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Chlamydiae
Chlamydiae
• Obligate intracellular bacteria, cause a spectrum of diseases in man
infecting eye, genital organs and lungs.
• Chlamydia trachomatis: 19 serovars, trachoma, genital chlamydiasis,
inclusion conjunctivitis, infant pneumonia (serotype D-K) and LGV
(lymphogranuloma venereum)
• Chlamydophila psittaci: history of exposure to birds; atypical
pneumonia, IE
• Chlamydophila pneumoniae: exclusively human pathogen, causes
atypical pneumonia (CAP), rhinitis, bronchitis
• Family Chlamydiaceae comprises of two genera:
1. Chlamydia: It has one pathogenic species, C.trachomatis
2. Chlamydophila: It has two pathogenic species—C. psittaci and C.
pneumoniae. They cause interstitial (atypical) pneumonia
• Chlamydia trachomatis: Most common agent of NGU
Life cycle of Chlamydia
EBs are the extracellular and infective form; attach to
the specific receptors on the host cells (e.g. squamous
epithelial cells)
Following entry, they transform into reticulate
bodies; which are the intracellular form
RBs are replicative form; divide by binary fission.
They are also the metabolically active form and can
synthesize their own nucleic acid, lipids and proteins
except ATP; hence, they are called as energy parasites
RBs present inside the vacuole may enlarge to form
inclusion bodies
Antigenic Structure
• Genus/group specific antigen: Chlamydial lipopolysaccharide (LPS) is
genus specific. It plays an important role in the pathogenesis, acts by
induction of TNF-α and other proinflammatory cytokines, which leads
to scarring and fibrosis
• Species specific protein Ag: They are present at the envelope surface
• Serovar specific Ags: They are the major outer membrane proteins
(MOMP), encoded by ompA gene
• Other antigens: Such as outer membrane complex proteins and heat
shock proteins, play important role in pathogenesis.
• Chlamydia trachomatis is primarily a human pathogen, causing ocular,
urogenital and neonatal infections
• Historically, based on the disease produced, C. trachomatis was subdivided
into two strains or biovars
1. TRIC (Trachoma-inclusion conjunctivitis)
2. Lymphogranuloma venereum (LGV) biovar
• Based on antigenic structure of MOMP (and its gene ompA)
of C. trachomatis, 18 serovars have been identified affecting
humans
• Serovars A, B, Ba and C are associated primarily with ocular disease
called trachoma—a form of chronic keratoconjunctivitis
• Serovars D–K are associated with—(1) genital tract infections (2)
infant pneumonia (interstitial pneumonia) and (3) ocular disease,
called inclusion conjunctivitis
• Swimming pool conjunctivitis in adults
• Ophthalmia neonatorum in new born
• Serovars L1–L3 causes a sexually transmitted infection,
lymphogranuloma venereum (LGV), an ulcerative genital disease
• Nongonococcal urethritis (NGU): C. trachomatis is the most common
cause of nongonococcal urethritis (NGU), responsible for 30–50% of
cases of NGU
• Postgonococcal urethritis (PGU):C. trachomatis is the most common
cause of PGU
• This occurs when patients with GU are treated with penicillin or
cephalosporin alone without adding any antichlamydial drugs (such
as azithromycin)
• C. trachomatis is the most common cause of epididymitis in males
• Reactive arthritis (Reiter’s syndrome): It consists of conjunctivitis,
urethritis (or, in females-cervicitis), arthritis, and characteristic
mucocutaneous lesions
• It occurs in 1–2% of cases of NGU, develops after 1–4 weeks after
genital infection
• It is the most common cause of peripheral inflammatory arthritis in
young men
• Knee, ankle, small joints of feet and sacroiliac joints are commonly
affected
• Most of the patients possess HLA-B27 haplotype
• Mucopurulent cervicitis is the most common manifestation in females
• may progress to endometritis, salpingitis (fallopian tube), PID (pelvic
inflammatory disease) and finally pelvic peritonitis
• Perihepatitis (Fitz–Hugh–Curtis syndrome)
• Lymphogranuloma venereum (LGV) is an invasive systemic sexually
transmitted infection, caused by Chlamydia trachomatis serovars L1,
L2, and L3.
