Chlamydiae

1
Chlamydiae
2
Biological Features

• Structure and chemical composition
• Developmental cycle
• Staining properties
• Antigens
• Growth and metabolism
• Characteristics of host-parasite relationship
• Classification

3
Structure and chemical composition

• a nonreplicating, infectious particle called the
  elementary body (EB)
• an intracytoplasmic form called the reticulate
  body (RB)

4
Structure and chemical composition
5
Structure and chemical composition

• The elementary body, which is covered by a rigid
  cell wall, contains a DNA genome with a molecular
  weight of 66 X 107 (about 600 genes, one-quarter
  of the genetic information present in the DNA of
  Escherichia coli).
• A cryptic DNA plasmid (7,498 base pairs) is also
  found. It contains an open reading frame for a
  gene involved in DNA replication.
• the elementary body contains an RNA polymerase
  responsible for the transcription of the DNA
  genome after entry into the host cell cytoplasm
  and the initiation of the growth cycle.
• Ribosomes and ribosomal subunits are present in
  the elementary bodies. Throughout the
  developmental cycle, the DNA genome, proteins,
  and ribosomes are retained in the membrane-bound
  reticulate body.

6
Developmental cycle

• EBs attach to the microvilli of susceptive cells.
• Penetration into the host cell via endocytosis or
  pinocytosis and forming phagosomes
• Fusion of lysomes with the EB-containing
  phagosome are inhibited
• EBs reorganize into the metabolically active RBs.
• RBs synthesize their own DNA, RNA and protein but
  lack the necessary metabolic pathways to produce
  high-energy phosphate compounds.
• Energy parasites.
• RBs replicate by binary fission and inclusion
  forms.
• RBs begin reorganizing into EBs.
• Cell ruptures and releasesthe infective Ebs.
• The developmental cycle takes 2448 hours.

7
Developmental cycle
8
Staining properties

• EBs stain purple with Giemsa stainin contrast to
  the blue of host cell cytoplasm.
• RBs stain blue with Giemsa stain.
• The Gram reaction of chlamydiae is negative or
  variable and is not useful in identification.
• Inclusions stain brightly by immunofluorescence
  ,with group-specific,species-specific, or
  serovar-specific antibodies.

9
Antigens

• Group(fenus)-specific antigens
• heat-stable LPS as an immunodominant component.
• Antibody to these antigens can be detected by CF
  and immunofluorescence
• Species-specific or serovar-specific antigens
• Antigens are mainly outer membrane
  proteins(MOMP).
• Specific antigens can best be detected by
  immunofluorescence,particularly using monoclonal
  antibodies.

10
Growth and metabolism

• Unable to synthesize ATP and depend on the host
  cell for energy requirements.
• Grow in cultures of a variety of eukaryotic cell
  lines
• McCoy cells are used to isolate chlamydiae
• C pneumoniae grows better in HL or Hep-2 cells.
• All types of chlamydiae proliferate in
  embryonated eggs,particularly in the yolk sac.
• The replication of chlamydiae can be inhibited by
  many antibacterial drugs.
• Cell wall inhibitors (penicillins) result in the
  production of morphologically defective forms but
  are not effective in clinical diseases.
• Inhibitors of protein synthesis
  (tetracyclines,erythromycins)are effective in
  most clinical infections.
• C trachomatis strains synthesize folates and are
  susceptible to inhibition by sulfonamides.

11
Classification

• C trachomatis
• Biovar trachoma
• Biovar lymphogranuloma venereum
• Biovar mouse
• C pneumoniae
• C psittaci
• C pecorum ?????

12
Transmission
13
Pathogenicity

• transmission
• Who is at risk
• Virulence factor
• Clinical syndromes
• Epidemiology
• immunity

14
Transmission

• C. trachomatis
• Sexually transmittedmost frequent bacterial
  pathogen in united states.
• Infected patients , who may be asymptomatic.
• Inoculation through break in skin or membranes.
• Passage to new born at birth.
• Trachoma spread to eye by means of contaminated
  hand,droplets,clothing, and flies.

15
Transmission

• C. pneumoniae
• Person-to-person spread by inhalation of
  infectious aerosols.
• No animal reservoir

• C. psittaci
• Infection acquired by contact with infected bird
  or animal(may appear healthy).
• Person-to-person infection very uncommon.

16
Who is at risk?

• C. trachomatis
• People with multiple sexual partners.
• Homosexuals,who are more at risk for LGV.
• Newborns born of infected mothers.
• Reiters syndrome young white men.
• Trachomachildren,particularly those in crowded
  living conditions where sanitation and hygiene
  are poor.

