Mycoplasma genitalium

Carina Bjartling

Dep of Gyn & Obst

Skane University Hospital, Malmö, Sweden

Mycoplasmas - class mollicutes

• Free-living small bacteria (0.3 - 0.5 μm)• Lack a rigid cell wall • Commonly found in the human urogenital tract:

- M. genitalium 580 bp (1-3%)- M.Hominis 665 bp (20-50%)- Ureaplasma urealyticum 840-950 kbp andU. parvum 751 kbp (40-80%)

Jensen and Unemo. WHO Manual. 2013

Urogenital mycoplasmas

Urogenital mycoplasmas

• M.hominis, U.urealyticum, U.parvum- commonly detected in healthy individuals

• Their association with urogenital infection in either men or women remains to be conclusively proven

Mycoplasma genitalium

• Well documented as an agent of NGU in men

• Sexually transmitted

• Documented as an agent of cervicitis in women

• Less well documented in PID

• Limited documentation as a patogen in ectopic pregnacy and TFI

• Scarse documentation as a patogen in adverse obstetrical outcome

Mycoplasma genitalium

• Documented association with HIV and recently a study showing M.genitalium infection to facilitate acquisition of HIV-1 (Mavedzenge SN et al, 2012)

• SARA- case reports but no systematic studies

Prevalences of M.genitaliumEstimated prevalences in 40 independent studies (27000 women) screened for M.genitalium world wide:- 7.3 % in high-risk population (0 – 42%)- 2.0 % in low-risk population (1- 5 %)- CT (4.2 %) and Ng (0.4 %) (USA) (McGowin et al, 2011)

Prevalence in Malmö, Sweden at the women’s clinic emergency service between 2003-2008 in 5519 women-MG- 2.1 %-CT- 2.8 % (Bjartling et al, 2012)

Clinical studies of M.genitalium and PID

Case –control studies:•Uno et al. 1997, Japan. 2/49 (4%) in cases, 0/80 (0%) in controls •Cohen et al. 2002, Kenya, Nairobi. 9/58 (16%) in cases, 1/57 (2%) in controls, endometrial specimen •Simms et al. 2003, UK. 6/45 (13%) in cases, 0/37 (0%) in controls •Cohen et al. 2005, Kenya, Nairobi. 9/123 (7%), abd. fluid- 1/123 (1%),•Haggerty et al. 2006, USA. 7/50 (14%),(8% in endometrial specimen)•Bjartling et al. 2012, Sweden. 4/81 (4.9%) in cases, 2/346 (0.6%) in controls

Prospective studies:•Oakeshott et al, 2010, UK. 3/77 (4%), 12 months follow up •Bjartling et al. 2010, Sweden, 6/49 (12%) in cases, 4/168 (2%) in controls, post abortal PID, 6 weeks follow up

Proportions of M.genitalium and C.trachomatis attributable to PID

M.genitalium

- 4- 16% (5 studies, 1997- 2012)

C.trachomatis

- 20- 55% (19 studies through the 1990s)

- 42% (POPI trial, 2004-2007)

Serological studies of M. genitalium, PID, TFI and ectopic pregnancy –

• Möller et al, 1984, UK. MG – ab in 40 % of 31 women with PID

• Lind et al, 1987, Denmark. No ass. between MG – ab and PID in 95 cases of salpingitis

• Clausen et al, 2001, Denmark, MG- ab in 22 % (29/132) TFI compared to 6.3 % (11/176) of the controls

• Jurstrand et al, 2007, Sweden, no sign. difference between MG –ab in PID, ectopic pregnancy and normal controls

• Svenstrup et al, 2008, Denmark. MG – ab in 17 % of 30 TFI cases compared to 4% of the controls

• Stephen et al, 2006, USA. 2.5 times higher infertility rate among women with MG in the endometrium . Register study 1982-2002

M.genitalium and adverse obstetric outcome

• Oakeshott et al 2004, UK, 1216 early pregnant, no ass with miscarriage , MG prevalence 0.7 %

• Labbe et al 2002, no sign ass with preterm delivery

• Kataoka et al, 2006, no ass for preterm delivery

• Edwards et al 2006, USA, Florida. 134 pregnant women, prospective study, preterm delivery, OR 3.48 (1.41- 8.57).

• Hitti et al 2010, ass with preterm delivery,OR 2.5 (1.2-5.0)

Diagnosis of M.genitalium

• Culture is insensitive and extremely slow

• Serologi has low specificity and low sensitivity

• NAAT is the only practical method for diagnosis

- technically demanding, organism load 100-fold lower than C.trachomatis

• No validated (FDA), commercially available assays

• Important to validate and quality assure in-house assays

• Real- time PCR- robust and lower risk of contamination than PCR

Genital specimen for diagnosis of M.genitalium

SummaryMen:

- FVU (67.0- 97.6%)

- Urethral swab (58.0- 82.5%),

Women:

- self collected vaginal swab (91.0%)

- clinician collected cervical swab (58.9- 74.3%)

- clinician collected vag swab (57.0- 72.6%)

- FVU (61.4- 88.0%)Jensen JS et al, 2004Wroblevski JK, 2006Jurstrand M et al, 2005Edberg A et al 2009Shipitsyna E, 2009Lillis RA, 2011Mobley et al 2012

Treatment of M.genitalium infections

• Cure rates of different antibiotics are relatively low and declining

• Cure rate azithromycin (1 g azithromycin):

– Settings with high usage of azithromycin: 40-85%

– Settings with low usage of azithromycin: 95-100%?

• Cure rate doxycycline:

– 17-45%

• Cure rate fluoroquinolones:

– Ofloxacin: 50%

– Moxifloxacin: 100%

Falk, et al. STI. 2003Jernberg, et al. IJSA. 2008Bjørnelius, et al. STI. 2008Mena, et al. CID. 2009Terada, et al. JIC. 2011 Twin, et al. PLoS. 2012Manhart, et al. CID. 2013

Treatment of M.genitalium infections

Antibiotics Treatment efficacy

Tetracyclin/Doxycyclin 20-40%

Azithromycin 1g x 1 65-90%

Azithromycin 500 mg dag 1 + 250 mg dag 2-5 70-100%

Ciprofloxacin, ofloxacin, levofloxacin 30-55%

Moxifloxacin >99%

Treatment of M.genitalium infections

First choice:

- Azithromycin 500 mg×1 day 1 + 250 mg×1 in the 4 following days

(ideally, test-of-cure in ≥14 days)

Second choice (if treatment failure and not as first choice!)- Moxifloxacin 400 mg×1 daily in 7 days

Jensen, personal communication, July 2013

Take home messages

• The estimated proportion of M.genitalium and C.trachomatis attributable to PID is about 2-16% and 20-55% respectively

• Focus on detection and treatment of M.genitalium (not M.Hominis or Ureaplasma spp)

• Important to validate and quality assure in-house assays • No clear guidance can be given in the choice of optimal genital

specimen but FVU in men and self collected vaginal specimen in women seems to have the highest bacterial load

• Cure rates of different antibiotics are relatively low and antimicrobial resistance and treatment failure in M.genitalium infections are common

• First choice for treament of M.genitalium infection is Azithromycin 500 mg×1 day 1 + 250 mg×1 in the 4 following days

Thank you