Resistance or infection? You Choose.

A hairy case of SH Infection

Is it azole resistance or just another infection?

Sexual health specialist Massimo Giola discusses Trichomonas vaginalis infection and treatment, including whether patients can drink alcohol while taking metronidazole.

Key points

• The gold standard for treatment of Trichomonas vaginalis infection is now a one-week course of metronidazole 400mg twice daily with food.
• T. vaginalis resistance to azole antiprotozoals is possible, albeit not common.
• The interaction between metronidazole and alcohol is “fake news”.
• Do not look for T. vaginalis in extragenital sites or in men who do not practice normal sex.

The endorsement of this article is by the RNZCG. It has approval of up to 0.25 CME credits to continue professional development purposes (1 credit per learning hour). To claim your credits, log in to your RNZCGP dashboard to record this activity in the CME part of your CPD program.

Nurses may also find that reading this article and reflecting on their Trich Test learning can be a professional development activity with the Nursing Council of New Zealand (up to 0.25 PD hours).

This time, the call asking me for advice came from a local GP. “Hello, do you have a minute to discuss a case? I have a woman with resistant trichomoniasis. She has already had two courses of metronidazole 2g stat and one week of metronidazole 400mg twice daily, but she keeps being positive. Before you ask, we did wait four weeks before taking another STD home profile test, as per NZSHS [New Zealand Sexual Health Society] rules.”

“We’d be happy to see her at the sexual health service if you could send through a referral. We might offer her a couple of things,” I replied. The referral arrived that day.

Resistance or another infection?

When presented with a clinical non-response to azoles, the first thing to rule out is another infection. Metronidazole has an efficacy well above 90 per cent and probably close to 96–97 per cent.

As trichomoniasis almost always doesn’t show symptoms in men (NZSHS recommends checking in men only in cases of persistent/recurrent urethritis, with negative checks for chlamydia and gonorrhoea and failing empiric treatment with doxycycline), the main challenge is usually getting treatment for the male partner or partners.

Assuming all STD Tested male partners from the last three months did a trace and got treatment, there have been no chances for another infection since the last treatment; one can start considering antimicrobial resistance as the cause. Laboratories in Aotearoa can test Trichomonas vaginalis isolates for azole resistance or send them away for checking.

Usually, the resistance depends on the dose, and it is beaten with a higher dose of azole with pharmacokinetic property enhancements over a longer period than usual. I use ornidazole up to 1g twice daily for 10 days, sometimes with per vaginam metronidazole suppositories (1g every eight hours), with (anecdotally) good results.

International rules tend to recommend high-dose tinidazole.

We do not have it in Aotearoa. Occasionally, Pharmac has approved a Named Patient Pharmaceutical Assessment application for funding and importation.

Beyond very-high-dose azoles, it becomes a mix of art and witchcraft. There is no data on the Trichomonas PCR test apart from case reports based on hearsay. Prolonged courses (28 days or more) of intravaginal boric acid suppositories seem to be a reasonable option when under the care of an experienced sexual health specialist with a specific interest in vulvovaginal problems.

The GP referred the case, which had dose-dependent azole-resistant Trichomonas vaginalis. It was treated successfully with high-dose ornidazole.

A self-perpetuating dogma

The disulfiram-like reaction (nausea and vomiting) that the intake of alcohol can set off while being on metronidazole treatment is an interesting example of a self-perpetuating dogma where pharmacology reviews and rules copy each other without proving the primary source of information. This possible side effect has been drilled into the brains of sexual health clinicians for generations, so much so that it was seen as a major hurdle when we updated the Aotearoa New Zealand STI Management Guidelines for use in primary care (sti.guidelines.org.nz), which now recommend one week of metronidazole as the preferred treatment option for trichomoniasis, rather than the stat dose. Trichomoniasissis Test argument was that no one can completely abstain from alcohol for a full week.

I hope my Trcho readers will be as shocked as I was when I read a review of this topic. The whole dogma of the metronidazole-related disulfiram-like interaction is based on animal studies (rats) and 10 anecdotal case reports.

The most recent proper STD study (a double-masked trial executed in 2002) found no disulfiram-like effect in 12 healthy volunteers. There were also no raised blood acetaldehyde levels, which resulted from the coadministration of metronidazole and alcohol, which was the putative mechanism of the reaction.¹

So far, I have not been bold enough to tell my patients they can drink alcohol freely while taking metronidazole. I am not scaring them anymore. I normally say, “You might get nausea if you drink alcohol while taking this trichomonas drug. If you wish, you can try a small amount and see what happens.”

Do not open cans of worms.

T. vaginalis is not the only flagellate protozoan potentially living in humans. We had a realisation that in 2021, when there was a COVID-related shortage of reagents for certain PCR platforms, we took some pharyngeal swabs from men who have sex with men and sent for Chlamydia trachomatis and Neisseria gonorrhoeae PCR, were run by the lab on the platform they use for the Trichomonas Vaginalis PCR test and came back positive. This caused quite a bit of excitement among nurses, doctors, and patients alike. Remember, when no vagina is involved in sex, there is no T. vaginalis.

A quick search cleared the mystery. T. tenax, an oral inhabitant commonly found in periodontal disease, is a well-known cause of false-positive T. vaginalis PCR.²Pentatrichomonas hominis is a gut commensal with no known pathogenic role. Although the issue is not as well studied as for T. tenax, it could give some false-positive Trichomonas vaginalis Test PCR results on rectal swabs.

So, the old rule applies. Do not request STD Urine tests unless you know what to do with both a positive and a negative result.

One more point

In case you are wondering about the title of this article, the word Trichomonas Test in Greek means “hairy unit”. You will know what I mean if you have ever seen a microphotograph or video of this pretty protozoan,

Massimo Giola is an infectious disease and sexual health physician. He is also the lead of the sexual health clinic services for Bay of Plenty and Lakes DHBs