Trichomoniasis

Trichomoniasis is estimated to be the most prevalent nonviral STI worldwide, affecting approximately 2.6 million persons in the United States (838,1055). Because trichomoniasis is not a reportable disease (1056), and no recommendations are available for general screening for T. vaginalis, the epidemiology of trichomoniasis has largely come from population-based and clinic-based surveillance studies. The U.S. population-based T. vaginalis prevalence is 2.1% among females and 0.5% among males, with the highest rates among Black females (9.6%) and Black males (3.6%), compared with non-Hispanic White women (0.8%) and Hispanic women (1.4%) (1057,1058). Unlike chlamydia and gonorrhea, T. vaginalis prevalence rates are as high among women aged >24 years as they are for women aged <24 years (1057). Among persons attending nine geographically diverse STD clinics, the trichomonas prevalence was 14.6% among women (1059), and a study of STD clinic attendees in Birmingham, Alabama, identified a prevalence of 27% among women and 9.8% among men (1060). Symptomatic women have a four times higher rate of infection than asymptomatic women (26% versus 6.5%) (1061). Rates are also high among incarcerated persons of both sexes at 9%–32% of incarcerated women (386,387,391,392,1062) and 3.2%–8% of incarcerated men (388). Women with a history of incarceration are two to five times more likely to have T. vaginalis (387,388,1063,1064). Other risk factors for T. vaginalis include having two or more sex partners during the previous year, having less than a high school education, and living below the national poverty level (1065). Women with BV are at higher risk for T. vaginalis (1066). Male partners of women with trichomoniasis are likely to have infection (1067), although the prevalence of trichomoniasis among MSM is low (179,1068).

The majority of persons who have trichomoniasis (70%–85%) either have minimal or no genital symptoms, and untreated infections might last from months to years (137,1069,1070). Men with trichomoniasis sometimes have symptoms of urethritis, epididymitis, or prostatitis, and women with trichomoniasis sometimes have vaginal discharge, which can be diffuse, malodorous, or yellow-green with or without vulvar irritation, and might have a strawberry-appearing cervix, which is observed more often on colposcopy than on physical examination (1071). Although many persons might be unaware of their infection, it is readily passed between sex partners during penile-vaginal sex (910) or through transmission of infected vaginal fluids or fomites among women who have sex with women (275,294).

Among persons who are sexually active, the best way to prevent genital trichomoniasis is through consistent and correct use of condoms (external or internal) (18). Partners of men who have been circumcised might have a somewhat reduced risk for T. vaginalis infection (1072,1073). Douching is not recommended because it might increase the risk for vaginal infections, including trichomoniasis (1074).

T.vaginalis causes reproductive morbidity and has been reported to be associated with a 1.4-times greater likelihood of preterm birth, premature rupture of membranes, and infants who are small for gestational age (1075). T. vaginalis was also determined to be associated with a 2.1-fold increased risk for cervical cancer in a meta-analysis (1076). Another meta-analysis of six studies reported a slightly elevated but not statistically significant association between T. vaginalis and prostate cancer (1077).

T. vaginalis infection is associated with a 1.5-fold increased risk for HIV acquisition and is associated with an increase in HIV vaginal shedding, which is reduced with T. vaginalis treatment among women without viral suppression (1078,1079). Among women with HIV infection, T. vaginalis infection is associated with increased risk for PID (1080–1082).

Diagnostic testing for T. vaginalis should be performed for women seeking care for vaginal discharge. Annual screening might be considered for persons receiving care in high-prevalence settings (e.g., STD clinics and correctional facilities) and for asymptomatic women at high risk for infection (e.g., multiple sex partners, transactional sex, drug misuse, or a history of STIs or incarceration). However, data are lacking regarding whether screening and treatment for asymptomatic trichomoniasis in high-prevalence settings for women at high risk can reduce any adverse health events and health disparities or reduce community infection burden. Decisions about screening can be guided by local epidemiology of T. vaginalis infection. Routine annual screening for T. vaginalis among asymptomatic women with HIV infection is recommended because of these adverse events associated with trichomoniasis and HIV infection.

