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Managing Trichomonas vaginalis infections
Author(s)
Emily S. Edwards, MS, CCRP
Patrick Duff, MD

 

CASE Woman with malodorous vaginal discharge

A 26-year-old nulligravid woman with 2 current sexual partners requests evaluation because she has a yellow-green frothy vaginal discharge that is slightly malodorous. One of her sexual partners has noted a similar discharge from his urethra. On physical examination, the clinician notes that the patient’s discharge emanates from the vaginal mucosa, and the exocervix has multiple punctate hemorrhages. Considerations in this case include:

  • What is the most likely diagnosis?
  • How should this patient be evaluated and treated?
  • Should the patient’s sexual partners be treated?

This clinical scenario is most consistent with a trichomonas infection, although other conditions, including bacterial vaginosis, gonorrhea, and chlamydia infection, must be considered in the differential diagnosis.

In this article, we examine the microbiology, epidemiology, clinical manifestations, and diagnosis and treatment of this common sexually transmitted infection (STI).

The causative microbe

Trichomonas vaginalis is a free-living flagellated protozoan that accounts for almost half of all nonviral STIs globally. It has a predilection for the mucosal epithelium of the genitourinary tract, including the vagina and urethra. Humans are the only known host for T vaginalis. The infection is transmitted through sexual intercourse, and the organism reproduces through binary fission in the lower genital tract of women and in the urethra and prostate of men.

This anaerobic trophozoite has 4 flagella anteriorly and 1 flagellum that projects posteriorly, with an undulating membrane that gives its characteristic motile appearance on saline microscopy.1

T vaginalis infection causes major mechanical stress on epithelial cells, which results in disruption of the plasma cell membrane and, ultimately, cell death. The necrotic cell fragments are then phagocytosed by trichomonads, thus accelerating the infection.2

Groups at risk

Trichomonal infections are not reportable to public health authorities, which makes assessing the true prevalence of infection difficult.

The World Health Organization estimated the incidence of infection to be more than 156 million cases globally in 2016, with a prevalence of 110.4 million people at any one time.3

The 2013-2014 National Health and Nutrition Examination Survey tested 4,057 men and women aged 18 to 59 years for T vaginalis and found a prevalence of 0.5% among men and 1.8% among women.4 The prevalence increased with age. There was a disproportionate burden of trichomonas infections in the non-Hispanic black population, with 4.2% of black men and 8.9% of black women affected.4

Targeted screening of urogenital samples for T vaginalis in a population of US women undergoing Chlamydia trachomatis/Neisseria gonorrhoeae screening demonstrated prevalence rates of 8.7%, 6.7%, and 1.7% for T vaginalis, C trachomatis, and N gonorrhoeae, respectively.5

 

Differences in prevalence estimates may be due to differences in the varying sensitivity of each testing modality and patient populations. In one study, nucleic acid amplification testing (NAAT) for T vaginalis detected rates as high as 11.3% in women and 6.1% in men undergoing evaluations at STI clinics.6

Continue to: Clinical manifestations of infection...

 

 

Clinical manifestations of infection

Most cases of T vaginalis remain in an asymptomatic carrier state, with up to 85% of women and 77% of men reporting no clinical symptoms.1 However, approximately one-third of asymptomatic carriers will experience symptoms within 6 months of infection acquisition. This latency in appearance of clinical symptoms certainly contributes to the high transmission rate of T vaginalis.

Infected men may experience purulent urethritis, dysuria, and postcoital pruritus. Common clinical symptoms in women include abnormal vaginal discharge that may be malodorous, purulent, thin, frothy, and yellow-green, as well as symptoms of dyspareunia and vulvar irritation. Punctate hemorrhages in the cervix (colpitis macularis) and vaginal walls (macular vaginitis) give the characteristic “strawberry appearance,” but these findings are seen in only 2% of affected women.7

Complications in ObGyn patients

Although T vaginalis once was regarded as more of an annoyance than a public health issue, awareness of the infection’s ramifications has increased in recent years. Because of these complications, treatment of both symptomatic and asymptomatic patients is clearly indicated.

Complications of trichomonal infection in men include balanoposthitis, epididymitis, prostatitis, urethritis, and infertility.7 In women, complications include infections of the adnexa, endometrium, and vestibular glands, as well as cervical neoplasia and increased co-infection rates with other STIs, such as bacterial vaginosis, chlamydia infection, gonorrhea, syphilis, and herpes simplex virus type 2.1

Infection in pregnancy. Adverse outcomes in pregnant women with T vaginalis infections at mid-gestation include low birth weight, preterm premature rupture of membranes, preterm delivery, and postpartum endometritis.8 A disproportionately larger share of the low birth weight rate associated with T vaginalis infections occurs in black women compared with white and Hispanic women.8 Perinatal transmission to newborns can cause fever; respiratory difficulties; urinary tract infections; nasal discharge; and, in female infants, vaginal discharge.9,10

Co-infection concerns. The increased rate of co-infection with human immunodeficiency virus type 1 (HIV-1) and T vaginalis is a major concern.11 One study found a higher concentration of HIV-1 in semen samples from men with T vaginalis and symptomatic urethritis.12 Further, T vaginalis was found in 17.4% of women with HIV screened at a public clinic in California, with almost 38% of black women affected.13 Trichomoniasis can increase the risk of HIV-1 acquisition by 1.52-fold (95% confidence interval, 1.04- to 2.24-fold), pointing toward a potential amplifying effect of T vaginalis on HIV transmission rates.14 This association may be based at least in part on the organism’s ability to cause microulcerations in the genital and urinary tract epithelium, thus creating pathways for other microorganisms to enter the vascular system.

