Chlamydia trachomatis

1. Chlamydial Infections &
Ophthalmia neonatorum
Presenter- Dr. Gaurav Shukla

2. • Leading cause of Ocular & Genital infections
• Pathogenicities:
1. Trachoma
2. Adult Inclusion conjunctivitis
3. Neonatal conjunctivitis
4. Infant pneumonia
5. Genital infections – Genital Chlamydiasis,
Lymphogranuloma venerum

3. Trachoma
• Greek word trakkus – rough (roughness of
conjunctiva)
• Caused by C. trachomatis types A, B & C.
• Chronic keratoconjunctivitis
• Transmitted by fingers, fomites, flies or dust
• Established trachoma passes through 4 stages
(I – IV).
• Infectivity is maximum in early cases, stage IV
is non infectious Once known as Egyptian
Ophthalmia.

4. • Most common cause of avoidable blindness in
underprivileged populations.(1)
• Endemic in parts of Asia & Africa.
• Its estimated that 146 million people have
active Trachoma and six million people are
blind due to complications of trachoma.(2)
• (1)Resnikoff S, Pascolini D, Etya’ale D, et al. Global data on visual
impairment in the year 2002. Bull WHO. 2004;82:844–851
• (2)Global Scientific Meeting on Eradication of Trachoma. Geneva 2003

5. • Obligate intracellular parasites of humans,
animals & birds.
• Resemble virus because of easy filterable and it
cannot multiply outside living cells/ tissues
• Resemble bacteria because of presence of cell
wall, multiply by binary fission, posses both DNA
& RNA
• Cannot synthesize ATP – depends on host cell for
energy & nutrient source. Hence, called Energy
Parasites

6. Classification
• Originally grouped as psittacosis-
lymphogranuloma - trachoma agents, due to
common features like-
• Obligate intracellular life cycle with particulate
cytoplasmic inclusions.
• Common complement fixing antigen
• Sensitivity to some antibiotics

7. • Gordan & Quan divided chlamydia into 2
groups-on the basis of inclusion morphology
and presence of glycogen in the inclusions.
• Chl. trachomatis- glycogen + & sulfadiazine
sensitive.
• Chl. psittaci- glycogen- & sulfonamide
resistant
• Additional 3rd chl. Pneumoniae(TWAR agent) =
respiratory agent

8. • 4 species in the Genus Chlamydia –
C. trachomatis,
C. psittaci, affects humans
C. pneumoniae
C. pecorum affects ruminants
• All are non-motile, gram negative; share
antigens, have both DNA and RNA.

9. • C.trachomatis : eye & genital infections, infant
pneumonia, and LGV (Lymphogranuloma
Venereum) in adults
• C.pneumoniae : different types of respiratory
infections.
• C.psittaci : psittacosis in man, ornithosis in
birds

10. Chlamydia trachomatis
• Gram negative
• Obligate intracellular parasite.
• Seen in places with poor personal and
community hygiene.
• Hot and dusty climate.
• Spreads by transfer of conjunctival secretions
by fingers, towels and flies.

11. Life cycle
• Chlamydia occur in 2 forms :
1. Elementary body – extracellular, infective form
2. Reticulate body – intracellular, growing &
replicative form
• Chlamydial microcolony within the host cell is
called Inclusion body.
• Mature inclusion body contains 100 - 500
elementary bodies

14. • C. psittaci – host cell is severely damaged, EBs
are released within 48 hrs by cell lysis
• C.trachomatis – mature inclusion body
appears to be exocytosed in 72- 96 hrs.

