Why Does Trichomonas vaginalis Continue to be a “Neglected” Sexually Transmitted Infection?

(See the Major Article by Patel et al on pages 211–7.)

Trichomonas vaginalis is the most common, curable nonviral sexually transmitted infection (STI) [1]. It is associated with premature rupture of membranes, preterm birth, low-birthweight infants, infertility, and increased risk of human immunodeficiency virus (HIV) acquisition [2–5]. Infected women may have vaginal discharge and/or irritation or be asymptomatic [6]. The majority of infections in men are asymptomatic, but T. vaginalis can cause nongonococcal urethritis [7]. Risk factors in women include older age, black race, lower socioeconomic status, and more sexual partners [8–10]. The epidemiology of T. vaginalis in men is not well known.

Several highly sensitive T. vaginalis nucleic acid amplification tests (NAATs) have been approved by the US and Drug Administration (FDA) for use in women on urine, vaginal swab (including self-collected), and endocervical specimens. These include the Aptima TV (Hologic Gen-Probe), the BD ProbeTec Qx (BD Viper System; Becton Dickinson), and GeneXpert TV (Cepheid) assay [11–13]. The GeneXpert TV assay was also approved by the FDA in 2016 for detection of T. vaginalis in urine specimens from male subjects [13, 14]. T. vaginalis NAATs can be performed on the same instrumentation platforms as NAATs for chlamydia and gonorrhea [15, 16]. Current treatments include a single oral dose of metronidazole (MTZ; 2 g), a single oral dose of tinidazole (2 g), or a 7-day oral course of MTZ (500 mg twice daily) [17]. For HIV-infected women with T. vaginalis, the 7-day MTZ regimen is most effective [18]. Concurrent treatment of sexual partners for T. vaginalis is recommended [17].

As discussed elsewhere [19–22], there are no established T. vaginalis screening, surveillance, or control programs for women or men in the United States. Because of this limited public health response, T. vaginalis is considered a “neglected STI” [21, 23]. With regards to screening, the most recent (2015) Centers for Disease Control (CDC) treatment guidelines for STI recommend routine screening only in symptomatic and asymptomatic HIV-infected women, at entry to care and annually thereafter [17]. There are no firm recommendations for screening in other populations. The CDC states that screening “might” be considered for persons in high-prevalence settings (STI clinics, correctional facilities) and asymptomatic persons at high risk; risk factors include multiple sex partners, exchange of sex for money or drugs, illicit drug use, and history of STI [17].

Regarding lack of surveillance, T. vaginalis has been said to meet only 3 of 7 criteria: frequency, associated disparities or inequities, and communicability; the other (unmet) criteria are severity, associated costs, preventability, and public interest [24]. Regarding severity, severe or disabling outcomes are said to be uncommon among asymptomatic patients with T. vaginalis, although this has not been studied extensively. A large multicenter randomized placebo-controlled trial conducted in the late 1990s to determine whether treatment of asymptomatic T. vaginalis reduced the incidence of preterm birth and low-birthweight infants among pregnant women found that the risk of preterm birth was greatest among asymptomatic women treated with MTZ compared with those receiving placebo [25]. However, this trial had multiple limitations [26], and the MTZ dosing regimen that was used is not used for T. vaginalis treatment today; additional studies are needed.

Regarding costs, minimal data are available regarding direct medical costs of T. vaginalis infection [27], and none are available regarding costs of adverse health outcomes associated with asymptomatic infection or sequelae associated with symptomatic infection (eg, pregnancy-related conditions, HIV infection, and time lost from work); additional studies are needed. Regarding preventability, it has been deemed unclear whether a national control program would succeed in reducing the prevalence of T. vaginalis infection [24], given ongoing challenges in chlamydia screening programs [28]. However, this has also not been systematically investigated. Finally, a perceived lack of public interest in T. vaginalis may reflect a lack of public knowledge [20]. Because of the lack of national screening and surveillance programs, there are no national control programs beyond clinical management of patients infected with T. vaginalis and their partners.

