Chlamydia trachomatis

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1 Chlamydia trachomatis From the eye To the anus

2 C.trachomatis C.trachomatis is the most common curable sexually transmitted infection in Britain. Approximately 5-10% of sexually active women under 24 and men between may be currently infected.

3 Chlamydia taxonomy Order :Chlamydiales Family :Chlamydiaceae Genus: Chlamydia Species :trachomatis, psittacci, pneumoniae

4 C.trachomatis Biovars: LGV strains, L 1- L 3 Trachoma strains A,B, B a &C-trachoma D-K oculogenital infections

5

6

7 C.trachomatis: historical perspective 1907 Halberstaedter & von Prowazek discover chlamydia 1910 Lindner found chlamydia inclusions in urethral specimens from men with NSU 1934 Thygeson described adult inclusion conjunctivitis 1950 s NGU was recognised as a specific entity and tetracyclines became treatment of choice

8 C.trachomatis: historical perspective 1957 T ang et al cultured Ct in egg yolk sac 1959 Ct first isolated from the eyes of a baby with IC and from its mother s cervix 1960 s Ct first isolated from the male urethra 1965 Gordon & Quang develop cell culture system 1979 Immuno-typing of Ct was introduced

9 C.trachomatis:Diagnosis Culture Immunofluorescence (IF) Enzyme immunoassay (EIA) Nucleic Acid Amplification Tests Serology

10 Cell Culture Cell culture Sensitivity 60-80% 100% specificity Expertise essential Expensive and only limited availability nationally Can be used on all specimen types Routine use is not recommended due to high cost and low sensitivity.

11 Enzyme immunoassays (EIAs) The sensitivity of the majority of EIAs is probably only 40-70% and their use is not recommended. This guideline recommends laboratories to move to the use of NAATs utilizing Department of Health dedicated funding. Should be not used on non-invasive specimens in women, nor on rectal or throat specimens in women or men.

12 Direct fluorescent antibody (DFA) Routine use is not recommended. Labour intensive, and although a >80% sensitivity is achievable, this requires skilled personnel using a cut off of 2 elementary bodies. Unsuitable for large numbers of specimens (>30/day). Will accommodate all specimen types including rectal and pharyngeal.

13 Nucleic Acid Amplification Tests NATS Polymerasechainreaction (PCR) Ligasechainreaction (LCR) Transcriptionmediated amplificationasay (TMA) Stranddisplacement amplification (SDA)

14 SDA Kit

15 Non-Gonococcal Urethritis (NGU) Aetiology: Chlamydia trachomatis 11-50% Mycoplasma genitalium 9-25% Trichomonas vaginalis 0-17% Ureaplasma urealyticum 0-5% HSV/adenoviruses 6% Others 30-80% No organism detectable 30-80%

16 Chlamydia:sampling sites Men: anterior urethra( 3-4 cm inside and rotate) Women: endocervix 1-2 cm plus urethra 1cm USE COTTON TIPPED PLASTIC SWABS FOR EIA OR MANUFACTURERS KIT FOR NAAT

17 Target populations for opportunistic Ct screening Termination of pregnancy. IUD fitting. Miscarriage. Ectopic pregnancy. Infertile couples. Women with lower abdominal pain,cervicitis,vaginal discharge, post-coital or IMB. Parents of neonates with ophthalmia neonatorum or pneumonitis Colposcopy patients Semen donors Antenatal patients STD clinic attenders Men with urethritis,epididymitis Partners of patients with chlamydial infection

18 Chlamydia: prevalence in women 4% of sexually active women attending GP s 10-15% of new GU clinic attenders 10-15% of all women attending for TOP Up to 25% of teenagers attending for TOP

19 Risk factors for C.trachomatis Age <25 years Single status Use of oral or no contraceptives New sexual partner in preceding 3 months Ethnic Group Low school leaving age Nulliparity