Making the diagnosis

The nonspecific symptoms of T vaginalis create a wide differential to consider. Vaginal discharge may be due to bacterial vaginosis, vulvovaginal candidiasis, physiologic discharge, atrophy, and nonspecific inflammation. The presence of malodorous and discolored discharge increases the likelihood of bacterial vaginosis or T vaginalis infection. Pruritus often is associated with candidiasis co-infection.

 

The diagnosis of trichomoniasis can be confirmed in the outpatient office with the use of saline microscopy, an inexpensive test that is based on observation of motile trichomonads in a wet mount of vaginal fluid. The sensitivity of the wet mount ranges from 44% to 68% compared with culture. Culture, traditionally using Diamond’s medium, has a sensitivity of 81% to 94% and was long the gold standard; however, culture has been replaced largely by molecular and antigen testing.

Three US Food and Drug Administration (FDA)-approved NAATs for T vaginalis currently are on the market; all can detect co-infection with gonorrhea and chlamydia from the same specimen. These tests include the Aptima T vaginalis rRNA target assay (Hologic, Bedford, Massachusetts) and the BD ProbTec T vaginalis Qx (TVQ) amplified DNA assay (BD Diagnostics, Baltimore, Maryland), both of which require up to 8 hours to yield results. The Xpert T vaginalis (TV) assay (Cepheid, Sunnyvale, California) is the first NAAT that is FDA approved for use with male urine (in addition to female urine), and it yields results in 60 to 90 minutes. Sensitivity for these NAAT assays ranges from 88% to 100%.15
 

Point-of-care testing is preferred for rapid diagnosis and for helping the clinician provide same-visit treatment for STIs. The Solana trichomonas assay (Quidel, San Diego, California) detects T vaginalis DNA and can yield results within 40 minutes, but it requires specialized equipment for running the samples. The AmpliVue trichomonas assay (Quidel, San Diego, California) is similar to the Solana assay but it is contained within a small handheld cartridge that does not require additional equipment. Sensitivities are 92% to 98% for Solona and 90.7% to 100% for AmpliVue. The OSOM trichomonas rapid test (Sekisui, Framingham, Massachusetts) uses antigen-detection immunochromatography to provide results in 10 to 15 minutes, with 83% to 92% sensitivity and 99% specificity for vaginal specimens.15,16

Continue to: The TABLE provides a summary...

 

 

The TABLE provides a summary of the clinical performance of the various tests for T vaginalis. 15-18

Treatment options

The 5-nitroimidazole agents, which include metronidazole and tinidazole, are the preferred agents for the treatment of trichomoniasis.

Dosing regimen. While a single oral dose of metronidazole 2 g has long been the mainstay of treatment for T vaginalis, this regimen recently has been questioned, at least in women, due to the high posttreatment positive rate of T vaginalis, which ranges from 5% to 37%.19,20 These cases may be due to reinfection by untreated sexual partners. They also may result from treatment failure, however, specifically inadequate treatment time.21 Overall, patients treated with single-dose metronidazole are 1.87 times more likely to experience treatment failure compared with those treated with a multidose regimen.19 Since many cases of T vaginalis infection are associated with bacterial vaginosis co-infection, recommending metronidazole 500 mg twice daily for 7 days is beneficial because this course provides optimal treatment for both infections.

Treatment during pregnancy. In the minds of some investigators, treatment of T vaginalis in asymptomatic pregnant women is problematic. One study demonstrated a similar to slightly increased risk of preterm delivery for metronidazole-treated patients compared with a placebo-treated group.22 Limitations of the study included atypical treatment dosing (2 doses of metronidazole 2 g given 48 hours apart at 16 to 23 weeks’ gestation and repeated at 24 to 29 weeks’ gestation) and a latency between the last dose of metronidazole and preterm delivery.22

We believe that all pregnant women, symptomatic or asymptomatic, should be treated because of the sexually transmitted nature of the infection and the probability that most asymptomatic carriers ultimately become symptomatic.

Cost of treatment. Generic oral metronidazole is very inexpensive. The approximate retail price for 14 metronidazole 500-mg tablets is $15.69 (www.goodrx.com). By contrast, a single-dose course of tinidazole (four 500-mg tablets) costs approximately $45. Accordingly, we reserve tinidazole for patients who have experienced a treatment failure with metronidazole or who cannot tolerate metronidazole.

Drug‒alcohol interaction. With both metronidazole and tinidazole, patients must abstain from alcohol during treatment and for 72 hours after completing therapy because these drugs have a disulfiram-like reaction with ethanol.
 

