Trichomonas Vaginalis Metronidazole Resistance Information

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T. vaginalis is a flagellated, anaerobic protozoan and is the most common non-viral sexually transmitted pathogen. Approximately half of female T. vaginalis infections are asymptomatic (1), as are most male infections. Symptomatic infections manifest as Trichomoniasis with symptoms of discharge (yellow, green or gray, sometimes frothy), odor, itching, and pain during urination and/or intercourse. Signs of infection include small red ulcerations on the vagina and/or cervix, positive amine (whiff) test and elevated pH. Wetmount microscopy of a vaginal swab often reveals white blood cells and rapidly motile trichomonads. However, detection of trichomonads by microscopy has a sensitivity of only 60%-75% (2) whereas polymerase chain reaction
(PCR) can detect T. vaginalis with a sensitivity of 85%-100% (3). Trichomoniasis is associated with a number of serious clinical complications, as pregnant women with Trichomoniasis are at increased risk for pre-term labor and delivery of low birth weight neonates (4, 5). In addition, Trichomoniasis is associated with HIV transmission (6, 7). Patients are normally treated with a single oral dose of metronidazole, an antibiotic used to treat infections caused by anaerobic bacteria and parasites. Although generally effective, some T. vaginalis strains are resistant to metronidazole. If metronidazole treatment fails, the only other approved treatment for Trichomoniasis is the related drug tinidazole. Therefore, identifying Trichomoniasisresistance to metronidazole can help guide clinicians in prescribing effective therapy for Trichomoniasis patients.

Epidemiology

  • There are more than seven million cases of Trichomoniasis each year in the United States (3).
  • The overall prevalence of T. vaginalis among American women is 3.2%, but varies dramatically by race, from. 1.3% for non-hispanic white women to 13.3% for nonhispanic black women (8).
  • Most sexually-transmitted infections are more prevalent among adolescents and young adults. however, Trichomoniasis has a similar prevalence among sexually active women of different age groups (3).
  • Although metronidazole treatment is reported to be 85%-95% effective (9), recent reports suggest that between 2.5% and 10% of clinical T. vaginalis isolates exhibit some degree of metronidazole-resistance (10,11).Trichomonas Vaginalis Metronidazole ResistancePathogenesis
  • T. vaginalis attaches to the vaginal epithelium and several T. vaginalis adhesins have been identified that mediate this binding (12).
  • After binding, T. vaginalistriggers detachment of cells through proteolytic activity, cytotoxicity and apoptosis. (3).
  • Patients infected with T. vaginalis produce circulating (IgG) and secreted (IgA) antibodies that recognize adhesins and prevent parasite adhesion; however, protection is only short-term as re-infection rates as high as 30% have been observed (3).

Laboratory Diagnosis

  • A cervico-vaginal specimen can be submitted for laboratory testing to detect T. vaginalis. Detection of trichomonads by PCR has a sensitivity of 85%-100% (3).
  • Currently, only the Centers for Disease Control and Prevention (CDC) can determine metronidazole susceptibility for T. vaginalis. A viable culture of T. vaginalis must be received, using a specialized collection and transport device.
  • Medical Diagnostic Laboratories can now detect metronidazole resistance in a subset of T. vaginalis specimens by Real-Time PCR. Our current assay detects a mutation that encodes a K80STOP change in the Tvntr6 protein, and has 40% sensitivity, 96% specificity, and a 91% positive predictive value (PPV) for the detection of T. vaginalis metronidazole resistance. This test was developed using 100 wellcharacterized T. vaginalis isolates from the CDC.

Clinical Benefits of Testing

  • The OneSwab®platform allows for the detection of T. vaginalis and associated metronidazole resistance in cervico-vaginal specimens.
  • Detection of metronidazole resistance can assist clinicians in administering effective treatment for Trichomoniasis patients.
  • Benefits of this system include: The use of highly sensitive and specific Real-Time PCR technology, simple and convenient sample collection, no refrigeration required before or after collection, specimen viability up to five (5) days, test dditions available up to 30 days and 24-48 hour turnaround time.

