INTRODUCTION

Trichomonas vaginalis is estimated to be the most common, curable non-viral sexually transmitted infection (STI) among women worldwide.¹ It is associated with adverse birth outcomes,² increased risk of acquisition and transmission of human immunodeficiency virus (HIV) and other STIs,^3,4,5 pelvic inflammatory disease (PID),^6,7 infertility,^8,9 and cervical cancer.¹⁰ African Americans are significantly more likely to be T. vaginalis-infected, signifying a predominant health disparity.¹¹ Beyond screening recommendations for HIV-infected women at entry to care and annually thereafter,¹² there are no screening, surveillance, or control programs for T. vaginalis. Thus, it is frequently considered a neglected STI.¹³ This chapter reviews the etiology, pathophysiology, epidemiology, clinical manifestations, diagnosis, and treatment (including partner management) of T. vaginalis infection, focusing on cisgender women.

ETIOLOGY AND PATHOPHYSIOLOGY

T. vaginalis is a parasitic pathogen primarily infecting squamous epithelial cells of the human genital tract, causing damage to these cells. It infects the female lower genital tract (vagina, urethra, and endocervix) and the male urethra and prostate. Humans are its only known natural host.^14,15 While transmission by fomites has been occasionally reported,^16,17,18,19 transmission mainly occurs during sex.²⁰ There have been conflicting data on the association between personal hygiene and T. vaginalis infection,^21,22 but in general, it is not thought to be a major factor. The incubation period of T. vaginalis is 4–28 days.²³ It does not have a cyst form and does not survive well in the environment, but has been identified outside the human body in warm and wet locations (i.e. moist towels) for >3 hours.¹⁶ It has its own microbiota, harboring two Mycoplasma species and a double-stranded RNA virus, T. vaginalis virus (TVV), which can contribute to its pathogenesis.^24,25 Of the four known TVV viruses, TVV1 and TVV2 have been linked to severity of genital symptoms²⁶ and TVV2 and TVV3 to surface expression of an immunogenic protein, P270, which is associated with cytotoxicity, cytoadherence, and host immune evasion.²⁷ The role of TVV4 is not elucidated. However, in a study of 355 US clinical T. vaginalis isolates, 40% of which were positive for TVV, there was no association between TVV positivity and genital symptoms, repeat infection, or metronidazole (MTZ) resistance, suggesting that TVV may be a commensal to T. vaginalis.²⁸

Infection is more common in women perhaps due to the anatomy of the female genital tract.^{29,30,31,32,33} Other possibilities could be due to spontaneous resolution in men (which may occur in some cases)^34,35 or less effective testing among asymptomatic men.^11,31,36,37 More T. vaginalis research has been done in symptomatic women, thus, its natural history in women has not been fully elucidated. However, several studies have found that, even after several months without treatment, most women still test positive.^38,39 A potential long natural history coupled with no screening recommendations (outside of HIV-infected women) may explain the finding that T. vaginalis is more prevalent in older women.¹¹ In contrast to women, persistence of T. vaginalis in men can be shorter (i.e. <1 month in some cases).³⁴ The greater likelihood of persistence in women is linked to greater availability of iron, an essential nutrient.^{15,33,40,41,42,43} Menstrual blood creates a rich growth medium which promotes attachment and growth of the parasite in the vaginal canal.^29,30

PREVALENCE AND EPIDEMIOLOGY

While not reportable, global estimates indicate that there are 156 million new cases of T. vaginalis infection among women and men annually.¹ The global prevalence of T. vaginalis among women (5.3%) is higher than that of chlamydia (3.8%), gonorrhea (0.9%), and syphilis (0.5%) combined.¹ In the US, the prevalence of T. vaginalis by urine nucleic acid amplification (NAAT) testing in a recent population-based study was 1.8% in women and 0.5% in men.¹¹ African Americans had a 4-fold higher prevalence than other groups, constituting a dramatic health disparity.¹¹ Unlike many STIs, T. vaginalis prevalence can be higher among older persons >45 years of age with rates ranging from 0.2% to 21.4%.⁴⁴ Population-based studies have also found that T. vaginalis rates are highest among those ≥25 years.⁴⁵ The prevalence of urethral infection in men who have sex with men (MSM), while low to non-existent in the US,⁴⁶ has been found to be 7% in South African MSM.⁴⁷ Although detection of T. vaginalis DNA occasionally occurs in extra-genital (oral, rectal) locations,^48,49 screening or diagnostic testing of these regions is not recommended.

