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Trichomonas vaginalis Infection in a Tertiary Care Vaginitis Center

Keating, Maria A. MD; Nyirjesy, Paul MD

doi: 10.1097/OLQ.0000000000000334
Original Study
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Background Trichomonas vaginalis infection (TVI) is one of the most common sexually transmitted diseases in the United States. We sought to determine the features of TVI in a referral-based vaginitis center, focusing on diagnosis and treatment of difficult cases.

Methods We conducted a retrospective review of all patients with TVI, based on International Classification of Diseases, Ninth Revision codes, seen at the Drexel Vaginitis Center between January 2008 and November 2013. Information collected on each subject included demographics, symptoms, examination findings, diagnostic tests, and treatment regimens.

Results Of approximately 4000 new patient visits during our study period, 80 subjects were identified with TVI. Twenty subjects presented with known TVI, with most having clinically resistant infections. Diagnosis was confirmed by saline microscopy in 45%, OSOM rapid test in 40%, and clinical history in the remaining 15%. Treatment regimens varied: 20% received single 2-g dosing of either metronidazole or tinidazole, 50% received high-dose regimens, 20% received therapy with vaginal paromomycin, and 10% underwent desensitization for nitroimidazole allergy. Sixty subjects had newly diagnosed TVI, with 35% diagnosed by saline microscopy, 41.7% by OSOM rapid test, and 23.3% by APTIMA. Treatment regimens for these subjects included single 2-g dosing in 88.3%, high-dose regimen in 8.3%, and other formulations in the remaining 3.4%. In total, 80% of our subjects returned for follow-up; all of whom were cured.

Conclusions T. vaginalis infection is a rare condition in a tertiary care vaginitis center and often requires nonstandard treatments. Among those who returned for follow-up, the cure rate was 100%.

Diagnosis and treatment of Trichomonas vaginalis infection can be challenging. In a referral-based vaginitis center, we found a low prevalence of trichomoniasis with a high success rate in treating persistent infection.

From the Department of Obstetrics and Gynecology, Drexel University College of Medicine, Philadelphia, PA

Conflict of interest: None declared.

M. Keating was awarded an IDSOG Travel Grant, sponsored by ABOG-EF, for presentation of this abstract at the 2014 IDSOG Annual Meeting.

Correspondence: Paul Nyirjesy, MD, Drexel University College of Medicine 245 N. 15th Street, MS 495 Philadelphia, PA 19102. E-mail: paul.nyirjesy@drexelmed.edu.

Received for publication March 6, 2015, and accepted June 26, 2015.

Trichomonas vaginalis is one of the most common sexually transmitted diseases in the United States, with an estimated 7.4 million new cases annually and a prevalence rate as high as 13% in African American women.1,2 Because T. vaginalis infection (TVI) is not a reportable sexually transmitted disease, there are incomplete data about its prevalence, rate of recurrence or persistence, and how much resistance exists among those infected.2 Recent evidence shows that TVI could be more prevalent than formerly thought, particularly in high-risk populations, such as HIV-infected and incarcerated women.3,4 In addition, TVI has been associated with an increased risk of preterm birth among African American women and increased risk of HIV acquisition.2

Saline microscopy is typically used to diagnose TVI, although this test has poor sensitivity that varies depending on the microscopist.5 With the advent of new higher-sensitivity tests for trichomoniasis, such as the recently Food and Drug Administration–approved APTIMA test that detects trichomonas RNA by amplification, diagnosis of TVI should become easier.5 Because most providers do not recommend that their patients return for a test of cure visit, rates of clinical resistance and reinfection in the United States are unknown, which further hampers a full understanding of TVI.

The objective of our study was to determine the features of TVI cases and examine our experience with this infection in a tertiary care vaginitis clinic. In this population, one would expect a mix of patients with misdiagnosis, incident cases, and refractory infections. Our goal was to review our experience with each of these groups of women with TVI to highlight important issues that may occur with women with TVI in the general population.

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METHODS

Our study protocol was approved by the Drexel University College of Medicine Institutional Review Board. Our subjects included all patients with TVI, based on International Classification of Diseases, Ninth Revision codes, seen at the Drexel Vaginitis Center between January 2008 and November 2013. Patients are referred to the center for persistent vulvovaginal symptoms either by their health care provider, mainly gynecologists, or by self-referral. Patient care at the center is provided by a board-certified gynecologist, who has also completed a fellowship in infectious diseases, and a women's health nurse practitioner. Each patient undergoes an evaluation that includes a standardized history and physical examination, measurement of vaginal pH, amine test, smears for saline and potassium hydroxide microscopy, and yeast cultures. Cultures and polymerase chain reaction testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and herpes simplex virus are obtained if clinically indicated.

