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INTRODUCTION: Trichomoniasis is frequent, parasitic and sexually transmitted infection of genitourinary tract. It is treated by metronidazole (5-nitroimidazole), according to protocol recommended by Center for Disease Control (CDC, formerly called: Communicable Disease Center) [19]. The resistance of Trichomonas vaginalis (TV) strains to metronidazole (MND) was described in USA in 1960, and later on in many European countries [8, 9, 10, 11, 12, 13]. In these cases, due to persistent trichomonas infection, it is necessary to repeat MND treatment with moderate modification of dose and/or length of its application. Nevertheless, oncogenic and toxic effects of MND have to be taken into consideration. AIM: The aim of this study was to investigate and analyse the incidence of TV in STD and lower susceptibility of certain TV strains to MND were analyzed. METHODS: In three-year period (1999-2001) 612 patients (244 females and 368 males) suspected of STD were examined clinically and microbiologically at the Institute of Dermatovenereology in Belgrade. The patients detected for TV were treated according to CDC protocol. The affected were considered cured if there was no manifest clinical infection, and no TV verified by microbiological test. RESULTS: TV was isolated in 216 patients (35.29% of all subjects). Trichomonas infection was found in 90 (36.88%) out of 244 tested females and in 126 (32.34%) of 368 males. Clinically manifested infection, with extensive urethral and vaginal secretion, was recorded in 161 patients, while the asymptomatic form was found in 55 subjects. This result indicates the predominance of manifested trichomonas infections (75.54% of cases). The difference of distribution of clinical forms of trichomoniasis, in relation to sex, was not statistically significant (chi 2 = 0.854; p > 0.05). The patients with verified trichomonas infection were treated by metronidazole according to CDC protocol. The recommended therapeutical scheme consisted of three phases proceeding in succession, in so far TV had not been eliminated by previous one. The number of cured patients, according to therapeutical phases, was shown in Table 4. Three patients (1.39%, 2 males and 1 female) were not cured in spite of all three completed phases of therapeutical protocol. In all three cases, TV was eliminated by MND application in dose of 3 g/daily, during two days. The failure of minute MND treatment was analyzed in relation to clinical forms of the infection (manifested or asymptomatic), as well as in relation to types of infection (single- or associated infection). The incidence of refractory trichomoniasis treated by a single metronidazole dose of 2 g was significantly higher in the group of patients with polyinfection (c2 = 18.270; p < 0.01). There was no significant difference of resistance to a single MND dose between the groups with manifested and asymptomatic trichomoniasis (chi 2 = 0.321; p < 0.01). DISCUSSION: The prevalence of TV in vaginal and urethral smears indicates the significant incidence of trichomoniasis in STD. TV was more frequently isolated in patients with clinically manifested infection. TV susceptibility to MND was tested in vitro in aerobic and anaerobic conditions. The resistance of strains under in vitro conditions did not correlate with refractory feature of trichomoniasis to MND application [7, 17, 18]. The success of trichomoniasis treatment depends upon multiple factors, including: a) TV susceptibility to drug, b) intravaginal redox potential, c) drug concentration in situ, d) associated microorganisms that may modify the amount of the drug available in situ [7, 18, 21]. The results of our investigation argue for the latter item, verifying that TV resistance to MND is higher in patients with polyinfection in relation to those with monoinfection (significant difference, chi 2 = 18.270; p < 0.01). Repeated administration of low metronidazole doses may prolong the therapy of trichomonas infections, while application of high doses (over 3 g/day) may result in undesired complications. Given the well-known fact that repeated sublethal doses induce the resistance, would it be more beneficial to begin with slightly higher metronidazole dose (3 g/day) during short period of time (3-5 days)? This will be the subject of our further investigation.