RISK FACTORS

While present in all races,¹¹ T. vaginalis infection is more common in African American women engaging in high-risk sexual behaviors. This includes multiple sex partners,^50,51 inconsistent condom use, illicit drug use during sex,⁵⁰ sex with partners using illicit drugs,^31,50,52,53 and transactional sex.^54,55,56,57 Other risk factors include early coitarche,⁵⁸ older age,^11,31,52,59 history of incarceration,^60,61 having less than a high school education,¹¹ and living below the national poverty level.^12,51

Women with bacterial vaginosis (BV) are at higher risk for T. vaginalis infection.^12,20,62 While vaginal dysbiosis has been associated with increased pathogenicity of T. vaginalis,⁶³ it is not clear if the presence of BV interferes with T. vaginalis treatment. In two randomized controlled trials, BV was found to increase metrodinazole (MTZ) treatment failure in HIV-infected women⁶⁴ but not in HIV-uninfected women.⁶⁵ This difference may be due to impaired immunity in HIV-infected women,⁶⁴ altered pharmacokinetics and pharmacodynamics of MTZ,⁶⁶ or inadequate power in the studies.⁶⁵ Additionally, women with HIV are at higher risk for T. vaginalis.^54,67 Several studies have also shown that women who have sex with women and men (WSWM) are at higher risk for T. vaginalis than women who have sex with women (WSW) and women who have sex with men (WSM).^31,68

COMPLICATIONS

Complications associated with T. vaginalis infection among women include adverse birth outcomes, risk of HIV and other STIs, PID, infertility, cervical infection, and cervical cancer.

Adverse Birth Outcomes

In a meta-analysis of 19 studies, significant associations were found between T. vaginalis and preterm delivery (PTD), premature rupture of membranes (PROM), and low birth weight.² However, the physiological mechanisms linking T. vaginalis and adverse birth outcomes are not well understood. One hypothesis is that PTD and PROM in T. vaginalis-infected pregnant women are related to maternal innate immune inflammatory responses to the parasite, which involve elevated cervical interleukin-8 (IL-8) and vaginal defensin levels.^8,69 These cytokines are markers of neutrophil activation, which has been associated with PTD and other adverse birth events. For example, cervical IL-8 is thought to trigger cervical ripening and dilatation.^70,71 Additionally, one study has shown an association between maternal T. vaginalis infection and intellectual disability in children born to infected mothers.⁷²

Risk of HIV and other STIs

A meta-analysis of 19 studies found that persons infected with T. vaginalis were 1.5 times more likely to acquire HIV than non-infected individuals (95% CI 1.3–1.7; p <0.001).⁷³ In another meta-analysis of 32 studies reporting k = 97 effect size, estimates of HIV acquisition risk due to non-viral STI infections among high-risk heterosexuals with chlamydia, gonorrhea, syphilis, Mycoplasma genitalium, and/or T. vaginalis, HIV acquisition risk was statistically significant for T. vaginalis-infected women (RR 1.54; 95% CI 1.31–1.82; k = 17).⁷⁴ The greater susceptibility to HIV among T. vaginalis-infected individuals is plausible for several reasons: (1) T. vaginalis damages host epithelial cell membranes which act as a structural barrier to HIV, (2) the host immune response to T. vaginalis stimulates an increased number of HIV target cells in the genital tract mucosa, and (3) T. vaginalis alters the normal vaginal microbiota, rendering it more permissive to the development of BV, which, in turn, increases HIV acquisition risk.⁷³

There is less direct evidence suggesting that HIV-infected individuals with T. vaginalis are more likely to transmit HIV. A review paper found that only 7 of 14 studies demonstrated a higher likelihood of HIV shedding in the genital tract of T. vaginalis-coinfected individuals compared to HIV-infected individuals without coinfection.⁷⁵ In other studies, vaginal shedding of HIV-1 RNA was decreased after T. vaginalis treatment in women from Kenya⁷⁶ and New Orleans, LA.⁷⁷ However, in the Kenyan cohort, the prevalence of vaginal HIV-1 DNA remained unchanged despite T. vaginalis treatment.

