Dr Edward Coughlan. Clinical Director Christchurch Sexual Health Christchurch

Transcription

1 Dr Edward Coughlan Clinical Director Christchurch Sexual Health Christchurch 16:30-17:25 WS #48: Mycoplasma Genitalium - The New Black 17:35-18:30 WS #58: Mycoplasma Genitalium - The New Black (Repeated)

2 Christchurch Sexual Health 314 Riccarton Road Mycoplasma genitalium Dr Edward Coughlan Clinical Director

3 Disclosures Educational grants to attend HIV meetings by ViiV

4 M genitalium- History and Biology NZ studies Other Studies of Prevalence and Associations Studies Concerning treatment Who to test,how to test, how to treat

5 History and Biology Initial isolation from 2 of 13 men with urethritis in 1980 Tully,Talyor-Robinson- Lancet 1981;1: Class of Mollicutes Very small No cell wall Very small genome 582,970 base pairs in a circular chromosome,coding for 521 genes

6 Lacks all the genes for amino acid synthesis Found preferentially in the genital tract Morphology flask shaped with a specialised tip structure Good at adhering

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11 Christchurch Pilot 46 men with diagnosed Urethritis 5 of these positive for M genitalium ( 10.8%) 1 of these had rectal chlamydia at the time of diagnosis,others negative for Gonorrhoea or Chlamydia All had a past history of chlamydia 2 had recurrent or persistent NGU

12 A Case-Control Study of Men with Non-Gonococcal Urethritis at Auckland Sexual Health Service Rates of Isolation of Mycoplasma genitalium Jackie Hilton* Sunita Azariah, Murray Reid

13 Method Men presenting to ASHS with symptoms of urethritis or asymptomatic men were invited to participate in the study. Men were given an information sheet and signed a consent form if they were agreeable to participate

14 Specific Infections Cases Controls X 2 p CT 70 (33.5%) MG 21 (10.0%) 8 (4.0%) 55.4 < (2.0%) 10.1 <0.005 co-infected* 4 (1.9%) - [*included in organism specific totals]

15 Conclusions In this sample the rate of isolation of MG from men with NGU was lowish (10%) The rate of co-infection with CT was very low If not specifically tested for, the 4 controls with MG would not have been detected. MG is a cause of NGU in MSM Azithromycin 1g stat has good efficacy as a treatment for MG BUT NOT ANY MORE

16 Auckland Sexual Health In women who were being screened for an STI Chlamydia trachomatis 10.7% M genitalium 8.4% N gonorrhoea 1.9% -Trichomoniasis 3.5%» Oliphant,Azariah 2013

17 Estimated prevalences in 40 independent studies (27 000) women 7.3% MG in high risk,2.0% low risk CT ( 4.2% ),NG (0.4%) USA

18 Urethritis Inoculation of male chimpanzees resulting in urethritis Brit J of Exp Path 1985,66: M genitalium prevalence in urethritis patients varies from 8% ( urology) to 29% among STD patients M genitalium prevalence in asymptomatic patients varies from 0% ( urology) to 9% among STD patients Uuskula Int J of STD and AIDS 2002;13:79-85

19 Urethritis Persistent urethral inflammation seen in a substantial number of men despite M genitalium eradication Bjornelius STI 2008 ;84:72-76 Relapsing /recurrent urethritis M genitalium +ve, respond initially to doxycycline clinically but still can isolate M gentilium then relapse Mena CID 2009 ;

20 Urethritis Wikstrom and Jenson found 40% of those patients with patients with NCNGU treated with doxycycline who failed treatment were M genitalium positive Wikstom Jensen STI 2006 ;82: Also men with M genitalium more often have urethritis with >10 PMNs/hpf than those with NMGNCNGU. Ie men with urethritis but none of these pathogens

21 Endometritis In this study-detected M genitalium in the cervix,endometrium or both in 9(16% ) of 58 women with histologically confirmed endometritis and in 1 ( 2%) of 57 without endometitritis Cohen Lancet Mar 2,2002,359,pg 765

22 Manhart et al showed women with M genitalium had 3.3 fold greater risk of Mucopurulent cervicitis Manhart JID 2003:187,

23 In contrast, other studies of high-risk female populations have failed to demonstrate an association between M. genitalium detection and cervicitis, despite high M. genitalium detection rates. In one prospective study of 170 women who presented to an STI clinic in France with abnormal vaginal discharge, the prevalence of M. genitalium was 38 percent,.