In the case of T. vaginalis testing, patients receive tests more sensitive than microscopy in the following situations: (1) history of trichomoniasis, (2) recurrent bacterial vaginosis, (3) excessive polymorphonuclear cells on saline microscopy, or (4) change in sexual partner in the last year. Higher-sensitivity tests for TVI include OSOM (Sekisui Diagnostics), APTIMA (Hologic, Inc), and culture. The OSOM rapid test qualitatively detects T. vaginalis antigen from genital swabs and provides immediate results in the office, for those whose insurance covers it. Nucleic acid amplification testing (i.e., APTIMA) and culture are also available, although results take several days to obtain.

Treatment regimens used for TVI at Drexel's vaginitis center can be divided into 3 categories: (1) standard, (2) high dose, and (3) paromomycin. Standard treatment was either metronidazole or tinidazole 2 g orally as a single dose or metronidazole 500 mg two times daily for 7 days. High-dose treatment included either tinidazole 1 g two or three times daily orally plus a 500-mg tablet placed vaginally at bedtime for 14 days or metronidazole 1 g three times daily orally plus a 500-mg tablet placed vaginally at bedtime for 14 days. In general, tinidazole was used preferentially to metronidazole unless tinidazole was not covered by the patient's insurance plan or the patient could not afford its cost (approximately $500 for a 14-day course). Paromomycin treatment, consisting of a 6.25% cream, was 5 g vaginally at bedtime for 14 days given either alone or in combination with tinidazole 1 g three times daily orally.

All patients who fail standard treatment of TVI and have no evidence of reinfection or noncompliance with treatment are prescribed high-dose regimens. Further escalation to a regimen containing paromomycin is considered for those patients who have taken high-dose regimens in the past with persistence of infection. There is no set number of treatment failures needed before paromomycin is prescribed, and the few subjects who require paromomycin are treated on an individual basis. Study subjects were considered to have a clinically resistant infection if they had persistent infection despite treatment with standard dosing and no reported reexposure to potentially infected partners.

After treatment of TVI, initial follow-up is scheduled 4 to 6 weeks after treatment is completed and a T. vaginalis culture is collected to document cure. After this visit, patients are advised to return in 3 months at which time the APTIMA test is sent to document sustained cure.

Information collected for each study subject included general demographics, symptoms, physical examination findings, sexual and behavioral history, saline microscopy findings, diagnostic tests used, and treatment regimens. This information was obtained from each study subject’s visit note in the electronic medical record. Cases of TVI were defined as patients with at least 1 test that was positive for trichomoniasis. The method of diagnosis was considered the first test that was positive for TVI. Saline microscopy was always done first followed by OSOM, if covered by the patient's insurance, and then APTIMA or culture. Subjects were divided between those with known TVI at the time of presentation to the clinic and those newly diagnosed. Study data were collected by author M. Keating and managed using Research Electronic Data Capture electronic data capture tools hosted at Drexel University. Research Electronic Data Capture is a secure, Web-based application designed to support data capture for research studies.6 Microsoft Excel (Microsoft, Redmond, WA) was used for data analysis. Descriptive statistics were used to analyze the data abstracted from the study subjects’ charts.

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RESULTS

Of an estimated 4000 new patient visits during our study period, 80 subjects with TVI were identified, approximately 0.02% of new patients. Twenty subjects were referred to the clinic with known trichomoniasis and 60 were newly diagnosed. The average age of these subjects was 40 years, with an age range from 18 to 70 years. Most subjects were single (n = 52; 65%) and African American (n = 55; 68.8%), with further demographic details outlined in Table 1. Most subjects reported vaginal discharge (68/70; 97.1%), with the next most common symptoms including vaginal odor (44/59; 74.6%) and vaginal itching (44/62; 71.0%). Fifty-five (80.9%) of 68 subjects had chronic vaginitis symptoms which had persisted for more than 4 weeks.

TABLE 1

TABLE 1

Table 2 outlines the findings of standard office testing in our TVI subjects. Findings on microscopy varied with pH higher than 4.5 in 85.3% of subjects, positive whiff test in 38.9%, and polymorphonuclear to epithelial cell ratio greater than 1 in 25.6%. Most subjects did not have any trichomonads detected on saline microscopy resulting in an overall sensitivity of 38.5%. Table 3 compares the method of diagnosis between participants with known infection and those newly diagnosed. The first diagnostic test that was positive for T. vaginalis was considered the method of diagnosis (e.g., if a subject had trichomonads seen on microscopy and a positive OSOM rapid test, the saline microscopy would be considered the method of diagnosis because it was completed first).

TABLE 2

TABLE 2

TABLE 3

TABLE 3

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.

TABLE 4

TABLE 4

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.

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DISCUSSION

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.

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