20 Risk factors for C.trachomatis Vaginal discharge Menstrual disturbance Cervical abnormalities Lower abdominal pain Post-coital bleeding Intermenstrual bleeding Presence of other genital tract infection

21 Risk factors for C.trachomatis Men with urethral discharge/dysuria, epididymitis Patients with reactive arthritis Infants with ON or neonatal pneumonitis Parents of infants with C.trachomatis Adults with conjunctivitis/tonsilitis/otitis media

22 C.trachomatis in women majority are symptom-free vaginal discharge menstrual disturbance urethral syndrome lower abdominal pain right/left hypochondrial pain rarely deafness/conjunctivitis

23 C.trachomatis complications in women Pelvic inflammatory disease in 10-40% of women if left untreated Tubal damage ( subfertility,ectopic pregnancy) Peri-hepatitis/peri-splenitis Transmission to the neonate

24 Morre et al. Int J STD & AIDS 2002;13(suppl 2) :12-18 The natural course of asymptomatic Chlamydia trachomatis infections: 45% clearance and no development of clinical PID after one year followup.

25 744 healthy women attending for medical prior to employment in Amsterdam. 30 (4%) had Chlamydia detected by urine PCR were the study group. 186 Ct-ve women used as controls, all followed up for one year. The person/year clearance rate was 44.5%. None of the Ct+ve women developed clinical symptoms or took anti-ct Rx. Asymptomatic infections may clear spontaneously without adverse sequaelae

26 C.trachomatis complications in men Epididymo-orchitis Reduced male fertility possibly related to elementary bodies sticking to sperms or by direct toxicity of chlamydial lipopolysaccharide Sexually Acquired reactive Arthritis(SARA, Reiter s syndrome) Men>>women

27 C.trachomatis complications Adult conjunctivitis Otitis media

28 Severe chlamydial cervicitis. Note contact bleeding, mucopus and follicles

29 Spread of Chlamydia from the cervix UPPER GENITAL TRACT CERVIX Male partner Neonate

30 Fitz-Hugh Curtis Syndrome: chlamydial peri-hepatitis

31 This 15 year old presented with a sub-preputial discharge. Note the slight urethral discharge which could easily be overlooked.

32 Chlamydia ophthalmia typically presents about days after birth though this child had co-existent gonococcal infection Remember to treat the mother and her partner

33 Adult chlamydial conjunctivitis Note mucopus & follicles This patient, referred from the eye dept had persistent conjunctivitis, no genital chlamydia was found.

34 OK So Whats the treatment then?

35 C.trachomatis: treatment of uncomplicated infection in adults Doxycycline 100mg bdx 7/7 Azithromycin 1 gm stat Oxytetracycline 500mg qid x10/7 Deteclo 300md bd x 7/7 Erythromycin 500mg qid x7-10/7 Erythromycin 500mg bd x 14/7 Ofloxacin 400mg od x 7/7 Amoxycillin 500 tds x7 days

36 European/UK LGV

37 Chlamydia trachomatis sub-types A-K strains cause the common ocular and urogenital infection. The L1-L3 strains cause ulcerative and systemic disease, lymphogranuloma venereum(lgv). Current European/UK LGV outbreak is caused by the L2b serovar

38 European/UK LGV There have been recent outbreaks of LGV, all due to type L2b in the UK. 2003/4 first cases were reported from Rotterdam in MSM who visited saunas, leather bars or sex parties. The disease spread from the Netherlands to Europe and North America & Canada. DNA typing suggests the disease may have started in San Francisco in the 1980 s.