24 its detection was not associated with signs (erythematous cervix, mucopurulent discharge, or 10 PMNs per high power field in the cervical smear) or symptoms of cervicitis

25 PID M. genitalium can ascend from the lower to upper genital tract after sexual transmission and several studies have observed associations between detection of the organism and clinical signs or symptoms of PID. In a meta-analysis of 10 studies, the pooled OR for PID among women with M. genitalium infection was 2.14(95% CI ) ( UpToDate)

26 In a prospective study of 2246 sexually active female college students, the baseline prevalence of M. genitalium in selfcollected vaginal specimens was low (3.3 percent), and there was a nonsignificant increase in incidence of PID over a 12- month period among women with detectable M. genitalium compared with those in whom it was not detected (risk ratio 2.35, 95% CI ) UPtoDATE

27 M genitalium in major STI syndromes ( J Jensen) Male NGU ++++ Numerous studies shows this association Around 15% of NGU and 20% of NCNGU Treatment failure leads to persistent symptoms Proctitis + Found in 2-5% of MSM, more in australia No obvious correlations

28 Epididymitis + Few trials Female NGU +++ Only in Scandinavia Cervicitis +++ Most studies show an association PID ++ Increasing evidence but?? Proportion of PID caused by M genitalium less than chlamydia

29 BV + Adverse Pregnancy Outcomes + Prevalence is low in pregnant women Male infertility?? Female Infertility + Serological studies Ectopic Pregnancy? Chronic Abdominal Pain?

30 Resistance Azithromycin binds to the 50S subunit of the ribosome ( includes 23S and 5S) =>inhibits translation of mrna => inhibits protein synthesis Resistance can occur with mutations in the 23S rrna gene => inhibit azithromycin binding

31 Resistance In vitro resistance mediated by mutations in the 23 S rrna gene Thought to occur as a result of single dose treatment of 1.0 gram azithromycin» Jensen CID 2008 :47,1546 Level of azithromycin resistance is very important and is influenced by treatment tradition

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33 Macrolide Resistance

34 M. genitalium antibiotic resistance Resistance development by single base pair change in the 23S rrna gene at the macrolide binding site Nucleotide position A2058 and A2059

35 Melbourne : Looked at individuals with treatment failure using pre and post treatment samples and looked for mutations in 23sRNA gene. All cases (20) of treatment failure had resistant mutations 9 (45%) had this pre and post treatment 11 (55%) had this post only ie induced» Plos Twin et al 2012

36 The development of resistance to the fluoroquinolones has shown to be linked to mutations in the gyr A and par C genes.

37 M. genitalium antibiotic resistance Second-line treatment using fluoroquinolone such as moxifloxacin Resistance development by single base pair change(s) in four genes important in DNA replication DNA gyrase genes gyra and gyrb Topoisomerase genes parc and pare Mutations occur in the quinolone resistance determining region (QRDR) of each gene Step-wise resistance development One mutation = low level resistance 2 or more = high level resistance

38 CE (Conformité Européene marking) = European quality clearance of new microbiological diagnostics M gen Testing Technologies in flux re FDA approval

39 Mycoplasma genitalium: Local Epidemiology

40 Who To Test Men with persistent/ recurrent urethritis, who have failed initial treatment with doxycycline 100mg bd 7/7 Current ongoing contacts of people who test positive for MG Women with persistent PID who have failed standard treatment

41 How to Test Use Speedex platform ( CHL not Southern Community) On request form need to state reason And test = M genitalium PCR Male urine test Female- vulvovaginal swab using the Abbott Multicollect ( may need to send them to SCL collection site)

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44 How to Treat Keeps changing Eg for M genitalium with no resistance 1 gram azithromycin Azithromycin 500mg stat then 250mg for 4 days Now Doxycline 100mg BD for 7 days then Azithromycin 1.0 gram stat then 500mg once a day for 3 days

45 How to Treat No resistance then Doxycline 100mg BD for 7 days then Azithromycin 1.0 gram stat then 500mg once a day for 3 days

46 If macrolide resistance present and azithromycin has been used AND failed Then apply for Special Authority online and use moxifloxacin 400mg for 7 days

47 If macrolide resistance present and azithromycin has NOT been used then need to fax a request for a waiver And use Moxifloxacin for 7 days

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49 IN all cases a test of cure 4 weeks after treatment completion NO sex until clear test of cure and partner test of cure

50 Refer in any failures after Moxifloxacin IF easier refer in if positive M genitalium test

51 Summary Treat initial urethritis with doxycline if gonorrhoea is unlikely. Don t order M genitalium testing as a screen Refer positives if easier

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53 Acknowledgements Canterbury Health Laboratories- Julie Creighton, Trevor Anderson.Anja Werno Melbourne (Marcus Chen,Cat Bradshaw) Staff Christchurch Sexual Healthespecially Dr Heather Young