Trichomonas vaginalis, an irritating protozoan or an important viral co-factor?

Review by Rughooputh, S and*Greenwell, P.

School of Biosciences

University of Westminster

115, New Cavendish Street

London W1 W 6UW.

*Corresponding author: greenwp@wmin.ac.uk

Key Words

Trichomonads, HIV, HPV, Cervical cancer

Introduction:

Trichomonas vaginalis (TV) is one of the most successful protozoan pathogens and the most common non-viral sexually transmitted disease with around 180 million new infections worldwide every year (Chavalitshewinkoon-Petmitr et al, 2003). Presentation in females is usually profuse purulent malodorous vaginal discharge and vaginal irritation although the infection can be sub-clinical or asymptomatic (Burja and Shurbaji, 2001). TV may also be associated with inflammation of the cervix termed “strawberry cervix”, that may mimic the cervical motion tenderness associated with PID (Moodeley et al, 2002). The changes in the cervical cells in women with TV have been likened to the changes seen in early CIN. In men infection often presents as urethritis (Krieger et al, 1993) and prostatitis (Ohkawa et al, 1992).

For many years TV infection has been seen as simply an irritating protozoan that was relatively easy to treat. However, recently, there has been evidence to implicate TV in pre-term delivery, low birth weight, infant mortality and predisposition to HIV and cervical cancer. (Dunne et al, 2003). Although all these areas are interesting, this article will only review the links between TV and HIV.

TV is a classical parasite that harvests almost all its nutrients and needs from its host. To accomplish such a task TV produces hydrolases to break down host proteins, oligosaccharides, DNA and lipids to provide itself with “building blocks” with which to reconstruct its own macromolecules (Lockwood et al, 1987., Alderete et al, 1991., Connaris and Greenwell, 1997., Das et al, 2002).

The problem from the point of view of the host is that in its quest for these “building blocks” TV produces a range of highly active enzymes that also destroy the protective mucin of the urogenital tract of the host allowing the TV to attach to the underlying cells and cause lesions. These lesions in turn provide a portal of entry for HIV, which under normal circumstances does not easily infect females. Indeed, heterosexual intercourse with a man infected with HIV carries a 1% risk of transmission of HIV to the female. Draper and colleagues (1998), studied the effect of TV on secretory leucocyte protease inhibitor (SLPI), that protects against viral infection, and found that, in vaginal secretions, the inhibitor was non functional due to the action of cysteine proteinases secreted by the trichomonads.

Studies from Africa have shown that the rate of HIV transmission is increased two fold in women with TV. In a study in four cities in Sub Saharan Africa, Buve and co-workers (2001) found a correlation between the prevalence of TV and HIV. The prevalence of trichomoniasis was higher in the cities with high numbers of HIV positive individuals with a mean of 31.8% as opposed to the cities with low HIV incidence where the prevalence of TV was only 10.4%.

Sorvillo and co-workers, (2001) calculated that in a country where the prevalence of TV was 25% (a level common in parts of Africa), if TV infection amplified transmission of HIV two-fold, then 20% of HIV transmission could be attributed to the presence of TV.

From an economic standpoint treatment of trichomoniasis is cheap and readily available whereas treatment for HIV is outside the reach of poor communities. Surely therefore, diagnosis and therapy for TV are vital. With reports of emerging strains resistant to metronidazole, the drug of choice for the treatment of TV infections, fewer patients clear infections and these are susceptible to acquiring lesions, making the penetration of other sexual transmitted infections (STIs) easier. Clearly, an understanding of the pathogenicity of sexually transmitted organisms and their interactions should allow development of both new diagnostic and treatment regimes.

Sadly, discussions on STIs have been taboo; there is a stigma attached to their acquisition and a reluctance both by governments and individuals to discuss the scale of the problem. Nevertheless, through education and the development of new treatments it may be possible to reduce levels of infections. However, in the UK where there is access to education, confidential counseling and screening and free medication, there has been an upsurge in the numbers of cases of STIs reported. In the quest to eradicate sexually transmitted diseases including HIV, the MRC in the UK will benefit from funding of £16 million from the Department for International Development for the next five years. In a move likely to provide a breakthrough in the treatment and prevention of STDs, US government agencies allocated $60 million in 2001 for the development of microbicides and in the UK, ML Laboratories is to start an MRC funded trial of a product that disrupts organism binding (Stone, 2003). Such microbicides could provide a safe and undetectable barrier to infection for women who currently cannot persuade their partners to use condoms. Currently, worldwide there is a problem that men refuse to use condoms thus endangering their partners. Female condoms have been singularly unacceptable and very costly. The use of microbicides could bring about a change in responsibility for protection from the man to the women would lead to women safeguarding their own sexual health.

