Approach Considerations
Evaluation for trichomoniasis is typically conducted in the outpatient setting. Trichomoniasis is not a nationally mandated reported sexually transmitted disease, although other sexually transmitted disease reporting requirements vary by state. [11]
After positive diagnosis, treatment should be instituted immediately and, whenever possible, in conjunction with all sexual partners. [11] Expedited partner therapy is a safe and effective means of treating the sexual partners of patients diagnosed with trichomoniasis and should be practiced whenever possible. [46, 50, 108] Both patient and partner should abstain from sex until pharmacological treatment has been completed and they have no symptoms.
Patients undergoing pharmacotherapy should be advised to avoid alcohol consumption during the course of treatment and for an appropriate amount of time after the completion of their medication.
Because trichomoniasis is an infection of multiple sites (eg. vaginal epithelium, Skene glands, Bartholin glands, and urethra), systemic treatment is needed. Because of the high rate of coinfection with other sexually transmitted infections (STIs), the healthcare provider should consider empiric treatment of gonorrhea and chlamydia. Patients should also be offered counseling and testing for HIV.
In clinical practice, repeat testing is rarely performed unless symptoms do not improve with drug treatment. However, the CDC recommends rescreening at 3 months posttherapy for sexually active women, as they have a high rate of reinfection. [96] Currently, no data are available on rescreening men.
Inpatient therapy is usually not required but may be indicated when resistance is present and intravenous (IV) therapy is indicated. For patients in whom treatment fails and in whom reinfection is ruled out, consultation with experts from the CDC may be advisable (770-488-4115). Consultation with an infectious diseases specialist, a gynecologist, or both may be helpful.
HIV
Patients who are HIV-positive should generally receive the same treatment as those who are HIV negative. The notable exception is that the multiday treatment drug regimen (metronidazole 500 mg twice daily for 7 days) was recently shown to be more effective in treating T vaginalis in HIV-positive women than a single-dose treatment (metronidazole 2 g single dose). [109] Thus, the CDC recommends considering the multidose treatment in HIV-positive women with trichomoniasis. [48] The CDC also recommends rescreening at 3 months after the completion of therapy for HIV-positive women due to the likelihood of recurrent or persistent infection and the increased risk of HIV transmission with comorbid trichomoniasis. [48, 49, 110, 111]
Pregnancy
Although the CDC does not take a definitive stance on treating trichomoniasis during pregnancy, it recommends a single 2-g dose of metronidazole if treatment is deemed necessary. One study has found an association between the use of metronidazole during pregnancy and premature delivery, but this result has not been reproduced by other studies. [112] Treatment of trichomoniasis during pregnancy may relieve symptoms of vaginal discharge or prevent the rare complication of neonatal respiratory infection with trichomoniasis. [11] Vertical transmission of trichomoniasis during delivery is relatively rare, but respiratory or genital infection of the newborn during delivery has been reported. [48]
Infected asymptomatic pregnant women may wish to defer treatment to after 37 weeks’ gestation. [48, 11]
In breastfeeding women, the CDC recommends stopping breastfeeding during the course of metronidazole treatment and for 12-24 hours after the last day. For treatment with tinidazole, the CDC recommends stopping breastfeeding for the course of treatment and for 3 days after the last dose. [48]
Treatment of pregnant women with tinidazole has not been well-studied, however animal studies suggest that the drug poses moderate risks. Use of tinidazole is not recommended in pregnant women. [11]
Pediatric populations
T vaginalis infection in a pediatric patient may suggest child abuse, although vertical transmission is also a possibility. Young girls may present with vaginal discharge.
Routine screening for trichomoniasis in asymptomatic pregnant women is not currently recommended.
