No abstract

Trichomonas vaginalis is a common sexually transmitted protozoan parasite. Although often considered simply a nuisance infection, T. vaginalis has been implicated in premature rupture of placental membranes and increases in the risk of acquiring human immunodeficiency virus. Metronidazole, a 5-nitroimidazole, is currently the drug of choice to treat T. vaginalis infection. Because some patients have severe reactions to metronidazole and others are infected with metronidazole-resistant T. vaginalis, we were prompted to investigate alternative therapies. Tinidazole, another 5-nitroimidazole used in other countries to treat T. vaginalis infections, and furazolidone, a nitrofuran presently used to treat giardiasis and infections with some anaerobic enteric bacteria, were investigated for effectiveness against 9 metronidazole-susceptible and 12 metronidazole-resistant T. vaginalis patient isolates. The in vitro aerobic and anaerobic minimum lethal concentrations (MLC) and the time for drug efficacy were determined. Tinidazole killed the metronidazole-susceptible isolates at a low MLC but was effective against only 4 of the 12 metronidazole-resistant isolates. In contrast, furazolidone was effective at a low MLC for all isolates. When tinidazole was effective, it required > 6 h to kill trichomonads. However, furazolidone killed both metronidazole-susceptible and resistant trichomonads within 2 to 3 h of exposure. These data suggest that furazolidone may be a good candidate for treating metronidazole-resistant trichomoniasis and that further investigation of this drug is warranted.

Trichomonas vaginalis, the causative agent for human trichomoniasis, is a problematic sexually transmitted disease mainly in women, where it may be asymptomatic or cause severe vaginitis and cervicitis. Despite its high prevalence, the genetic variability and drug resistance characteristics of this organism are poorly understood. To address these issues, genetic analyses were performed on 109 clinical isolates using three approaches. First, two internal transcribed spacer (ITS) regions flanking the 5.8S subunit of the ribosomal DNA gene were sequenced. The only variation was a point mutation at nucleotide position 66 of the ITS1 region found in 16 isolates (14.7%). Second, the presence of a 5.5-kb double-stranded RNAT. vaginalis virus (TVV) was assessed. TVV was detected in 55 isolates (50%). Finally, a phylogenetic analysis was performed based on random amplified polymorphic DNA data. The resulting phylogeny indicated at least two distinct lineages that correlate with the presence of TVV. A band-sharing index indicating relatedness was created for different groups of isolates. It demonstrated that isolates harboring the virus are significantly more closely related to each other than to the rest of the population, and it indicated a high level of relatedness among isolates with in vitro metronidazole resistance. This finding is consistent with the hypothesis that drug resistance toT. vaginalis resulted from a single or very few mutational events. Permutation tests and nonparametric analyses showed associations between metronidazole resistance and phylogeny, the ITS mutation, and TVV presence. These results suggest the existence of genetic markers with clinical implications for T. vaginalisinfections.