17
Who is at risk?

• C. pneumoniae
• High prevalence of infections throughout
  lifemost infections asymptomatic.
• Diease most common in adults.

• C. psittaci
• Disease most common in adults.
• Occupations at increased risk include
  veterinarians,zookeepers,pet shop workers,and
  employees in poultry processing plants

18
Virulence factors

• C. trachomatis
• Intracellular replication,
• prevention of phagolysosomal?????fusion,
• survival of infectious EBs as a result of
  cross-linkage of membrane proteins.

19
Virulence factors

• C. pneumoniae
• Intracellular replication
• prevention of phagolysosome?????fusion
• ability to infect and destroy ciliated epithelial
  cells of respiratory tract,smooth muscle
  cells,endothelial cells,and macrophages
• extracellular survival of infectious EBs.

20
Virulence factors

• C. psittaci
• Intracellular parasite,
• prevention of phagolysosomal fusion,
• survival of infectious EBs as result of
  cross-linkage of membrane proteins.

21
Clinical syndromes

• C. trachomatis
• Trachoma
• Adult inclusion conjunctivitis
• Neonatal conjunctivitis
• Infant pneumonia
• Ocular lymphogranuloma
• venereum
• Urogenital infections
• Reiters syndrome
• Lymphogranuloma venereum

22
Clinical syndromes

• C. pneumoniae
• Bronchitis
• Pneumonia
• Sinusitis???
• Pharyngitis
• atherosclerosis??????

23
Clinical syndromes

• C. psittaci
• psittacosis

24
Epidemiology

• Trachoma
• Trachoma is still prevalent in Africa and Asia,
  and sporadic cases occur all over the world.
• The disease flourishes in hot, dry areas where
  there is a shortage of water and where standards
  of hygiene are low.
• The agent is spread to the eyes by flies, dirty
  towels, fingers, or cosmetic eye pencils.
• The initial infection usually occurs in
  childhood, and the active disease eventually
  appears (mostly by 10 to 15 years of age).
  Trachoma may leave a residuum of permanent
  lesions that can lead to blindness.
• Chlamydia trachomatis also resides in the genital
  tract, cervix, and urethra of adults, and genital
  infection is spread sexually.

25
Epidemiology

• Lymphogranuloma venereum
• Lymphogranuloma venereum persists in the genital
  tract of infected persons.
• LGV is a chronic sexually transmitted disease
  caused by serotype L1,L2,and L3.
• Because C trachomatis is able to infect both the
  eyes and the urogenital tract, antitrachoma
  campaigns involving only ocular treatments are
  futile.
• It occurs sporadically in North America
  ,Australia ,and Europe but is highly prevalent in
  Africa, Asia and South America.
• Male homosexuals are the major reservoir of
  disease.
• Acute LGV is seen more frequently in
  men,primarily because symptomatic infection is
  less common in women.

26
Epidemiology

• Chlamydia pneumoniae
• Chlamydia pneumoniae spreads in human
  populations by respiratory tract infections.
• It is the agent of atypical pneumonia in
  hospitalized patients as well as in young
  individuals with an acute respiratory disease.
• It has caused epidemics in Scandinavia.
• Studies of the prevalence of antibodies to C
  pneumoniae in humans around the world showed that
  it also prevails in Japan, Panama, and North
  America.

27
Epidemiology

• Chlamydia psittaci
• the cause of psittacosis in birds and
  occasionally in humans,
• it is carried by wild and domestic birds,
  including poultry.
• The severity of psittacosis in humans has been
  considerably reduced by the susceptibility of C
  psittaci to antibiotics.

28
Immunity

• C. trachomatis
• Untreated infections tend to be chronic with
  persistence of the agent for many years.
• Little is known about active immunity.
• The coexistence of latent infection,antibodies,and
  cell-mediated reactions is typical of many
  chlamydial infections.

29
Immunity

• C. pneumoniae
• Little is known about active or potentially
  protective immunity.
• Prolonged infections can occur with C.
  pneumoniae, and asymptomatic carriage may be
  common.

30
Immunity

• C. psittacosis
• Immunity in animals and humans is incomplete.
• A carrier state in humans can persist for 10
  years after recovery.
• During this period, the agent may continue to be
  excreted in the sputum.
• Live or inactivated vaccines induce only partial
  resistance in animals.
• They have not been used in humans.

