Friday, May 6, 2011

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


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.

19 comments:

Beyond Anon said...


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?


Since re-infection of each other is not very useful, I would expect this strain of C. albicans to make those infected more promiscuous so that they could go on to infect other people with that strain.

It would be interesting to see what proteins/hormones its DNA codes for.

ItsTheWooo2 said...

The first thing I thought of when I considered all the information is probably that women who have candida infections are more likely to have glucose metabolism disorders (diabetes/subclinical diabetes). Glucose metabolism disorders in females can trigger excessively high androgen levels (PCOS or related problems). High androgen levels in females orient her toward more masculine like sexual behavior (being sexually risky and hypersexual and having unconventional sexual practices).

The link between candida infections and female hypersexuality is probably androgens, mediated through high blood sugar/high insulin levels.


Women with good blood sugar control are more likely to have low androgens, and will exhibit feminine sexual behavior (i.e. not inclined to have all sorts of kinky sex).

This is related to the finding that heavy women tend to enjoy sex and crave sex more than thin women. It's not that being fat makes you happy, it's more that fat women tend to have high testosterone because their blood sugar and insulin, as a group, are imbalanced. This is not true of ALL fat women, but fat women as a group are more likely to have elevated testosterone because of the fact that blood sugar disorders cause both elevated androgens and accrual of body fat in females.


It doesn't seem likely that a fungus can modulate female sexual behavior. It's much more likely that fungal growth is just another sign of an underlying physical condition - fungal infections are a major sign of diabetes and compromised immunity.

ItsTheWooo2 said...

If it were found that patients with severe mental illness & psychosis are 10 times more likely to have vaginal candidiasis and diabetic neuropathy, the obvious conclusion to be drawn is that antipsychotic medications cause diabetes/prediabetes, which then cause fungal infections. Since schizophrenics often take (or are forced to take) zyprexa and seroquel, they develop blood sugar disorders, which then lead to diabetes.

It would be way less likely to assume that candidia causes psychosis and neuropathy, wouldn't you agree?

High testosterone leads to crazy sexual behavior, and high testosterone in females is a consequence of blood sugar pathologies. Candida and fungal problems are another consequence.

Anonymous said...

I look forward to the next part.

Funny how we are receptive to plausible explanations of manipulation of other species by parasites yet resist such ideas as /likely in our own species.

Perhaps it's the word "manipulation" that makes many discount the plausiblility. We don't think of rhino viruses as "manipulating" people as if they have free will to do so; but they have certainly evolved to benignity in order to get around since usually they leave us upright, walking around, going to work until they manage to spread themselves. Whoops, the active voice I used in the previous sentence implies will. Revision: they [the viruses]manage to be spread by hosts walking around coughing and sneezing and touching objects others touch.

I wonder how the frequent use of antibiotics, which leave candida free to flourish, has affected their evolution.

Anonymous said...

I forgot to add a question--babies can acquire yeast infections as they exit the birth canal. I wonder if they can also acquire them during their time in the uterus?

Tod said...

Couldn't high testosteronization and consequent lower immunity and high sex drive explain the associations with increased sexual repertoire in men and women?

I'm not sure if casual sex (especially the non-vaginal acts) were common enough to spread the bug very much up until recently. From what I've read, before the 1950's hardly anyone would admit to doing things like that.

If Candida albicans is adapted to sexual transmission its prevalence must surely have increased geometrically in the last 40 years.

Tod said...

The changes should we expect if it is adapted to both sexes in humans ought to be ones that make the infected man more attractive to women.

T. gondii is adapted to rats but there is evidence can be sexually transmitted (in domestic dogs at least).Toxo affects the personality of humans but while it is said to make women more flirtatious it turns infected men into scruffy loners.

It may be that it is difficult to affect the sexual behavior of both men and women. I'd expect that the easiest tweak for a bug to make is to disable a women's innate choosiness and faithfulness.

Lets face it men are optimized for the winning of women and quite opportunistic as far as illicit sex is concerned. A bug is unlikely to be able to make them much more charming or unfaithful

The easiest tweak to increase a males sexual success would be to make them more extroverted.

Anonymous said...

Tod-- (Toxo affects the personality of humans but while it is said to make women more flirtatious it turns infected men into scruffy loners.)

I thought there was also some evidence that Toxo may promote risk taking in males, and risk taking is associated with male sexual pursuit.

Admittedly, I am no expert on this.

Tod said...

Toxo makes men more prone to have accidents not likely to take risks.
There is a difference.