References
  1. Kissinger P. Epidemiology and treatment of trichomoniasis. Curr Infect Dis Rep. 2015;17:484.
  2. Midlej V, Benchimol M. Trichomonas vaginalis kills and eats—evidence for phagocytic activity as a cytopathic effect. Parasitology. 2010;137:65-76.
  3. Rowley J, Vander Hoorn S, Korenromp E, et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Organ. 2019;97:548–562P.
  4. Patel EU, Gaydos CA, Packman ZR, et al. Prevalence and correlates of Trichomonas vaginalis infection among men and women in the United States. Clin Infect Dis. 2018;67:211-217.
  5. Ginocchio CC, Chapin K, Smith JS, et al. Prevalence of Trichomonas vaginalis and coinfection with Chlamydia trachomatis and Neisseria gonorrhoeae in the United States as determined by the Aptima Trichomonas vaginalis nucleic acid amplification assay. J Clin Microbiol. 2012;50:2601-2608.
  6. Schwebke J, Merriweather A, Massingale S, et al. Screening for Trichomonas vaginalis in a large high-risk population: prevalence among men and women determined by nucleic acid amplification testing. Sex Transm Dis. 2018;45:e23-e24.
  7. Petrin D, Delgaty K, Bhatt R, et al. Clinical and microbiological aspects of Trichomonas vaginalis. Clin Microbiol Rev. 1998;11:300-317.
  8. Cotch MF, Pastorek JG II, Nugent RP, et al. Trichomonas vaginalis associated with low birth weight and preterm delivery. The Vaginal Infections and Prematurity Study Group. Sex Transm Dis. 1997;24:353-360.
  9. Smith LM, Wang M, Zangwill K, et al. Trichomonas vaginalis infection in a premature newborn. J Perinatol. 2002;22:502-503.
  10. Temesvári P, Kerekes A, Tege A, et al. Demonstration of Trichomonas vaginalis in tracheal aspirates in infants with early respiratory failure. J Matern Fetal Neonatal Med. 2002;11:347-349.
  11. Kissinger P, Adamski A. Trichomoniasis and HIV interactions: a review. Sex Transm Infect. 2013;89:426-433.
  12. Cohen MS, Hoffman IF, Royce RA, et al; AIDSCAP Malawi Research Group. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. Lancet. 1997;349:1868-1873.
  13. Sorvillo F, Kovacs A, Kerndt P, et al. Risk factors for trichomoniasis among women with human immunodeficiency virus (HIV) infection at a public clinic in Los Angeles County, California: implications for HIV prevention. Am J Trop Med Hyg. 1998;58:495-500.
  14. McClelland RS, Sangare L, Hassan WM, et al. Infection with Trichomonas vaginalis increases the risk of HIV-1 acquisition. J Infect Dis. 2007;195:698-702.
  15. Van Gerwen OT, Muzny CA. Recent advances in the epidemiology, diagnosis, and management of Trichomonas vaginalis infection. F1000Res. 2019;8:F1000 Faculty Rev-1666.
  16. Gaydos CA, Klausner JD, Pai NP, et al. Rapid and point-of-care tests for the diagnosis of Trichomonas vaginalis in women and men. Sex Transm Infect. 2017;93(S4):S31-S35.
  17. Rivers CA, Muzny CA, Schwebke JR. Diagnostic rates differ on the basis of the number of read days with the use of the InPouch culture system for Trichomonas vaginalis screening. J Clin Microbiol. 2013;51:3875-3876.
  18. Van Der Pol B, Williams JA, Taylor SN, et al. Detection of Trichomonas vaginalis DNA by use of self-obtained vaginal swabs with the BD ProbeTec Qx assay on the BD Viper System. J Clin Microbiol. 2014;52:885-889.
  19. Howe K, Kissinger P. Single-dose compared with multidose metronidazole for the treatment of trichomoniasis in women: a meta-analysis. Sex Transm Dis. 2017;44:29-34.
  20. Duff P. Should the length of treatment for trichomoniasis in women be reconsidered? OBG Manag. 2017;29(3):48-49.
  21. Krashin JW, Koumans EH, Bradshaw-Sydnor AC, et al. Trichomonas vaginalis prevalence, incidence, risk factors and antibiotic-resistance in an adolescent population. Sex Transm Dis. 2010;37:440-444.
  22. Klebanoff MA, Carey JC, Hauth JC, et al; National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. N Engl J Med. 2001;345:487-493.
Author and Disclosure Information

Ms. Edwards is a fourth-year medical student at the University of Florida College of Medicine, Gainesville.

Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.

The authors report no financial relationships relevant to this article.

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Author(s)
Emily S. Edwards, MS, CCRP
Patrick Duff, MD
Author(s)
Emily S. Edwards, MS, CCRP
Patrick Duff, MD
Author and Disclosure Information

Ms. Edwards is a fourth-year medical student at the University of Florida College of Medicine, Gainesville.

Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.

The authors report no financial relationships relevant to this article.

Author and Disclosure Information

Ms. Edwards is a fourth-year medical student at the University of Florida College of Medicine, Gainesville.

Dr. Duff is Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville.

The authors report no financial relationships relevant to this article.

 

CASE Woman with malodorous vaginal discharge

A 26-year-old nulligravid woman with 2 current sexual partners requests evaluation because she has a yellow-green frothy vaginal discharge that is slightly malodorous. One of her sexual partners has noted a similar discharge from his urethra. On physical examination, the clinician notes that the patient’s discharge emanates from the vaginal mucosa, and the exocervix has multiple punctate hemorrhages. Considerations in this case include:

  • What is the most likely diagnosis?
  • How should this patient be evaluated and treated?
  • Should the patient’s sexual partners be treated?

This clinical scenario is most consistent with a trichomonas infection, although other conditions, including bacterial vaginosis, gonorrhea, and chlamydia infection, must be considered in the differential diagnosis.

In this article, we examine the microbiology, epidemiology, clinical manifestations, and diagnosis and treatment of this common sexually transmitted infection (STI).

The causative microbe

Trichomonas vaginalis is a free-living flagellated protozoan that accounts for almost half of all nonviral STIs globally. It has a predilection for the mucosal epithelium of the genitourinary tract, including the vagina and urethra. Humans are the only known host for T vaginalis. The infection is transmitted through sexual intercourse, and the organism reproduces through binary fission in the lower genital tract of women and in the urethra and prostate of men.

