Mycoplasma and Ureaplasma

1. Mycoplasma and Ureaplasma

2. Family: Mycoplasmataceae • Genus: Mycoplasma • Species: M. pneumoniae • Species: M. hominis • Species: M. genitalium • Genus: Ureaplasma • Species: U. urealyticum 16 species colonize humans, the above have been associated with disease.

3. Diseases Caused by Mycoplasma Organism Disease M. pneumoniae Upper respiratory tract disease, tracheobronchitis, atypical pneumonia, (chronic asthma?) M. hominis Pyelonephritis, pelvic inflammatory disease, postpartum fever M. genitalium Nongonococcal urethritis U. urealyticum Nongonococcal urethritis, (pneumonia and chronic lung disease in premature infants?) Note that: Other organisms in the family of Mycoplasmataceae infect humans but a disease association is not known.

4. Morphology and Physiology • Smallest free-living bacteria (0.2 - 0.8 mm) many can pass through a 0.45 µm filter, mistaken for viruses • Small genome size (M. pneumoniae is ~800 Kbp) • Require complex media for growth • Facultative anaerobes • Except M. pneumoniae - strict aerobe • Lack a cell wall, membrane contains sterols no cell wall means these are resistant to penicillins, cephalosporins, vancomycin, etc. • Grow slowly by binary fission • Doubling time can be as long as 16 hours, extended incubation needed

5. “Fried Egg” Colonies of some Mycoplasmas

6. Colony morphology, cont’d • Except for M. pneumoniae colonies which have a • granular appearance, described as being mulberry shaped mulberry

7. Morphology and Physiology, cont’d • Require complex media for growth, including sterols • Major antigenic determinants are glycolipids and proteins, some cross reaction with human tissues • Requirements for growth allow one to differentiate between species • M. pneumoniae - glucose • M. hominis - arginine • U. urealyticum - urea (buffered media due to growth inhibition by alkaline media) • M. genitalium - difficult to culture

8. Pathogenesis • Adherence • P1 pili (M. pneumoniae) • Movement of cilia ceases (ciliostasis) • Clearance mechanism stops resulting in cough • Toxic metabolic products • Peroxide and superoxide • Inhibition of catalase • Immunopathogenesis • Activate macrophages • Stimulate cytokine production • Superantigen (M. pneumoniae) Inflammatory cells migrate to infection and release TNF-a then IL-1 and IL-6

9. Transmission electron photomicrograph of a hamster trachea ring infected with M. pneumoniae. Note the orientation of the M. pneumoniae through their specialized tip-like organelle, which permits close association with the respiratory epithelium. M, mycoplasma; m, microvillus; C, cilia. Image used with permission. From Baseman and Tully, Emerging Infectious Diseases 3

10. Mycoplasma pneumoniae • Tracheobronchitis • Atypical pneumonia (walking pneumonia) • More common in school-age children and young adults but everyone is susceptible (theory that adults might be partially immune due to previous exposure) • Estimate of 2,000,000 cases in USA annually, possibly resulting in 100,000 hospitalizations • Not a reportable disease, so true incidence is not known

11. Epidemiology - M. pneumoniae • Occurs worldwide • No seasonal variation • Proportionally higher in summer and fall • Epidemics occur every 4-8 year

12. Epidemiology - M. pneumoniae • Spread by aerosol route (Confined populations) • Disease of the young (5-20 years), although all ages are at risk

13. Clinical Syndrome - M. pneumoniae • Tracheobronchitis • 70-80% of infections • Pneumonia • Approximately 10% of infections • Mild disease but long duration • “Primary atypical pneumonia” • “Walking pneumonia”

14. Clinical Syndrome - M. pneumoniae • Incubation - 2-3 weeks • Fever, headache and malaise • Persistent, dry, non-productive cough • Respiratory symptoms • Patchy bronchopneumonia, may precede symptoms • acute pharyngitis may be present • Organisms persist • Slow resolution • Rarely fatal • Note: Muscle pain and GI symptoms usually not present

15. Immunity - M. pneumoniae • Complement activation • Alternative pathway • Phagocytic cells • Antibodies • IgA important • Delayed type hypersensitivity • More severe disease (immunopathogenesis)

16. Laboratory Diagnosis - M. pneumoniae • Microscopy • Difficult to stain • This process can help eliminate other organisms • Culture (definitive diagnosis) • Sputum (usually scant) or throat washings • Special transport medium needed • Must suspect M. pneumoniae • May take 2-3 weeks or longer, 6 hour doubling time with glucose and pH indicator included • Incubation with antisera to look for inhibition, not a typical test

17. Laboratory Diagnosis - M. pneumoniae • Serology • Complement fixation • May take 4-6 weeks • Fourfold rise in titer (requires collection two samples 3-4 weeks apart) • Relatively insensitive • Cold agglutinins • 1/3 - 2/3 of patients • I antigen • Appear first • Non-specific and insensitive • ELISA • Not commercially available

18. Laboratory Diagnosis - M. pneumoniae • Molecular diagnosis • PCR-based tests are being developed and these are expected to be the diagnostic test of choice in the future. • These should have good sensitivity and be specific

19. Treatment and PreventionM. pneumoniae • Treatment • Tetracycline in adults (doxycycline) or erythromycin (children) • Newer fluoroquinolones (in adults) • Resistant to cell wall synthesis inhibitors • Prevention • Avoid close contact • Isolation is not practical due to length of illness • No vaccine, although attempted

20. M. hominis, M. genitalium andU. urealyticum • Clinical syndromes • M. hominis - pyelonephritis, pelvic inflammatory disease and postpartum fever • M. genitalium - nongonococcal urethritis • U. urealyticum - nongonococcal urethritis • Epidemiology • Colonization at birth - usually cleared but could persist • sexually active adults with M. hominis - 15% • with U. urealyticum - 45% -75% • Colonization with M. genitalium - ??

21. M. hominis, M. genitalium and U. urealyticum • Laboratory diagnosis • Culture (except M. genitalium) • Treatment and prevention • Treatment • Tetracycline or erythromycin • U. urealyticum is resistant to tetracycline • M. hominis is resistant to erythromycin and sometimes to tet, Clindamycin for these resistant strains • Prevention • Abstinence or barrier protection • No vaccine