Anonymous said...

Nice theory. But where is the evidence?

Anonymous said...

Tod,

That's right, sorry--my memory failed me. Didn't they find that reaction times of guys with Toxo were slowed somewhat? So that may account for the increase in auto and bike accidents in males who have high antibody counts.

Tod said...

T. gondii is adapted to infuence the behavior of rats in a very specific way. "The infection is highly precise, as it does not affect a rat's other fears such as the fear of open spaces or of unfamiliar smelling food."

In men T. gondii does not seem to be adapted to alter behavior so as to facilitate sexual transmission of Toxo; a scruffy accident prone loner is not going to get much is he ?

However in women Toxo seems to have an effect on behavior that may be consistent with sexual transmission (which may be possible with Toxo)

I was thinking out loud and musing about psuedo-adaptation; Candida albicans may affect sexual behavor but is that a real adaptation to influence a human male to spread the infection or just a side effect?

As men are already inclined to want sex with random women C. albicans would have to produce a change in their their sexual behavior which would be maladaptive for the man. The example that springs to mind is a propensity for infected men to indulge in non-procreative sexual behavior.

Anonymous said...

Tod: "The example that springs to mind is a propensity for infected men to indulge in non-procreative sexual behavior."

Do I understand your point? This "non-procreative sexual behavior" could mean anal and/or oral sex, yes, but did you also mean to suggest that "non-procreative sexual behavior" could include an attraction for and sex with an infertile target... such as another male....?

Tod said...

A predilection in Candida albicans infected men for a sexual repertoire which includes (necessarily non-procreational) heterosexual sex would be more convincing evidence for C. albicans being the cause of that behavior than just having a lot of procreational sex. I don't think exclusive homosexuality would offer a bug an advantage over bisexual promiscuity though; a hole is a hole from the bug's perspective.

Peter Frost said...

Beyond Anon,Tod, and others,

Male-to-female transmission of C. albicans is much less effective than female-to-male transmission. The big payback from male behavior modification is not increased male promiscuity. It's something else.

Its the Wooo2,

If C. albicans affects sex hormone levels, this might be the proximate means of behavior manipulation.

It doesn't matter whether this effect began accidentally. This is how evolution works. An accidental affect is seized by natural selection and then refined to make it work better.

Tod and others,

T. gondii is the only other microbe that has been suspected of behavior manipulation in humans. But I think C. albicans is a likelier candidate, if only because there is such a large pool of this microbe for natural selection to act upon.

Anonymous said...

"The big payback from male behavior modification is not increased male promiscuity. It's something else."

Paul Ewald says one has to think like a bug. I am having trouble thinking like a bug on this one. Of course, I am assuming that the fungi, which are now in the male, want to keep spreading, yet I can't figure how increased male masturbation would accomplish that unless he's doing something with his semen that I haven't yet imagined...

Maybe I'm just not kinky enough?

Tod said...

1) Female transmits C. albicans to male partner

2) Infection with C albicans causes the male's behavior to alter in a way which leads to his woman becoming dissatisfied with their relationship. [One possible mechanism is that the man loses interest in vaginal sex and becomes obsessed with oral and anal, consequently he spends a lot of time watching porn/mastrubating (modern porn centres around oral and anal)]

3) Woman's vaginal equilibrium is upset by partner having vaginal sex after oral or anal (partner's penis has bugs on it from the mouth or rectum) and she gets Vulvovaginal candidiasis (VVC), infection.

4)Woman becomes dissatisfied with partner and has sex with another man.

Anonymous said...

I just read Tod's last post. I did think of the woman losing interest in the man (since he's into excessive masturbation) and that fact leading to her eventual disinterest in him and her eventual sex with other men, but I didn't think of Tod's step #3.

I'll stay tuned. I'm out of my league.

ItsTheWooo2 said...

Peter,
C. albicans does NOT affect hormone levels. You added that in to preserve your hypothesis that yeast is causing women to have sex.

GLUCOSE affects insulin, which affects female hormone levels (more testosterone).

GLUCOSE also leads to more yeast infections such as C. albicans.

Overweight women are noted to be more sexual, presumably because of poor blood sugar control and higher testosterone levels (heavier women have higher testosterone). THey also have more yeast infections.

You are seeing a sign (more yeast infections correlating with more sex) and you are assuming the yeast is causing the sex, when it is much more likely that an underlying metabolic condition is resulting in more sex and more infections. Glucose - > insulin & testosterone & infections.