A hairy case of trichomoniasis: Azole resistance or reinfection?

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 testing positive. Before you ask, we did wait four weeks before retesting, as per NZSHS [New Zealand Sexual Health Society] guidelines.”

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

When presented with a clinical non-response to azoles, the first thing to rule out is reinfection. In fact, metronidazole (particularly the seven-day course that is now the preferred option) has an efficacy well above 90 per cent, and probably close to 96–97 per cent.

As trichomoniasis is almost always asymptomatic in men (NZSHS recommends testing in men only in cases of persistent/recurrent urethritis, with negative tests for chlamydia and gonorrhoea and failing empiric treatment with doxycycline), the main challenge is usually to get the male partner(s) treated.

Assuming all male partners from the last three months have been traced and treated, and there have been no opportunities for reinfection since the last treatment, one can start considering antimicrobial resistance as the cause. Laboratories in Aotearoa can test, or send away for testing, Trichomonas vaginalis isolates for azole resistance.

Usually, though, the resistance is dose dependent and can be overcome with a higher dose of an azole with enhanced pharmacokinetic properties, given for a longer duration than usual. Personally, I have been known to 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 guidelines tend to recommend high-dose tinidazole, which we do not have in Aotearoa, but occasionally Pharmac has approved a Named Patient Pharmaceutical Assessment application for funding and importation of it.

Beyond very-high-dose azoles, it becomes a mix of art and witchery, as there are no data apart from anecdotal case reports. 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.

In fact, the case referred by the GP did have dose-dependent azole-resistant T. vaginalis and was treated successfully with high-dose ornidazole.

The disulfiram-like reaction (nausea and vomiting) allegedly triggered by the intake of alcohol while being on metronidazole treatment is an interesting example of a self-perpetuating dogma where pharmacology reviews and guidelines just copy each other without verifying the primary source of the information. This possible side effect has been drilled into the brains of sexual health clinicians for generations, so much so that it was perceived as a major obstacle 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. The argument was that no one can completely abstain from alcohol for a full week.

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

The most recent proper study (a double-blind trial performed in 2002) found no disulfiram-like effect whatsoever in 12 healthy volunteers, and no raised blood acetaldehyde levels resulting from 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, but, for sure, I am not scaring them senseless anymore. I normally say, “You might feel nauseous if you drink alcohol while taking this drug, but if you wish, you can try a small quantity and see what happens.”

T. vaginalis is not the only flagellate protozoan potentially living in humans. We realised that in 2021, when, due to a COVID-related shortage of reagents for certain PCR platforms, some pharyngeal swabs taken 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 T. vaginalis PCR 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 literature search clarified the mystery – T. tenax, an oral inhabitant commonly found in periodontal disease, is a well-known cause of false-positive T. vaginalis PCR.² Pentatrichomonas hominis is a gut commensal with no known pathogenic role, and although the issue is not as well studied as for T. tenax, conceivably it could give some false-positive T. vaginalis PCR results on rectal swabs.

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

In case you are wondering about the title of this article, the word Trichomonas in Greek means “hairy unit”. If you have ever seen a microphotograph or video of this very pretty protozoan (particularly when it swims in a saline wet mount – youtu.be/rim2dXF3Oac), you will know what I mean.

Massimo Giola is an infectious disease and sexual health physician, and clinical lead of the sexual health services for Bay of Plenty and Lakes DHBs