Of the 20 subjects with known infection, 9 (45%) were diagnosed by saline microscopy, 8 (40%) by OSOM rapid test, and 3 based on clinical history. The 3 subjects diagnosed by clinical history included (1) a patient who was already undergoing treatment of resistant TVI with high-dose tinidazole and paromomycin at the start of our study period; (2) a referred patient who had recently finished a course of high-dose tinidazole for resistant TVI, a treatment regimen that had been recommended by our clinic to the patient's health practitioner; and (3) a patient who was referred after exposure to a partner with known TVI.
In the 20 subjects referred to the clinic with known TVI, 14 presented with clinically resistant infections, 2 had nitroimidazole allergy, and 4 presented with known infections that had not yet been treated or exposure to infected partners. In general, these subjects had symptoms for many months before presentation at the vaginitis center with an average symptom duration of 34 months, ranging from 2 months to 13 years. Among these subjects, 10 (50%) received a high-dose regimen, 4 (20%) had paromomycin, 4 (20%) received standard treatment, and 2 (10%) underwent desensitization for nitroimidazole allergy. Most subjects (n = 9; 90%) receiving high-dose regimens were prescribed tinidazole, with just 1 subject cured by a high-dose metronidazole regimen. Of the 4 subjects who had vaginal paromomycin treatment, 3 received combination therapy with oral tinidazole and 1 received paromomycin alone. Seventeen (85%) of the 20 subjects had follow-up visits. Of these, 100% had cure documented by negative diagnostic test results after treatment, 8 (47%) with a negative culture result, 5 (29.4%) with a negative APTIMA result, and 4 (23.5%) with a negative OSOM rapid test result. Of those with documented cure, 15 (88.2%) were cured after one course of treatment, and 2 (11.8%) were cured after 2 treatment courses.
Sixty subjects were newly diagnosed with TVI, and these included both new and long-term patients who were receiving ongoing treatment of other vulvovaginal conditions. Methods of diagnosis included saline microscopy (n = 21; 35%), OSOM rapid test (n = 25; 41.7%), and APTIMA (n = 14; 23.3%). As expected, most of these subjects responded to standard treatment (n = 53; 88.3%), with the remaining subjects requiring high-dose therapy (n = 5; 8.3%), paromomycin (n = 1; 1.7%), or desensitization for allergy (n = 1; 1.7%). The high-dose regimens varied, with 2 subjects receiving metronidazole and 3 receiving tinidazole. The patient who received vaginal paromomycin had a severe nitroimidazole allergy but was not able to undergo desensitization due to the risks associated with it, given her other medical conditions. She was therefore prescribed vaginal paromomycin alone, which effectively cured her trichomoniasis.
Among these 60 subjects, 78% (n = 47) returned for follow-up and 100% were cured. Forty-two (89.4%) were cured after one treatment course, and the remaining subjects (n = 5) required 2 courses of treatment. Most subjects (n = 45; 95.7%) had cure documented by negative results on high-sensitivity tests (e.g., OSOM rapid test, APTIMA, or culture). The breakdown of testing used to document cure was as follows: saline microscopy (n = 2; 4.2%), OSOM rapid test (n = 18; 38.3%), APTIMA (n = 15; 31.9%), and culture (n = 12; 25.5%). Tables 3 and 4 provide a comparison between the diagnostic tests and treatment regimens for subjects with known versus newly diagnosed infection.
Approximately one-third of our study subjects had concomitant vulvovaginal infections or other conditions diagnosed at the same time as TVI, with bacterial vaginosis being by far the most common (n = 21; 26%). Other concomitant diagnoses included vulvovaginal candidiasis (n = 4; 5.0%), desquamative inflammatory vaginitis (n = 2; 2.5%), cervicitis (n = 1; 1.25%), and lichen simplex chronicus (n = 1; 1.25%). In total, 27 subjects (33.8%) had a vulvovaginal diagnosis in addition to trichomoniasis, which may have altered their saline microscopy findings or symptomatic presentation. Two of the study subjects had HIV, one presented with resistant TVI and was treated with high-dose tinidazole, and the other was diagnosed with both TVI and bacterial vaginosis and was treated with 2 g of metronidazole followed by 500 mg twice daily for 14 days.
T. vaginalis infection is an uncommon condition in a tertiary care vaginitis center, with less than 1% of our patients presenting with this diagnosis. We feel that this reflects the low-risk population at our center with a low overall TVI prevalence. In addition, difficult cases in the general community may either be missed or lost to follow-up, thus not getting referred to a tertiary care center. The overall population demographics at the Drexel Vaginitis Center are 80% white, 63% married, 80% have completed some college, and 21% are menopausal. The most common diagnoses for new patients at our center are noninfectious conditions, including contact dermatitis, vulvovaginal candidiasis, atrophic vaginitis, and vulvar vestibulitis.7 In comparison, the subset of the population with TVI is mostly African American and single, which highlights why this infection may be so infrequently diagnosed in our center.
Despite the relatively few cases of TVI during our study period, it is important to note that, if we had relied on microscopy alone, we would have missed cases more than half the time. Although microscopy was performed by very experienced microscopists, the sensitivity of saline microscopy in our population was 38.5%, which is significantly lower than sensitivity ranges quoted in the literature.5,8 These findings are in contrast to those of Dan and Sobel,9 who used saline microscopy and culture to diagnose TVI in a chronic vaginitis clinic from 1990 to 1994, where only 2 (4.4%) of 45 cases had T. vaginalis detected by culture after negative saline microscopy. Our relatively low sensitivity may be due to selection bias, where patients with higher organism load might have been diagnosed and treated without requiring referral to a tertiary clinic, or possibly due to the presence of other vulvovaginal conditions, which may have made it more difficult to perform accurate microscopy.
