The demon within

Candida albicans. Some strains have adapted to sexual transmission. Have they gone so far as to manipulate host behavior?

Vulvovaginal candidiasis (VVC), commonly known as vaginal yeast infection, affects 70-75% of sexually active women at least once and 5-8% recurrently (Li et al., 2008). It is usually caused by Candida albicans, a single-celled fungus that reproduces asexually.

Although C. albicans can colonize many body sites, some strains have specifically adapted to the vagina. This evolutionary trajectory seems to have gone through three levels of adaptation:

Adaptation to vaginal environments

Vaginally adapted strains are a small subset of C. albicans. In China, two strains account for almost 60% of all VVC cases, yet neither is present at extragenital sites (Li et al., 2008). In the United States, C. albicans strains are much more diverse in the male partners of women without VVC than in the vaginas of women with or without VVC (Schmid et al., 1993).

Adaptation to sexual transmission

These vaginal strains seem to have also adapted to sexual transmission, specifically female-to-male transmission. Once VVC develops, they can spread to the host’s male partner by colonizing his glans penis via vaginal intercourse (Li et al., 2008) or his oral cavity via cunnilingus (Schmid et al., 1995). Vagina-to-vagina transmission has also been attested in lesbian couples (Bailey et al., 2008).

There is evidence of genetic changes for sexual transmissibility. Vaginal strains adhere better to saliva-coated surfaces than do other strains (Schmid et al., 1995). In the male partner, they tend to displace non-vaginal strains of C. albicans (Schmid et al., 1993).

Adaptation to certain sexual behaviors

Although a relationship clearly exists between sexual behavior and VVC, it is not a simple one of cause and effect. This is the conclusion of two research teams, Hellberg et al. (1995) and Reed et al. (2003), who sought to identify those aspects of sexual behavior that correlate with VVC.

Hellberg et al. (1995) found no significant association between VVC and the main indicators of vaginal sexual activity: (1) frequency of vaginal sex; (2) history of multiple sexual partners (more than 10 lifetime partners); and (3) sex with more than one partner during the last six months.

There were, however, significant associations with (1) early age of first intercourse, (2) casual sex with previous unknown partners in the past month, (3) vaginal sex during menstruation, (4) oral sex (fellatio), and (5) receptive anal sex.

Reed et al. (2003) reported similar findings. VVC was not significantly associated with frequency of vaginal sex, lifetime number of partners, and duration of current relationship. But there were significant associations with cunnilingus in the past month and masturbation in the past month. Unlike Hellberg et al. (1995), there were no significant associations with early age of first intercourse or frequency of receptive anal sex.

Reed et al. (2003) also found two risk factors in the male partner: early age of first intercourse and masturbation in the past month. There were no significant associations with his marital status, lifetime number of partners, previous partners with VVC, personal history of yeast infections, or reported fellatio or cunnilingus in the past month.

This is all rather puzzling. Occurrence of VVC was related not to vaginal sex but rather to non-vaginal sex, i.e., fellatio, cunnilingus, and masturbation. Even more puzzling, Reed et al. (2003) failed to find any association between VVC and the presence of C. albicans in the male partner, including his oral cavity. The authors concluded that the relationship between VVC and sexual behavior is not primarily one of sexual transmission:

If the association between orogenital contact and recurrent Candida vulvovaginitis is not mediated by transmission of the organism, how might increased risk be conferred? Previous study of the immunopathogenesis of recurrent Candida vulvovaginitis suggests that a delicate equilibrium exists among C. albicans, vaginal bacterial flora, and vaginal defense mechanisms, and that changes in the host environment promote the transformation of C. albicans from a saprophytic to a pathogenic existence. We suggest that the effects of genital washing with saliva—from either the male or the female—might upset this balance […] (Reed et al., 2003)

But how would this vaginal equilibrium be upset by the woman fellating her male partner? And how would it be upset by her male partner masturbating—alone and by himself?

Manipulation of host behavior?