39 UK LGV As of Dec 05, 292 cases in UK by the end of July 2006 this rose to 398. Now widespread in UK but mainly in London & Brighton. Scotland have 11 cases and Wales, all from Swansea have 3 confirmed plus 2 unconfirmed. From lecture given by Dr Helen Ward, HPAC for Infections, London. BASHH May 06

40 UK LGV 3 UK cases are in heterosexual men, the remaining in MSM s. 95% of cases are white and 70% indigenous. 84% present with symptoms, range 1day to 18 months. From lecture given by DrHelen Ward, HPAC for Infections, London. BASHH May 06

41 UK LGV 79% have rectal discharge. 69% anorectal pain. 58% rectal bleeding. 29% tenesmus. 25% constipation. Other symptoms, diarrhoea, wt loss, malaise. Typically no inguinal lymphadenopathy is noted. From lecture given by Dr Helen Ward, HPAC for Infections, London. BASHH May 06

42 European/UK LGV Chlamydia trachomatis immunotypes and proctitis LGV immunotypes cause a primary ulcerative proctitis and a histological picture of giant cell formation and granulomas, similar to Crohns. Non LGV immunotypes cause a milder infection associated with rectal pain, bleeding and diarrhoea LGV proctitis is linked with HIV positivity and high numbers of partners in last 6 months.

43 UK LGV 76% are co-infected with HIV 20% have Hep C 40% have other STI s From lecture given by Dr Helen Ward, HPAC for Infections, London. BASHH May 06

44 Williams & Churchill BMJ 14 th Jan 2006 Water soluble enema of 33yr old HIV+ve MSM showing rectal stricture with ulceration. Initially diagnoised as UC and Rx with oral prednisolone and mesalazine. Symptoms 22 months prior to diagnosis of LGV given 6 weeks of doxycycline but still likely to need surgical management of his stricture

45 LGV Diagnosis is by NAAT testing of rectal swabs and chlamydia serology. Use B&D female SDA kit. Titre >1:256 is diagnostic as is 4 fold rise in titre. From lecture given by Dr Helen Ward, HPAC for Infections, London. BASHH May 06

46 LGV Treatment is with 3 weeks of doxycycline (100mg bd). Or erythromycin 500mg qid x 21days. Or azithromycin 1gm weekly for 3 weeks. Screen for HIV, Hep B, HepC, Syphilis. Recent partners should be treated epidemiologically. From lecture given by Dr Helen Ward, HPAC for Infections, London. BASHH May 06

47 Lymphogranuloma venereum: the Swansea experience Dr Anona Blackwell

48 Case 1 HIV +ve Date of presentation: 8/11/04. MSM Age 34 years LSI 5/12 Manchester. 4 month history of pain,bloody stools,mucous, tenesmus. Previously admitted in Manchester for severe haemorrhagic proctitis. Rx Mesalazine, metronidazole, Lamisil.

49 Case 1 OE :severe haemorrhagic proctitis,perianal HSV ulceration Other STI s: Hep B e antigen+ve, HSV +ve perianal ulcer Rectal Ct contaminated but Psitt/LGV serology +1/512, IFA +ve 1/4000 Rx doxycycline100mg bd x 21 days

50 Case 2 HIV +ve Date of presentation: 13/1/05. MSM Age 40 years, SI in Germany & Belgium. 6 month history of pain,bloody stools,mucous, tenesmus, constipation,diarrhoea,wt loss, debilitation. Previously investigated in Germany for severe haemorrhagic proctitis. Rx Mesalazine, high fibre diet, anal dilator.

51 Case 2 OE :severe haemorrhagic proctitis, perianal fissure Other STI s: HIV, naturally immune to Hep A&B Rectal Ct not taken but Psitt/LGV serology +1/256, IFA +ve 1/4096 Rx doxycycline 100mg bd x 1 month

52 Case 3 HIV+ve Date of presentation: 5/7/05. MSM Age 54 years. 5 day history of rectal bleeding,mucous & tenesmus. Anal SI with local men.

53 Case 3 OE : mild proctitis. Other STI s: HIV & HSV of L buttock. Rectal Ct +ve for L2 serotype. Psitt/LGV serology negative. Rx doxycycline 100mg bd x 1 month.

54 Case 4 HIV -ve Date of presentation: 22/11/05. MSM Age 50 years. SI Local, plus Brighton. 1 month history of pain,bloody stools. Previously admitted to Glangwili with severe rectal bleeding. Rx Antibiotics in Glangwili.