This anaerobic trophozoite has 4 flagella anteriorly and 1 flagellum that projects posteriorly, with an undulating membrane that gives its characteristic motile appearance on saline microscopy.1

T vaginalis infection causes major mechanical stress on epithelial cells, which results in disruption of the plasma cell membrane and, ultimately, cell death. The necrotic cell fragments are then phagocytosed by trichomonads, thus accelerating the infection.2

Groups at risk

Trichomonal infections are not reportable to public health authorities, which makes assessing the true prevalence of infection difficult.

The World Health Organization estimated the incidence of infection to be more than 156 million cases globally in 2016, with a prevalence of 110.4 million people at any one time.3

The 2013-2014 National Health and Nutrition Examination Survey tested 4,057 men and women aged 18 to 59 years for T vaginalis and found a prevalence of 0.5% among men and 1.8% among women.4 The prevalence increased with age. There was a disproportionate burden of trichomonas infections in the non-Hispanic black population, with 4.2% of black men and 8.9% of black women affected.4

Targeted screening of urogenital samples for T vaginalis in a population of US women undergoing Chlamydia trachomatis/Neisseria gonorrhoeae screening demonstrated prevalence rates of 8.7%, 6.7%, and 1.7% for T vaginalis, C trachomatis, and N gonorrhoeae, respectively.5

 

Differences in prevalence estimates may be due to differences in the varying sensitivity of each testing modality and patient populations. In one study, nucleic acid amplification testing (NAAT) for T vaginalis detected rates as high as 11.3% in women and 6.1% in men undergoing evaluations at STI clinics.6

Continue to: Clinical manifestations of infection...

 

 

Clinical manifestations of infection

Most cases of T vaginalis remain in an asymptomatic carrier state, with up to 85% of women and 77% of men reporting no clinical symptoms.1 However, approximately one-third of asymptomatic carriers will experience symptoms within 6 months of infection acquisition. This latency in appearance of clinical symptoms certainly contributes to the high transmission rate of T vaginalis.

Infected men may experience purulent urethritis, dysuria, and postcoital pruritus. Common clinical symptoms in women include abnormal vaginal discharge that may be malodorous, purulent, thin, frothy, and yellow-green, as well as symptoms of dyspareunia and vulvar irritation. Punctate hemorrhages in the cervix (colpitis macularis) and vaginal walls (macular vaginitis) give the characteristic “strawberry appearance,” but these findings are seen in only 2% of affected women.7

Complications in ObGyn patients

Although T vaginalis once was regarded as more of an annoyance than a public health issue, awareness of the infection’s ramifications has increased in recent years. Because of these complications, treatment of both symptomatic and asymptomatic patients is clearly indicated.

Complications of trichomonal infection in men include balanoposthitis, epididymitis, prostatitis, urethritis, and infertility.7 In women, complications include infections of the adnexa, endometrium, and vestibular glands, as well as cervical neoplasia and increased co-infection rates with other STIs, such as bacterial vaginosis, chlamydia infection, gonorrhea, syphilis, and herpes simplex virus type 2.1

Infection in pregnancy. Adverse outcomes in pregnant women with T vaginalis infections at mid-gestation include low birth weight, preterm premature rupture of membranes, preterm delivery, and postpartum endometritis.8 A disproportionately larger share of the low birth weight rate associated with T vaginalis infections occurs in black women compared with white and Hispanic women.8 Perinatal transmission to newborns can cause fever; respiratory difficulties; urinary tract infections; nasal discharge; and, in female infants, vaginal discharge.9,10

Co-infection concerns. The increased rate of co-infection with human immunodeficiency virus type 1 (HIV-1) and T vaginalis is a major concern.11 One study found a higher concentration of HIV-1 in semen samples from men with T vaginalis and symptomatic urethritis.12 Further, T vaginalis was found in 17.4% of women with HIV screened at a public clinic in California, with almost 38% of black women affected.13 Trichomoniasis can increase the risk of HIV-1 acquisition by 1.52-fold (95% confidence interval, 1.04- to 2.24-fold), pointing toward a potential amplifying effect of T vaginalis on HIV transmission rates.14 This association may be based at least in part on the organism’s ability to cause microulcerations in the genital and urinary tract epithelium, thus creating pathways for other microorganisms to enter the vascular system.

Making the diagnosis

The nonspecific symptoms of T vaginalis create a wide differential to consider. Vaginal discharge may be due to bacterial vaginosis, vulvovaginal candidiasis, physiologic discharge, atrophy, and nonspecific inflammation. The presence of malodorous and discolored discharge increases the likelihood of bacterial vaginosis or T vaginalis infection. Pruritus often is associated with candidiasis co-infection.

 

The diagnosis of trichomoniasis can be confirmed in the outpatient office with the use of saline microscopy, an inexpensive test that is based on observation of motile trichomonads in a wet mount of vaginal fluid. The sensitivity of the wet mount ranges from 44% to 68% compared with culture. Culture, traditionally using Diamond’s medium, has a sensitivity of 81% to 94% and was long the gold standard; however, culture has been replaced largely by molecular and antigen testing.

