Chapter 18. Trichomoniasis

• • In women, findings include motile trichomonads visible on vaginal wet mount, positive culture for Trichomonas vaginalis, and Pap smear result that is positive for trichomonads.
• • In men, diagnosis is often presumptive, after failure to respond to standard treatment for nongonococcal urethritis (NGU).

Trichomoniasis is one of the three major causes of symptomatic infectious vaginitis, along with candidiasis and bacterial vaginosis, and is the only one known to be sexually transmitted. Despite being a readily diagnosed and treated infection, trichomoniasis is not a reportable one, and control of the infection has received relatively little emphasis from public health control programs for sexually transmitted diseases (STDs). The annual incidence of Trichomonas vaginalis infections in the United States has been estimated at 5 million cases. The World Health Organization has estimated that this infection accounts for almost half of all curable STDs worldwide.

Trichomoniasis is the exception to the rule that applies to most STDs in that it is more difficult to diagnose in men than in women. Currently available diagnostic methods for trichomoniasis in men lack sensitivity and availability. Therefore, most men are treated either as a result of sexual exposure to an infected woman or as part of an algorithm for persistent NGU.

T vaginalis, a flagellated parasite, is the causative agent of this infection. Although two other species of Trichomonas infect humans (Trichomonas tenax and Trichomonas hominis), T vaginalis is the only one that infects the urogenital tract. Trichomonas infects the squamous epithelium of the vagina and ectocervix and often causes an inflammatory response in the host manifested clinically by purulent discharge. The pathogenesis in men is poorly understood.

As with any STD, unprotected sex is a risk factor for acquisition of infection. Limiting the number of sex partners or using condoms helps to prevent infection.

Symptoms and Signs

Symptoms of trichomoniasis in women include vaginal discharge, irritation, and pruritus; however, about half of all women infected with T vaginalis are asymptomatic. Occasionally women report vague lower abdominal pain. Signs of infection in women include vaginal discharge, odor, and edema or erythema, but these may be absent. Occasionally, erythematous, punctuate lesions may be seen on the ectocervix, the so-called “strawberry cervix.”

In men, the prevalence and spectrum of disease is far less well characterized; the infection usually appears to be asymptomatic; however, it has been suggested as an increasingly important cause of NGU.

Laboratory Findings

Diagnosis of trichomoniasis in women is usually accomplished via direct microscopic examination of the vaginal fluid (wet mount); however, even when performed by skilled diagnosticians the sensitivity of this test is only 60% overall and may be less in asymptomatic women. In addition to motile trichomonads, white blood cells may be present. The vaginal pH may be elevated or normal. (Normal pH is generally associated with a low number of trichomonads.) Bacterial vaginosis is a frequent coinfection with trichomoniasis. Culture media is commercially available and is currently the “gold standard” for diagnosis (InPouch TV, BioMed Diagnostics, White City, OR). Polymerase chain reaction (PCR) techniques are under development but have thus far shown variable results.

Diagnosis in general is much more difficult in men, and the best culture results are obtained by combining urethral swabs and urine sediment for culture. Nonetheless, it is highly likely, as suggested by PCR results, that this approach lacks sensitivity.

A recently approved point-of-care antigen detection test (Genzyme Corporation, Cambridge, MA) has a sensitivity and specificity of 78% and 98%, respectively, compared with culture, which is superior to wet mount. This test may be of value in settings where microscopy is not possible.

Special Tests

Trichomonads may be visualized on Papanicolaou (Pap) smears. A recent meta-analysis found the sensitivity and specificity of this technique to be 60% and 95%, respectively. Confirmation of the finding of trichomonads using another method has been recommended by some authors; however, most clinicians only have access to wet mount evaluation, which as stated lacks sensitivity.

Other causes of vaginal complaints include yeast vaginitis, bacterial vaginosis, and atrophic vaginitis. Vaginal complaints should never be diagnosed without analyzing objective laboratory data.

Trichomoniasis has been associated with preterm birth in cross-sectional studies. Prospective trials on the treatment of trichomoniasis in pregnancy to prevent preterm birth suggested that such treatment may actually increase the risk of preterm birth rather than decreasing it, as predicted; however, there were limitations to both studies. One study, which used much higher doses of metronidazole than are recommended, was halted after the trend toward preterm birth was noted and thus did not enroll the number of women needed for a definitive analysis. The second study was a subanalysis of a study designed to answer questions relating to STD and HIV risk and thus was not primarily designed to answer questions regarding risks of preterm birth associated with treatment of trichomoniasis in pregnancy. Since the publication of these papers, the CDC has not revised its recommendations for treatment of trichomoniasis during pregnancy.