To make sense of all this, we should perhaps reverse the direction of causality. Perhaps some vaginal strains of C. albicans have reached a third level of adaptation, i.e., manipulation of host behavior to increase opportunities for sexual transmission. Perhaps they somehow weaken the host’s sexual inhibitions and incite her to maximize contact between her vaginal fluids and colonizable sites on her partner’s body.

Does this sound like science fiction? Keep in mind that parasites manipulate host behavior in many non-human animals, and some of these parasites are likewise fungi (see here). Moreover, C. albicans has evolved the ability to cross the blood-brain barrier and colonize sites in the human brain (Jong et al., 2001). According to an autopsy of macaque brains, this microbe can recognize different kinds of neural tissue:

An ex vivo adhesion assay was used to examine adhesion of Candida albicans yeast cells to brain tissue of the primate Macaca mulata. Tissues from frontal lobes and striatum (caudate, putamen, and portions of the globus pallidus) were used in the assay. Yeast cells adhered to gray matter at about six times the level of adhesion to white matter. The fungus was able to bind to different cell types within the cortex, basal ganglia, and white matter. (Denaro et al., 1995)

One can imagine a multi-stage process of development:

1. “Behavior-modifying” C. albicans colonizes the vagina as a commensal organism with low virulence and no VVC. The ensuing period of latency might last a long time.

2. Meanwhile, the microbe spreads to other sites within the host’s body, including certain areas of the brain that influence sexual behavior.

3. Once this secondary colonization is complete, the area of primary colonization enters a highly infectious stage, i.e., VVC. The microbe is now ready to spread to her sexual partner.

And how will it influence her partner’s behavior? We cannot find the answer by studying his behavior before and during VVC—as in current studies. We must examine his subsequent behavior, i.e., once this strain of C. albicans has spread to his body and replaced other strains. Are there any behavioral changes?

But, then, what sort of changes should we expect?

(to be cont’d)

References

Bailey, J.V., R. Benato, C. Owen, and J. Kavanagh. (2008). Vulvovaginal candidiasis in women who have sex with women, Sexually Transmitted Diseases, 35, 533–536

Brainwashed by a parasite, Neurophilosophy, August 9, 2007
http://scienceblogs.com/neurophilosophy/2007/08/brainwashed_by_a_parasite.php

Denaro, F.J., J.L. Lopez-Ribot, and W.L. Chaffin. (1995). Adhesion of Candida albicans to brain tissue of Macaca mulata in an ex vivo assay, Infection and Immunity, 63, 3438-3441

Hellberg, D., B. Zdolsek, S. Nilsson, and P-A. Mårdh. (1995). Sexual behavior of women with repeated episodes of vulvovaginal Candidiasis, European Journal of Epidemiology, 1, 575-579, 1995

Jong, A.Y., M.F. Stins, S-H. Huang, S.H.M. Chen, K.S. Kim. (2001). Traversal of Candida albicans across human blood-brain barrier in vitro, Infection and Immunity, 69, 4536-4544.

Li, J., S-R. Fan, X-P. Liu, D-M Li, Z-H. Nie, F. Li, H. Lin, W-M. Huang, L-L. Zong, J-G. Jin, H. Lei, and F-Y. Bai. (2008). Biased genotype distributions of Candida albicans strains associated with vulvovaginal candidosis and candidal balanoposthitis in China, Clinical Infectious Diseases, 47, 1119–25.

Reed, B.D., P. Zazove, C.L. Pierson, D.W. Gorenflo, and J. Horrocks. (2003). Candida transmission and sexual behaviors as risks for a repeat episode of Candida vulvovaginitis, Journal Of Women’s Health, 12, 979-989.

Schmid, J., P.R. Hunter, G.C. White, A.K. Nand, and R.D. Cannon. (1995). Physiological traits associated with success of Candida albicans strains as commensal colonizers and pathogens, Journal of Clinical Microbiology, 33, 2920–2926.

Schmid, J., M. Rotman, B. Reed, C.L. Pierson, and D.R. Soll. (1993). Genetic similarity of Candida albicans strains from vaginitis patients and their partners, Journal of Clinical Microbiology, 31, 39-46.