Concomitant infection with T. vaginalis has been associated with a higher incidence of genital HSV-2 infection⁷⁸ as well as genital HSV-2 shedding.⁷⁹ It has also been associated with the presence of other STIs including chlamydia, gonorrhea, and human papillomavirus (HPV).^4,80

Pelvic Inflammatory Disease

T. vaginalis is not traditionally considered an STI associated with pelvic inflammatory disease (PID). However, in an older study of 119 South African women, those infected with T. vaginalis had a significantly higher risk of PID than those without (p = 0.03).⁶ When these women were stratified according to their HIV status, the risk of PID in HIV-infected women with T. vaginalis increased significantly (p = 0.002); no association was found in women without HIV.⁶ More recently, among 647 women in the PID Evaluation and Clinical Health (PEACH) study, T. vaginalis was isolated from the vagina in 12.8% of women and the odds of having endometritis at baseline was twice as high among T. vaginalis-infected women with compared to women without T. vaginalis infection (adjusted OR (AOR): 1.9, 95% CI 1.0–3.3). Infertility and recurrent PID were also more common among T. vaginalis-infected women.⁷

Infertility

A meta-analysis of eight studies found that T. vaginalis was associated with a 1.7 times greater risk of infertility in women (95% CI 1.25–2.31).⁸¹ Similarly, a meta-analysis of five studies found that T. vaginalis was associated with a 1.91 times greater risk of infertility in men (95% CI 1.02–3.58).⁸¹ This is thought to be due to inflammatory damage of female reproductive organs and changes in the vaginal environment resulting in decrease or loss of reproductive function in women.⁸¹ In men, T. vaginalis itself or the induced inflammatory response can impair sperm cells, causing a decrease in cell viability or death, resulting in a decrease or loss of reproductive function.⁸¹

Cervical Infection and Cervical Cancer

While thought to be a vaginal infection, there is some evidence to suggest that T. vaginalis causes cervical involvement. A small study of 64 symptomatic female STI clinic attendees presenting with cervico-vaginal discharge found that 6.4% of cervical infections were attributable to T. vaginalis.⁸² Regarding the risk of cervical cancer, a study of Tanzanian women found that those infected with T. vaginalis were 6.5 times more likely to have high-risk HPV, suggesting an indirect link between T. vaginalis and cervical neoplasia.⁴ In addition, a meta-analysis of 17 studies found that T. vaginalis-infected women had a higher risk of cervical neoplasia (OR 2.06, 95% CI: 1.77–2.39), with HPV co-infection playing an important role.¹⁰

SIGNS AND SYMPTOMS

The “classic” symptoms of T. vaginalis infection include vaginal odor and a yellow-green, frothy, malodorous vaginal discharge.^{12,29,52,83,84} However, a large number of infected women have minimal or no symptoms (83–89%).⁸⁵ Half of infected asymptomatic women, however, may become symptomatic within 6 months.¹⁴ Infected women can also develop cyclic symptoms that are worse during menstruation.²⁹ Symptomatic women may note additional symptoms including genital pruritis, dysuria, and dyspareunia.

On exam, signs may include vaginal erythema, malodorous, frothy, vaginal discharge, colpitis macularis or “strawberry cervix” (present in <5% of women;^86,87 rises to nearly 50% with colposcopy)⁸⁷, and elevated vaginal pH >4.5.²⁰ However, infection may also be present in the setting of a normal vaginal pH.²⁰

DIAGNOSIS

T. vaginalis is traditionally diagnosed at the point-of-care (POC) by wet mount microscopy of vaginal secretions for motile trichomonads (sensitivity 44–68%; specificity 100%)⁸⁸ (Figure 1). This test must be performed within 10–20 minutes or the trichomonads will lose their viability, increasing the likelihood of a false negative test. The OSOM^® rapid test (Sekisui Diagnostics, California) is another POC test (results ≤10 minutes) that uses antibodies to detect T. vaginalis protein antigens in vaginal secretions (sensitivity 82–95%; specificity 97–100%, compared to wet mount and culture). It is a qualitative test that should be used in symptomatic women or contacts to T. vaginalis.⁸⁸ When present, T. vaginalis antigens bind antibodies resulting in the formation of a blue line on the test strip. This test does not require microscopy however is more expensive than wet mount.

An additional POC sero-diagnostic test is currently in development (MedMira Rapid Vertical Flow (RVF®) Technology).⁸⁹ This novel test detects α-actinin blood antibodies, a highly immunogenic T. vaginalis protein not found among other microorganisms that has no identity with the human homolog, in serum or whole blood specimens.⁸⁹ The MedMira Rapid Vertical Flow test cartridge has a membrane including a vertical procedural/reagent control line and a spot that becomes readily visible within 5 minutes if there is a positive reaction with α-actinin antibody present in serum or whole blood specimens. One area of future research associated with this test is the need to address the temporal nature and duration of serum anti-T. vaginalis antibody response after infection and cure, including the possibility of long-lasting serum antibody, which may not be indicative of active infection.