If TV infection predisposes to HIV, does it also allow other viruses access to the urogenital tract? Recent work by Sayed el-Ahl and co-workers (2002) has shown that of 48 invasive cervical cancer and 100 random age matched female controls, 19% and 5% respectively had antibodies to TV, suggesting that, at some stage the cancer patients had contact with TV. Patients with TV infections had a threefold increased likelihood of contracting cervical cancer, hence TV can be categorised as an important co-factor in the pathogenesis of cervical cancer. Since there is a strong proven link between cancer of the cervix and HPV, is TV a co-factor in the acquisition of this virus?

One thing is clear TV is not just an irritating protozoan!

Reference:

Alderete, J.F; Newton, E; Dennis, C and Neala, K.A.(1991) The vagina of women infected with Trichomonas vaginalis has numerous proteinases and antibody to trichomonad proteinases. Genitourin Med  67 p331-4.

Burja, I.T and Shurbaji, M.S. (2001) Clinical impact of identifying Trichomonas vaginalis on cervicovaginal (Papanicolaou) smears. Diagnostic Cytopathology. 24(3) p195-199.

Buve, A; Weiss, H.A; Laga, M; Van Dyck, E; Musonda, R; Zekeng, L; Kahindo, M; Anagonou, S; Morison, L; Robinson, N.J and Hayes, R.J. (2001). The epidemiology of trichomoniasis in women in four African cities. AIDS. 15(Suppl 4) pS89-96.

Chavalitshewinkoon-Petmitr, P; Ramdja, M; Kajorndechakiat, S; Ralph, R.K; Denny, W.A and Wilairat, P. (2003) In vitro susceptibility of Trichomonas vaginalis to AT-specific minor groove binding drugs. J Antimicrob Chemother. 52(2) p287-9.

Connaris, S and Greenwell, P. (1997). Glycosidases in mucin-dwelling protozoans. Glycoconj J. 14(7) p879-82.

Das, S; Stevens, T, Castillo, C; VillasenÇ’r,A; Arredondo, H and Reddy K. (2002). Lipid metabolism in mucous-dwelling amitochondriate protozoa. International Journal for Parasitology. 32 p655-675.

Draper, D; Donohoe, W; Mortimer, L and Heine, R.P.(1998). Cysteine proteases of Trichomonas vaginalis degrade secretory leucocytes protease inhibitor. J Infect Dis. 178(3) p815-19.

Dunne, R.L; Dunn, L.A; Upcroft, P; O'Donoghue, P.J and Upcroft, J.A. (2003). Drug resistance in the sexually transmitted protozoan Trichomonas vaginalis. Cell Res.13(4) p239-49.

Krieger, J.N; Verdon, M; Siegel, N and Holmes, K.K. (1993). Natural history of urogenital trichomoniasis in men. J Urol. 149 p1455-58.

Lockwood,B.C; North, M.J; and Scott, K.I. (1987). The use of a highly sensitive electrophoretic method to compare the proteinases of trichomonads. Mol Biochem Parasitol. 24 p89-95.

Moodley, P; Wilkinson, D; Connolly C. Moodley, J and Sturm A.W (2002) Trichomonas vaginalis is associated with Pelvic Inflammatory Disease in women infected with Human Immunodeficiency Virus. CID. 34 p519-522.

Ohkawa, M; Yamaguchi, K; Tokunaga, S; Nakashima, T and Shinichi, F. (1992). The incidence of Trichomonas vaginalis in chronic prostatitis patients determined by culture using a new modified liquid medium. J Infect Dis. 166 p1205-6.

Sayed el-Ahl, S.A; el-Wakil,H.S; Kamel, N.M and Mahmoud, M.S. (2002). A preliminary study on the relationship between Trichomonas vaginalis and cervical cancer in Egyptian women. J Egypt Soc Parasitol. 32(1) p167-78.

Sorvillo, F; Smith, L; Kerndt, P and Ash,L.(2001). Trichomonas vaginalis, HIV and African-Americans. Emerg Infect Dis. 7(6) p927-32.

Stone, A.(2003). Protect and survive. New scientist 177 (2381) p42-44.