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Case of the Month

September 2016

Case of the Month – September 2016 Dr Marcelle le Roux – Sefako Makgatho Health Science University

A 23-year old student was seen at the termination of pregnancy clinic and recruited to take part in a Sexually Transmitted Infection (STI) prevalence study. She was asymptomatic and on examination had a moderate vaginal discharge. Recruitment is anonymous; therefore the results were not reported to her. She did however, receive syndromic treatment for vaginal discharge. A nucleic acid amplification test was positive for Mycoplasma genitalium.

http://cmr.asm.org/content/24/3/498.full

Question 1: What are Mycoplasmas?

Answer to Q1

Mycoplasma genitalium (M. genitalium) is one of the smallest prokaryotes capable of replication, lacks a cell wall and has a characteristic pear/flask shape with a terminal tip organelle (1). M. genitalium has several virulence factors that are responsible for its pathogenicity. These includes its ability to adhere to host epithelial cells, the release of enzymes and the ability to evade the host immune response by antigenic variation. The term “genital mycoplasmas” refers to a category of several different species of sexually transmitted bacteria most notably Mycoplasma genitalium, but also less common species, such as Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum.

M. genitalium is an emerging cause of sexual transmitted infections (STIs) and has been implicated in urogenital infections of men and women around the world (2). More than 25 years after its initial isolation from men with non-gonococcal urethritis (NGU), M. genitalium is now recognised as an important aetiological agent of acute and persistent male NGU. In women, M genitalium has been significantly associated with both cervicitis and pelvic inflammatory disease (PID) (2). The role of this organism in male urogenital disease is a significant advancement in our knowledge of STIs, but its role in the inflammatory reproductive tract diseases of women is still not very clear.

Currently, there are no evidence-based guidelines specifically for the treatment of M. genitalium infection. Within South Africa, M. genitalium pathogens are treated under the terminology associated with STI syndromic management, i.e. male urethritis syndrome (MUS), vaginal discharge syndrome (VDS) and lower abdominal pain syndrome (LAP). (3). Doxycycline is dispensed as part of the antibiotic cocktail for each of these syndromes, primarily to treat Chlamydia trachomatis. M. genitalium has been associated with HIV co-infections in a number of previous studies (4). An urgent consensus is required on how best to treat M. genitalium infections, particularly in areas with substantial burden of HIV infection.

In comparison with other STIs there is less information about the global prevalence of M. genitalium. The prevalence of M. genitalium in men with non-chlamydial NGU (NCNGU) ranges from 10%-45% and in general population from 1% to 3.3% (5).

Question 2: With which gynaecological disorders is M. genitalium significantly associated?

Answer to Q2

Cervicitis (inflammation of the cervix): Cervicitis can make vaginal intercourse painful, and can cause vaginal discharge or bleeding — it was found that women infected with M. genitalium were six times more likely to bleed after vaginal intercourse than uninfected sexually active women. M. genitalium occurs in up to 30% of women diagnosed with cervicitis.

Pelvic inflammatory disease (PID): Infection with M. genitalium more than doubles one’s risk for PID, which can lead to infertility, chronic pelvic pain, and increased risk for ectopic pregnancy. While PID is usually caused by gonorrhoea or chlamydia, M. genitalium occurs in up to 22 percent of PID cases. There is also some evidence that M. hominis can cause PID as well.

Preterm birth: Infection with M. genitalium poses a risk for preterm birth, in which a baby is born before a pregnancy has reached 37 weeks.

Question 3: How is M. genitalium diagnosed and how is it managed?

Answer to Q3

Since M. genitalium cannot be cultured on standard laboratory media, nucleic acid amplification tests (NAATs) are used for detection. These include conventional and real-time PCR tests as well as transcription mediated amplification assays. However, so far, none of them have been approved by the FDA. Most of the PCR assays target the adhesion gene which is thought to be conserved.