Trichomonas culture (InPouch® system [BioMed Diagnostics, White City, OR]) has previously been the gold standard for diagnosis (sensitivity 44–81%; specificity 100%).^88,90 Specimens from women (vaginal swabs) or men (urethral swabs, urine sediment, and/or semen; multiple specimens recommended to increase yield) should be used to inoculate the culture medium <1 hour after collection.⁸⁸ However, this test is categorized by the Clinical Laboratory Improvement Amendments (CLIA) as moderately complex, as it requires incubation at 37°C and reading over multiple days.⁹¹

The availability of highly sensitive and specific T. vaginalis molecular diagnostic assays has grown rapidly. These assays can be further divided into molecular amplified assays (i.e. AmpliVue and Solana assays),^92,93 instrument-based assays (i.e. Hologic Aptima T. vaginalis nucleic acid amplification test [NAAT], Becton Dickinson [BD] ProbeTec Qx T. vaginalis NAAT, BD Max CT/GC/TV2 NAAT, Cepheid GeneXpert T. vaginalis NAAT, Roche Cobas MG/TV NAAT, and the Abbott Alinity m STI assay (including T. vaginalis NAAT testing),^{94,95,96,97,98} and instrument-free assays (i.e. Visby GC/CT/TV NAAT testing device).⁹⁹ These assays, with their respective sensitivities and specificities, specimen types in women, complexity, and time to results, are detailed in Table 1. Several of these assays can provide testing results within 1 hour or less (i.e. AmpliVue [45–50 minutes]; Solana [<40 minutes]; Cepheid GeneXpert [40–63 minutes], and Visby [25 minutes]).

TREATMENT AND FOLLOW-UP

5-nitroimidazoles (MTZ, tinidazole [TDZ], and secnidazole [SEC]) are the primary class of drugs used for T. vaginalis treatment. For decades, the CDC and World Health Organization have recommended single dose 2-g oral MTZ as the preferred treatment for T. vaginalis, with oral MTZ 400–500 mg twice daily for 7 days or single-dose 2-g oral TDZ as alternative therapies. The recommended treatment was changed to the 7-day oral MTZ dose for HIV-infected women more than a decade ago in response to a multi-center randomized controlled trials demonstrating superiority of the 7-day oral MTZ dose over singe-dose.⁶⁴ A subsequent meta-analysis¹⁰¹ and multi-center trials⁶⁵ more recently found similar results in HIV-uninfected women. In vivo pharmacokinetic and pharmacodynamic effects of MTZ may be playing a role in single-dose oral MTZ treatment failure, necessitating a longer treatment regimen in women.⁶⁶ Two hypotheses for this finding are (1) competition for oral MTZ by BV-associated bacteria in the vaginal microbiota of T. vaginalis-infected women and (2) inadequate accumulation of the active metabolites of MTZ when only a single, oral dose is given.⁶⁶ Thus, the 7-day oral MTZ regimen is currently the recommended treatment regimen for all women with single dose 2-g oral TDZ remaining as an alternative.^12,102 Given the lack of a comparable randomized controlled trials in men, single dose 2-g oral MTZ remains the recommended therapy for men with single dose 2-g oral TDZ as an alternate.¹² While it is never recommended to drink alcohol with any medication, it is now understood that moderate alcohol consumption should not be a barrier to oral metronidazole use during the treatment of T. vaginalis.

If a woman is still infected with T. vaginalis after multi-dose oral MTZ and has been re-exposed to an untreated sexual partner, she should be re-dosed with the same treatment regimen. If she has not been re-exposed, she should be re-treated with either 2-g of oral MTZ or TDZ daily for 7 days.¹² If a male is still infected with T. vaginalis after treatment with single dose 2-g oral MTZ and has been re-exposed to an untreated sexual partner, he should be re-dosed with single dose 2-g oral MTZ. If he has not been re-exposed, he should be given a course of oral MTZ 500 mg twice daily for 7 days.¹²

Most recently, a randomized, double-blind, placebo-controlled, delayed-treatment study evaluating the efficacy and safety of a single 2-g dose of oral SEC, a second generation 5-nitroimidazole with a longer half-life (17–19 hours), in 147 women with trichomoniasis was conducted.¹⁰³ At the test-of-cure (TOC) visit 6−12 days after randomization, the microbiologic cure rate was 92.2% (95% CI: 82.7–97.4) in the SEC group and 1.5% (95% CI: 0.0–8.0) in the placebo group (p <0.001).¹⁰³ For women who received placebo at baseline, the opposite treatment was given at TOC to ensure all participants were treated per standard of care. SEC was well tolerated in this study. The most frequent adverse events were vulvovaginal candidiasis and nausea (2.7% each). SEC has since been FDA approved for T. vaginalis treatment in adolescent and adult women and men ≥12 years. It is also FDA approved for BV treatment in women¹² and is the only single-dose oral regimen available for both vaginal infections.¹⁰⁴