15. Immunology
Three major Ags
1. Group specific Ag – heat stable, common to all
chlamydiae, a lipopolysaccharide resembling LPS of
GNB. Present in all stages.
2. Species specific protein Ags – present at the
envelope surface, help in classifying chlamydia into
species
3. Ag for Intraspecies typing – found only in some
members of a species, located on major OMP
(MOMP), demonstrated by micro- IF. Classifies
species into serovars/ serotypes

16. Variants of Chlamydia
• C. trachomatis – 2 biovars: TRIC & LGV
1. TRIC – Trachoma, Inclusion conjunctivitis
- divided into 12 serovars -
(A,B,Ba,C,D,E,F,G,H,I,J,K)
2. LGV – Lymphogranuloma venereum – 3
serovars(L1,L2,L3)

18. Human diseases
• Species Serotype Disease
• C. trachomatis A, B, Ba, C Endemic blinding
trachoma
• C. trachomatis D to K Inclusion conjunctivitis.
Genital chlamydiasis
• C. trachomatis L1, L2, L3 Lymphogranuloma
venereum
• C. psittaci Many serotypes Psittacosis
• C. pneumoniae Acute resp. disease

19. India Statement
• Review of the epidemiological studies carried out in the past in India.

20. Clinical features
• Active phase (seen in pre school age group.)
• Cicatricial phase (seen in middle age group.)
WHO simplified trachoma grading scheme as ‘FISTO’
F- T. inflammation Follicular.
I- T. inflammation Intense.
S- T. Scarring.
T- T. Trichiasis.
O- Corneal Opacity

21. • WHO grading of trachoma
• TF = trachomatous inflammation (follicular): five or more
follicles (>0.5 mm) on the superior tarsal plate
• TI = trachomatous inflammation (intense): diffuse involvement
of the tarsal conjunctiva, obscuring 50% or more of the normal
deep tarsal vessels; papillae are present
• TS = trachomatous conjunctival scarring: easily visible fibrous
white tarsal bands
• TT = trachomatous trichiasis: at least one lash touching the
globe.
• CO = corneal opacity sufficient to blur details of at least part of
the pupillary margin

22. Dawson, Jones, and Tarizzo 1981:
Modified WHO or FPC system
• The system selects the upper tarsal conjunctiva to
provide an “index of trachomatous inflammation in
the eye as a whole”
• Zones are defined by two imaginary lines which, as
viewed on the everted tarsal surface, are
approximately parallel with the upper tarsal border
and curve upward towards their lateral extremities

23. • Zone 1 includes the
entire upper tarsal border
and adjacent lateral tarsal
surface
• Zone 2 occupies the area
between zones 1 and 3
and extends to the lateral
quarters of the lid margin
• zone 3 includes the tarsal
conjunctiva adjacent to
the central half of the lid
margin and, at its center,
covers just less than half
the vertical extent of the
tarsal surface

24. Upper tarsal
follicles (F) are
• Graded F0 for no
follicles
• F1 for follicles present
but no more than five
in zones 2 and 3
together
• F2 for more than five
follicles in zones 2 and
3 together but less
than five in zone 3, and
• F3 for five or more
follicles in each of the
three zones
Upper tarsal papillary
hypertrophy
• P0 for absent, normal
appearance;
• P1 for minimal, individual
vascular tufts (papillae)
prominent but deep
subconjunctival vessels on
the tarsus not obscured
• P2 for moderate, more
prominent papillae and
normal vessels appear
hazy even when seen by
the naked eye; and
• P3 for pronounced,
conjunctiva thickened and
opaque, normal vessels on
the tarsus are hidden over
more than half of the
surface
Conjunctival scarring (C)
C0 for no scarring on the
conjunctiva
C1 for mild, fine, scattered
scars on the upper tarsal
conjunctiva or scars on the
other parts of the
conjunctiva
C2 for moderate, more
severe scarring but without
shortening or distortion of
the upper tarsus; and
C3 for severe scarring with
distortion of the upper
tarsus.

25. Pathophysiology
TF and TI stages, the main cell type is the polymorphonuclear
leukocyte (PMN).
As the infection progresses during this stage, the number of
PMNs decrease and lymphocytes start to become more
numerous.
As the trachomatous infection progresses to the TS stage,
cicatricial changes start to occur. Histologically, subepithelial
fibrous membrane formation, squamous metaplasia, and loss
of goblet cells occur.

