The Chlamydia Dr. Mohamed Al-Sweify Classification, Structure and Physiologic characters In 1999 the family has been divided into two genera, Genus Chlamydia Genus Chlamydophila. Chlamydia trachomatis Chlamydophila pneumoniae Chlamydophila psittaci Chlamydiaceae were once considered viruses…why? The following are bacterial properties, presented by Chlamydiae 1) inner and outer membranes similar to those of gram-negative bacteria 2) contain DNA and RNA 3) possess prokaryotic ribosomes 4) synthesize their own proteins, nucleic acids, and lipids 5) susceptible to numerous antibiotics. Unlike other bacteria, the Chlamydiaceae have a unique developmental cycle, forming metabolically inactive infectious forms (elementary bodies, EBs) and metabolically active, noninfectious forms (reticulate bodies RBs). Family Chlamydiaceae: STRUCTURE EBs are resistant to many harsh environmental factors (like spores). No rigid Peptidoglycan layer. EB outer membrane proteins are extensively cross- linked by S-S bonds. EB binds to receptors on host cells and stimulate uptake by cell. The RBs are the replicating chlamydial (active form). No extensive cross-linked proteins in RBs, so it’s osmotically fragile; RBs are protected only by being intracellular. Chlamydiaceae has a genus-specific LPS, and species- and strain-specific outer membrane proteins. Family Chlamydiaceae: PHYSIOLOGY Chlamydiaceae replicate by a unique intracellular growth cycle: هام – EBs (300-400 nm) become attached to the microvilli of susceptible cells, followed by active penetration. – Being internalized, they remain within cytoplasmic phagosomes, where the replicative cycle proceeds. – Fusion of lysosomes with EB-containing phagosome and subsequent intracellular killing is inhibited. Phagolysosomal fusion is prevented if the EB outer membrane is intact. If damaged or the bacteria are inactivated by heat or coated with antibodies, phagolysosomal fusion and bacterial killing occur.!! Replication…continued – Within 6-8 h, EB reorganizes into larger (0.8-1µ), metabolically active RB. – RB is able to synthesize their own DNA, RNA, and protein. – Chlamydiaceae are energy parasites because they use host cell ATP for energy needs. – RB replicates by binary fission, for the next 18-24 h. Histologic stains can readily detect the phagosome with accumulated RBs, called an inclusion. – 18-24 hours after infection, the RB starts reorganizing into the smaller EB, and between 48- 72 h, the cell ruptures and then releases the infective EBs. Life Cycle of Chlamydiaceae 1) Chlamydia trachomatis Small, gram-negative rods with no PGs layer in cell wall. Strict human pathogen..with a limited host range. LPS antigen are shared by Chlamydia and Chlamydophila species.. Major outer membrane proteins are species specific C. trachomatis is subdivided into 2 biovars: Trachoma and LGV, and further into serovars: – LGV is associated with serovars L1-L3. – Endemic trachoma is associated with serovars A-C. – Urogenital tract infections (urethritis, epididymitis, cervicitis, endometritis, salpingitis), conjunctivitis, perihepatitis, and Reiter's syndrome are associated with serovars D-K. Receptors for EBs are primarily restricted to nonciliated columnar, cuboidal, and transitional epithelial cells. However, range of cells that C. trachomatis can infect is limited: – The LGV biovar replicates in mononuclear phagocytes in the lymphatic system. The clinical manifestations of chlamydial infections are caused by: (1) Direct destruction of cells during replication. (2) Host inflammatory response. Epidemiology Most common sexually transmitted bacteria in United States: – It is estimated that 2.8 million Americans are infected each year and as many as 50 million new infections occur annually worldwide. Ocular trachoma worldwide (most common in Middle East, North Africa, India), with blindness developing in 7 to 9 million patients LGV highly prevalent in Africa, Asia, and South America Pathogenesis of Chlamydia trachomatis Infections Chlamydiae gain access through minute abrasions or lacerations. non-LGV serovars stimulates a severe inflammatory response (neutrophils, lymphocytes, and plasma cells). LGV lesions form in the lymph nodes with granuloma formation. The lesions may become necrotic, attract PMNL, and spreads inflammation to surrounding tissues. Subsequent rupture of the