Re-testing for T. vaginalis is recommended, preferably by NAAT, for all sexually active women between 3 weeks and 3 months after the end of treatment regardless of whether or not their sexual partner(s) were treated.¹² The optimal time for repeat T. vaginalis NAAT testing after completion of multi-dose oral MTZ was ≥3 weeks in a recent study;¹⁰⁵ repeat NAAT testing before this time carries the risk of detecting remnant T. vaginalis nucleic acid that can still exist. If re-testing by 3 months is not possible, women should be re-tested whenever they next seek medical care.¹²

MANAGEMENT OF T. VAGINALIS IN SPECIAL SITUATIONS

Infants

T. vaginalis has been noted to be transmitted perinatally in case reports,¹⁰⁶ although it is rare. In female newborns, T. vaginalis acquisition during birth may cause vaginal discharge during the first week of life.¹⁰⁷ Respiratory infection in newborns is also possible.¹⁰⁸

Pregnant and Lactating Women

Several meta-analyses have found MTZ to be safe in all stages of pregnancy^109,110 and its use in pregnancy is supported by current national guidelines.¹² TDZ use should be avoided in pregnancy based on preclinical data suggesting it poses a moderate risk.¹² Limited data are available on the use of SEC in pregnancy; however, there is no evidence of adverse developmental outcomes in animal studies.¹⁰⁴

In lactating women administered MTZ, withholding breastfeeding during treatment and for 12–24 hours after the last dose will reduce the exposure of the infant to MTZ. For women treated with TDZ, interruption of breastfeeding is recommended during treatment and for 3 days after the last dose.¹¹¹

5-nitroimidazole Hypersensitivity

The most common reactions associated with 5-nitroimidazoles (primarily MTZ) are immediate, type I IgE-mediated hypersensitivity reactions, occurring with 1–2 hours of drug exposure. This includes urticaria and hives with potential life-threatening manifestations such as angioedema, bronchospasm, and anaphylaxis.¹¹² Type II and IV hypersensitivity reactions have been less commonly described.^{113,114,115,116} The prevalence of MTZ hypersensitivity was found to be ~0.15% in a study of 2,375,424 Kaiser Permanente health plan members.¹¹⁷

Although uncommon, treatment for T. vaginalis-infected patients with a true history of 5-nitroimidazole hypersensitivity is challenging.¹¹⁸ If a prior IgE-mediated hypersensitivity reaction has been confirmed based on history and/or drug provocation testing,¹¹⁸ desensitization to the 5-nitroimidazole is the first line of treatment.¹² Oral^113,119 and intravenous¹²⁰ protocols for desensitization have been published, primarily involving MTZ. Intensive monitoring is required during the desensitization process due to the need for frequent drug administration and monitoring for reactions; thus, it should be performed in the inpatient setting.¹¹⁸ After completion of a desensitization protocol, patients are able to safely take oral MTZ for 4–5 half-lives of the drug (half-life = 7–8 hours), approximately 2 days.¹¹⁷ If the drug is not continued at regular intervals after completion of the desensitization protocol, it will need to be restarted from the beginning to avoid breakthrough reactions.¹¹⁷

For patients in which desensitization is not an option, use of other 5-nitroimidazoles such as TDZ or SEC is not recommended because of the risk of cross-reactivity¹¹⁵ and alternative treatment options outside of the 5-nitroimidazoles should be used.^12,118 Use of these alternative treatments is anecdotal, limited to vaginal formulations (the majority of which have to be compounded), and may not reach all sites infected with T. vaginalis (i.e. Bartholin’s and Skene’s glands).^12,118 One option is a prolonged course of vaginal boric acid 600 mg twice daily for 60 days, either alone^121,122 or in combination with vaginal clotrimazole.¹²³ Another option is vaginal paromomycin 6.25% cream daily for 8–14 days.^124,125,126 However, topical use of this medication can result in painful vulvar ulcers that are self-limited and resolve once treatment is discontinued. Lubricating jelly applied to the vulva before use has been successful in preventing the development of these ulcers in some women.¹²⁶

Persistent Infection

For those experiencing persistent infection not due to sexual re-exposure, a trichomonas culture kit from the Centers for Disease Control and Prevention (CDC) can be requested to perform drug resistance testing (404–718–4141; https://www.cdc.gov/laboratory/specimen-submission/detail.html?CDCTestCode=CDC-10239). CDC has experience with MTZ and TDZ susceptibility testing for 5-nitroimidazole-resistant T. vaginalis as well as management of infected patients. Based on resistance testing results, an alternative treatment regimen may be recommended.

