Chlamydial infections & ophthalmia neonatorum

Chlamydia trachomatis

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

2. Leading cause of Ocular & Genital infections Pathogenicities : Trachoma Adult Inclusion conjunctivitis Neonatal conjunctivitis Infant pneumonia 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 3 rd 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 : Elementary body – extracellular, infective form Reticulate body – intracellular, growing & replicative form Chlamydial microcolony within the host cell is called Inclusion body . Mature inclusion body contains 100 - 500 elementary bodies

12. 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.

13. Immunology Three major Ags Group specific Ag – heat stable, common to all chlamydiae , a lipopolysaccharide resembling LPS of GNB. Present in all stages. Species specific protein Ags – present at the envelope surface, help in classifying chlamydia into species 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

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

15. 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

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

17. 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

18. 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

19. 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

20. 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

21. 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.

22. 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.

23. 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)

24. 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.

25. Follicles

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

27. Pannus

28. Herbert’s pits

29. 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

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

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

32. 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.

33. Conjunctival follicles and progressive developing Arlt’s line

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

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

36. Artl,s line

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

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

39. 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

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

41. Diagnosis Mainly depends on clinical findings. Lab tests approaches available:- Microscopic demonstration of inclusion or elementary bodies- G iemsa 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.

42. 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.

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

44. 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 .

45. IF staining

46. 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

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

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

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

50. 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

51. 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

52. Guidelines for Elimination of Blinding Trachoma 1997: WHO establishes the G lobal Alliance for the E limination of Blinding T rachoma by 2020 (GET2020) 1998: World Health Assembly signs resolution endorsing the Alliance and encourages countries to eliminate trachoma (WHA 51.11)

53. 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

54. 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

55. 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

56. 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

57. 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

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

59. 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

60. 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.

61. • 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.

62. 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.

63. 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)

64. Incidence It is estimated to be 0.5% in developed countries and as high as 17% in some underdeveloped countries Risk factors- Prematurity Maternal infections present in birth canal Exposure to infectious organism. Ocular trauma during delivery. Poor prenatal care Poor hygienic delivery conditions Silver nitrate exposure

65. 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

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

67. 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

68. 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

69. 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.

70. 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.

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