Overview of diagnostic tests for M. pneumoniae.

Abbreviations: AD, advanced diagnostic test; CFT, complement fixation test; CNS, central nervous system; CSF, cerebrospinal fluid; EIA, enzyme immunoassay; IFA, immunofluorescent assay; Ig, immunoglobulin; NAATs, nucleic acid amplification tests; PA, particle agglutination assay; PCR, polymerase chain reaction; RD, routine diagnostic test; RepMP, repeated M. pneumoniae DNA. References: [13], [15]–[24].1Qualitative statements included because of the wide range of test performances, which depend on the assay, the patient cohort (children and/or adults), the reference standard (PCR, culture, and/or serology), the respiratory specimen (for PCR), and the time point of the sample collection after disease onset (for EIA)—e.g., sensitivities and specificities for PCR [17], [18]: 79%–100% and 96%–99%; IgM EIA (in relation to PCR) [19]: 35%–77% and 49%–100%; and for IgG EIA [17], [19]: 37%–100% (no indication on specificity because of missing information on previous M. pneumoniae infections).2Epidemiological differentiation of clinical strains on the basis of differences in the P1 gene by PCR or in the number of repetitive sequences at a given genomic locus by multilocus variable-number tandem-repeat analysis (MLVA) [23].3Largely replaced by EIA.4Kinetics of antibody responses in blood.IgM: onset: within 1 week after the onset of symptoms; peak: 3–6 weeks; persistence: months (to years). IgG: onset and peak: 2 weeks after IgM; persistence: years (to lifelong); reinfection in adults may lead directly to an IgG response in the absence of an IgM response. IgA: onset, peak, and decrease earlier than IgM.5Antibody responses in the CNS differ from blood. There is no switch from an IgM to an IgG response, the pattern of IgM, IgG, and IgA synthesis remains rather constant and depends on the cause, and there is a long-lasting and slow decay of intrathecal antibody synthesis [22]. In M. pneumoniae encephalitis, a dominant IgM response has been observed [29].6The prevalence of serum IgA determined by EIA has been shown to be very low in PCR-positive children with symptomatic respiratory tract infection (2.0%) [13].7To our knowledge, no validated test is available.8Immunoblotting with a combination of at least five specific M. pneumoniae proteins showed sensitivities (in relation to PCR) of 83% (IgM), 51% (IgG), and 64% (IgA), and specificities of 94%–100% (IgM), 98%–100% (IgG), and 93%–97% (IgA) [24].