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Treatment Considerations

  • Treatment guidelines for Trichomoniasis are available from the CDC http://www.cdc.gov/std/treatment/2010/vaginal-discharge.htm. (Accessed March 28, 2012).
  • First-line therapy is a single 2 gram dose of oral metronidazole.
  • If initial therapy fails, and re-infection can be excluded, the patient can be treated with 500 milligrams of oral metronidazole twice per day for 7 days.
  • If treatment is still not effective, consider using oral metronidazole or tinidazole, 2 grams per day for 5 days.
  • Patients should avoid alcohol during metronidazole or tinidazole treatment, as well as for 24 hours after the end of metronidazole treatment and 72 hours after the end of tinidazole treatment.
  • If treatment is still unsuccessful, contact the CDC for a consultation.Frequently

Asked Questions (FAQ)

  • What does a positive result mean for the detection of the Tvntr6 K80STOP mutation? A positive result indicates a >90% likelihood that the T. vaginalis present in the specimen exhibits some degree of resistance to metronidazole. It is not known if this level of resistance is associated with clinical failure to metronidazole treatment.
  • What does a negative result mean for the detection of the Tvntr6 K80STOP mutation? As our current assay only detects 40% of resistant T. vaginalisisolates, a negative result is inconclusive. It does not mean that the T. vaginalisin question is susceptible or resistant to metronidazole.

References

  1. Fouts AC, Kraus SJ. 1980. Trichomonas vaginalis: reevaluation of its clinical presentation and laboratory diagnosis. J Infect Dis 141:137-143.
  2. Krieger JN, Tam MR, Stevens CE, Nielsen IO, Hale J, Kiviat NB, Holmes KK. 1988. Diagnosis of trichomoniasis. Comparison of conventional wetmount examination with cytologic studies, cultures, and monoclonal antibody staining of direct specimens. JAMA 259:1223-7.
  3. Schwebke JR, Burgess D. 2004. Trichomoniasis. Clin Microbiol Rev 17:794-803, table of contents.
  4. Cotch MF, Pastorek JG 2nd, Nugent RP, Hillier SL, Gibbs RS, Martin DH, Eschenbach DA, Edelman Rao AV, Rhoads GG. 1997. Trichomonas vaginalis associated with low birth weight and preterm delivery. The Vaginal Infections and Prematurity Study Group. Sex Transm Dis 24:353-60.
  5. Minkoff H, Grunebaum AN, Schwarz RH, Feldman J, Cummings M, Crombleholme W, Clark L, Pringle G, McCormack WM.1984. Risk factors for prematurity and premature rupture of membranes: a prospective study of the vaginal flora in pregnancy. Am J Obstet Gynecol 150:965-72.
  6. Laga M, Manoka A, Kivuvu M, Malele B, Tuliza M, Nzila N, Goeman J, Behets F, Batter V, Alary M, et al.1993. Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. AIDS 7:95-102.
  7. Wang CC, McClelland RS, Reilly M, Overbaugh J, Emery SR, Mandaliya K, Chohan B, NdinyaAchola J, Bwayo J, Kreiss JK. 2001. The effect of treatment of vaginal infections on shedding of human immunodeficiency virus type 1. J Infect Dis 183:1017-22.
  8. Sutton M, Sternberg M, Koumans EH, McQuillan G, Berman S, Markowitz L. 2007. The prevalence of Trichomonas vaginalis infection among reproductiveage women in the United States, 2001-2004. Clin Infect Dis 45:1319-26.
  9. Lossick JG.1990. Treatment of sexually transmitted vaginosis/vaginitis. Rev Infect Dis 12 Suppl 6:S665-81.
  10. Schmid G, Narcisi E, Mosure D, Secor WE, Higgins J, Moreno H. 2001. Prevalence of metronidazoleresistant Trichomonas vaginalisin a gynecology clinic. J Reprod Med 46:545-9.
  11. Schwebke JR, Barrientes FJ. 2006. Prevalence of Trichomonas vaginalis isolates with resistance to metronidazole and tinidazole. Antimicrob Agents Chemother 50:4209-10.
  12. Hirt RP, Noel CJ, Sicheritz-Ponten T, Tachezy J, Fiori PL. 2007. Trichomonas vaginalis surface proteins: a view from the genome. Trends Parasitol 23:540-7.