiratory infection, or extrapulmonary manifestations, or when an elderly person, very young child or infant was involved. Moreover, the benefit of antimicrobial therapy was not always appreciated, allowing untreated persons to continue to spread the infection within their families, schools and communities. Spread among susceptible populations is also facilitated by the fact that many infectious persons are asymptomatic or very mildly ill and may not take precautions to limit exposure to others.
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Knowledge gained over the past several years has proven that M. pneumoniae is a significant respiratory pathogen in persons of all ages, sometimes causing severe respiratory disease, and it may induce clinically significant manifestations in extrapulmonary sites by direct invasion and/or immunologic effects. Although most cases can be managed on an outpatient basis, M. pneumoniae is estimated to cause more than 100,000 adults hospitalizations each year in the USA [1]. Cytadherence and subsequent close association of the organism on the respiratory tract mucosa lead to a variety of effects that induce local inflammation and stimulate the host immune system to produce additional manifestations. The ability to detect acute M. pneumoniae infection has improved substantially owing to the development and commercialization of improved serological immunoassays, some of which are now point-of-care tests, and the introduction of molecular-based nucleic acid-amplification assays available in some clinical reference laboratories. Despite these significant advances, much remains to be learned about how this organism invades the body, interacts with the host immune system and produces disease. The biological properties of M. pneumoniae and typical clinical manifestations of infection were comprehensively reviewed in 2004 [1] and are not revisited here, since these aspects have not changed dramatically since then. The present article focuses on newer knowledge gained about how this organism produces disease, multisystem extrapulmonary manifestations, how infections can be detected using currently available technology and a discussion of future perspectives and unmet needs.
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