31
Diagnosis

• Most diseases caused by the chlamydiae are
  diagnosed on the basis of their clinical
  manifestations.
• Eye damage caused by C trachomatis is typical, as
  are the vesicles in the infected urogenital
  tract.
• Diagnosis of pneumonitis requires laboratory
  testing

32
Diagnosis

• Chlamydia trachomatis can be identified
  microscopically in scrapings from the eyes or the
  urogenital tract. Inclusion bodies in scraped
  tissue cells are identified by iodine staining of
  glycogen present in the cytoplasmic vacuoles in
  infected cells.
• To isolate the agent, cell homogenates that
  contain the chlamydial elementary bodies are
  centrifuged onto the cultured cells (e.g.,
  irradiated McCoy cells).
• After incubation, typical cytoplasmic inclusions
  are seen in the cells stained with Giemsa stain
  or iodine.

33
Diagnosis

• Staining with iodine can distinguish between
  inclusion bodies of C trachomatis and C psittaci,
  as only the former contain glycogen.
• Each chlamydial agent can also be identified by
  using specific immunofluorescent antibodies
  prepared against either C trachomatis or C
  psittaci.
• Homogenates or exudates of infected tissues also
  have been used to isolate the agent in the yolk
  sac of embryonated eggs.

34
Diagnosis

• Sera and tears from infected humans are used to
  detect anti-Chlamydia antibodies by the
  complement fixation or microimmunofluorescence
  tests.
• The latter is useful for identifying specific
  serotypes of C trachomatis.
• Fluorescent monoclonal antibodies are used to
  stain C trachomatis elementary bodies in urethral
  and cervical exudates.

35
Diagnosis

• It is possible to diagnose C trachomatis in
  tissue biopsy specimens by in situ DNA
  hybridization with cloned C trachomatis DNA
  probes.
• DNA from C trachomatis isolates can be examined
  by restriction endonuclease analysis.
• The DNA cleavage pattern of C trachomatis
  isolates differs greatly from that of DNA from C
  psittaci isolates.
• DNAs of the agents of trachoma and
  lymphogranuloma venereum differ in their cleavage
  patterns, and this allows identification of the
  biovars

36
Diagnosis

• Chlamydia pneumoniae DNA has 10 percent homology
  with C trachomatis or C psittaci
• C pneumoniae isolates have 100 percent homology.
  Chlamydia pneumoniae isolates can be diagnosed by
  hybridization with a specific DNA probe that does
  not hybridize to other chlamydiae.
• Two additional serologic tests are in use
• the microimmunofluorescence test with C
  pneumoniae-specific elementary body antigen, and
  the complement fixation test, which measures
  Chlamydia antibodies.

37
Prevention and control

• C. trachomatis
• It is difficult to prevent C. trachomatis
  infections because the population with endemic
  disease frequently has limited access to medical
  care.
• It is difficult to eradicate the disease within a
  population and to prevent reinfections.
• Chlamydia conjunctivitis and genital infections
  are prevented through the use of safe sexual
  practices and the prompt treatment of symptomatic
  patients and their sexual partners.

38
Prevention and control

• C. pneumoniae
• Treatment is with tetracycline or erythromycin.
• Failures are common.
• Retreament maybe required.

39
Prevention and control

• C. psittaci
• Tetracycline or erythromycin is used for
  treatment.
• Infections should be controlled in domestic and
  imported pet birds using chlortetracycline.

40
Treatment

• C. trachomatis
• Ocular,genital respiratory infections
• In endemic areas,sulfonamides,erythromycins,and
  tetracyclines have been used to suppress
  chlamydiae and bacteria that cause eye
  infections.
• Genital infections inclusion conjunctivitis
• It is essential that chlamydial infections be
  treated simultaneously in both sex partners and
  in offspring to prevent reinfection.
• tetracyclines are commonly used in non pregnant
  in fected females.
• Erythromycin is given to pregnant women.
• LGV
• The sulfonamides and tetracyclines have been used
  with food results especially in the early stages.
• Little is known about active immunity.

41
Treatment

• C. pneumoniae
• It is susceptible to the macrolides and
  tetracyclines and to some fluoroquinolones.
• Treatment with doxycycline, azithromycin,or
  clarithromycin appears to benefit patients with
  the infection.
• The symptoms may continue after routine courses
  of therapy with erythromycin,doxycyclinbe, or
  tetracycline.
• These drugs should be given for 10- to 14-day
  courses.

42
Treatment

• C. psittacosis
• tetracyclines. Are the drugs of choice and should
  be continued for 10 days.
• It may not free the patient from the agent.
• Intensive antiviotic treament may also delay the
  normal course of antibody development.
• Strains may become drug-resistant.
• With antibiotic therapy the mortality rate is 2?
  or less.