Resistance rates in T. vaginalis for MTZ and TDZ have ranged from 4.3 to 10%,¹²⁷ although these data are not contemporary; resistance rates of SEC among clinical T. vaginalis isolates are unknown. In vitro resistance may not always correlate with clinical treatment failure,¹²⁸ especially in pregnant women,⁵⁷ but use of alternative treatment regimens following drug resistance testing results in cure of resistant infections in >80% of cases, suggesting that there is a benefit to this testing.¹²⁹

Alternative treatment regimens for infections demonstrating in vitro resistance may include 2-g oral MTZ or TDZ daily for 7 days.¹² If a patient fails the 7-day regimen of high-dose oral MTZ or TDZ, additional treatment options have had successful results in women. One is high-dose oral TDZ 2-g daily plus vaginal TDZ 500 mg twice daily for 14 days.¹³⁰ If this fails, high-dose oral TDZ (1-g three times daily) plus vaginal paromomycin (4 g of 6.25% cream nightly) for 14 days can be considered.¹³¹ Recently, a case report of successful treatment of a T. vaginalis-infected woman with 5-nitroimidazole resistance was also published using an extended regimen of 2-g oral SEC daily in combination with intra-vaginal boric acid 600 mg twice daily for 14 days.¹³²

HIV-Infected Women

In a randomized controlled trial of HIV-infected women co-infected with T. vaginalis, 7-day oral MTZ was found to be superior to single-dose 2-g oral MTZ;⁶⁴ this superiority only occurred in the presence of BV.¹³³ Studies have found that protease inhibitors used for the treatment of HIV may interfere with the efficacy of single-dose 2-g oral MTZ among HIV-infected women.^134,135

T. vaginalis screening (and treatment for positive cases) at entry to care and annually is recommended for HIV-infected women.¹² It has been estimated that if the recommendation for T. vaginalis screening and treatment among HIV-infected women were followed, the lifetime cost of new HIV infections prevented would be ~$159,264,000 and could potentially prevent new HIV cases due to female-to-male transmission.¹³⁶

Partner Management

Male sexual partners of persons infected with T. vaginalis also likely to also have infection. One recent study in Melbourne, Australia found that, among men with T. vaginalis-infected partners, the rate of infection was 18.6% compared to 0.5% among those who did not have a T. vaginalis-infected partner (p <0.001).¹³⁷ Sexual partners of index cases of T. vaginalis infection should be treated. Commonly, patients are told to tell their partners to seek testing and treatment. Providers can also consider treating partners of positive patients presumptively. One method is expedited partner therapy (EPT), the practice of treating sexual partner(s) of patients diagnosed with an STI by providing a prescriptions or the medication to the patient to take to his/her partner(s) without the health care provider first examining the partner.

One randomized controlled trial demonstrated that partner treatment with single-dose 2-g oral TDZ resulted in a >4 fold reduction in repeat infections among T. vaginalis-infected index women.¹³⁸ However, two other studies using single-dose 2-g oral MTZ for male partners of T. vaginalis-infected women found either no effect of EPT¹³⁹ or a borderline effect.¹⁴⁰ While it is possible that the two studies that used MTZ were either underpowered or did not use a correct control arm, it is also possible that oral TDZ is a better treatment for men. No data exist on the use of oral SEC in the setting of EPT.

FUTURE DIRECTIONS

Given that most studies have examined outcomes of symptomatic T. vaginalis infection in women, additional studies are needed to examine the importance of asymptomatic infection. This is necessary given the proliferation of T. vaginalis molecular diagnostic tests, including POC tests.⁹⁹ Additional study of the role of T. vaginalis in contributing to PID is also needed, especially among HIV-uninfected women. Regarding treatment, contemporary data on rates of T. vaginalis resistance among 5-nitroimidazoles, including SEC, are needed. In addition, the role of oral SEC in the treatment of persistent T. vaginalis infection and in the setting of EPT should also be further investigated.

PRACTICE RECOMMENDATIONS*