INTRODUCTION — Trichomoniasis is a genitourinary infection with the protozoan Trichomonas vaginalis. It is the most common nonviral sexually transmitted disease (STD) worldwide. Females are affected more often than males. Trichomoniasis is one of the three common infectious causes of vaginal complaints among reproductive-aged females, along with bacterial vaginosis and candida vulvovaginitis, and a cause of urethritis in males; however, the infection is often asymptomatic.

Related topics on the approach to the evaluation of vulvovaginitis and urethritis are presented separately:

●(See "Approach to females with symptoms of vaginitis".)

●(See "Urethritis in adult males".)

In this topic, we use "woman/en" to refer to genetic females and use the terms "women" or "patients" as they are used in the studies presented. However, we encourage the reader to consider the specific counseling and treatment needs of transgender and gender diverse individuals.

BACKGROUND

Microbiology and transmission — The organism responsible for trichomoniasis is the flagellated protozoan T. vaginalis, which principally infects the squamous epithelium in the urogenital tract: vagina, urethra, and paraurethral glands [1]. Other less common sites include the cervix, bladder, Bartholin glands, and prostate. Humans are the only natural host, and it is the most common nonviral sexually transmitted infection (STI) worldwide [2,3]. The parasite is a pear- or round-shaped organism with four anterior flagella and an undulating membrane that cause the characteristic motility seen on a diagnostic wet-mount slide [4]. (See 'Microscopy and pH' below.)

Trichomoniasis is virtually always sexually transmitted [5]. Although survival on fomites has been reported, transmission by fomites has not been directly proven [6]. Women can acquire the disease from both women and men, while men typically acquire the infection from women and do not usually transmit the infection to other men [7-9]. The incubation period is unknown; however, in vitro studies suggest an incubation period of 4 to 28 days in approximately 50 percent of patients [10]. Coexistence of T. vaginalis and bacterial vaginosis pathogens is common; coinfection rates ranging from 20 to 60 to 80 percent have been reported [11,12]. (See "Bacterial vaginosis: Clinical manifestations and diagnosis" and "Bacterial vaginosis: Treatment".)

Prevalence — Trichomonal infection does not need to be reported to public health authorities, so prevalence is difficult to determine. Prevalence estimates vary according to the population studied and method used for diagnosis. For example, a meta-analysis of 18 studies including over 37,000 women from low- and middle-income African countries reported a prevalence rates of 2 to nearly 30 percent, depending on the age range and risk status of the population [13]. In 2008, the World Health Organization estimated that over 276 million new cases occurred globally, and approximately 187 million people were infected at any one time [14].

The best estimate of the prevalence of trichomoniasis in reproductive-age women in the United States was provided by the National Health and Nutrition Examination Survey (NHANES), in which a nationally representative sample of 3754 women ages 14 to 49 years self-collected vaginal swab specimens that were subsequently evaluated for T. vaginalis by polymerase chain reaction (PCR) [15]. The overall prevalence of T. vaginalis was 3.1 percent and increased with age. Prevalence was highest in non-Hispanic Black women (13.3 percent) and lowest in non-Hispanic White women (1.3 percent). These estimates remained relatively stable in an analysis using urine samples from 4463 female participants in the 2013 to 2016 NHANES, which found a prevalence of 2.1 percent in women overall and similar disparities between non-Hispanic Black women (9.56 percent) versus non-Hispanic White women (0.81 percent) [16]. Urine samples have a lower sensitivity than cervicovaginal swabs, which likely accounts for the slightly lower prevalence estimates.

When nucleic acid amplification testing (NAAT) is used to detect T. vaginalis, the overall prevalence is higher than that reported by the NHANES study and ranges from approximately 5 to 16 percent, depending on the clinical setting (5 to 7 percent in family planning, internal medicine/family practice, and obstetrics and gynecology offices to 16 percent in prisons and sexually transmitted infection [STI] clinics) [17,18]. In contrast to the NHANES study, these women were tested because of symptoms or the presence of risk factors for chlamydia or gonorrhea. Lastly, a study in 15 STI clinics participating in the STI Surveillance Network reported the prevalence of T. vaginalis was 26 percent among 17,952 symptomatic women tested, 6.5 percent among 3909 asymptomatic women screened, and 29 percent among 92 HIV-infected women tested/screened [19].

The age distribution of trichomoniasis infections in women appears to differ from other STIs. In a PCR study of cervicovaginal samples obtained during gynecologic examinations, the peak rate of detection for T. vaginalis occurred in women ages 47 to 53 years, compared with 14 to 20 years for Chlamydia trachomatis [20]. In addition, while rates of chlamydia infection rapidly declined after peak detection, T. vaginalis infections had a bimodal distribution with infection peaks occurring in women ages 21 to 22 years and 48 to 51 years.

T. vaginalis can be identified in 70 percent of the male sexual partners of infected women [21], although carriage in men is often self-limited (see 'Treatment of sex partners' below). A study using an educational internet program to offer sexually active men free NAATs for T. vaginalis on self-collected specimens reported an overall prevalence of 3.7 percent among the 1699 men, and the highest prevalence by age group was in men aged 40 to 49 years (5.2 percent) [22].

Prevention — The risk of acquiring T. vaginalis infection can be reduced by consistent use of condoms and limiting the number of sexual partners. Spermicidal agents such as nonoxynol-9 reduce the rate of transmission [23].

●(See "External (formerly male) condoms".)

●(See "Internal (formerly female) condoms".)