Three US Food and Drug Administration (FDA)-approved NAATs for T vaginalis currently are on the market; all can detect co-infection with gonorrhea and chlamydia from the same specimen. These tests include the Aptima T vaginalis rRNA target assay (Hologic, Bedford, Massachusetts) and the BD ProbTec T vaginalis Qx (TVQ) amplified DNA assay (BD Diagnostics, Baltimore, Maryland), both of which require up to 8 hours to yield results. The Xpert T vaginalis (TV) assay (Cepheid, Sunnyvale, California) is the first NAAT that is FDA approved for use with male urine (in addition to female urine), and it yields results in 60 to 90 minutes. Sensitivity for these NAAT assays ranges from 88% to 100%.15
 

Point-of-care testing is preferred for rapid diagnosis and for helping the clinician provide same-visit treatment for STIs. The Solana trichomonas assay (Quidel, San Diego, California) detects T vaginalis DNA and can yield results within 40 minutes, but it requires specialized equipment for running the samples. The AmpliVue trichomonas assay (Quidel, San Diego, California) is similar to the Solana assay but it is contained within a small handheld cartridge that does not require additional equipment. Sensitivities are 92% to 98% for Solona and 90.7% to 100% for AmpliVue. The OSOM trichomonas rapid test (Sekisui, Framingham, Massachusetts) uses antigen-detection immunochromatography to provide results in 10 to 15 minutes, with 83% to 92% sensitivity and 99% specificity for vaginal specimens.15,16

Continue to: The TABLE provides a summary...

 

 

The TABLE provides a summary of the clinical performance of the various tests for T vaginalis. 15-18

Treatment options

The 5-nitroimidazole agents, which include metronidazole and tinidazole, are the preferred agents for the treatment of trichomoniasis.

Dosing regimen. While a single oral dose of metronidazole 2 g has long been the mainstay of treatment for T vaginalis, this regimen recently has been questioned, at least in women, due to the high posttreatment positive rate of T vaginalis, which ranges from 5% to 37%.19,20 These cases may be due to reinfection by untreated sexual partners. They also may result from treatment failure, however, specifically inadequate treatment time.21 Overall, patients treated with single-dose metronidazole are 1.87 times more likely to experience treatment failure compared with those treated with a multidose regimen.19 Since many cases of T vaginalis infection are associated with bacterial vaginosis co-infection, recommending metronidazole 500 mg twice daily for 7 days is beneficial because this course provides optimal treatment for both infections.

Treatment during pregnancy. In the minds of some investigators, treatment of T vaginalis in asymptomatic pregnant women is problematic. One study demonstrated a similar to slightly increased risk of preterm delivery for metronidazole-treated patients compared with a placebo-treated group.22 Limitations of the study included atypical treatment dosing (2 doses of metronidazole 2 g given 48 hours apart at 16 to 23 weeks’ gestation and repeated at 24 to 29 weeks’ gestation) and a latency between the last dose of metronidazole and preterm delivery.22

We believe that all pregnant women, symptomatic or asymptomatic, should be treated because of the sexually transmitted nature of the infection and the probability that most asymptomatic carriers ultimately become symptomatic.

Cost of treatment. Generic oral metronidazole is very inexpensive. The approximate retail price for 14 metronidazole 500-mg tablets is $15.69 (www.goodrx.com). By contrast, a single-dose course of tinidazole (four 500-mg tablets) costs approximately $45. Accordingly, we reserve tinidazole for patients who have experienced a treatment failure with metronidazole or who cannot tolerate metronidazole.

Drug‒alcohol interaction. With both metronidazole and tinidazole, patients must abstain from alcohol during treatment and for 72 hours after completing therapy because these drugs have a disulfiram-like reaction with ethanol.
 

 

CASE Woman with malodorous vaginal discharge

A 26-year-old nulligravid woman with 2 current sexual partners requests evaluation because she has a yellow-green frothy vaginal discharge that is slightly malodorous. One of her sexual partners has noted a similar discharge from his urethra. On physical examination, the clinician notes that the patient’s discharge emanates from the vaginal mucosa, and the exocervix has multiple punctate hemorrhages. Considerations in this case include:

  • What is the most likely diagnosis?
  • How should this patient be evaluated and treated?
  • Should the patient’s sexual partners be treated?

This clinical scenario is most consistent with a trichomonas infection, although other conditions, including bacterial vaginosis, gonorrhea, and chlamydia infection, must be considered in the differential diagnosis.

In this article, we examine the microbiology, epidemiology, clinical manifestations, and diagnosis and treatment of this common sexually transmitted infection (STI).

The causative microbe

Trichomonas vaginalis is a free-living flagellated protozoan that accounts for almost half of all nonviral STIs globally. It has a predilection for the mucosal epithelium of the genitourinary tract, including the vagina and urethra. Humans are the only known host for T vaginalis. The infection is transmitted through sexual intercourse, and the organism reproduces through binary fission in the lower genital tract of women and in the urethra and prostate of men.

This anaerobic trophozoite has 4 flagella anteriorly and 1 flagellum that projects posteriorly, with an undulating membrane that gives its characteristic motile appearance on saline microscopy.1

T vaginalis infection causes major mechanical stress on epithelial cells, which results in disruption of the plasma cell membrane and, ultimately, cell death. The necrotic cell fragments are then phagocytosed by trichomonads, thus accelerating the infection.2

Groups at risk

Trichomonal infections are not reportable to public health authorities, which makes assessing the true prevalence of infection difficult.