Our results underscore the high level of suspicion for TVI that should be maintained in the primary care setting where this infection is often overlooked and, likely, underdiagnosed because higher-sensitivity testing is not yet routine. Because saline microscopy, the standard method of diagnosis, has very low sensitivity, higher sensitivity tests should be considered, particularly in high-risk populations.
Our data also demonstrate the importance of remembering that new TVI can always be acquired and that subtle changes in the symptoms of long-term vaginitis patients can indicate the presence of TVI. Therefore, it is important to inquire about changes in sexual partners or behavior at each visit. In addition, unexpected saline microscopy findings, such as a preponderance of polymorphonuclear leukocytes, should spark further testing for TVI. This is highlighted by our long-term patients who were newly diagnosed as having TVI during their ongoing care for other vulvovaginal conditions.
In our cases of clinical resistance, defined as persistent infection despite treatment with standard dosing and no reported reexposure to potentially infected partners, we typically escalated treatment to a high-dose or paromomycin-containing regimen, depending on which prior treatments had been used. As previously described by Nyirjesy et al.,10 we informed all of our patients who were prescribed paromomycin to apply a generous amount of vaseline to the vulva to prevent ulcers. As a result, this treatment was well tolerated and none of our patients developed vulvar ulcers, a known adverse effect of paromomycin cream.
In patients with clinical resistance, we did not use in vitro susceptibility testing because, in our prior experience, the results do not always correlate with in vivo findings and therefore have limited utility in informing clinical management. Eighty percent of our subjects (n = 64) had a documented cure, with 89% (n = 57) of those requiring just one course of treatment. This is a notable achievement as many of the patients referred to our clinic with resistant TVI had undergone multiple treatment regimens in the past without cure. Prior studies have described treatment approaches to resistant TVI, including success with high-dose regimens of metronidazole or tinidazole, or paromomycin cream either alone11 or in combination with oral tinidazole.10,12 One of our study subjects who received paromomycin in combination with tinidazole was previously described in the literature, but the other 4 cases provide further evidence that paromomycin, either alone or in combination with tinidazole, is a viable option for cases refractory to standard regimens.
Allergy to nitroimidazoles and the success of desensitization have been previously described in the literature. Oral and intravenous incremental dosing protocols, in which increasing doses of metronidazole are given over the course of 1 day, have been successfully used to desensitize patients, as described by Helms et al.13 Recent data were published which provides guidelines for a modified, more gradual increase in dosing for an oral regimen.14 In our 3 subjects with allergy who were successfully treated, we confirmed that desensitization by an allergist followed by a standard treatment regimen for TVI is effective.
Although this retrospective review was inherently limited by its nature as a descriptive study that was not powered for statistical analyses, it provides useful information about the diagnosis and successful treatment of TVI in a tertiary care setting. Some of our data were incomplete due to data abstraction from office notes, which were not always complete, despite use of a standard note form. Our findings confirm the importance of higher-sensitivity tests in successfully identifying women with TVI and documenting cure. We encourage more widespread use of these tests in the primary care setting, particularly for high-risk populations. Finally, our experience confirms that, for clinically resistant cases, there are options for therapy that are highly effective.
1. Weinstock H, Berman S, Cates W. Sexually transmitted disease among American youth: Incidence and prevalence estimates, 2000. Perspect Sex Reprod Health 2004; 36: 6–10.
2. Bachmann LH, Hobbs MM, Sena AC, et al. Trichomonas vaginalis
genital infections: Progress and challenges. Clin Infect Dis 2011; 53: S160–S172.
3. Nijhawan AE, DeLong AK, Celentano DD, et al. The association between Trichomonas
infection and incarceration in HIV-seropositive and at-risk HIV-seronegative women. Sex Transm Dis 2011; 38: 1094–1100.
4. Van Der Pol B, Kwok C, Pierre-Louis B, et al. Trichomonas vaginalis
infection and human immunodeficiency virus acquisition in African women. J Infect Dis 2008; 197: 548–554.
5. Chapin K, Andrea S. APTIMA Trichomonas vaginalis
, a transcription-mediated amplification assay for detection of Trichomonas vaginalis
in urogenital specimens. Expert Rev Mol Diagn 2011; 11: 679–688.
6. Harris PA, Taylor R, Thielke R, et al. Research Electronic Data Capture (REDCap): A metadata driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42: 377–381.
7. Nyirjesy P, Leigh RD, Mathew L, et al. Chronic vulvovaginitis in women older than 50 years: Analysis of a prospective database. J Low Genit Tract Dis 2012; 16: 24–29.
9. Dan M, Sobel JD. Trichomoniasis as seen in a chronic vaginitis clinic. Infect Dis Obstet Gynecol 1996; 4: 77–84.
10. Nyirjesy P, Gilbert J, Mulcahy L. Resistant trichomoniasis: successful treatment with combination therapy. Sex Transm Dis 2011; 38: 962–963.
11. Nyirjesy P. Managing resistant Trichomonas vaginitis
. Curr Infect Dis Rep 1999; 1: 389–392.
12. Nyirjesy P, Sobel JD, Weitz V, et al. Difficult-to-treat trichomoniasis: Results with paromomycin cream. Clin Infect Dis 1998; 26: 986–988.
13. Helms DJ, Mosure DJ, Secor WE, et al. Management of Trichomonas vaginalis
in women with suspected metronidazole hypersensitivity. Am J Obstet Gynecol 2008; 198: 370–377.
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14. Gendelman SR, Pien LC, Gutta RC, et al. Modified oral metronidazole desensitization protocol. Allergy Rhinol (Providence) 2014; 5: 66–69.