• The clinical course in three stages- First stage: Painless ulcer develops
on the penis or vulva after an incubation period of 3 days to 6 weeks
• Second stage: Inguinal lymph nodes in the groin become enlarged,
tender and soft (called bubo)
• Fistulae: Buboes may breakdown and discharge may spread externally
as chronic fistulae
• Groove sign (unilateral) may be present, as a result of enlargement of
nodes below the inguinal ligament
LGV
• Third stage: Occurs in untreated cases, especially in women and
homosexual men- Rectal stricture or rectovaginal and rectal fistulae
• Esthiomene—the vulva, scrotum or penis may undergo edematous
granulomatous hypertrophy
• Elephantiasis of the vulva or scrotum
• Lab Diagnosis of LGV is usually based on serology; Biopsy is
contraindicated as there is a risk of sinus tract formation
• C. pneumoniae is an exclusively human pathogen. It is transmitted from
person to person by inhalational route.
• Atypical pneumonia: C. pneumoniae is a common cause of atypical
(interstitial) pneumonia accounting for 10% of cases of community-
acquired pneumonia
• Upper respiratory tract involvement is frequent, such as pharyngitis and
sinusitis
• Atherosclerosis: There is a strong evidence of association between C.
pneumoniae and atherosclerosis of coronary and other arteries
• Asthma and COPD: C. pneumoniae may cause exacerbations of bronchial
asthma and COPD (chronic obstructive pulmonary disease)
• Interstitial or atypical pneumonia: It refers to infection of interstitial
space of lungs
• Cough is characteristically non-productive. Radiologically, it presents
as patchy reticulonodular opacities (chest X-ray) and ground glass
opacities (CT scan)
• C. psittaci is a pathogen of parrots and other psittacine birds causing
psittacosis
• Reservoirs: Pet birds (parrots, parakeets, macaws, and cockatiels) and
poultry (turkeys and ducks) act as natural reservoir of infection
• Mode of transmission: C. psittaci can be transmitted to humans by
inhalation of aerosols from avian nasal discharges and from infectious
avian fecal or feather dust
• Clinical manifestations: Incubation period ranges from 5–19 days. It can
present as—(1) Respiratory manifestation (most common form), varies
from a mild influenza-like syndrome to an interstitial pneumonia, (2) rarely
septicemia and typhoid-like syndrome
• Treatment: Tetracycline is the drug of choice, given 250 mg four times
a day for at least 3 weeks to avoid relapse.
• Erythromycin (500 mg four times a day, per oral) is given alternatively.
• Microscopy: Detects chlamydial inclusion bodies
• Gram staining, Lugol’s iodine and other stains such as Castaneda,
Machiavello or Gimenez stains
• Direct IF: Used for direct detection of inclusion bodies.
• Antigen detection (LPS antigens): By enzyme immunoassays
• Culture: was the gold standard method
• Egg (yolk sac), mice inoculation and cell line culture
• Cell lines of choice-
• McCoy, HeLa for C. trachomatis
• HEp2 for C.pneumoniae
• ELISA, MIF, uses the species and serovar specific MOMP (major outer
membrane protein) antigen
• Direct detection of inclusion bodies by direct IF
• Frei test: It is a skin test, used in the past to demonstrate type IV
hypersensitivity reaction in LGV
• Inclusion bodies: given various names such as
• Halberstaedter–Prowazek (H–P) body in trachoma
• Miyagawa corpuscle in LGV
• LCL body (Levinthal-Cole-Lillie) body in psittacosis
Anti-Chlamydia microimmunofluorescence test (MIF).