●(See "Pericoital contraception: Diaphragm, cervical cap, spermicides, and sponge".)

SCREENING — In the United States, the Centers for Disease Control and Prevention recommend screening for T. vaginalis in all HIV-infected women, annually and at their initial prenatal visits [9]. In addition, screening is reasonable for HIV-uninfected women at increased risk of Trichomonas infection, including those with new or multiple partners or a history of sexually transmitted infections. Screening for men is not recommended.

Issues related to screening for T. vaginalis are discussed separately. (See "Screening for sexually transmitted infections", section on 'Trichomonas'.)

CLINICAL FEATURES AND CONSEQUENCES

Females — In women, trichomoniasis ranges from an acute, severe inflammatory disease to an asymptomatic carrier state. Common signs and symptoms of acute infection include a purulent, malodorous, thin discharge associated with burning, pruritus, dysuria, frequency, lower abdominal pain, or dyspareunia [24]. However, in women with proven infection, only 11 to 17 percent present with typical symptoms [25]. Symptoms may be worse during menstruation [26]. Postcoital bleeding can occur. In chronic infection, signs and symptoms are milder and may include pruritus and dyspareunia, with scanty vaginal secretion. Up to 85 percent of infected individuals are asymptomatic, although many of these eventually develop symptoms [9,27]. Asymptomatic carriage can persist for prolonged periods of time (at least three months); thus, it is often not possible to ascertain when or from whom the infection was acquired [28,29].

Physical examination often reveals erythema of the vulva and vaginal mucosa. The classically described green-yellow, frothy, malodorous discharge occurs in 10 to 30 percent of symptomatic women. Punctate hemorrhages may be visible on the vagina and cervix (ie, strawberry cervix) in 2 percent of cases (picture 1) [30].

Consequences of trichomoniasis vary by population:

●Nonpregnant females – Untreated trichomonal vaginitis may progress to urethritis or cystitis. In addition, T. vaginalis has been associated with a range of adverse reproductive health outcomes, including cervical neoplasia [31,32], posthysterectomy cuff cellulitis or abscess [33], pelvic inflammatory disease [34,35], and infertility [36]. It may also increase women's susceptibility to acquiring HIV infection by up to twofold [37-39]. Trichomoniasis in HIV-infected individuals is associated with an increased risk of HIV transmission to uninfected partners [40-42]. There is some evidence that treatment of trichomoniasis reduces HIV shedding [40,41,43].

●Pregnant individuals – T. vaginalis infection during pregnancy is associated with adverse obstetric outcomes including premature rupture of the membranes, preterm delivery, and delivery of a low birth weight infant [27,44-47]. In a 2014 systematic review and meta-analysis of the association between T. vaginalis and perinatal outcomes, the risk of preterm birth was increased by 42 percent among infected women (relative risk 1.42, 95% CI 1.15-1.75; nine studies) [48]. The risks of premature rupture of membranes and delivery of a small for gestational age infant were similarly increased, but each of these findings was based on only two studies. Whether treatment in pregnancy affects these risks, positively or negatively, is unclear [9]. (See 'Pregnant individuals' below.)

●Newborns – Infants born to infected mothers may contract infection during delivery. Signs and symptoms in neonates may include fever, respiratory problems, urinary tract infection, nasal discharge, and, in girls, vaginal discharge [49-52]. Treatment of asymptomatic infants is not necessary as spontaneous resolution will occur when estrogen levels wane to normal prepubescent levels [53].

Males — In men, T. vaginalis infection is asymptomatic in over three-quarters of cases and often transient (spontaneous resolution within 10 days) [21,53]. However, untreated infection can persist for months [54]. Symptoms, when present, are the same as those for urethritis from any cause and consist of a clear or mucopurulent urethral discharge and/or dysuria. They may also have mild pruritus or burning sensation in the penis after sexual intercourse. (See "Urethritis in adult males", section on 'Clinical manifestations'.)

T. vaginalis in men has been associated with prostatitis, balanoposthitis, epididymitis, infertility, and prostate cancer. (See "Approach to infectious causes of dysuria in the adult man" and "Risk factors for prostate cancer", section on 'Trichomonas vaginalis infection'.)

DIAGNOSIS — For women and men, the diagnosis of T. vaginalis is based on laboratory testing (motile trichomonads on wet mount, positive culture, positive nucleic acid amplification test, or positive rapid antigen or nucleic acid probe test) that confirms T. vaginalis [55].

DIAGNOSTIC EVALUATION

Female evaluation — Microscopy is often the first step in the diagnostic evaluation for trichomoniasis because microscopy is important in the evaluation of vaginal discharge. Microscopy is convenient and low cost, although less accurate than other tests. If the microscopic evaluation is positive for trichomonads, no further trichomonal testing is indicated. For women with nondiagnostic (or negative) wet-mount slides on microscopy, nucleic acid amplification tests (NAAT) are performed. If NAAT is not available, rapid diagnostic kits, or culture are performed instead. The choice of test is based on availability and cost.

Women undergoing testing for trichomoniasis are generally tested for chlamydia and gonorrhea infections as well. The diagnostic approach to women with vaginal discharge is reviewed separately. (See "Approach to females with symptoms of vaginitis" and "Screening for sexually transmitted infections", section on 'Screening recommendations'.)