Pharmacologic Therapy
5-Nitroimidazole drugs are the only widely used pharmacological treatment for trichomoniasis. In the United States, several of these drugs, metronidazole, tinidazole, and secnidazole are approved by the FDA for trichomoniasis. The CDC recommends the following drug schedules in the treatment of trichomoniasis [11] :
-
A single 2-g dose of metronidazole, tinidazole, or secnidazole
-
A schedule of 500 mg of metronidazole, taken twice daily for 7 days
Each drug schedule has advantages and disadvantages, but, ultimately, they yield similar cure rates. In a 2003 Cochrane review, metronidazole and tinidazole had comparable efficacy in treating trichomoniasis. [1] Randomized clinical trials comparing single 2-g doses have also shown metronidazole and tinidazole to be equally effective. [11] With recommended dosages, the expected cure rate of trichomoniasis is 95%. Tinidazole is generally more expensive than metronidazole but also seems to persist in serum longer. [11] Some research suggests that tinidazole has fewer side effects than metronidazole, but not all studies have found this result. [1, 113, 114]
The advantages of single-dose therapy with metronidazole or tinidazole over the week-long metronidazole schedule include better patient compliance and a lower total dose. The week-long metronidazole schedule may be more effective in treating trichomoniasis in HIV-infected women. [109]
Because trichomoniasis is an infection of multiple sites, systemic (oral) treatment is needed. Topical medications are not recommended by the CDC, as they are unlikely to reach therapeutic levels. Topical metronidazole and other antimicrobials yield low cure rates (< 50%). [11]
The mechanism of action for these drugs is not completely understood. It is thought that target organisms preferentially reduce the 5-nitro group on the molecule, creating active metabolites that disrupt the helical structure of DNA. This prevents nucleic acid synthesis and eventually leads to cell death. [115]
Patients should not consume alcohol during the course of treatment and for several days afterwards, as nitroimidazoles can create a disulfiram-like intolerance reaction, [116] continue abstaining from alcohol for 72 hours after metronidazole or tinidazole, and for 48 hours after secnidazole. [48] Treating the patient’s sexual partners to prevent reinfection further improves the cure rate. Where legal, this may be easier to accomplish with expedited partner therapy. [14]
Despite the widespread use of nitroimidazoles in the treatment of trichomoniasis, resistance to these drugs is rare and is typically solved by increasing the dose or switching to another nitroimidazole. [1] The CDC has reported incidents of trichomoniasis resistant to metronidazole that were susceptible to tinidazole. [117, 118] When standard treatment regimens fail, a regimen of 2 g of oral metronidazole or tinidazole for 5 days may be considered. [57] Inpatient intravenous (IV) therapy may be indicated when resistance is present.
For patients in whom treatment fails and in whom reinfection is ruled out, consultation with experts from the CDC may be advisable (770-488-4115). Consultation with an infectious diseases specialist, a gynecologist, or both may be helpful.
Patients allergic to this class of drug should be referred to an allergist for desensitization.
Metronidazole
Before the introduction of tinidazole and secnidazole, metronidazole was the treatment of choice for trichomoniasis. Metronidazole is typically administered as either a single-dose therapy taken with food or a 500-mg therapy taken twice daily with food for 7 days. Single-dose therapy is as effective as prolonged therapy, although single-dose therapy causes slightly fewer side effects and increases drug adherence. [11]
The 7-day schedule of metronidazole therapy may be more effective in treating trichomoniasis in women with HIV infection and should be considered in this population. [109] A modified 7-day schedule (400 mg 3 times a day) should be considered in breastfeeding women. [11] Studies suggest that this schedule produces a lower concentration of metronidazole in breast milk over longer periods. [119, 120]
Treatment failure with single-dose metronidazole therapy increased from 0.4% to 3.5% between 1999 and 2002. [121] Reports now describe resistance to metronidazole approaching 5%-10%. If standard treatment with either single-dose or multidose therapy fails, a regimen of 2 g of oral metronidazole or tinidazole for 5 days may be considered. [11]
Metronidazole gel is effective in less than 50% of trichomoniasis cases and is not recommended to treat trichomoniasis. [122]
Patients should not consume alcohol during the course of treatment or during the 24 hours after the completion of the medication. [48]
Metronidazole in pregnancy
Metronidazole crosses the placenta in pregnancy. A number of clinical trials and meta-analyses have not shown it to have teratogenic effects. [122, 123] The National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network presented data suggesting that metronidazole treatment of asymptomatic carriers of T vaginalis increased the risk of preterm birth. [124, 125] This was a controversial conclusion in that the investigators treated T vaginalis infection with 4 doses of 2 g metronidazole, which is significantly more than what is standard practice. The women included in the study were between 16 and 23 weeks’ gestational age, suggesting a significant delay in treatment. A subsequent study by Mann et al showed no increased risk of preterm birth with the use of metronidazole for the treatment of trichomoniasis. [126]
Although the CDC does not take a definitive stance on treating trichomoniasis during pregnancy, it recommends a single 2-g dose of metronidazole if treatment is deemed necessary. [11] Treatment of trichomoniasis during pregnancy may relieve symptoms of vaginal discharge or prevent the rare complication of neonatal respiratory infection with trichomoniasis. Treatment has not been shown to reduce the incidence of preterm-delivery associated with T vaginalis infection. [11] Vertical transmission of trichomoniasis during delivery is relatively rare, but respiratory or genital infection of the newborn during delivery has been reported. [8] Infected asymptomatic pregnant women may wish to defer treatment until after 37 weeks’ gestation. [48]
Tinidazole
Like metronidazole, tinidazole is typically given as a single-dose therapy of 2 g taken with food. Randomized clinical trials comparing single 2-g doses have shown metronidazole and tinidazole to be equally effective. [11] Cure rates range from 86%-100%. [48] Tinidazole has a longer half-life (12-14 hours) than metronidazole (6-7 hours). For resistant infections, some recommend using 2 g twice daily for 14 days. [118]
Patients on tinidazole therapy should not consume alcohol during therapy or for 72 hours after completion of the medication. [48]
Tinidazole in pregnancy
Tinidazole should not be used in pregnant women. Animal studies have demonstrated adverse effects on fetal development. [11]
In lactating women, it is recommended that breastfeeding be withheld during treatment and for 3 days after the last dose. [11]
Secnidazole
Secnidazole gained FDA approval in June 2021 for treatment of trichomoniasis caused by T vaginalis in adult females. Because trichomoniasis is transmitted sexually with potentially serious sequelae, treat partners of infected patients simultaneously to prevent reinfection. In 2022, the indication was expanded to include males and adolescents aged 12 years and older.