The World Health Organization estimated the incidence of infection to be more than 156 million cases globally in 2016, with a prevalence of 110.4 million people at any one time.3

The 2013-2014 National Health and Nutrition Examination Survey tested 4,057 men and women aged 18 to 59 years for T vaginalis and found a prevalence of 0.5% among men and 1.8% among women.4 The prevalence increased with age. There was a disproportionate burden of trichomonas infections in the non-Hispanic black population, with 4.2% of black men and 8.9% of black women affected.4

Targeted screening of urogenital samples for T vaginalis in a population of US women undergoing Chlamydia trachomatis/Neisseria gonorrhoeae screening demonstrated prevalence rates of 8.7%, 6.7%, and 1.7% for T vaginalis, C trachomatis, and N gonorrhoeae, respectively.5

 

Differences in prevalence estimates may be due to differences in the varying sensitivity of each testing modality and patient populations. In one study, nucleic acid amplification testing (NAAT) for T vaginalis detected rates as high as 11.3% in women and 6.1% in men undergoing evaluations at STI clinics.6

Continue to: Clinical manifestations of infection...

 

 

Clinical manifestations of infection

Most cases of T vaginalis remain in an asymptomatic carrier state, with up to 85% of women and 77% of men reporting no clinical symptoms.1 However, approximately one-third of asymptomatic carriers will experience symptoms within 6 months of infection acquisition. This latency in appearance of clinical symptoms certainly contributes to the high transmission rate of T vaginalis.

Infected men may experience purulent urethritis, dysuria, and postcoital pruritus. Common clinical symptoms in women include abnormal vaginal discharge that may be malodorous, purulent, thin, frothy, and yellow-green, as well as symptoms of dyspareunia and vulvar irritation. Punctate hemorrhages in the cervix (colpitis macularis) and vaginal walls (macular vaginitis) give the characteristic “strawberry appearance,” but these findings are seen in only 2% of affected women.7

Complications in ObGyn patients

Although T vaginalis once was regarded as more of an annoyance than a public health issue, awareness of the infection’s ramifications has increased in recent years. Because of these complications, treatment of both symptomatic and asymptomatic patients is clearly indicated.

Complications of trichomonal infection in men include balanoposthitis, epididymitis, prostatitis, urethritis, and infertility.7 In women, complications include infections of the adnexa, endometrium, and vestibular glands, as well as cervical neoplasia and increased co-infection rates with other STIs, such as bacterial vaginosis, chlamydia infection, gonorrhea, syphilis, and herpes simplex virus type 2.1

Infection in pregnancy. Adverse outcomes in pregnant women with T vaginalis infections at mid-gestation include low birth weight, preterm premature rupture of membranes, preterm delivery, and postpartum endometritis.8 A disproportionately larger share of the low birth weight rate associated with T vaginalis infections occurs in black women compared with white and Hispanic women.8 Perinatal transmission to newborns can cause fever; respiratory difficulties; urinary tract infections; nasal discharge; and, in female infants, vaginal discharge.9,10

Co-infection concerns. The increased rate of co-infection with human immunodeficiency virus type 1 (HIV-1) and T vaginalis is a major concern.11 One study found a higher concentration of HIV-1 in semen samples from men with T vaginalis and symptomatic urethritis.12 Further, T vaginalis was found in 17.4% of women with HIV screened at a public clinic in California, with almost 38% of black women affected.13 Trichomoniasis can increase the risk of HIV-1 acquisition by 1.52-fold (95% confidence interval, 1.04- to 2.24-fold), pointing toward a potential amplifying effect of T vaginalis on HIV transmission rates.14 This association may be based at least in part on the organism’s ability to cause microulcerations in the genital and urinary tract epithelium, thus creating pathways for other microorganisms to enter the vascular system.

Making the diagnosis

The nonspecific symptoms of T vaginalis create a wide differential to consider. Vaginal discharge may be due to bacterial vaginosis, vulvovaginal candidiasis, physiologic discharge, atrophy, and nonspecific inflammation. The presence of malodorous and discolored discharge increases the likelihood of bacterial vaginosis or T vaginalis infection. Pruritus often is associated with candidiasis co-infection.

 

The diagnosis of trichomoniasis can be confirmed in the outpatient office with the use of saline microscopy, an inexpensive test that is based on observation of motile trichomonads in a wet mount of vaginal fluid. The sensitivity of the wet mount ranges from 44% to 68% compared with culture. Culture, traditionally using Diamond’s medium, has a sensitivity of 81% to 94% and was long the gold standard; however, culture has been replaced largely by molecular and antigen testing.

Three US Food and Drug Administration (FDA)-approved NAATs for T vaginalis currently are on the market; all can detect co-infection with gonorrhea and chlamydia from the same specimen. These tests include the Aptima T vaginalis rRNA target assay (Hologic, Bedford, Massachusetts) and the BD ProbTec T vaginalis Qx (TVQ) amplified DNA assay (BD Diagnostics, Baltimore, Maryland), both of which require up to 8 hours to yield results. The Xpert T vaginalis (TV) assay (Cepheid, Sunnyvale, California) is the first NAAT that is FDA approved for use with male urine (in addition to female urine), and it yields results in 60 to 90 minutes. Sensitivity for these NAAT assays ranges from 88% to 100%.15
 

Point-of-care testing is preferred for rapid diagnosis and for helping the clinician provide same-visit treatment for STIs. The Solana trichomonas assay (Quidel, San Diego, California) detects T vaginalis DNA and can yield results within 40 minutes, but it requires specialized equipment for running the samples. The AmpliVue trichomonas assay (Quidel, San Diego, California) is similar to the Solana assay but it is contained within a small handheld cartridge that does not require additional equipment. Sensitivities are 92% to 98% for Solona and 90.7% to 100% for AmpliVue. The OSOM trichomonas rapid test (Sekisui, Framingham, Massachusetts) uses antigen-detection immunochromatography to provide results in 10 to 15 minutes, with 83% to 92% sensitivity and 99% specificity for vaginal specimens.15,16

Continue to: The TABLE provides a summary...