In this issue of Clinical Infectious Diseases, Patel et al [29] provide much needed, updated epidemiological data on the prevalence and correlates of T. vaginalis infection in a nationally representative sample of the adult civilian, noninstitutionalized US population 18–59 years of age (2013–2014 National Health and Nutrition Examination Survey [NHANES] cycle). Overall, the prevalence of T. vaginalis was 1.2%, significantly higher in women (1.8%) than in men (0.5%). It was also higher among blacks (6.8%; 8.9% in women and 4.2% in men), compared with other racial/ethnic groups (0.4%), signifying a pronounced racial disparity that continues to exist [8, 10, 30]. As Patel et al discuss, multiple factors probably play a role in this racial disparity [10]. They also note that the racial disparity for T. vaginalis seems to exceed that observed for chlamydia, herpes simples virus (HSV) 2, and human papillomavirus. Data on genital symptoms were not collected in this cycle of NHANES and were thus not reported.

This study is timely for several reasons. First, nationally representative data on T. vaginalis prevalence have not been published in more than a decade [8] (NHANES participants from 2005–2012 were not tested for T. vaginalis). The first report of T. vaginalis national prevalence data in US women (aged 14–49 years) came from the 2001–2004 NHANES cycle and was 3.1% (self-collected vaginal swab samples were evaluated with a T. vaginalis polymerase chain reaction test) [8]. At that time, chlamydia, gonorrhea, HSV-1, HSV-2, syphilis, and HIV were more common among women with T. vaginalis [31]. This 3.1% prevalence of T. vaginalis in US women from NHANES 2001–2004 was higher than the combined prevalence of both gonorrhea (0.24%) and chlamydia (2.2%) among US women (aged 14–39 years) around the same time in the 1999–2002 NHANES cycle [32].

Second, T. vaginalis infection was diagnosed using the Hologic Gen-Probe Aptima TV assay on urine specimens from women and men, an assay that was not available in prior NHANES cycles. (Although the Hologic Gen-Probe Aptima TV assay can be used to test urine specimens from men, FDA clearance has not been sought for this purpose.) Third, the national prevalence of T. vaginalis among US men >26 years old has not been previously determined. Only the National Longitudinal Study of Adolescent Health previously found the prevalence of T. vaginalis in male adolescents (grades 7–12) to be 1.7%, slightly lower than in female adolescents (2.8%) [33].

The results of the study by Patel et al [29] highlight the fact that T. vaginalis continues to be a highly prevalent STI among US women and men, particularly in the black population. They underscore the fact that US screening, surveillance, and control programs for T. vaginalis are needed. Successful STI control measures have included use of sensitive screening tests; treatment of infected partners; accurate reporting of cases; availability of effective, affordable, single-dose medications; and initiation of mandatory reporting to the CDC [22]. Sensitive screening tests and effective, affordable, single-dose medications (MTZ is the most affordable treatment for any STI) are currently available for T. vaginalis.

Multiple highly accurate, rapid, and point-of-care tests are also available for T. vaginalis diagnosis [34], including the Affirm VPIII test, the OSOM rapid antigen Trichomonas test, the AmpliVue assay, the Solana Trichomonas assay, and the Cepheid GeneXpert TV assay (which offers rapid results in <40 minutes for positive tests) [13]]. Routine T. vaginalis screening programs using NAATs for diagnosis in women and men have started in some HIV and STI clinics across the country [30, 35] and in 1 cohort of women under community supervision in New York City [36], but this is not yet widespread practice. Patient-delivered partner therapy for T. vaginalis may have some benefit for partner management (ie, may be cost saving compared with partner referral) [37, 38] and is potentially allowable in some states [17] but also not routinely practiced. What is needed is a commitment from the public health community to scale up national control efforts, including significant increases in funding directed toward T. vaginalis. A first step could be initiation of routine T. vaginalis screening programs among women presenting to STI clinics across the country.

Overall, the data presented by Patel et al [29] provide an opportunity to reevaluate our current efforts regarding control (or lack thereof) of T. vaginalis. Continuing to ignore the alarming rates of this neglected STI on a national level, particularly in the black population, is a disservice to our patients and our ability to improve their sexual and reproductive health.

Notes

Financial support. C. A. M. is supported by the National Institute of Allergy and Infectious Diseases (grant K23AI106957-01A1).

Potential conflicts of interest. The author: No potential conflicts of interest. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.