Approval was based a US multicenter trial in 147 women with confirmed positive T vaginalis culture. Cure rates were significantly higher in the secnidazole group compared with placebo (92.2% vs 1.5%) for the modified intent-to-treat population and for the per-protocol population (94.9% vs 1.7%). Cure rates were 100% (4/4) in women with HIV and 95.2% (20/21) in women with bacterial vaginosis. [127]
Secnidazole in pregnancy
Data are not available for use of secnidazole in pregnant women during pregnancy. In animal reproduction studies, there were no adverse developmental outcomes when secnidazole was administered orally to pregnant rats and rabbits during organogenesis at doses up to 4 times the clinical dose.
Advise patients that breastfeeding is not recommended during treatment with secnidazole and for 96 hr after administration. Other nitroimidazole derivatives are present in human milk Because of the potential for serious adverse reactions, including tumorigenicity.
Clotrimazole
The CDC does not currently recommend the use of clotrimazole for treatment of trichomoniasis. Clotrimazole vaginal tablets have been used in the past; however, in a study by duBouchet et al, the cure rate was only 11% with this mode of therapy. [128]
Diet and Activity
Patients should be instructed to avoid alcohol while taking metronidazole, tinidazole, or other nitroimidazole drugs. The interaction of these drugs with alcohol may cause a disulfiram-like reaction. [129]
Modifying sexual behavior helps reduce the incidence of infection. Patients should avoid sex until drug therapy is completed and all symptoms have disappeared. [57] Treatment of the patient’s partner is crucial for minimizing reinfection. Thereafter, consistent use of condoms and other barrier contraceptives reduces the chance of infection. (See Prevention.)
Prevention
Abstinence from sexual intercourse prevents trichomoniasis, except in cases of vertical transmission. Male condoms are the best and most reliable protection against T vaginalis transmission during intercourse. [130] Limiting the number of sexual partners and using diaphragms have been shown to protect against the transmission of trichomoniasis. [38] Although the efficacy of female condoms is undefined, they may also provide some protection from T vaginalis infection. [57, 11, 131]
Spermicides that contain nonoxynol-9 may decrease the risk of trichomoniasis [132] , although frequent use may be associated with an increased risk of HIV infection and other sexually transmissible agents owing to the disruption of the genital epithelium. The CDC does not recommend the use of nonoxynol-9 spermicides for the prevention of trichomoniasis. [57, 11]
Long-Term Monitoring
Infected women who are sexually active have a high rate of reinfection. Rescreening sexually active women at 3 months posttreatment has been reviewed and studied and is recommended. [48, 133] Evidence is currently insufficient to support a similar recheck in male patients, but it may be undertaken at physician discretion.
Because trichomoniasis has a high rate of comorbidity with other STIs, providers should consider empiric treatment of infections that frequently coexist with trichomoniasis, such as gonorrhea and chlamydia. Patients should be advised to follow up on results of other studies performed.
If symptoms persist despite pharmacotherapy, patients should follow up with their primary care providers. Persistent treatment failures may require metronidazole susceptibility testing through the CDC.
Sexual partners of patients infected with trichomoniasis must be treated to prevent reinfection. Patient and sexual partners should abstain from sexual intercourse until they have both completed therapy and are asymptomatic. [57] In areas where it is legal, expedited partner therapy may be useful in efficiently treating all sexual partners of the patient. [14]
-
Trichomonas vaginalis on a saline wet mount at 40X on the microscope. Several motile parasites transit through the field, surrounded by white blood cells and squamous epithelial cells.
-
Life cycle of Trichomonas vaginalis. T vaginalis trophozoite resides in female lower genital tract and in male urethra and prostate (1), where it replicates by binary fission (2). The parasite does not appear to have a cyst form and does not survive well in the external environment. T vaginalis is transmitted among humans, the only known host, primarily via sexual intercourse (3). Image courtesy of Centers for Disease Control and Prevention.
-
Trichomonas vaginalis. (A) Two trophozoites of T vaginalis obtained from in vitro culture, stained with Giemsa. (B) Trophozoite of T vaginalis in vaginal smear, stained with Giemsa. Images courtesy of Centers for Disease Control and Prevention.
-
Trichomoniasis overview.
-
Trichomoniasis life cycle.