26. • pathognomonic Arlt’s line on the tarsus as well as
decreased mucin production
The contraction of the subepithelial fibrous tissue
formed by collagen fibers and anterior surface
drying - chronic cicatrization and entropion
formation
Corneal opacity (CO)

27. Follicular phase
• Mucopurulent conjunctivitis with follicular
reaction.
• Presence of 5 or more follicles at least 0.5mm
diameter in central part of upper tarsal
conjunctiva.
• Follicles in trachoma can reach up to 5mm in
diameter never seen in non trachomatous
conditions.
• In later stages pannus can develop.

29. Follicles

30. Peri-limbal subepithelial corneal infiltrates may appear
after 2–3 weeks

31. Pannus

33. Herbert’s pits

34. Intense inflammatory trachoma
• Inflammatory thickening of upper tarsal
conjunctiva.
• Velvety thickening with papillae
• It’s a precursor to conjunctival scarring.
• Risk factor for blindness later

35.  Dense papillary hypertrophy & diffuse infiltration with mild
mucopurulent conjunctivitis
 Mild purulent discharge indicates bacterial infection- most
commonly hemophilus aegypticus

36. Intense inflammation
 The tarsal conjunctiva is thickened and inflamed.
 There is diffuse inflammatory infiltration with enlarged vascular
papillae.
 Deep conjunctival vessels are not visible.

37. Trachomatous scarring
• Conjunctival scars are sign of past inflammation
and future Trichiasis.
• Low grade conjunctivits
• Dacrocystitis
• May be associated with dry eye.
• Cicatricial trachoma is prevalent in middle age.
• Linear or stellate conjunctival scars in mild cases
• Arlt’s line characteristic finding on superior tarsal
conjunctiva.

38. Conjunctival follicles and progressive developing Arlt’s line

39. Follicles & scarring in progressive trachoma.
Repeated cycles of inflammation causes scarring

40. Scarring
Lymphoid follicles & infiltration in b/w linear scars

41. Artl,s line

42. Trichiasis
• Sub-conjunctival
fibrosis leads to lid
distortion and
causes eyelashes
to rub on cornea.
• Trichiasis,
distichiasis,
corneal
vascularization

43. Corneal opacity
• If left untreated
leads to corneal
opacity
• Visible corneal
opacity over
pupillary margin
that blurs the
part of pupillary
margin.

44. Mc Callan’s stages (1908)
Stage 1 – Incipient trachoma
hyperemia, immature follicles
Stage 2- Established trachoma
2a – mature follicles
2b – mature follicles + papillae+ corneal progressive
pannus
Stage 3- Cicatrizing trachoma
Stage 4- Healed trachoma
entropion ,trichiasis

45. Sequelae & Complication
• Dry eye.
• Trachomatous ptosis.
• Entropion.
• Corneal bacterial superinfection.
• Blindness.
• Only complication- Ulceration.

46. Diagnosis
• Mainly depends on clinical findings.
• Lab tests approaches available:-
Microscopic demonstration of inclusion or elementary
bodies- Giemsa stain (Halberstaedter Prowazek bodies)
• Isolation of chlamydia
• Demonstration of chlamydial ag
– PCR
– DFA(direct fluorescent antibody)
– ELISA.
• Demonstration of abs or hypersensitivity
• Culture on mc coy cells.

47. • Gram negative but stained better by Giemsa,
Castaneda or Machiavello stains
• Giemsa Stain: Elementary body & the Reticulate
body stains blue in cytoplasm
• Lugol’s iodine: rapid & simple screening method
for ocular infections, stains glycogen matrix of C.
trachomatis
• Immunoflurescence staining: more sensitive &
specific, by using monoclonal Abs. Identifies
inclusion bodies as well as extracellular
elementary bodies. Used for ocular, cervical or
urethral specimens.

48. • Demonstration
of characteristic
inclusion bodies
(Halberstaedter
Prowazek or HP
bodies) in
conjunctival
scrapings by
Giemsa.