55 Case 4 OE :severe haemorrhagic proctitis. Other STI s: Naturally immune to Hep B,meatal wart. Rectal Ct +ve,l2 serotype Psitt/LGV serology +1/512, IFA +ve 1/4096. Rx Doxycycline 100mg bd x 21 days,well after Rx.

56 Case 5 HIV -ve Date of presentation: 23/11/05 MSM Age 27 years LSI Aug 05 Birmingham sex club. 3 month history of pain,bloody stools,mucous, tenesmus, weakness. Previously investigated for severe haemorrhagic proctitis, on W/L for admission. Rx Mesalazine, Predsol foam.

57 Case 5 OE :severe haemorrhagic proctitis. Other STI s perianal warts. Rectal Ct +ve,l2 serotype Psitt/LGV serology +1/128, IFA +ve 1/4096. Given 21 days of doxycycline but developed a loose ano-rectal stricture, intersphincteric perianal abscess and a low anal fistula.

58 Summary 5 cases of anorectal LGV All in MSM s 3/5 HIV positive, all Hep C negative 4/5 late diagnosis 1/5 developed complications Serology may be negative in early stages Suspect LGV in any MSM with rectal bleeding

59 Classical LGV

60 Lymphogranuloma venereum(lgv) LGV is a systemic disease caused by one of three invasive serovars, L1-3 of Chlamydia trachomatis. Classically it is a disease which mainly presents in heterosexual travellers from area where it is endemic, including Africa, India and South East Asia.

61 Classical Lymphogranuloma venereum(lgv) It presents in three stages: The primary lesion, which appears 3-30 days after infection, is a painless papule,pustule or ulcer, often in the coronal sulcus in men and posterior vaginal wall or fourchette in women

62 Classical Lymphogranuloma venereum painless ulcer

63 Groove sign with fistula formation

64 Classical Lymphogranuloma venereum The tertiary stage presents as progressive spread of Ct in the anogenital tissues with tissue destruction. There may be proctitis, acute proctocolitis mimicking Crohns, fistulae and chronic disfigurement.

65 Tertiary LGV with tissue destruction and distortion

66 Non-Gonococcal Urethritis (NGU) Aetiology: Chlamydia trachomatis 11-50% Mycoplasma genitalium 9-25% Trichomonas vaginalis 0-17% Ureaplasma urealyticum 0-5% HSV/adenoviruses 6% Others 30-80% No organism detectable 30-80%

67 Mycoplasma genitalium This bacterium is now recognised as an STI but screening tests are not yet commercially available. The organism is fastidious and culture is difficult with the organism taking weeks or months to grow. NAAT tests are the only option.

68 Mycoplasma genitalium M.g is found in the highest prevalence in men with CT negative NGU. M.g seem to cause the more severe forms of Ct negative NGU. Systematic studies linking M.g to epididymitis & prostatitis are lacking but it has been found in the urethra of men with epididymitis and in prostatic tissue of men with prostatitis.

69 Mycoplasma genitalium In women Mg is found in the genital tract and is detected more often in those with symptoms/signs and those with an infected partner. Mg is associated with cervicitis, urethritis and has been found in the endometrium of women with pelvic inflammatory disease. Serological studies suggest a strong association between past infection with Mg and tubal factor infertility.

70 Mycoplasma genitalium Rx Azithromycin 500mg stat then 250mg daily x 5 days Azithromycin 500mg od x 5-7 days Moxifloxacin(a quinolone) 400mg odx7 days For suspected Mg PID use azithromycin 500mg od x14 days

71 Useful Websites bashh.org This is our association s website and gives details of all STI s and their management and has lots of useful information including the addresses and phone numbers of UK clinics.(british Association for Sexual Health & HIV)

72 AND FINALLY.

73 Time to go home

74 Thanks for listening

75 SYPHILIS IS BACK!

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