The Chlamydia

					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.