Extragenital T. vaginalis is possible but highly uncommon compared with genital infections. A study of 500 men in San Francisco, California, reported a 0.6% rate of rectal T. vaginalis (1083); however, this might reflect deposition of T. vaginalis DNA and not necessarily active infection. Few studies of extragenital T. vaginalis among women have been published. The efficacy, benefit, and cost-effectiveness of extragenital screening are unknown, and no tests are FDA cleared for extragenital testing; therefore, rectal and oral testing for T. vaginalis is not recommended.

Diagnostic Considerations

Wet-mount microscopy traditionally has been used as the preferred diagnostic test for T. vaginalis among women because it is inexpensive and can be performed at the POC; however, it has low sensitivity (44%–68%) compared with culture (1084–1086). To improve detection, clinicians using wet mounts should attempt to evaluate slides immediately after specimen collection because sensitivity decreases quickly to 20% within 1 hour after collection (1087). More highly sensitive and specific molecular diagnostic options are available, which should be used in conjunction with a negative wet mount when possible.

NAATs are highly sensitive, detecting more T. vaginalis infections than wet-mount microscopy among women (1060). The Aptima T. vaginalis assay (Hologic) is FDA cleared for detection of T. vaginalis from symptomatic or asymptomatic women. Reliable samples include clinician-collected endocervical swabs, clinician-collected vaginal swabs, female urine specimens, and liquid Pap smear specimens collected in PreservCyt Solution (Hologic) (698,1088). This assay detects RNA by transcription-mediated amplification with a sensitivity of 95.3%–100% and specificity of 95.2%–100%, compared with wet mount and culture (1088,1089). Among women, vaginal swabs and urine specimens have <100% concordance (1084). This assay has not been FDA cleared for use among men and should be internally validated in accordance with CLIA regulations before use with urine or urethral swabs from men. The Probe Tec TV Q^x Amplified DNA Assay (Becton Dickinson) is FDA cleared for detection of T. vaginalis from vaginal (patient-collected or clinician-collected) swabs, endocervical swabs, or urine specimens from women and has sensitivity of 98.3% and specificity of 99.6%, compared with wet mount and culture (1090). Similar to the Aptima T. vaginalis assay, this test is only FDA cleared for use among women and should be internally validated for use with men. The Max CTGCTV2 assay (Becton Dickinson) is also FDA cleared for detection of T. vaginalis in patient-collected or clinician-collected vaginal swab specimens and male and female urine specimens, with sensitivity and specificity of 96.2%–100% and 99.1%–100%, respectively, depending on the specimen type, compared with wet mount and culture (1091). GeneXpert TV (Cepheid) is a moderately complex rapid test that can be performed in ≤1 hour and can be used at the POC (1092). It has been FDA cleared for use with female urine specimens, endocervical swabs, patient-collected or clinician-collected vaginal specimens, and male urine specimens, with sensitivity and specificity of 99.5%–100% and 99.4%–99.9% (1007), respectively, compared with wet mount and culture.

Multiple FDA-cleared rapid tests are available for detecting T. vaginalis with improved sensitivities and specificities, compared with wet mount. The Osom trichomonas rapid test (Sekisui Diagnostics) is an antigen-detection test that uses immunochromatographic capillary flow dipstick technology that can be performed at the POC by using clinician-obtained vaginal specimens. Results are available in approximately 10–15 minutes, with sensitivities of 82%–95% and specificity of 97%–100%, compared with wet mount, culture, and transcription-mediated amplification (1089,1093,1094). A study of 209 women aged 14–22 years reported that >99% could correctly perform and interpret a vaginal self-test by using the Osom assay, with a high correlation with clinician interpretation (96% agreement; κ = 0.87) (1094). The Osom test should not be used with men because of low sensitivity (38% compared with Aptima) (1095). The Solana trichomonas assay (Quidel) is another rapid test for the qualitative detection of T. vaginalis DNA and can yield results <40 minutes after specimen collection. This assay is FDA cleared for diagnosing T. vaginalis from female vaginal and urine specimens from asymptomatic and symptomatic women with sensitivity >98%, compared with NAAT for vaginal specimens, and >92% for urine specimens (1096). The Amplivue trichomonas assay (Quidel) is another rapid test providing qualitative detection of T. vaginalis that has been FDA cleared for vaginal specimens from symptomatic and asymptomatic women, with sensitivity of 90.7% and specificity of 98.9%, compared with NAAT (1097). Neither the Osom assay nor the Affirm VP III test is FDA cleared for use with specimens from men.

