Transcript Epidemiology and clinical manifestation of new variant

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 and
U. parvum 751 kbp (40-80%)
Urogenital mycoplasmas
Jensen and Unemo. WHO Manual. 2013
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.genitalium
Estimated 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
Summary
Men:
- 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, 2004
Wroblevski JK, 2006
Jurstrand M et al, 2005
Edberg A et al 2009
Shipitsyna E, 2009
Lillis RA, 2011
Mobley 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. 2003
Jernberg, et al. IJSA. 2008
Bjørnelius, et al. STI. 2008
Mena, et al. CID. 2009
Terada, et al. JIC. 2011
Twin, et al. PLoS. 2012
Manhart, 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 2055% 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