Acquisition of the human immunodeficiency virus (HIV) has been associated with trichomoniasis in several African studies, possibly as a result of local inflammation that is often caused by the parasite. Transmission of HIV also appears to be enhanced by coinfection with T vaginalis. In a study conducted in Malawi among men with urethritis, the median HIV RNA concentration in seminal fluid was significantly higher in men with trichomoniasis than in men with symptomatic urethritis due to an unidentified cause. In addition, successful treatment of trichomonal urethritis reduced levels of HIV RNA to levels similar to those seen in uninfected controls.

Standard Regimen

In most patients, trichomoniasis is easily treated with a 2-g single dose of metronidazole. Resistant strains occur and may be increasing in prevalence. The resistance is relative and can often but not always be overcome with increased doses; however, side effects from metronidazole (eg, nausea and metallic taste) are common and may limit the dose. It has been reported that patients may experience a reaction similar to a disulfiram reaction, with nausea and flushing after ingesting ethanol. Although a review of the literature shows no convincing evidence for this type of reaction, this potential side effect is included in the manufacturer’s warnings. Therefore, patients should be cautioned to avoid alcohol while undergoing treatment. Metronidazole may prolong the prothrombin time in patients who take warfarin, presumably by competing for binding sites on serum proteins. Rarely, transient black discoloration of the tongue may appear.

Tinidazole, which is also a nitroimidazole, was recently licensed in the United States to treat trichomoniasis using a 2-g single oral dose. It has a more favorable pharmacokinetic profile and is associated with fewer gastrointestinal side effects than metronidazole. Cost, however, may limit its routine use in this setting.

The reported cure rate with the recommended 2-g dose of metronidazole or tinidazole is 97%. Sex partners should also be treated. Infected women and their sex partners should be instructed to avoid intercourse until the patient and partner(s) are cured. An alternative regimen consists of metronidazole, 500 mg twice daily for 7 days. Metronidazole intravaginal gel has limited efficacy and should not be used. Although controversy persists about the safety of metronidazole in pregnancy, there has never been a documented case of fetal malformation attributed to its use, even in the first trimester. Occasionally patients are allergic to metronidazole (and to tinidazole, because it is a related nitroimidazole). In these patients, desensitization is the only option, because there is no other effective pharmacologic treatment.

Trichomoniasis should be considered in men with persistent NGU. Because there currently is no reliable commercially available test for T vaginalis in men, these patients should be empirically treated with metronidazole if they fail to respond to an initial course of doxycycline or azithromycin therapy for NGU.

Patients with trichomoniasis should be screened for other STDs, and STD prevention messages should be delivered. “Test of cure” examinations are not routinely indicated, because cure rates are high.

Antimicrobially Resistant Infection

An estimated 2.5–5% of all cases of trichomoniasis display some level of resistance to treatment with metronidazole. This resistance is relative and can usually be overcome with higher doses of oral metronidazole. For patients who do not respond to the standard treatment regimen and have not been reinfected, higher doses of metronidazole (eg, a 2-g single oral dose once daily for 3–5 days) can be tried. Some authorities recommend higher doses of oral medication in combination with pharmacy-prepared intravaginal preparations. Intravenous formulations offer no advantage over oral drug formulations. There are limited anecdotal reports of success with paromomycin cream; however, this therapy may also be associated with a high incidence of local side effects. Tinidazole may be an effective option for patients with metronidazole-resistant infection. In one study of 20 patients with clinically refractory trichomoniasis (failure to respond to therapy with oral metronidazole, at least 500 mg twice daily for 7 days), high doses of oral and vaginal tinidazole (2–3 g orally plus 1–1.5 g intravaginally for 14 days) resulted in cure rates of 92%, and none of the patients discontinued therapy due to side effects.

Clinicians should consider referral to an infectious disease or STD specialist for women with trichomoniasis that is resistant to standard therapy.

Overall cure rates in treatment of trichomoniasis are high, and the prognosis is excellent. Occasionally patients with a highly resistant strain of T vaginalis require multiple courses of therapy.

• • For patients who do not respond to the standard treatment regimen for trichomoniasis and have not been reinfected, higher doses of metronidazole (eg, a 2-g single oral dose once daily for 3–5 days) can be tried.