49. Microscopic appearance
• A monolayer of
tissue culture cells
has been exposed
to cells of chlamydia
trachomatis.
Infected cells within
the cell sheet have a
cytoplasm with a
granular
appearance.

50. IF staining

51. Demonstration of antigens
• Micro – IF : infected ocular or genital samples
are stained with fluorescent conjugated Ab
• ELISA – best for screening large number of
specimens, detects LPS Ag
• Molecular methods - PCR

52. Yolk sac of 6 - 8 days old chick embryo.
Tissue culture – McCoy, HeLa cell lines
* C. psittaci carry the risk of laboratory
infection

53. Treatment
• Local application of antibiotics
• Oral administration - Tetracycline or
Doxycycline for several weeks
• Single dose Azithromycin
• Control – mass education & chemotherapy

54. Treatment
• WHO developed SAFE strategy
• S – Surgical care.
• A – Antibiotics.
• F – Facial cleanliness.
• E – Environmental improvement.

55. • Surgery includes lid surgery to correct trichiasis and
entropion.
• Antibiotics : WHO recommendations-
– Oral Azithromycin as a single dose ( 1 gm for
adults and 20mg/kg in children)
– Tetracycline eye ointment(twice a day for 6 weeks)
– Patient and all family members to be treated

56. • Personal and Community Hygiene
• Facial cleanliness : patients education reduces
the risk of spread and severity of the disease
• Environmental changes : improving the quality
of water supply, better sanitation reduces
prevalence

57. Guidelines for Elimination of Blinding
Trachoma
• 1997: WHO establishes the Global Alliance for
the Elimination of Blinding Trachoma by 2020
(GET2020)
• 1998: World Health Assembly signs resolution
endorsing the Alliance and encourages
countries to eliminate trachoma (WHA 51.11)

59. What is meant by Elimination?
• Ultimate Intervention
Goals
• Prevalence of TF <5% in
1-9 year olds
• Prevalence of TT is <0.1%
in pop’n
Trachoma Signs
Follicular Trachoma: TF
Intense Trachoma : TI
Scarring Trachoma: TS
Trachomatous Trichiasis: TT
Corneal Opacity: CO

60. Inclusion conjunctivitis
• Adult form -Also known as Swimming pool
conjunctivitis.
• Usually spreads by sexual transmission from
genital source of infection.
• Caused by serotypes D-K.
• Neonatal form - “Inclusion Blenorrhoea”
• Develops when the infant is in birth canal
• Appears 5-12 days after birth,
• Prevented by local application of antibiotics

61. • Clinical features:-
• follicular and papillary hypertrophy, superficial
punctate keratitis with occasional pannus.
• Diagnosis is same as that for trachoma.
• Treatment systemic antibiotics like Tetracycline
250mg QID, Doxycycline 100mg BD for 14
days.
• Azithromycin 1gm single dose is also effective

63. Lymphogranuloma venereum
• Most commonly caused by L2 type
• Incubation period – 3 days to 5 wks
• 1° lesion – small painless papulovesicular lesion
on external genitalia
• 2° stage – after 2 wks, lymphatic spread to
draining LNs (men – inguinal, women –
intrapelvic & pararectal)
• 3° stage – chronic, lasts for several years; scarring
& lymphatic blockage
• Late sequelae more distressing in women – rectal
strictures, elephantiasis of vulva

64. • Ocular involvement with LGV is extremely
uncommon.
• When present, it can manifest as Parinaud’s
oculoglandular syndrome, a condition in which
patients present with a severe papillary
conjunctivitis as well as massive tender posterior
cervical and preauricular lymphadenopathy

65. Laboratory Diagnosis of LGV
• Demonstration of elementary bodies in
materials aspirated from bubos (inguinal)
• Isolation – cell cultures
• Serology – detection of Abs
1. Micro- IF 1: 512 or more
• Frei Test – test using crude chlamydial Ag,
not done now.

