Complications

- Trichomoniasis

Long considered a “minor” STD with few associated complications, infection with T. vaginalis has recently been implicated as a cause of preterm delivery in several studies. In a large multicenter study, after adjusting for demographic, behavioral, and microbiological variables, T. vaginalis was significantly associated with low birth weight, premature rupture of membranes, and preterm delivery (relative risk, 1.4) (20). Similarly, Minkoff et al. also documented a significant correlation between trichomoniasis and premature rupture of membranes (75). In that study, the incidence of this complication at term was 27.5% in women with T. vaginalis infection versus 12.8% in those without (P 75). In another study of pregnant adolescents, T. vaginalis was independently associated with prematurity and low birth weight (36).

Veterinary data further support a contribution of Trichomonas infections to adverse outcomes of pregnancy. Bovine venereal trichomoniasis is a cause of abortion in cattle, and a Trichomonas vaccine reduces the occurrence of this complication (104). The exact linkages between colonization or infection of the lower tract in pregnancy and prematurity remain speculative. The leading hypothesis is that infection triggers local cytokine release, which in turn triggers the onset of labor (76), a hypothesis for which data continue to accumulate. Several studies have found associations between the presence of biochemical substances (which may be involved in the initiation of labor) in the vaginal fluid of pregnant women and lower genital tract infections. These substances include phospholipase A₂, sialidases, endotoxin, and interleukin-1 alpha (11, 12, 73, 86). Infections associated with elevated levels of these substances within the vaginal or cervical fluids have included trichomoniasis as well as bacterial vaginosis and C. trachomatis infection (11, 12, 73, 86). Investigators have also shown a relationship between the presence of elevated cytokine levels in the amniotic fluid and preterm labor. Hillier et al. studied afebrile patients with intact membranes who presented with preterm labor at or before 34 weeks of gestation. They found that the presence of cytokines in the amniotic fluid was related to amniotic fluid infection, histologic chorioamnionitis, and premature delivery (39). In summary, lower genital tract infections, including trichomoniasis, have been linked to elevated levels of enzymes and cytokines within the vaginal fluid and the presence of cytokines within the amniotic fluid has been linked to chorioamnionitis and premature delivery.

Prospective studies of treatment of trichomoniasis during pregnancy for the prevention of preterm birth have yielded disappointing results. Among women with asymptomatic infection who were treated with metronidazole during the second and third trimesters of pregnancy, a trend toward increased preterm delivery was seen compared to the placebo group. However, the dose of metronidazole used was four times the recommended dose. In addition, the study was stopped prematurely due to a slow accrual of subjects and to the trend for increased risk of preterm delivery in the treatment group (52). A second study, conducted in Uganda, also found that treatment of trichomoniasis during pregnancy resulted in an increase in the incidence of preterm birth. However, this study was actually a subgroup analysis of a larger trial and was not properly designed to answer the question of the effect of treatment of T. vaginalis during pregnancy on preterm birth (51). Therefore, the question remains unanswered.

Acquisition of HIV has been associated with trichomoniasis in several African studies, possibly as a result of the local inflammation often caused by the parasite. Leroy et al. found a significant difference between the prevalence of trichomoniasis among a cohort of HIV-infected and noninfected pregnant women in Rwanda (20.2 and 10.9%, respectively; P = 0.0007) (61). In a prospective study by Laga et al., the incidence of trichomoniasis was significantly associated with HIV seroconversion (odds ratio, 1.9) in a multivariate analysis of a cohort of women in Zaire (57). The associations between HIV and trichomoniasis, as well as other STDs, may relate to (i) increased shedding of HIV as a result of the local inflammation produced by the STD, (ii) increased susceptibility to HIV as a result of the macro- or microscopic breaks in mucosal barriers caused by the STD, (iii) a higher prevalence of STDs among HIV-infected individuals as a result of common risk factors for both infections, and/or (iv) an increased susceptibility to STDs as a result of the immunosuppression associated with HIV infection. Given the higher prevalence and incidence of trichomoniasis than most other treatable STDs in most studies to date, the attributable fraction of HIV acquisitions due to trichomoniasis may eclipse the relative contribution of other STDs (107).

Transmission of HIV is enhanced by coinfection with T. vaginalis. In a study conducted in Malawi, the median HIV RNA concentration in the seminal fluid of men with urethritis was significantly higher in the men with trichomoniasis than in those with symptomatic urethritis due to an unidentified cause (40). In addition, successful treatment of trichomonal urethritis reduced the levels of HIV RNA so that they were similar to those seen in uninfected controls (87).