Preferred tests

Microscopy and pH — The presence of motile trichomonads on wet mount is diagnostic of infection, but they are identified in only 60 to 70 percent of culture-confirmed cases (picture 2 and figure 1) [56]. The motion is jerky and spinning (movie 1 and movie 2); organisms remain motile for 10 to 20 minutes after collection of the sample. The slide should be evaluated soon after obtaining the specimen as sensitivity decreases over time, with up to 20 percent decrease reported one hour after collection [9,57,58]. Fixation and staining is not useful because T. vaginalis may not have the typical pear-shaped flagellated form; instead, it may resemble polymorphonuclear leukocytes or lose morphologic characteristics during fixation and staining, making the etiologic identification difficult [59].

Other findings that are typically present with T. vaginalis infection include an elevated vaginal pH (>4.5) and an increase in polymorphonuclear leukocytes on saline microscopy. However, these additional findings are not diagnostic as they can be found in other vaginal infections (table 1).

Nucleic acid amplification test — NAATs detect RNA by transcription-mediated amplification (polymerase chain reaction [PCR] or reverse transcriptase), are highly sensitive and specific, and have become the accepted gold standard for the diagnosis of T. vaginalis [60]. Test limitations include the need for instrumentation and laboratory analysis. In a study of test samples from 303 female sex workers, test sensitivity was highest for vaginal samples and lowest for first-voided urine specimens (86 versus 63 percent, all infections) [61].

One of the most commonly used tests, the Aptima T. vaginalis assay (Hologic), uses target capture and transcription mediated nucleic acid amplification to detect species-specific ribonucleic acid (RNA) for T. vaginalis on a single vaginal swab or urine specimen [62]. Reported sensitivity ranges from 95 to 100 percent and specificity ranges from 95 to 100 percent [9,63-65]. The Aptima T. vaginalis assay has demonstrated superior performance in side-by-side comparisons with other diagnostic methods in all patient populations and specimen types tested (vaginal discharge, urine). The Aptima T. vaginalis assay is approved by the US Food and Drug Administration (FDA) [65]. Because the prevalence of Trichomonas is equal to or greater than chlamydia and gonorrhea, there is an increasing trend toward screening for all three infections simultaneously with NAAT [60]. A separate assay is currently required for N. gonorrhoeae and C. trachomatis (eg, Aptima Combo 2).

Other available NAATs include Amplicor (Roche), AmpliVue (Quidel), BD ProbeTec TV Q^x (BD Diagnostics), NuSwab VG (LabCorp), Solana (Quidel), Xpert TV (Cepheid) assays. Few are approved by the FDA, but all are likely to be reliable. The BD MAX vaginal panel, which is FDA approved, also tests for bacterial vaginosis and Candida species [66]. There are no studies comparing one test with another. Amplicor (Roche) is a PCR assay for detection of N. gonorrhoeae and C. trachomatis that has been modified to detect T. vaginalis in vaginal/endocervical swabs or urine; sensitivity and specificity are 88 to 97 percent and 98 to 99 percent, respectively [28]. NuSwab VG (LabCorp) is a nucleic acid amplification single specimen assay for the detection of trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis.

Rapid antigen and DNA hybridization probes — Rapid diagnostic kits can be useful in areas of high prevalence (eg, sexually transmitted disease [STI] clinics and clinics serving populations with high prevalence rates) where microscopy or culture is not available. The following tests can be performed by the clinician at the point of care and are commercially available.

●AFFIRM VPIII – The Affirm VPIII Microbial Identification System (Becton Dickinson) test uses a DNA hybridization probe on a vaginal swab specimen. Results are available in 45 minutes. Although sensitivity and specificity have been reported to exceed 95 percent, in side-by-side testing, this method was inferior to target capture and transcription mediated amplification (sensitivity 63.4 versus 100 percent [63]).

●OSOM Trichomonas Rapid Test – The OSOM Trichomonas Rapid Test (Sekisui Diagnostics) is a rapid antigen test that uses an immunochromatographic technology on a vaginal swab specimen. Testing can be done at the point of care, and results are available in 10 minutes. It has sensitivity of 82 to 95 percent and specificity of 97 to 100 percent [67-70].

Test comparison — The excellent performance characteristics of the above tests are illustrated by the following comparative studies, which compare performance of traditional and rapid testing methods:

●One study recruited 330 sexually active adolescent females seeking care at a teen health clinic or emergency department and tested them for T. vaginalis using the four test methods discussed above: wet mount, culture (InPouch TV), rapid antigen testing (OSOM TV), and transcription-mediated amplification testing (APTIMA TV) [71]. The sensitivities of the four methods were 65, 96, 90, and 98 percent, respectively.

●Another study enrolled 296 female and 298 male subjects seeking care at a STD clinic [62]. Specimens from each subject were tested for trichomoniasis using transcription-mediated amplification (APTIMA TV), wet mount microscopy, culture, and PCR tests. The subject was diagnosed with trichomoniasis if any of these tests were positive. In women, vaginal swab APTIMA TV was more sensitive than wet mount or culture (96.6 versus 54.6 and 75.0 percent, respectively). In men, urethral swab APTIMA TV was more sensitive than culture or PCR (95.2 versus 28.6 and 54.8 percent, respectively).

●In a third study, specimens were retrieved consecutively from 766 patients with vaginal complaints and/or with histories suggestive of a STD and tested by both the AFFIRM and the APTIMA T. vaginalis assays [63]. Overall, 5.1 percent of patients were positive for T vaginalis (defined as a specimen with two positive test results for T. vaginalis by two different molecular assays). The APTIMA assay was statistically more sensitive than the AFFIRM assay (100 versus 63.4 percent); specificity was similar (APTIMA 100 percent, AFFIRM 99.9 percent).