Chlamydia trachomatis inclusion bodies (brown) in
McCoy cell culture
• For obligate intracellular organisms, CMI remains the only effective
immune response
• CFT was widely used for detection of complement fixing antibodies in
Rickettsia, Chlamydia, Mycoplasma Infections
• A fourfold rise in specific IgM antibody titer between acute- and
convalescent-phase serum samples
• NAATs are currently the diagnostic assays of choice for chlamydial
infection as recommended by the CDC, replacing the so called gold
standard culture methods; opacity protein gene or 16S or 23S rRNA
Rx:
• For uncomplicated genital infection or trachoma or adult
conjunctivitis:
• Azithromycin is the drug of choice given as single dose of 1 gram
tablet, per oral
• Alternatively doxycycline, tetracycline, erythromycin or ofloxacin can
be given for at least a duration of 7 days
• Both the sex partners should be treated
• Ceftriaxone should be added to the regimen as co-infec. with
gonococcus may be present in most
• For complicated genital infection: Doxycycline (100 mg twice daily), or
erythromycin (500 mg four times daily) are the drugs of choice, given
for:
• 2 weeks for pelvic inflammatory disease and epididymitis
• 3 weeks for LGV- Longer treatment course is necessary; doxycycline
for 21 days is drug of choice. Azithromycin (weekly once for 3 weeks)
can be given alternatively
• Trachoma is a chronic keratoconjunctivitis, caused by C. trachomatis
serovars A, B, Ba and C
• Mode of transmission: Trachoma is transmitted through direct contact
(fingers and fomites) with discharges from the eyes of the infected patients
or indirect contact through contaminated clothes or flies
• Acute infection: It presents as follicular conjunctivitis (inflammation of
conjunctival lymphoid follicles) and papillary hyperplasia
• Late stage: Recurrent infection leads to conjunctival scarring or
cicatrization, concretions (whitish deposits), trichiasis (eyelashes falling on
eyeball) and corneal ulcers progressing to opacity and blindness
• Worldwide, the hyperendemic areas of trachoma include sub-Saharan
Africa, Middle East, and Southeast Asia including India
• Prevention: WHO has initiated an action plan called SAFE strategy, aiming
towards global elimination of trachoma, and prevention of blindness-
• Surgery: Needed in advanced stage to prevent corneal blindness
• Antibiotic (azithromycin single dose): Mass administration is given; the
target population chosen depends upon the prevalence of trachoma in
children in the area
• Facial hygiene such as frequent face wash and avoidance of use of common
towel, handkerchief
• Environmental sanitation to reduce transmission
• Topical therapy such as tetracycline or erythromycin eye ointment, given 4
times a day for 6 weeks
• Systemic therapy: Azithromycin is the drug of choice, given for 4 days.
Alternatives include tetracycline or doxycycline.
• Systemic antibiotic is indicated if the ocular infection is severe or when
there is associated genital infection
• The incidence of ophthalmia neonatorum (both gonococcal and
chlamydial) has been reduced dramatically after institution of appropriate
preventive measures during delivery
• Rx:topical ointment (erythromycin or tetracycline) plus oral erythromycin
given for 21 days.

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Chlamydiae.pptx

  • 2. Chlamydiae • Obligate intracellular bacteria, cause a spectrum of diseases in man infecting eye, genital organs and lungs. • Chlamydia trachomatis: 19 serovars, trachoma, genital chlamydiasis, inclusion conjunctivitis, infant pneumonia (serotype D-K) and LGV (lymphogranuloma venereum) • Chlamydophila psittaci: history of exposure to birds; atypical pneumonia, IE • Chlamydophila pneumoniae: exclusively human pathogen, causes atypical pneumonia (CAP), rhinitis, bronchitis
  • 3. • Family Chlamydiaceae comprises of two genera: 1. Chlamydia: It has one pathogenic species, C.trachomatis 2. Chlamydophila: It has two pathogenic species—C. psittaci and C. pneumoniae. They cause interstitial (atypical) pneumonia • Chlamydia trachomatis: Most common agent of NGU
  • 4. Life cycle of Chlamydia EBs are the extracellular and infective form; attach to the specific receptors on the host cells (e.g. squamous epithelial cells) Following entry, they transform into reticulate bodies; which are the intracellular form RBs are replicative form; divide by binary fission. They are also the metabolically active form and can synthesize their own nucleic acid, lipids and proteins except ATP; hence, they are called as energy parasites RBs present inside the vacuole may enlarge to form inclusion bodies
  • 5. Antigenic Structure • Genus/group specific antigen: Chlamydial lipopolysaccharide (LPS) is genus specific. It plays an important role in the pathogenesis, acts by induction of TNF-α and other proinflammatory cytokines, which leads to scarring and fibrosis • Species specific protein Ag: They are present at the envelope surface • Serovar specific Ags: They are the major outer membrane proteins (MOMP), encoded by ompA gene • Other antigens: Such as outer membrane complex proteins and heat shock proteins, play important role in pathogenesis.