Culture, such as the InPouch system (BioMed Diagnostics), was considered the most sensitive method for diagnosing T. vaginalis infection before molecular detection methods became available. Culture has sensitivity of 44%–75% and specificity of <100% (698,1086,1098). For women, vaginal secretions are the preferred specimen type for culture because urine culture is less sensitive (698,1099,1100). For men, culture specimens require a urethral swab, urine sediment, or semen. To improve diagnostic yield, multiple specimens from men can be used to inoculate a single culture. Cultures require an incubator and are necessary for T. vaginalis drug susceptibility testing. The InPouch specimen should be examined daily for 5 days over a 7-day period to reduce the possibility of false negatives (1101).

Although T. vaginalis might be an incidental finding on a Pap test, neither conventional nor liquid-based Pap smears are considered diagnostic tests for trichomoniasis; however, women with T. vaginalis identified on a Pap smear should be retested with sensitive diagnostic tests and treated if infection is confirmed (1102,1103).

Treatment

Treatment reduces symptoms and signs of T. vaginalis infection and might reduce transmission. Treatment recommendations for women are based on a meta-analysis (1104) and a multicenter, randomized trial of mostly symptomatic women without HIV infection (1105). The study demonstrated that multidose metronidazole (500 mg orally 2 times/day for 7 days) reduced the proportion of women retesting positive at a 1-month test of cure visit by half, compared with women who received the 2-g single dose. No published randomized trials are available that compare these doses among men.

The nitroimidazoles are the only class of medications with clinically demonstrated efficacy against T. vaginalis infections. Tinidazole is usually more expensive, reaches higher levels in serum and the genitourinary tract, has a longer half-life than metronidazole (12.5 hours versus 7.3 hours), and has fewer gastrointestinal side effects (1106,1107). In randomized clinical trials, recommended metronidazole regimens have resulted in cure rates of approximately 84%–98% (1108), and the recommended tinidazole regimen has resulted in cure rates of approximately 92%–100% (1108–1112). Randomized controlled trials comparing single 2-g doses of metronidazole and tinidazole indicated that tinidazole is equivalent or superior to metronidazole in achieving parasitologic cure and symptom resolution (1110,1113,1114).

Metronidazole gel does not reach therapeutic levels in the urethra and perivaginal glands. Because it is less efficacious than oral metronidazole, it is not recommended.

Other Management Considerations

Providers should advise persons with T. vaginalis infections to abstain from sex until they and their sex partners are treated (i.e., when therapy has been completed and any symptoms have resolved). Testing for other STIs, including HIV, syphilis, gonorrhea, and chlamydia, should be performed for persons with T. vaginalis.

Follow-Up

Because of the high rate of reinfection among women treated for trichomoniasis, retesting for T. vaginalis is recommended for all sexually active women approximately 3 months after initial treatment regardless of whether they believe their sex partners were treated (137,1115). If retesting at 3 months is not possible, clinicians should retest whenever persons next seek medical care <12 months after initial treatment. Data are insufficient to support retesting men after treatment.

Management of Sex Partners

Concurrent treatment of all sex partners is vital for preventing reinfections. Current partners should be referred for presumptive therapy. Partners also should be advised to abstain from intercourse until they and their sex partners have been treated and any symptoms have resolved. EPT might have a role in partner management for trichomoniasis (129,1116) and can be used in states where permissible by law (https://www.cdc.gov/std/ept/legal/default.htm); however, no partner management intervention has been demonstrated to be superior in reducing reinfection rates (129,130). Although no definitive data exist to guide treatment for partners of persons with persistent or recurrent trichomoniasis among whom nonadherence and reinfection are unlikely, partners might benefit from being evaluated and receiving treatment (see Recurrent Trichomoniasis).