Less accurate

Culture — Culture of vaginal secretions on Diamond's medium was considered the gold standard method for diagnosing T. vaginalis infection before the development of molecular detection methods [72]. Culture offers high sensitivity (up to 95 percent) and specificity (>95 percent). However, this test is not widely available and takes up to seven days to obtain a result. Culture is useful in patients with elevated vaginal pH and increased numbers of polymorphonuclear leukocytes but an absence of motile trichomonads and clue cells on wet mount, when microscopy is unavailable or yields ambiguous results, or when NAATs are not available. The "InPouch" T. vaginalis culture system has high sensitivity (over 80 percent), takes ≤3 days to obtain results, and is commercially available [73,74].

Cervical cytology — Trichomonads are sometimes reported as an incidental finding on tests performed for cervical cancer screening. Liquid-based cervical cytology is not a sensitive test for diagnosis of trichomoniasis, but treatment of women with trichomonads noted on liquid-based cervical cytology is reasonable since specificity is high. In a study that performed both liquid-based cervical cytology and culture for T. vaginalis on 203 consecutive women, 28 had a liquid-based smear positive for trichomonads, and 44 had positive cultures [75]. Although sensitivity of liquid-based smears for Trichomonas infection was low (61 percent), specificity was high (99 percent), resulting in a false-positive rate of only 1 percent.

Conventional Pap smears do not perform as well for diagnosis of trichomoniasis. Sensitivity is similar (51 to 63 percent) to liquid-based tests, but false-positive results are common (7 percent) [76]. This makes the positive predictive value poor in a low prevalence population. Thus, a conventional Pap smear should not be used to diagnose trichomoniasis. Asymptomatic women with trichomonads identified on a conventional Pap smear should be evaluated by wet mount and then NAAT, culture, or rapid test if the wet mount is negative and treated only if the diagnosis is confirmed.

Male evaluation — The most reliable methods for diagnosis of Trichomonas urethritis in the male are by culture or a NAAT (ie, PCR or transcription-mediated amplification) of first fraction urine or a urethral swab specimen [62,77]. Saline microscopy of a urethral swab specimen has low sensitivity and is not recommended. (See "Urethritis in adult males".)

DIFFERENTIAL DIAGNOSIS — For women, vaginal discharge is a nonspecific symptom that can be caused by vaginal infections, cervical infections, and, less commonly, atrophy and irritation.

●Vaginal infections – The most common infections responsible for vaginal discharge, odor, pruritus, and/or discomfort are bacterial vaginosis (BV), Candida vulvovaginitis, and trichomoniasis; these infections account for over 90 percent of cases [78]. The clinical features that distinguish among these infections are presented in the table (table 1). Detailed discussions of the clinical manifestations and management of BV and vulvovaginal candidiasis are presented separately:

•(See "Bacterial vaginosis: Clinical manifestations and diagnosis".)

•(See "Bacterial vaginosis: Treatment".)

•(See "Candida vulvovaginitis: Clinical manifestations and diagnosis".)

•(See "Candida vulvovaginitis: Treatment".)

●Cervical infections – The sexually transmitted cervical infections gonorrhea and chlamydia also cause symptomatic vaginal discharge, but less commonly than vaginal infections [79,80]. In two studies of women presenting with symptomatic vaginal discharge in resource-limited countries, cervical infection with either gonorrhea or chlamydia was present in 5 to 24 percent of women compared with vaginal infection (ie, BV, vulvovaginal candidiasis, or trichomoniasis) in over 50 percent of women [79,80]. Organism-specific testing is required to identify the infectious cause(s) of vaginal discharge. Clinical presentations and management of cervical sexually transmitted infections are discussed elsewhere:

•(See "Clinical manifestations and diagnosis of Neisseria gonorrhoeae infection in adults and adolescents".)

•(See "Treatment of uncomplicated Neisseria gonorrhoeae infections".)

•(See "Clinical manifestations and diagnosis of Chlamydia trachomatis infections".)

•(See "Treatment of Chlamydia trachomatis infection".)

●Other – Less common causes of vaginal discharge that could be mistaken for trichomoniasis include vaginal atrophy/atrophic vaginitis in postmenopausal women, retained foreign body, irritants and allergens (ie, dermatitis), desquamative inflammatory vaginitis, and several rarer entities, including some systemic medical disorders. Targeted testing is performed to exclude infection, including T. vaginalis. Once infectious etiologies have been excluded, then the evaluation continues to exclude noninfectious causes. (See "Approach to females with symptoms of vaginitis", section on 'Women without a diagnosis after initial evaluation'.)

For men, urethritis is typically caused by a sexually transmitted pathogen. Similar to vaginal discharge in women, urethritis is a nonspecific symptom in men and testing is performed to identify or exclude infectious organisms, most commonly Neisseria gonorrhoeae, Chlamydia trachomatis, and Mycoplasma genitalium. The evaluation and management of men with urethritis is presented elsewhere. (See "Urethritis in adult males".)

INITIAL TREATMENT

5-nitroimidazole drugs — The 5-nitroimidazole drugs (metronidazole, tinidazole, or secnidazole) are the only class of drugs that provide curative therapy of trichomoniasis (algorithm 1). Most strains of T. vaginalis are highly susceptible to these agents [81]. Randomized trials using these drugs have generally reported cure rates of 90 to 95 percent [82-85]. Choice of agent is generally determined by availability, preference for single-day therapy, and cost. Management of nitroimidazole-resistant Trichomonas is discussed below. (See 'Refractory cases' below.)