  • 6. • Chlamydia trachomatis is primarily a human pathogen, causing ocular, urogenital and neonatal infections • Historically, based on the disease produced, C. trachomatis was subdivided into two strains or biovars 1. TRIC (Trachoma-inclusion conjunctivitis) 2. Lymphogranuloma venereum (LGV) biovar • Based on antigenic structure of MOMP (and its gene ompA) of C. trachomatis, 18 serovars have been identified affecting humans
  • 7. • Serovars A, B, Ba and C are associated primarily with ocular disease called trachoma—a form of chronic keratoconjunctivitis • Serovars D–K are associated with—(1) genital tract infections (2) infant pneumonia (interstitial pneumonia) and (3) ocular disease, called inclusion conjunctivitis • Swimming pool conjunctivitis in adults • Ophthalmia neonatorum in new born • Serovars L1–L3 causes a sexually transmitted infection, lymphogranuloma venereum (LGV), an ulcerative genital disease
  • 8. • Nongonococcal urethritis (NGU): C. trachomatis is the most common cause of nongonococcal urethritis (NGU), responsible for 30–50% of cases of NGU • Postgonococcal urethritis (PGU):C. trachomatis is the most common cause of PGU • This occurs when patients with GU are treated with penicillin or cephalosporin alone without adding any antichlamydial drugs (such as azithromycin) • C. trachomatis is the most common cause of epididymitis in males
  • 9. • Reactive arthritis (Reiter’s syndrome): It consists of conjunctivitis, urethritis (or, in females-cervicitis), arthritis, and characteristic mucocutaneous lesions • It occurs in 1–2% of cases of NGU, develops after 1–4 weeks after genital infection • It is the most common cause of peripheral inflammatory arthritis in young men • Knee, ankle, small joints of feet and sacroiliac joints are commonly affected • Most of the patients possess HLA-B27 haplotype
  • 10. • Mucopurulent cervicitis is the most common manifestation in females • may progress to endometritis, salpingitis (fallopian tube), PID (pelvic inflammatory disease) and finally pelvic peritonitis • Perihepatitis (Fitz–Hugh–Curtis syndrome)
  • 11. • Lymphogranuloma venereum (LGV) is an invasive systemic sexually transmitted infection, caused by Chlamydia trachomatis serovars L1, L2, and L3. • The clinical course in three stages- First stage: Painless ulcer develops on the penis or vulva after an incubation period of 3 days to 6 weeks • Second stage: Inguinal lymph nodes in the groin become enlarged, tender and soft (called bubo) • Fistulae: Buboes may breakdown and discharge may spread externally as chronic fistulae • Groove sign (unilateral) may be present, as a result of enlargement of nodes below the inguinal ligament
  • 12. LGV • Third stage: Occurs in untreated cases, especially in women and homosexual men- Rectal stricture or rectovaginal and rectal fistulae • Esthiomene—the vulva, scrotum or penis may undergo edematous granulomatous hypertrophy • Elephantiasis of the vulva or scrotum • Lab Diagnosis of LGV is usually based on serology; Biopsy is contraindicated as there is a risk of sinus tract formation
  • 13. • C. pneumoniae is an exclusively human pathogen. It is transmitted from person to person by inhalational route. • Atypical pneumonia: C. pneumoniae is a common cause of atypical (interstitial) pneumonia accounting for 10% of cases of community- acquired pneumonia • Upper respiratory tract involvement is frequent, such as pharyngitis and sinusitis • Atherosclerosis: There is a strong evidence of association between C. pneumoniae and atherosclerosis of coronary and other arteries • Asthma and COPD: C. pneumoniae may cause exacerbations of bronchial asthma and COPD (chronic obstructive pulmonary disease)
  • 14. • Interstitial or atypical pneumonia: It refers to infection of interstitial space of lungs • Cough is characteristically non-productive. Radiologically, it presents as patchy reticulonodular opacities (chest X-ray) and ground glass opacities (CT scan)
  • 15. • C. psittaci is a pathogen of parrots and other psittacine birds causing psittacosis • Reservoirs: Pet birds (parrots, parakeets, macaws, and cockatiels) and poultry (turkeys and ducks) act as natural reservoir of infection • Mode of transmission: C. psittaci can be transmitted to humans by inhalation of aerosols from avian nasal discharges and from infectious avian fecal or feather dust • Clinical manifestations: Incubation period ranges from 5–19 days. It can present as—(1) Respiratory manifestation (most common form), varies from a mild influenza-like syndrome to an interstitial pneumonia, (2) rarely septicemia and typhoid-like syndrome
  • 16. • Treatment: Tetracycline is the drug of choice, given 250 mg four times a day for at least 3 weeks to avoid relapse. • Erythromycin (500 mg four times a day, per oral) is given alternatively.
