Trichomoniasis is a sexually transmitted infection (STI) caused by the motile protozoan Trichomonas vaginalis and is the most prevalent nonviral STI, both in the United States and globally.1 In the United States, there are an estimated 7.4 million incident cases of T. vaginalis each year; far exceeding rates of both Chlamydia trachomatis (2.8 million new cases)2 and Neisseria gonorrhoeae (>700,000).2 In the United States, T. vaginalis prevalence rates range from 1.3% to 46.9% in women older than 30, and women of color being disproportionately infected by this infection.3–5
Trichomoniasis prevalence rates, both worldwide and in the United States, are thought to be largely underestimated due to a lack of reporting, minimal clinical presentation, and the poor sensitivity of T. vaginalis diagnostic testing. Screening for T. vaginalis is generally limited to women demonstrating overt symptoms, even though 45% to 65% of patients do not present with typical clinical symptoms.6,7 Further, when diagnostics are ordered,8–10 most clinical protocols rely on direct examination by wet mount microscopy. However, wet mount is an insensitive diagnostic method with sensitivity ranging from 35% to 60%6,11 when compared to more robust methods like the nucleic acid amplification test (NAAT) (sensitivity of 96.7% and specificity of 97.5%).12–14
Further, since symptoms may be absent or mild, infected individuals may not seek treatment or limit their sexual activity and therefore are more likely to transmit the infection. In a longitudinal study of the natural history of T. vaginalis among urban adolescent women, approximately a quarter of participants (57/245) became infected during a 3-month follow-up period (95% confidence intervals [CI], 19.9%–28.5%) and nearly 32% of women with incident cases experienced multiple infections.7
Infection with T. vaginalis has been definitively linked to increased risk of human immunodeficiency virus (HIV) acquisition and transmission. In a prospective study of 203 HIV-positive women from 1996 to 1998, Wang et al15 discovered that treating T. vaginalis led to a 4.2-fold reduction in cell-free HIV-1 (3.4–3.05 log10 copies/swab; P < 0.001), but not HIV-infected cells, in vaginal fluids. A recent nested case–control study found that infection with T. vaginalis increases the likelihood of HIV infection acquisition by 2 to 3 fold.14 T. vaginalis was more prevalent among cases than controls (11.3% vs. 4.5%, P = 0.002) and a T. vaginalis diagnosis was correlated with HIV seroconversion (adjusted odds ratio, 2.74; 95% CI, 1.25–6.00) demonstrating that T. vaginalis significantly impacts HIV acquisition.
In an effort to inform future strategies for T. vaginalis control among women at high-risk for HIV, we conducted 2 studies in Indianapolis (Indiana) to determine whether minor changes to screening protocol would result in improved T. vaginalis case finding. Study 1 describes the increase in positivity rates among women seeking care at a local public health sexually transmitted disease (STD) clinic when NAAT is used in lieu of wet mount microscopy. Study 2 compares the effect of universal screening for T. vaginalis to targeted testing based on self-reported symptoms among incarcerated women. Indianapolis was chosen as the study site because it historically had some of the highest rates of STD in the United States16 and is currently experiencing an increase in cases of syphilis and chlamydia. Given the frequent occurrence of concomitant STD and having a T. vaginalis infection increases HIV susceptibility,8,9,13,14 we wanted to explore methods to improve case finding as an STD control strategy.
Laboratory records were reviewed to determine the number of female public health STD clinic patients, at least 18 years of age, who were tested for T. vaginalis DNA between October and December 2008. Samples were collected using a self-administered vaginal specimen and were tested using a previously described polymerase chain reaction (PCR) that is a modification of the Amplicor CT/NG assay (Roched Molecular, United States).6 We reviewed the electronic medical records of these patients to determine whether wet preparation microscopy had also been ordered at the time of the patient's clinical visit and whether T. vaginalis infection was correctly diagnosed using PCR. We then compared the rate of positivity detected using wet preparation microscopy to the number of cases found when we utilized PCR.
Samples were obtained from women incarcerated in a privately operated minimum security facility in Marion County (Indiana) that is a designated STD sentinel surveillance site. For surveillance purposes, self-obtained vaginal swabs from all consenting women arriving in the facility are routinely tested for chlamydia and gonorrhea. PCR for T. vaginalis was routinely offered only to those women with symptoms (targeted screening for trichomonas). For this evaluation, we prospectively performed PCR for trichomonas on all vaginal samples routinely collected for chlamydia/gonorrhea testing (universal screening of all women willing to be tested). Due to the sensitivity of working with a detainee population, historic controls were used to compare the number of cases identified by targeted versus universal screening. No alternate T. vaginalis diagnostics were performed. The number of cases of T. vaginalis identified by universal screening was compared with the number of cases identified during a control period in which only targeted testing was performed. To control for the possibility of rapid shifts in disease prevalence, rates of C. trachomatis and N. gonorrhoeae were compared across the 2 periods as well.
For both studies, the Indiana University/Clarian Institutional Review Board approved all data collection and analysis procedures.
A total of 1674 women were screened for STD at the Bell Flower Clinic between October and December 2008. Based on self-reported symptoms of discharge, dysuria, or pelvic pain, 222 (13.2%) were screened for T. vaginalis using both wet preparation microscopy and PCR. Microscopy as the diagnostic tool detected T. vaginalis in 6 of 222 (2.7%) patients. PCR as the diagnostic tool detected T. vaginalis in 30 of 222 (13.5%) patients. PCR resulted in a 5-fold increase in T. vaginalis case finding.