●Metronidazole – For initial treatment of female patients, we suggest a seven-day course of metronidazole 500 mg orally twice daily. While past guidelines have included treatment with a single 2 g oral dose of metronidazole, trials comparing the single- and multiple-day metronidazole regimens in women with and without HIV have demonstrated higher cure rates four weeks after treatment with the seven-day regimen [84,86]. An open-label trial comparing the two regimens among 623 enrolled women reported a significantly higher cure rate with seven-day versus single-dose treatment (89 versus 81 percent, respectively) [87]. Treatment success was evaluated with nucleic acid amplification testing or culture. Reports of adverse events, including gastrointestinal distress, were similar between the two treatment arms as was reported adherence (96 percent in the seven-day arm and 99 percent in the single-dose arm).

Treatment with topical metronidazole gel is not advised because the gel formulation does not reach therapeutic levels in the urethra and paravaginal glands and less efficacious compared with oral treatment [9].

●Tinidazole – Tinidazole is an alternative treatment for trichomoniasis and is given as a single 2 g oral dose [9]. Compared with metronidazole, tinidazole generally causes fewer gastrointestinal side effects, but the cost may be higher and the drug may be less available. Although tinidazole was significantly more effective than metronidazole in several randomized trials, most of these trials were subject to bias since outcome was assessed by clinicians who were not blinded to the patient's treatment group [84].

●Secnidazole – Secnidazole is a single 2 g oral treatment for trichomoniasis [88]. Compared with placebo for treatment of trichomoniasis, cure rates of 92 percent were reported at 6- to 12-day follow-up, which is comparable to the other 5-nitroimidazole single-dose regimens in that short follow-up period [85,86]. Gastrointestinal side effects were reported in <5 percent of participants in either arm, which is lower than rates reported with single-dose metronidazole [87]. While secnidazole may be preferred by patients for its single-day dosing, the cost may be higher because it is a newer treatment. Additionally, there are no head-to-head efficacy comparisons of single-dose secnidazole and the seven-day metronidazole regimen.

Allergy to 5-nitroimidazole drugs — Therapy with drugs other than 5-nitroimidazoles is an option, but cure rates are low (≤50 percent) [89,90]. Given the low efficacy of alternate drug therapies, we suggest patients with an IgE mediated allergy to metronidazole or tinidazole be referred for desensitization rather than using an alternative class of drugs [9]. Desensitization is very effective: In one series, all 15 women who underwent desensitization subsequently eradicated their infections [91].

OUR APPROACH — Treatment is indicated for both symptomatic and asymptomatic persons (algorithm 1). Treatment reduces the prevalence of T. vaginalis carriage in the population, relieves symptoms, and reduces the risk of sequelae (including acquisition/transmission of HIV) [9].

Nonpregnant females — Treatment is indicated in all nonpregnant females diagnosed with trichomoniasis, even if asymptomatic (algorithm 1). The rationale for treatment of asymptomatic females is that, if left untreated, they continue to transmit the infection to sexual partners and up to one-third of asymptomatic females become symptomatic within six months [26]. As reviewed above, metronidazole 500 mg orally twice a day for seven days is the preferred treatment. (See '5-nitroimidazole drugs' above.)

Treatment with a single 2 g oral dose of either tinidazole or metronidazole (ie, four 500 mg tablets) is associated with lower rates of cure [84,92]. Although older studies reported similar cure rates for single- and multiple-dose regimens (cure rate for single dose: 81 to 88 percent; cure rate for multiple dose: 85 to 90 percent) [82,84,87,93], a meta-analysis of six trials reported a higher treatment failure rate for single-dose compared with multiple-dose treatments (pooled risk ratio 1.80, 95% CI 1.07-3.03; p <0.03 in HIV-negative women) [86]. In combination with the results of the randomized trial comparing single dose to multiple dose [87], these data suggest that females who are able to complete the multiple-dose regimen appear to benefit from the longer treatment. By contrast, advantages of single-dose therapy include better compliance and possibly decreased Candida superinfection (although there is no evidence of decreased Candida superinfection). However, side effects (eg, nausea, vomiting, headache, metallic taste, dizziness) appear to be dose-related and thus occur less frequently with the lower doses used in multiple-dose, prolonged therapy [84]. The authors reserve single-dose therapy for those who are unable to complete a multiple-dose treatment course.

Oral or vaginal therapy — Oral is preferred to vaginal therapy since systemic administration achieves higher drug levels and therapeutic drug levels in the urethra and periurethral glands, which serve as endogenous reservoirs of organisms that can cause recurrence. Cure rates for vaginal therapy with metronidazole gel are ≤50 percent, which is significantly lower than with oral therapy, and therefore vaginal therapy with metronidazole is not recommended [9,84].

Follow-up — We retest all women treated for a documented Trichomonas infection, regardless of whether they believe their sex partners were treated. Repeat testing is ideally performed with a nucleic acid amplification test (NAAT), which can be done as soon as two weeks after and within three months of completing treatment. If testing is not possible within three months of initial treatment, then testing is advised up to 12 months from initial treatment. This is consistent with recommendations from the Centers for Disease Control and Prevention in the United States [9]. If NAAT is not available, retesting with the same modality used to make the initial diagnosis (or a more sensitive test) is advised. The rationale for repeat testing is that reinfection rates of up to 17 percent have been reported in women treated for trichomoniasis.