  • 17. • Microscopy: Detects chlamydial inclusion bodies • Gram staining, Lugol’s iodine and other stains such as Castaneda, Machiavello or Gimenez stains • Direct IF: Used for direct detection of inclusion bodies. • Antigen detection (LPS antigens): By enzyme immunoassays • Culture: was the gold standard method • Egg (yolk sac), mice inoculation and cell line culture • Cell lines of choice- • McCoy, HeLa for C. trachomatis • HEp2 for C.pneumoniae
  • 18. • ELISA, MIF, uses the species and serovar specific MOMP (major outer membrane protein) antigen • Direct detection of inclusion bodies by direct IF • Frei test: It is a skin test, used in the past to demonstrate type IV hypersensitivity reaction in LGV
  • 19. • Inclusion bodies: given various names such as • Halberstaedter–Prowazek (H–P) body in trachoma • Miyagawa corpuscle in LGV • LCL body (Levinthal-Cole-Lillie) body in psittacosis
  • 20. Anti-Chlamydia microimmunofluorescence test (MIF). Chlamydia trachomatis inclusion bodies (brown) in McCoy cell culture
  • 21. • For obligate intracellular organisms, CMI remains the only effective immune response • CFT was widely used for detection of complement fixing antibodies in Rickettsia, Chlamydia, Mycoplasma Infections • A fourfold rise in specific IgM antibody titer between acute- and convalescent-phase serum samples • NAATs are currently the diagnostic assays of choice for chlamydial infection as recommended by the CDC, replacing the so called gold standard culture methods; opacity protein gene or 16S or 23S rRNA
  • 22. Rx: • For uncomplicated genital infection or trachoma or adult conjunctivitis: • Azithromycin is the drug of choice given as single dose of 1 gram tablet, per oral • Alternatively doxycycline, tetracycline, erythromycin or ofloxacin can be given for at least a duration of 7 days • Both the sex partners should be treated • Ceftriaxone should be added to the regimen as co-infec. with gonococcus may be present in most
  • 23. • For complicated genital infection: Doxycycline (100 mg twice daily), or erythromycin (500 mg four times daily) are the drugs of choice, given for: • 2 weeks for pelvic inflammatory disease and epididymitis • 3 weeks for LGV- Longer treatment course is necessary; doxycycline for 21 days is drug of choice. Azithromycin (weekly once for 3 weeks) can be given alternatively
  • 24. • Trachoma is a chronic keratoconjunctivitis, caused by C. trachomatis serovars A, B, Ba and C • Mode of transmission: Trachoma is transmitted through direct contact (fingers and fomites) with discharges from the eyes of the infected patients or indirect contact through contaminated clothes or flies • Acute infection: It presents as follicular conjunctivitis (inflammation of conjunctival lymphoid follicles) and papillary hyperplasia • Late stage: Recurrent infection leads to conjunctival scarring or cicatrization, concretions (whitish deposits), trichiasis (eyelashes falling on eyeball) and corneal ulcers progressing to opacity and blindness
  • 25. • Worldwide, the hyperendemic areas of trachoma include sub-Saharan Africa, Middle East, and Southeast Asia including India • Prevention: WHO has initiated an action plan called SAFE strategy, aiming towards global elimination of trachoma, and prevention of blindness- • Surgery: Needed in advanced stage to prevent corneal blindness • Antibiotic (azithromycin single dose): Mass administration is given; the target population chosen depends upon the prevalence of trachoma in children in the area • Facial hygiene such as frequent face wash and avoidance of use of common towel, handkerchief • Environmental sanitation to reduce transmission
  • 26. • Topical therapy such as tetracycline or erythromycin eye ointment, given 4 times a day for 6 weeks • Systemic therapy: Azithromycin is the drug of choice, given for 4 days. Alternatives include tetracycline or doxycycline. • Systemic antibiotic is indicated if the ocular infection is severe or when there is associated genital infection • The incidence of ophthalmia neonatorum (both gonococcal and chlamydial) has been reduced dramatically after institution of appropriate preventive measures during delivery • Rx:topical ointment (erythromycin or tetracycline) plus oral erythromycin given for 21 days.