 

 

The TABLE provides a summary of the clinical performance of the various tests for T vaginalis. 15-18

Treatment options

The 5-nitroimidazole agents, which include metronidazole and tinidazole, are the preferred agents for the treatment of trichomoniasis.

Dosing regimen. While a single oral dose of metronidazole 2 g has long been the mainstay of treatment for T vaginalis, this regimen recently has been questioned, at least in women, due to the high posttreatment positive rate of T vaginalis, which ranges from 5% to 37%.19,20 These cases may be due to reinfection by untreated sexual partners. They also may result from treatment failure, however, specifically inadequate treatment time.21 Overall, patients treated with single-dose metronidazole are 1.87 times more likely to experience treatment failure compared with those treated with a multidose regimen.19 Since many cases of T vaginalis infection are associated with bacterial vaginosis co-infection, recommending metronidazole 500 mg twice daily for 7 days is beneficial because this course provides optimal treatment for both infections.

Treatment during pregnancy. In the minds of some investigators, treatment of T vaginalis in asymptomatic pregnant women is problematic. One study demonstrated a similar to slightly increased risk of preterm delivery for metronidazole-treated patients compared with a placebo-treated group.22 Limitations of the study included atypical treatment dosing (2 doses of metronidazole 2 g given 48 hours apart at 16 to 23 weeks’ gestation and repeated at 24 to 29 weeks’ gestation) and a latency between the last dose of metronidazole and preterm delivery.22

We believe that all pregnant women, symptomatic or asymptomatic, should be treated because of the sexually transmitted nature of the infection and the probability that most asymptomatic carriers ultimately become symptomatic.

Cost of treatment. Generic oral metronidazole is very inexpensive. The approximate retail price for 14 metronidazole 500-mg tablets is $15.69 (www.goodrx.com). By contrast, a single-dose course of tinidazole (four 500-mg tablets) costs approximately $45. Accordingly, we reserve tinidazole for patients who have experienced a treatment failure with metronidazole or who cannot tolerate metronidazole.

Drug‒alcohol interaction. With both metronidazole and tinidazole, patients must abstain from alcohol during treatment and for 72 hours after completing therapy because these drugs have a disulfiram-like reaction with ethanol.
 