Males with urethritis — The same treatment regimens are used in men as in nonpregnant women, with preference given to single-dose treatment with either oral metronidazole or tinidazole, 2 g, to improve compliance. There are no data to suggest that men would derive additional benefit from a longer course of therapy. The clinical evaluation and management of men with urethritis are discussed in detail separately. (See "Urethritis in adult males".)

Treatment of sex partners — Treatment of sex partners is identical to that for nonpregnant females, with preference for a single-dose regimen to maximize compliance (ie, single 2 g oral dose of either tinidazole). Treatment of sex partners is indicated because maximal cure rates in infected women are achieved when their sexual partners are treated simultaneously [94]. Concurrent treatment also prevents transmission to other sexual contacts. After single-dose therapy of sexual contacts, patients should abstain from intercourse until all partners have waited at least seven days since taking the last antibiotic dose. There are no studies on how long trichomonads remain viable after treatment is initiated or completed.

It is not mandatory to identify the organism in a partner before treating (ie, Expedited Partner Therapy [EPT]), given the high rate of concurrent carriage (30 to 70 percent [21]), difficulty of diagnosis in males, lower compliance when the partner is asked to visit his health care provider, and the convenience, low morbidity, and low cost of empiric treatment. Similarly, all female sex partners also should be treated. The rates of concurrent trichomoniasis infections in women who have sex with women is not known.

Ideally, if possible, sexual partners should be referred for diagnostic evaluation because concurrent sexually transmitted infections, such as chlamydia and gonorrhea, are common and should be diagnosed and treated, if present [95,96]. However, if the one partner has been diagnosed with chlamydia or gonorrhea, EPT is also an option for these infections [95].

Counseling — Previous guidelines have recommended avoiding alcohol due to a potential disulfiram-like reaction associated with nitroimidazoles. However, several authors have reviewed the cases that are the basis of these reports and have not identified any convincing data to suggest that this is a true association [97]. Disulfiram inhibits acetaldehyde dehydrogenase, leading to increased concentrations of acetaldehyde, while in vitro experiments show a decrease in acetaldehyde with addition of metronidazole [98]. Thus, we do not feel strongly that patients need to be counseled to avoid alcohol while using metronidazole.

Patients should be instructed to avoid intercourse until they and their sex partners have completed treatment and are asymptomatic, which generally takes approximately one week. (See 'Treatment of sex partners' above.)

SPECIAL POPULATIONS

Pregnant individuals

Treatment and dosing options — Metronidazole 500 mg orally twice a day for seven days is the preferred treatment for pregnant individuals. While both single- and multiple-dose regimens are acceptable, we reserve the single-dose regimen for pregnant individuals who are unable to complete seven days of treatment or prefer single-dose therapy. There are no specific data comparing single-dose and multiple-dose regimens in pregnant individuals. However, there are no reasons to think that efficacy is different in pregnant patients, and, although tolerance may be diminished because many pregnant women have significant nausea or vomiting, some clinicians have historically preferred metronidazole 500 mg twice daily orally for five to seven days to lessen medication-induced nausea and vomiting [99].

There is limited information on the safety of tinidazole or secnidazole in pregnancy; therefore, we avoid their use, especially in the first trimester [88,100]. Although clotrimazole 1% cream inserted vaginally often results in symptomatic relief, it does not eradicate the organisms and therefore is not advised. For these reasons, oral metronidazole therapy is preferred.

Rationale for treatment — Given the association of T. vaginalis infection with adverse pregnancy outcomes [48], symptomatic pregnant women with confirmed infection are treated [92]. Additionally, asymptomatic trichomoniasis can be diagnosed during pregnancy with routine screening of HIV-infected or high-risk women. Although treatment of asymptomatic pregnant women is not universal [92], we believe the benefits of treatment, including reduced partner and perinatal transmission, outweigh potential risks. A historical concern regarding treatment of asymptomatic pregnant women comes from one trial [101] and subsequent meta-analysis (based heavily on the trial) [102], which reported an increased risk of preterm birth in women treated with metronidazole therapy compared with untreated women. However, the trial had multiple limitations, including starting screening in the second trimester, and subsequent studies have not reported adverse outcomes from treatment [48,103-105].

While metronidazole crosses the placenta [106], it appears to be low risk. Cross-sectional and cohort studies have not reported teratogenicity or mutagenic effects in humans, although studies suggest the drug is mutagenic in bacteria and carcinogenic in mice [102-104,107].

As with nonpregnant women, when T. vaginalis is confirmed and treated in a pregnant woman, we retest the woman at a follow-up visit and treat all sexual partners. (See 'Follow-up' above and 'Treatment of sex partners' above.)

Breastfeeding individuals — We treat breastfeeding individuals with metronidazole 500 mg orally twice a day for seven days. This approach differs from the Centers for Disease Control and Prevention (CDC) guideline that suggests 400 mg orally three times a day for seven days. While the study referenced by the CDC reported that three times daily dosing produced a lower metronidazole concentration in breast milk [92,108], limitations include that the study had data on only seven infants, more frequent dosing may be more challenging for patients, and 400 mg tablets are not universally available. For those individuals who are unable or unlikely to complete a seven-day treatment course, single-dose therapy is a reasonable alternative.