Historical control data were extracted from testing performed in the population of 362 incarcerated females opting to be tested for STD from April to July 2007, immediately preceding our study. Using a targeted screening approach based on self-reported symptoms yielded 97 of 362 women who were screened for T. vaginalis testing; 51 of 97 symptomatic women screened were identified as positive for trichomonas DNA (Table 1). However, this approach detected trichomonas in only 14% of the entire female detainee population (51/362).
When T. vaginalis testing was performed on all samples (471) collected from August to November 2007, as opposed to only those with self-reported symptoms, 208 cases of T. vaginalis were detected. Although the trichomonas positivity rate in the historic control group, 52.6% (95% CI, 42.6, 62.6) was high, as would be suspected when testing a targeted population, the rate observed during universal screening (44.2% [95% CI, 42.6%, 45.7%]) was not significantly lower and over 4 times as many cases were detected.
We also compared positivity rates for gonorrhea and Chlamydia between the 2 time periods in order to rule out any rapid shifts in overall disease rates. During the historical control period, the prevalences of chlamydia and gonorrhea were 10.5% and 9.1%, respectively. The rates were similar during the universal screening period, 57 of 471 (12.1%) and 25 of 471 (5.3%) for chlamydia and gonorrhea, respectively, which suggests that a shift in overall disease prevalence had not occurred between the 2 time periods.
We present 2 studies that demonstrate how changing screening protocols, by utilizing improved diagnostic tools and applying universal screening, resulted in increased case finding for T. vaginalis among high-risk women. As a result of these studies, the procedures used in Marion County have been changed to include the following: (1) NAAT testing for trichomonas in all wet mount negative women being tested for chlamydia and gonorrhea and (2) inclusion of trichomonas in all orders for chlamydia and gonorrhea testing on samples obtained from the Department of Corrections. Although this study was performed using a laboratory-developed assay (modified PCR), evidence of the performance of other NAAT for detection of trichomonas nucleic acids suggests that the specific method is not critical. As commercially available tests that allow chlamydia, gonorrhea, and trichomonas testing on the same platform become available,10 these tests should be considered for inclusion in the routine screening process in women at high risk for negative outcomes associated with T. vaginalis infection.
Improving detection of T. vaginalis is critical, given that when left untreated, T. vaginalis can lead to increased susceptibility to coinfections including HIV. Infections are frequently missed due to ineffective clinic screening protocols including the restriction of screening to women demonstrating overt symptoms and the use of insensitive diagnostic methods. Given the exceptionally low number of women diagnosed with trichomonas in nationally representative studies of prevalence (2.3%–3.1%)4 targeting services exclusively to symptomatic women will fail to address the need to reduce the burden of disease in high-risk populations.12 In order to achieve this goal, modified clinic screening protocols are needed.
In our first study, routine clinical diagnosis using wet mount missed 24 of 30 (80%) of T. vaginalis cases demonstrating that microscopy is an ineffective diagnostic tool for this pathogen given its low sensitivity compared to NAAT. In our second study, historical controls were used to compare case finding using targeted diagnostics of symptomatic women to universal screening of women in a correctional facility. Universal screening, in a high-prevalence population, resulted in a 4-fold increase in the number of positive cases found. Clearly, because of the asymptomatic nature of this infection, control of this disease is unlikely to be successful when only women with symptoms are tested.
A limitation of these analyses is that PCR results could only be compared to wet mount microscopy results when the test was ordered by the clinician; some patients did not have a wet mount ordered and were therefore not included in our analysis during the first study and microscopy was not available for any women in the correctional setting (second study). This may lead to an incorrect representation of the number of cases undiagnosed, however, this limitation would not account for a 5-fold increase in detection using PCR. Among the female detainee sample, STI screening is an optional service; not all women choose to participate, thus the true prevalence of infection in this population remains unknown. However, this applies to the rates of chlamydia and gonorrhea as well and these were similar among the 2 study periods suggesting that there has not been a dramatic increase in overall prevalence of STI in this population.
Aggressive testing, treatment, and surveillance programs should be instituted due to the burden of T. vaginalis cases and the substantial evidence linking T. vaginalis to adverse health outcomes, including pelvic inflammatory disease,17 preterm delivery and low birth weight,18 and cervical cancer.19 Most importantly, this pathogen is suspected to have played a major role in the HIV pandemic because it increases viral shedding in HIV-infected individuals and causes inflammation in genital tissues that increase susceptibility in HIV-negative partners.15,20
The prevalence of T. vaginalis coupled with its negative impact on health makes this STI a significant public health concern. In order to reduce rates of this infection, a call to action is necessary and should include improved diagnostic tools, modifying clinic screening protocols, and addition of this important infection to the list of notifiable diseases should be considered. Bundling T. vaginalis testing with gonorrhea and chlamydia may be necessary for detecting this infection in high-prevalence populations who are also at risk for HIV. However, studies of the cost-benefit of T. vaginalis control programs are clearly warranted in order to provide justification for the addition of this test to the standard panel of tests offered by STD control programs.
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