66. Treatment
The current recommended treatment is
• doxycycline 100 mg twice a day for 3 weeks
or
• erythromycin 500 mg four times a day for 3 weeks,
or
azithromycin 1 g every week for 3 weeks.
In addition, aspiration of the affected lymph nodes may
be required to relieve pain and to prevent ulcer
formation

67. Ophthalmia Neonatorum
• Ophthalmia neonatorum is conjunctivitis in the
first month of life.
• • Chemical etiologies - in first 24−48 hours after
birth.
• • Gonococcal etiologies - in first 2−5 days after
birth.
• • Chlamydial infections are most common- first
5−14 days after birth.
• • Viral etiologies (including herpetic) - 6−14 days
after birth.

68. • • Early treatment is imperative to prevent
local and systemic disease
• • Prophylaxis remains critical in reducing
disease
• Decreased immunity, absence of Ig A, lack of
tears and lymphoid tissue are predisposing
factors.

69. • Broadly classified as-
– Non infective causes.
– Infective causes.
• Secondary too Silver nitrate eye drops.
• Crede’s method
– Silver nitrate is a surface active agent which
inactivates gonococci and was used as prophylaxsis.
– 90% of children receiving AgNO3 developed mild
transient conjunctival congestion.
• It was later found to be toxic to conjunctiva and is
rarely used now a days.

70. Infective causes
• Chlamydia (Most common)
• Bacteria-
– Neisseria gonorrohea (Most dangerous)
– Staph. aureus, Staph. Epidermidis.
– Strep. Pneumoniae, Strep. Viridans
– E.coli, proteus, klebsiella
• Viruses
– Herpes simplex (Very rare)

71. Incidence
• It is estimated to be 0.5% in developed
countries and as high as 17% in some
underdeveloped countries
Risk factors-
oPrematurity
oMaternal infections present in birth canal
oExposure to infectious organism.
oOcular trauma during delivery.
oPoor prenatal care
oPoor hygienic delivery conditions
oSilver nitrate exposure

72. Onset
Agent Onset Disappear
Chemical 24 hours 2-4 days.
Gonococcal 2-7 days depends on response to Rx
Chlamydia 5-14 days Depends on response to Rx

73. Hyperacute neonatal
conjunctivitis caused
by Neisseria
gonorrhoeae. (A)
Markedly edematous
eyelids and grossly
purulent discharge. (B)
Thick, purulent
discharge, conjunctival
chemosis, and papillary
hypertrophy.

74. Diffential diagnosis
• Congenital NLD obstruction
• Infectious keratitis
• Congenital glaucoma
• Preseptal /Orbital cellulitis
Lab tests
• Conjunctival smear for Gram’s and Giemsa
stain.
• Culture on blood and chocolate agar
• Elisa , PCR and ligase chain reaction

75. • Chylamadial conjunctivits
– Unilateral or bilateral watery discharge
– Pseudo-membrane, pannus and opacification can
occur in few patients.
– Erythromycin or tetracycline applied within 1 hr of
delivery eliminates the chance of infection.
• Treatment
– Erythromycin drops QID with oral erythromycin
syrup 50mg/kg/day for 2-3 weeks.
– Azithromycin 10mg/kg for 3days.
– Mother and sexual partners should be Rx

76. • Gonococcal conjunctivitis
– Most severe with Lid Odema, Eryethema,
discharge & membranes progressing to ulcer and
perforation if Rx is delayed.
– Rx is Erytromycin or Bacitracin ointment every 2-4
hrs along with i.v Penicillin G 1lac units/kg/day in
four divided doses. OR
– Ceftriaxone 50mg/kg i.m as single dose for 7 days
– Topical saline drops to remove the discharge
– Followed up on daily basis for improvement or
worsening, follow up by pediatrician for Rx
systemic complications.

77. • HSV keratoconjunctivitis
– Acyclovir e/o 5 times a day or triflurothymidine
1% drops every 2 hrs for a week.
– IV Acyclovir 45mg/kg/day for 14-21 days
depending on presence or absence of CNS
involment.
• Prognosis
– Is usually good with early diagnosis and prompt
treatment.

78. Thank you