While metronidazole is secreted in breast milk, breastfed infants receive metronidazole doses that are lower than those used to treat infections in infants. Nevertheless, some clinicians recommend deferring breastfeeding for 12 to 24 hours following maternal single-dose treatment because the relative infant dose of metronidazole is high (29 percent) with maternal administration of the 2 g one-time dose [109]. For women who wish to avoid any metronidazole exposure to their infants, we advise pumping and expelling breast milk for 12 hours. There are no data comparing 12- and 24-hour windows.

There are no human data supporting an association between metronidazole exposure from breastfeeding and cancer; however, an association with carcinogenesis in rodents has been demonstrated [110]. Outcomes data of maternal metronidazole use did not show a significant increase in adverse events compared with use of other antimicrobials, although a cohort study found a nonsignificant trend toward more loose stools and more candidal colonization in metronidazole-exposed infants.

In mothers using tinidazole, which has a longer half-life than metronidazole, the CDC suggests interrupting breastfeeding for three days after the last dose [92].

HIV-infected females — HIV-infected women with T. vaginalis are treated with metronidazole 500 mg twice per day for seven days [92]. We do not use single-dose metronidazole for treatment of these women, given the high prevalence of asymptomatic bacterial vaginosis (BV) coinfection and other factors that may render metronidazole less effective in this population.

In a trial where 270 HIV-positive women with culture-confirmed T. vaginalis were randomly assigned to treatment with metronidazole 2 g single dose or metronidazole 500 mg twice per day for seven days, single-dose therapy was less effective than multiple-day therapy [111]. The seven-day treatment group had a lower rate of positive cultures 6 to 12 days after treatment completion (8.5 percent [11/130 women] versus 16.8 percent [21/125 women]; relative risk [RR] 0.5, 95% CI 0.25-1.00) and at 3 months (11 percent [8/73 women] versus 24.1 percent [19/79 women]; RR 0.46, 95% CI 0.21-0.98). Of note, all women were given a 2 g metronidazole dose to deliver to their sex partners. In another trial, HIV-infected women on antiretroviral therapy had 2.6-fold greater risk of persistent trichomoniasis than HIV-infected women not on antiretroviral therapy, but this risk could be minimized by multiday dosing [112].

Additionally, there is a high prevalence of BV in HIV-infected/T. vaginalis-infected women, and there is an apparent association between the presence of BV and early failure of single-dose metronidazole treatment of trichomoniasis [113]. As with all women, the CDC suggests retesting HIV-infected women three months after completion of therapy based on the high proportion of recurrent or persistent T. vaginalis infection in this population and the association between HIV and this infection [92]. As with other populations, sexual partners of HIV-infected patients diagnosed with Trichomonas infection should be treated as well. (See "HIV and women", section on 'Bacterial vaginosis, genital ulcers, and pelvic inflammatory disease' and "Bacterial vaginosis: Treatment" and 'Treatment of sex partners' above.)

REFRACTORY CASES — The most common causes of treatment failure are noncompliance and reinfection.

●Medication noncompliance – The most common cause of continued infection and symptoms is medication misuse or noncompliance. Medication compliance is enhanced with single-dose therapy. Patients with recurrent symptoms and likely medication misuse or noncompliance are retreated with the initial treatment above. (See 'Initial treatment' above.)

●Reinfection – Reinfection from untreated or undertreated sexual partners is another source of continued infection. For patients with persistent symptoms in whom reinfection is likely, we repeat treatment with either another seven-day course, or a single 2 g oral dose of metronidazole or tinidazole and retreat all sexual partners as well.

●Recurrent infection – Reinfection is unlikely if the sexual partners were treated concurrently and sexual intercourse was avoided until both partners completed treatment. Women who fail a single dose of metronidazole 2 g can be treated with oral metronidazole 500 mg twice daily for seven days (total dose 7 g) [92]. Sexual partner(s) should be treated as well. If this regimen fails, tinidazole or metronidazole is administered orally at a dose of 2 g per day for seven days (total dose 14 g). These regimens can be effective in patients with low levels of metronidazole resistance, which was noted in 4 percent of T. vaginalis isolates of women attending sexually transmitted disease clinics in six cities in the United States [114].

●Refractory or resistant infection – If both of the above regimens fail, the Centers for Disease Control and Prevention (CDC) recommends in vitro culture and drug susceptibility testing (available from the CDC Division of STD Prevention, telephone 404-718-4141) and referral to a specialist. For patients with documented refractory infection, therapeutic options include maximum tolerated doses of oral tinidazole (2 to 3 g daily in divided doses) for 14 days. Considerable success with tinidazole in refractory disease has been reported, although the optimal dose has not been established [115,116]. One woman with confirmed metronidazole and tinidazole resistant trichomoniasis was successfully treated with high-dose tinidazole, 1 gm three time a day for 14 days, and intravaginal boric acid, 600 mg, twice daily for 28 days [117].

Metronidazole-resistant T. vaginalis has been documented [118,119]. Cross resistance to tinidazole is frequent but not inevitable [118,120]. Patients with high-level metronidazole resistance are usually successfully treated by prolonged and high-dose tinidazole therapy. High-dose tinidazole has a better safety profile and is better tolerated than high-dose metronidazole. Case reports have described successful use of nimorazole, ornidazole, niridazole, furazolidone, and hamycin [53], whereas a trial of nitazoxanide in three women with difficult to eradicate T. vaginalis reported lack of efficacy [72].