lymph node leads to formation of abscesses or sinus tracts. Infection does not confer long-lasting immunity. Rather, reinfection characteristically induces a vigorous inflammatory response with subsequent tissue damage. – This response produces the vision loss in patients with chronic ocular infections, and scarring with sterility and sexual dysfunction in patients with genital infections. Clinical Situations of C. trachomatis Infection 1. Trachoma: Chronic, inflammatory granulomatous process of eye surface, leading to corneal ulceration, scarring, pannus formation, and blindness 2. Adult inclusion conjunctivitis: Acute process with mucopurulent discharge, dermatitis, corneal infiltrates, and corneal vascularization in chronic disease 3. Neonatal conjunctivitis: Acute process characterized by a mucopurulent discharge 4. Infant pneumonia: After a 2- to -3-week incubation period, the infant develops rhinitis, followed by bronchitis with a characteristic dry cough 5. Urogenital infections: Acute process involving the genitourinary tract with characteristic mucopurulent discharge; asymptomatic infections common in women. ...5) Urogenital …..cont. – Most genital tract infections in women are asymptomatic (80% , vs. 25% in men). When symptomatic, it includes bartholinitis, cervicitis, endometritis, perihepatitis, salpingitis, and urethritis. External os of cervix Purulent cervicitis due to C. trachomatis ~ 35-50% of nongonococcal urethritis are caused by C. trachomatis. Dual infections with both C. trachomatis and Neisseria gonorrhoeae are common Symptoms of the chlamydial infection develop after successful treatment of the gonorrhea… why ? C.trachomatis grown in HeLa cell culture showing RB. Clinical Picture of Lymphogranuloma Venereum Primary lesion: a painless papule or ulcer appears at site of infection (penis, urethra, glans, scrotum, vaginal, cx, vulva) and is overlooked, especially that it heals rapidly…! At this stage, patient may have fever, headache, and myalgia. Second stage: inflammation and swelling of regional l. nodes. Inguinal nodes become painful, fluctuant buboes that gradually enlarge and can rupture, forming draining fistulas. Again; patient suffer from systemic symptoms as fever, chills, anorexia, headache, meningismus, myalgias, and arthralgia. Proctitis is common in women with LGV, resulting from lymphatic spread from the cervix or the vagina. Proctitis develops in men after anal intercourse or as the result of lymphatic spread from the urethra. Untreated LGV may resolve at this stage or may progress to a chronic ulcerative phase, in which genital ulcers, fistulas, strictures, or genital elephantiasis develop. Diagnostic Procedures for C. trachomatis 1) Nucleic acid amplification tests (NAATs), including: (1) polymerase chain reaction (PCR) (2) ligase chain reaction (LCR) (3) strand displacement amplification (SDA). NAATs are highly sensitive (90%-98%) and, if properly monitored, are very specific. First-voided urine from a patient with urethritis can be used. NAATs are currently considered the tests of choice for the laboratory diagnosis of genital C. trachomatis infection. 2) Cytology Examination of Giemsa-stained cell scrapings for the presence of inclusions was the first method used for the diagnosis of C. trachomatis infection. However, this method is insensitive and is not recommended. 3) Culture The isolation of C. trachomatis in cell culture remains the most specific method of diagnosing C. trachomatis infections. The sensitivity of culture is compromised if inadequate specimens are used and if chlamydial viability has been lost during transport of the specimen. It has been estimated that the sensitivity of the findings yielded by a single endocervical specimen may be only 70% to 85%. Treatment LGV be treated with a tetracycline (e.g., doxycycline) for 21 days. Macrolide (erythromycin, azithromycin) or sulfisoxazole is recommended for children younger than 9 years, pregnant women, and patients unable to tolerate tetracyclines. Ocular and genital infections in adults should be treated with one dose of azithromycin or doxycycline for 7 days. Chlamydia conjunctivitis and genital infections are prevented through the use of safe sex practices and the prompt treatment of symptomatic patients and their sexual partners.
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