Recurrent Trichomoniasis

A recurrent infection can result from treatment failure (antimicrobial-resistant T. vaginalis or host-related problems), lack of adherence, or reinfection from an untreated sex partner. In the case of a recurrent infection, the origin of the repeat infection should be assessed because most recurrent infections likely result from reinfection. Retesting can be considered in cases of persistent or recurrent trichomoniasis with culture, the preferred test. If NAAT is used, it should not be conducted before 3 weeks after treatment completion because of possible detection of residual nucleic acid that is not clinically relevant (1117).

The nitroimidazoles are the only class of antimicrobials known to be effective against trichomonas infection. Metronidazole resistance occurs in 4%–10% of cases of vaginal trichomoniasis (1116,1118). Tinidazole resistance is less well studied but was present in 1% of infections in one study (1116). Overall, more T. vaginalis isolates have reported susceptibility to tinidazole than metronidazole (1119). Multidose oral metronidazole is more effective than single-dose treatment, particularly for women who are symptomatic or have a history of T. vaginalis (1120).

Nitroimidazole-resistant trichomoniasis is concerning because few alternatives to standard therapy exist. If treatment failure occurs in a woman after completing a regimen of metronidazole 500 mg 2 times/day for 7 days and she has been reexposed to an untreated partner, a repeat course of the same regimen is recommended. If no reexposure has occurred, she should be treated with metronidazole or tinidazole 2 g once daily for 7 days. If a man has persistent T. vaginalis after a single 2-g dose of metronidazole and has been reexposed to an untreated partner, he should be retreated with a single 2-g dose of metronidazole. If he has not been reexposed, he should be administered a course of metronidazole 500 mg 2 times/day for 7 days.

For persons who are experiencing persistent infection not attributable to reexposure, clinicians should request a kit from CDC to perform drug-resistance testing (https://www.cdc.gov/laboratory/specimen-submission/detail.html?CDCTestCode=CDC-10239). CDC is experienced with susceptibility testing for nitroimidazole-resistant T. vaginalis and can provide guidance regarding treatment in cases of drug resistance. On the basis of drug resistance testing, an alternative treatment regimen might be recommended. Treatments for infections demonstrating in vitro resistance can include metronidazole or tinidazole 2 g daily for 7 days. If a patient has treatment failure after the 7-day regimen of high-dose oral metronidazole or tinidazole, two additional treatment options have been determined to have successful results for women. The first is high-dose oral tinidazole 2 g daily plus intravaginal tinidazole 500 mg 2 times/day for 14 days (1121). If this regimen fails, high-dose oral tinidazole (1 g 3 times/day) plus intravaginal paromomycin (4 g of 6.25% intravaginal paromomycin cream nightly) for 14 days should be considered (1122).

Alternative regimens might be effective but have not been systemically evaluated; therefore, consultation with an infectious disease specialist is recommended. Clinical improvement has been reported with intravaginal boric acid (1123,1124) but not with nitazoxanide (1123–1125). The following topically applied agents have minimal success (<50%) and are not recommended: intravaginal betadine (povidone-iodine), clotrimazole, acetic acid, furazolidone, GV, nonoxynol-9, and potassium permanganate (1126). No other topical microbicide has been reported to be effective against trichomoniasis.

Special Considerations

Drug Allergy, Intolerance, and Adverse Reactions

Metronidazole and tinidazole are both nitroimidazoles. Patients with an IgE-mediated-type hypersensitivity reaction to 5-nitroimidazole antimicrobials should be managed by metronidazole desensitization according to published regimens (1127,1128) and in consultation with an allergy specialist. The optimal treatment for patients with T. vaginalis who are unable to be desensitized has not been systematically investigated and is based on case reports, some of which report using paromomycin or boric acid for treating T. vaginalis (1123,1129).

Pregnancy

T. vaginalis infection among pregnant women is associated with adverse pregnancy outcomes, particularly premature rupture of membranes, preterm delivery, and delivery of infants who are small for gestational age (1075). One randomized trial of pregnant women with asymptomatic trichomoniasis reported no substantial difference in preterm birth after treatment with 2 g of metronidazole 48 hours apart during 16–23 and 24–29 weeks’ gestation, compared with placebo (1130). However, that trial had multiple limitations, including use of an atypical metronidazole regimen. Another multicenter observational study of asymptomatic pregnant women in sub-Saharan Africa, the majority with HIV infection, reported neither trichomoniasis nor its treatment appeared to influence the risk for preterm birth or a low-birthweight infant (1131).