Rare patients who do not have a response to nitroimidazoles have been treated with topical paromomycin (250 mg daily for two weeks) [121]. Paromomycin is not available commercially in the United States as a cream and has to be made by a compounding pharmacy. Little is known about this preparation, but severe local side effects (pain, mucosal ulceration) can occur [122]. We advise not using it. Other topical agents that have a limited (<50 percent) cure rate and therefore are not recommended by the CDC include intravaginal povidone-iodine, clotrimazole, acetic acid, gentian violet, nonoxynol-9, and potassium permanganate [92].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sexually transmitted infections".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Trichomoniasis (The Basics)")

RESOURCES FOR PATIENTS AND CLINICIANS — The following organizations provide information for patients and clinicians at no cost.

●Division of STD Prevention (DSTDP) Centers for Disease Control and Prevention

●American Sexual Health Association (ASHA)

●Planned Parenthood

SUMMARY AND RECOMMENDATIONS

●Microbiology – Trichomoniasis is caused by the protozoa Trichomonas vaginalis. It is virtually always sexually transmitted and can be identified in 70 percent of the male sexual partners of infected females. Coinfection with other sexually transmitted diseases (STDs) and bacterial vaginosis is common. (See 'Microbiology and transmission' above.)

●Clinical sequelae of infection – Untreated trichomonal vaginitis may progress to urethritis or cervicitis. T. vaginalis has been associated with a range of adverse reproductive health outcomes, including cervical neoplasia, posthysterectomy cuff cellulitis or abscess, atypical pelvic inflammatory disease, infertility, and preterm birth. It may also increase females' susceptibility to HIV-1 infection. (See 'Clinical features and consequences' above.)

●Clinical features – Clinical manifestations range from an asymptomatic carrier state to an acute, severe inflammatory disease. (See 'Clinical features and consequences' above.)

•Females – Signs and symptoms include a purulent, malodorous, thin discharge with associated burning, pruritus, dysuria, frequency, and dyspareunia.

•Males – Males are often asymptomatic but can develop urethritis.

•Asymptomatic individuals – Asymptomatic carriage can persist for prolonged periods of time (at least three months); thus, it is often not possible to ascertain when or from whom the infection was acquired.

●Diagnosis – The diagnosis of T. vaginalis is based on laboratory testing (motile trichomonads on wet mount (picture 2), positive culture, positive nucleic acid amplification test [NAAT], or positive rapid antigen or nucleic acid probe test). (See 'Diagnosis' above.)

•We suggest NAAT (if available) in patients with suggestive clinical findings (eg, elevated vaginal pH, increased numbers of polymorphonuclear leukocytes but an absence of motile trichomonads and clue cells on wet mount) or when microscopy is unavailable or unreliable.

•If NAAT for trichomoniasis is not available, rapid antigen tests or DNA hybridization probes for diagnosis of T. vaginalis are commercially available and can be used as an alternative to NAAT or culture. (See 'Rapid antigen and DNA hybridization probes' above.)

•None of the clinical features of trichomoniasis is sufficiently sensitive or specific to allow a diagnosis based upon signs and symptoms alone.

●Treatment – Treatment is indicated for both symptomatic and asymptomatic females and males. Treatment reduces the prevalence of T. vaginalis carriage in the population, relieves symptoms, and reduces the risk of sequelae (including acquisition/transmission of HIV). (See 'Initial treatment' above.)

•Nonpregnant females – For nonpregnant females and their sex partners, we suggest a seven-day course of metronidazole, 500 mg twice daily (Grade 2C). The single-dose regimen is a reasonable alternative for those who are unable to complete a seven-day treatment regimen or who prefer single-day treatment. Oral administration is significantly more effective than topical administration. (See 'Nonpregnant females' above.)

•Pregnant females – We recommend treating symptomatic pregnant females with confirmed T. vaginalis infections (Grade 1B). In addition, we suggest treating asymptomatic pregnant individuals with confirmed infection (Grade 2B). We prefer the seven-day regimen and reserve the single-dose regimen for patients who are unable to complete a seven-day treatment course. (See 'Pregnant individuals' above.)

•Males with urethritis – The same treatment regimens are used in males as for nonpregnant females, with preference given to single-dose treatment with either oral metronidazole or tinidazole, 2 g, to improve compliance. (See 'Males with urethritis' above.)

•HIV-infected females – For HIV-infected females with T. vaginalis, we suggest metronidazole 500 mg twice per day for seven days rather than single-dose therapy (Grade 2B). (See 'HIV-infected females' above.)

•Refractory infection – For patients with refractory trichomoniasis, increasing the dose and duration of metronidazole or tinidazole are the primary options. (See 'Refractory cases' above.)

•Partner therapy – Although expedited partner therapy (EPT) is effective for treatment of Trichomonas infections, we prefer that sexual partners be evaluated so they can be screened for other STIs. However, EPT is reasonable if compliance is an issue. (See 'Treatment of sex partners' above.)

●Additional points

•STI screening – Patients should be screened for other sexually transmitted infections (STIs). (See "Screening for sexually transmitted infections".)

•Post-treatment care – Patients should be instructed to avoid intercourse until they and their partners have completed treatment and are asymptomatic, which generally takes approximately one week. (See 'Counseling' above.)

•Repeat testing – Females treated for a documented trichomonal infection are retested within three months following treatment regardless of whether they believe their sex partners were treated. Testing with NAAT can be done as soon as two weeks after completing treatment. (See 'Follow-up' above.)