Patients with symptoms are treated syndromically with tetracyclines, fluoroquinolones or macrolides (depending on local recommendations) regardless of the detection of C. trachomatis or M. genitalium. In this setting, the syndromic treatment approach, as prescribed by the South African Department of Health, is followed with a single dose of azithromycin (DOH, 2015). (3)

Although genital mycoplasma symptoms might mimic those of gonorrhoea, treatment with ceftriaxone (the recommended treatment for gonorrhoea) won’t have any effect on M. genitalium as it does not have a cell wall.

Genital mycoplasma symptoms might also be confused with chlamydia, and drugs that cure chlamydia might kill M. genitalium as well. Azithromycin, which is the drug of choice for chlamydia, is thought to be reasonably effective against genital mycoplasmas, but it also seems that M. genitalium‘s resistance to this drug is on the rise, as cure rates have declined from 85 to 40 percent. Doxycycline, which is also given to cure chlamydia, only cures M. genitalium in 31 percent of cases. Reduced susceptibility to specific fluoroquinolones has been reported. More testing needs to be done, but at this time it seems that moxifloxacin is the most effective cure for M. genitalium. (6.7)
Answer to Q3

Since M. genitalium cannot be cultured on standard laboratory media, nucleic acid amplification tests (NAATs) are used for detection. These include conventional and real-time PCR tests as well as transcription mediated amplification assays. However, so far, none of them have been approved by the FDA. Most of the PCR assays target the adhesion gene which is thought to be conserved.

Patients with symptoms are treated syndromically with tetracyclines, fluoroquinolones or macrolides (depending on local recommendations) regardless of the detection of C. trachomatis or M. genitalium. In this setting, the syndromic treatment approach, as prescribed by the South African Department of Health, is followed with a single dose of azithromycin (DOH, 2015). (3)

Although genital mycoplasma symptoms might mimic those of gonorrhoea, treatment with ceftriaxone (the recommended treatment for gonorrhoea) won’t have any effect on M. genitalium as it does not have a cell wall.

Genital mycoplasma symptoms might also be confused with chlamydia, and drugs that cure chlamydia might kill M. genitalium as well. Azithromycin, which is the drug of choice for chlamydia, is thought to be reasonably effective against genital mycoplasmas, but it also seems that M. genitalium‘s resistance to this drug is on the rise, as cure rates have declined from 85 to 40 percent. Doxycycline, which is also given to cure chlamydia, only cures M. genitalium in 31 percent of cases. Reduced susceptibility to specific fluoroquinolones has been reported. More testing needs to be done, but at this time it seems that moxifloxacin is the most effective cure for M. genitalium. (6.7)

References

  1. Waites KB and Taylor-Robinson D: Mycoplasma and ureaplasma. Manual of Clinical Microbiology, ed 10. Edited by Versalovic J., Carroll K., Funke G., Jorgensen J., Landry M., and Warnock DW. Washington, DC, ASM Press, 2011, 970-985.
  2. Jensen JS. Mycoplasma genitalium infections.Diagnosis, clinical aspects, and pathogenesis.Dan Med Bull 2006; 53(1): 1-27.
  3. Department of Health, Sexually Transmitted Infections: Management Guidelines 2015: http://www.kznhealth.gov.za/family/STI-guidelines-2015.pdf
  4. Mavedzenge S and Weiss H. 2009. Association of Mycoplasma genitalium and HIV infection: A systematic review and meta-analysis. AIDS. 23: 611-620.
  5. Taylor-Robinson D, Jensen JS. Clin Microbiol Rev. 2011; 24(3):498-514
  6. Bissessor M, Tabrizi SN, Twin J, et al.Macrolide resistance and azithromycin failure in a Mycoplasma genitalium-infected cohort and response of azithromycin failures to alternative antibiotic regimens. Clin Infect Dis 2015; 60(8): 1228-1236.
  7. Couldwell DL, Lewis DA. Mycoplasma genitalium infection: current treatment
options, therapeutic failure, and resistance-associated mutations. Infect Drug Resist. 2015; 8:147-161.

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