Although metronidazole crosses the placenta, data indicate that it poses a low risk to the developing fetus (1040,1042,1132). No evidence of teratogenicity or mutagenic effects among infants has been found in multiple cross-sectional and cohort studies among pregnant women examining single-dose (2 g) and multidose metronidazole regimens (1040,1131–1135).

Symptomatic pregnant women, regardless of pregnancy stage, should be tested and treated. Treatment of T. vaginalis infection can relieve symptoms of vaginal discharge for pregnant women and reduce sexual transmission to partners. Although perinatal transmission of trichomoniasis is uncommon, treatment might also prevent respiratory or genital infection in the newborn (1136,1137). Clinicians should counsel symptomatic pregnant women with trichomoniasis about the potential risks and benefits of treatment and about the importance of partner treatment and condom use in the prevention of sexual transmission. The benefit of routine screening for T. vaginalis in asymptomatic pregnant women has not been established.

Metronidazole is secreted in breast milk. With maternal oral therapy, breastfed infants receive metronidazole in doses that are lower than those used to treat infections among infants, although the active metabolite adds to the total infant exposure. Plasma levels of the drug and metabolite are measurable but remain less than maternal plasma levels (https://www.ncbi.nlm.nih.gov/books/NBK501922). Although multiple reported case series studies demonstrated no evidence of adverse effects among infants exposed to metronidazole in breast milk, clinicians sometimes advise deferring breastfeeding for 12–24 hours after maternal treatment with metronidazole (1051). In one study, maternal treatment with metronidazole (400 mg 3 times/day for 7 days) produced a lower concentration in breast milk and was considered compatible with breastfeeding over longer periods (1052).

Data from studies involving human subjects are limited regarding tinidazole use during pregnancy; however, animal data indicate this drug poses moderate risk. Thus, tinidazole should be avoided for pregnant women, and breastfeeding should be deferred for 72 hours after a single 2-g oral dose of tinidazole (https://www.ncbi.nlm.nih.gov/books/NBK501922).

HIV Infection

Up to 53% of women with HIV have T. vaginalis infection (1115,1138). T. vaginalis infection among these women is substantially associated with pelvic inflammatory disease (1082). Among women who are not virally suppressed, treatment of trichomoniasis is associated with decreases in genital tract HIV viral load and viral shedding (1079,1139); however, no difference might occur among women who are virally suppressed (1140). Because of the high prevalence of T. vaginalis among women with HIV and the potential for adverse reproductive health, poor birth outcomes, and possibly amplified HIV transmission, routine screening and prompt treatment are recommended for all women with HIV infection; screening should occur at entry to care and then at least annually thereafter.

A randomized clinical trial involving women with HIV and T. vaginalis infection demonstrated that a single dose of metronidazole 2 g orally was less effective than 500 mg 2 times/day for 7 days (1105). Factors that might interfere with standard single-dose treatment for trichomoniasis among women with HIV include high rates of asymptomatic BV infection, ART use, changes in vaginal ecology, and impaired immunity (1141). Thus, to improve cure rates, women with HIV who receive a diagnosis of T. vaginalis infection should be treated with metronidazole 500 mg orally 2 times/day for 7 days. For pregnant women with HIV, screening at the first prenatal visit and prompt treatment, as needed, are recommended because T. vaginalis infection is a risk factor for vertical transmission of HIV (1142).

Treatment

Treatment reduces symptoms and signs of T. vaginalis infection, cures infection, and might reduce transmission. Likelihood of adverse outcomes among women with HIV infection is also reduced with T. vaginalis therapy.

If a woman with HIV infection experiences treatment failure, the protocol outlined is recommended (see Recurrent Trichomonas). Other management considerations, follow-up, and management of sex partners should be performed as for women without HIV infection. Treatment of men with HIV infection should follow the same guidelines as for men without HIV.

For women with HIV who receive a diagnosis of T. vaginalis infection, retesting is recommended 3 months after treatment; NAAT is encouraged because of higher sensitivity of these tests. Data are insufficient to support retesting of men with trichomonas and HIV infection.

Next