References
  1. Kissinger P. Epidemiology and treatment of trichomoniasis. Curr Infect Dis Rep. 2015;17:484.
  2. Midlej V, Benchimol M. Trichomonas vaginalis kills and eats—evidence for phagocytic activity as a cytopathic effect. Parasitology. 2010;137:65-76.
  3. Rowley J, Vander Hoorn S, Korenromp E, et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Organ. 2019;97:548–562P.
  4. Patel EU, Gaydos CA, Packman ZR, et al. Prevalence and correlates of Trichomonas vaginalis infection among men and women in the United States. Clin Infect Dis. 2018;67:211-217.
  5. Ginocchio CC, Chapin K, Smith JS, et al. Prevalence of Trichomonas vaginalis and coinfection with Chlamydia trachomatis and Neisseria gonorrhoeae in the United States as determined by the Aptima Trichomonas vaginalis nucleic acid amplification assay. J Clin Microbiol. 2012;50:2601-2608.
  6. Schwebke J, Merriweather A, Massingale S, et al. Screening for Trichomonas vaginalis in a large high-risk population: prevalence among men and women determined by nucleic acid amplification testing. Sex Transm Dis. 2018;45:e23-e24.
  7. Petrin D, Delgaty K, Bhatt R, et al. Clinical and microbiological aspects of Trichomonas vaginalis. Clin Microbiol Rev. 1998;11:300-317.
  8. Cotch MF, Pastorek JG II, Nugent RP, et al. Trichomonas vaginalis associated with low birth weight and preterm delivery. The Vaginal Infections and Prematurity Study Group. Sex Transm Dis. 1997;24:353-360.
  9. Smith LM, Wang M, Zangwill K, et al. Trichomonas vaginalis infection in a premature newborn. J Perinatol. 2002;22:502-503.
  10. Temesvári P, Kerekes A, Tege A, et al. Demonstration of Trichomonas vaginalis in tracheal aspirates in infants with early respiratory failure. J Matern Fetal Neonatal Med. 2002;11:347-349.
  11. Kissinger P, Adamski A. Trichomoniasis and HIV interactions: a review. Sex Transm Infect. 2013;89:426-433.
  12. Cohen MS, Hoffman IF, Royce RA, et al; AIDSCAP Malawi Research Group. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. Lancet. 1997;349:1868-1873.
  13. Sorvillo F, Kovacs A, Kerndt P, et al. Risk factors for trichomoniasis among women with human immunodeficiency virus (HIV) infection at a public clinic in Los Angeles County, California: implications for HIV prevention. Am J Trop Med Hyg. 1998;58:495-500.
  14. McClelland RS, Sangare L, Hassan WM, et al. Infection with Trichomonas vaginalis increases the risk of HIV-1 acquisition. J Infect Dis. 2007;195:698-702.
  15. Van Gerwen OT, Muzny CA. Recent advances in the epidemiology, diagnosis, and management of Trichomonas vaginalis infection. F1000Res. 2019;8:F1000 Faculty Rev-1666.
  16. Gaydos CA, Klausner JD, Pai NP, et al. Rapid and point-of-care tests for the diagnosis of Trichomonas vaginalis in women and men. Sex Transm Infect. 2017;93(S4):S31-S35.
  17. Rivers CA, Muzny CA, Schwebke JR. Diagnostic rates differ on the basis of the number of read days with the use of the InPouch culture system for Trichomonas vaginalis screening. J Clin Microbiol. 2013;51:3875-3876.
  18. Van Der Pol B, Williams JA, Taylor SN, et al. Detection of Trichomonas vaginalis DNA by use of self-obtained vaginal swabs with the BD ProbeTec Qx assay on the BD Viper System. J Clin Microbiol. 2014;52:885-889.
  19. Howe K, Kissinger P. Single-dose compared with multidose metronidazole for the treatment of trichomoniasis in women: a meta-analysis. Sex Transm Dis. 2017;44:29-34.
  20. Duff P. Should the length of treatment for trichomoniasis in women be reconsidered? OBG Manag. 2017;29(3):48-49.
  21. Krashin JW, Koumans EH, Bradshaw-Sydnor AC, et al. Trichomonas vaginalis prevalence, incidence, risk factors and antibiotic-resistance in an adolescent population. Sex Transm Dis. 2010;37:440-444.
  22. Klebanoff MA, Carey JC, Hauth JC, et al; National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. N Engl J Med. 2001;345:487-493.
References
  1. Kissinger P. Epidemiology and treatment of trichomoniasis. Curr Infect Dis Rep. 2015;17:484.
  2. Midlej V, Benchimol M. Trichomonas vaginalis kills and eats—evidence for phagocytic activity as a cytopathic effect. Parasitology. 2010;137:65-76.
  3. Rowley J, Vander Hoorn S, Korenromp E, et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: global prevalence and incidence estimates, 2016. Bull World Health Organ. 2019;97:548–562P.
  4. Patel EU, Gaydos CA, Packman ZR, et al. Prevalence and correlates of Trichomonas vaginalis infection among men and women in the United States. Clin Infect Dis. 2018;67:211-217.
  5. Ginocchio CC, Chapin K, Smith JS, et al. Prevalence of Trichomonas vaginalis and coinfection with Chlamydia trachomatis and Neisseria gonorrhoeae in the United States as determined by the Aptima Trichomonas vaginalis nucleic acid amplification assay. J Clin Microbiol. 2012;50:2601-2608.
  6. Schwebke J, Merriweather A, Massingale S, et al. Screening for Trichomonas vaginalis in a large high-risk population: prevalence among men and women determined by nucleic acid amplification testing. Sex Transm Dis. 2018;45:e23-e24.
  7. Petrin D, Delgaty K, Bhatt R, et al. Clinical and microbiological aspects of Trichomonas vaginalis. Clin Microbiol Rev. 1998;11:300-317.
  8. Cotch MF, Pastorek JG II, Nugent RP, et al. Trichomonas vaginalis associated with low birth weight and preterm delivery. The Vaginal Infections and Prematurity Study Group. Sex Transm Dis. 1997;24:353-360.
  9. Smith LM, Wang M, Zangwill K, et al. Trichomonas vaginalis infection in a premature newborn. J Perinatol. 2002;22:502-503.
  10. Temesvári P, Kerekes A, Tege A, et al. Demonstration of Trichomonas vaginalis in tracheal aspirates in infants with early respiratory failure. J Matern Fetal Neonatal Med. 2002;11:347-349.
  11. Kissinger P, Adamski A. Trichomoniasis and HIV interactions: a review. Sex Transm Infect. 2013;89:426-433.
  12. Cohen MS, Hoffman IF, Royce RA, et al; AIDSCAP Malawi Research Group. Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1. Lancet. 1997;349:1868-1873.
  13. Sorvillo F, Kovacs A, Kerndt P, et al. Risk factors for trichomoniasis among women with human immunodeficiency virus (HIV) infection at a public clinic in Los Angeles County, California: implications for HIV prevention. Am J Trop Med Hyg. 1998;58:495-500.
  14. McClelland RS, Sangare L, Hassan WM, et al. Infection with Trichomonas vaginalis increases the risk of HIV-1 acquisition. J Infect Dis. 2007;195:698-702.
  15. Van Gerwen OT, Muzny CA. Recent advances in the epidemiology, diagnosis, and management of Trichomonas vaginalis infection. F1000Res. 2019;8:F1000 Faculty Rev-1666.
  16. Gaydos CA, Klausner JD, Pai NP, et al. Rapid and point-of-care tests for the diagnosis of Trichomonas vaginalis in women and men. Sex Transm Infect. 2017;93(S4):S31-S35.
  17. Rivers CA, Muzny CA, Schwebke JR. Diagnostic rates differ on the basis of the number of read days with the use of the InPouch culture system for Trichomonas vaginalis screening. J Clin Microbiol. 2013;51:3875-3876.
  18. Van Der Pol B, Williams JA, Taylor SN, et al. Detection of Trichomonas vaginalis DNA by use of self-obtained vaginal swabs with the BD ProbeTec Qx assay on the BD Viper System. J Clin Microbiol. 2014;52:885-889.
  19. Howe K, Kissinger P. Single-dose compared with multidose metronidazole for the treatment of trichomoniasis in women: a meta-analysis. Sex Transm Dis. 2017;44:29-34.
  20. Duff P. Should the length of treatment for trichomoniasis in women be reconsidered? OBG Manag. 2017;29(3):48-49.
  21. Krashin JW, Koumans EH, Bradshaw-Sydnor AC, et al. Trichomonas vaginalis prevalence, incidence, risk factors and antibiotic-resistance in an adolescent population. Sex Transm Dis. 2010;37:440-444.
  22. Klebanoff MA, Carey JC, Hauth JC, et al; National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. N Engl J Med. 2001;345:487-493.
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