Does a fungus cause baldness?

Endgame for an ant (Wikicommons)

Is male pattern baldness (MPB) caused by a pathogen? The question may seem silly because the genetic causation is obvious. MPB is normally a male problem, and family background is important. If your male relatives go bald at an early age, the chances are good that you will too.

Genetic causation does not exclude environmental causation, however. I will argue here that a pathogen, specifically lipid-dependent yeasts of the Malassezia genus, has evolved the ability to accelerate the onset of MPB. I will also argue that this is not a side effect of infection. It is key, in fact, to the pathogen’s survival and reproduction.

The germ theory

MPB in young men was once widely blamed on a pathogen. This germ theory was first put forward by a French dermatologist, Raymond Sabouraud:

In recent years our knowledge of this subject has been much increased by the researches of Unna, Sabouraud, and others. These investigators would lead us to look upon all forms of baldness as parasitic in origin. They say that thinning of the hair, whether general or beginning on the crown or at the temples and forehead (alopecia pityrodes), can be produced by a micro- organism. [...] Sabouraud thinks the micro-bacillus of oily seborrhoea finds its way into the hair follicle and causes sebaceous hyper- secretion; then hypertrophy of the sebaceous glands; next, progressive papillary atrophy; finally, death of the hair. (Waldo 1883)

The identity of the pathogen was a matter of debate. Sabouraud attributed baldness to a bacterium and seborrhea to a yeast initially named Pityrosporum ovale and now classified as the genus Malassezia. Antimicrobials, particularly sulfur ointments and shampoos, became popular treatments for seborrhea and MPB.

This germ theory fell out of favor in the mid-20th century. Ainsworth (1956, p. 589), in his review of the literature, concluded that P. ovale was usually harmless:

During the nineteenth century it was widely held that P. ovale was responsible for the various disorders (and particularly seborrheic dermatitis) with which it is commonly associated. Sabouraud cautiously attributed pityriasis (dandruff) to P. ovale but modern opinion is even more sceptical and during the past two decades the view most generally accepted is that of Ota and Huang (1933) who after a careful experimental investigation and a study of the evidence obtained by others concluded that P. ovale is merely an inoffensive saprophyte of man.

Similarly, Ludwig (1968) wrote: "Due to a misinterpretation of the role of oil seborrhea, which so frequently accompanies the development of common baldness, Sabouraud came to the erroneous conclusion that common baldness results from a chronic infection of the scalp by his 'microbacilli'."

The medical community was in no mood to investigate Sabouraud’s germ theory any further. This was a time when causation of disease was increasingly framed in terms of genetics or lifestyle, rather than infection by a pathogen:

During the first half of the 20th century, researchers began to confront another major barrier of crypticity: long delays between the onset of infection and the onset of disease. Long delays make cause-effect linkages cryptic because other events that occur during the intervening time can form the basis of alternative causal explanations. As the delay in onset of symptoms increases, the number of such events and, hence, the number of alternative hypotheses of causation increases. The alternative hypotheses may focus on specific environmental insults, or may interpret delayed, persistent symptoms as natural wear and tear, particularly if infections are ubiquitous. (Cochran et al. 2000)

Since the turn of the millennium there has been a renewed interest in Malassezia and its role in seborrhea and MPB (Arash et al. 2002; Dawson 2007; Sastry 2004).

Going beyond the proximal cause

Today, there is a growing consensus that seborrhea is caused by the lipid-dependent yeast Malassezia, most likely the species M. globosa and M. restricta (Dawson 2007). The mode of action is less certain. Malassezia degrades sebum and releases unsaturated fatty acids, which may in turn stimulate sebum production (Dawson 2007). Alternatively, it may increase conversion of testosterone to the more active dihydrotestosterone (DHT), thus causing not only excessive sebum production but also MPB. This effect has been shown with acne, a skin condition that overlaps with seborrhea in many ways. When biopsies were taken from affected and unaffected areas in 32 subjects with acne, it was found that "acne bearing skin produced from 2 to 20 times more dihydrotestosterone than normal back skin" (Sansone and Reisner 1971).

What would Malassezia gain from DHT? We know that DHT boosts production of sebum, which contains the fat that this pathogen feeds on. Sebum may also help to shield it from the body's immune system.

There nonetheless remains one apparent flaw in this germ theory: Malassezia is common, yet only a minority of young men develop MPB. It seems, then, that some men are more genetically susceptible than others to MPB. This is part of the reason, but another reason is that some Malassezia species are better than others at altering the chemistry of the skin. The species most implicated in seborrhea are M. globosa and M. restricta (Dawson 2007). Studies of a related skin infection, Pityriasis versicolor, have found M. globosa to be more implicated than M. restricta (Saad et al 2013; Salah et al. 2005). In a review of the literature, Zarei-Mahmoudabadi et al. (2013) conclude that M. globosa is the main cause of seborrhea:

Different Malassezia species were reported as causative agents of SD in the different countries. Lee et al. (23) reported M. restricta as the most important species in Korean SD patients. In addition, Prohic (26) in a study from Bosnia and Herzegovina believes that M. restricta (27.5%) is the main agents of SD and M. globosa (17.5%) and M. slooffiae (15%) are the next agents. In a molecular study by Tajima et al. (11), M. restricta and M. globosa were detected as the predominate agents of SD. In contrast, in Hedayati et al. study in north of Iran M. globosa was reported as the most frequently agent on scalp and face lesions, whereas M. furfur had most frequency on trunk lesions (24). In the present study, out of the 110 scalp scales that were cultured on Dixons agar, 24.5% yielded Malassezia that the most frequently Malassezia species was M. globosa (40.7%), followed by M. pachydermatis (22.2%), M. furfur (11.1%) and M. restricta (7.4%).

Nine Malassezia species are found on human hosts (Dawson et al. 2018). It is likely that different species compete against each other for sites on the body surface. Colonization by an aggressively seborrheic species is thus probably impeded if another species is already present. Indeed, the relative distribution of these species varies from one ethnic group to another and from one geographical area to another (Dawson et al. 2018).

Is Malassezia sexually transmitted?

There may be another side to infection by Malassezia. It colonizes not only the scalp but also the male genital region, particularly if the man is uncircumcised:

Recently, several authors have noted Malassezia spp. as part of the microflora of healthy uncircumcised male genital regions in 49.2% of the population, in contrast to circumcised male patients, in which Malassezia spp. are identified in 22.4% of the population (2, 3). Mayser et al. assumed that Malassezia yeasts find favorable growth conditions in the lipid-rich milieu of the preputial area because of its free sebaceous glands (i.e., Tyson's glands seem to be important) (Khadar et al. 2008)

It is known that yeasts, like Malassezia, can spread from one person to another through sexual contact (Spinillo et al. 1992). The pathogen can thus enhance its own reproductive success by influencing its host's sexual behavior. Premature hair loss may therefore be one of its strategies for spreading to other hosts.

Keep in mind that men in pre-modern societies were divided into age classes, and the transition from one class to the next was determined by visible physical changes: the growth spurt of childhood, the appearance of body and facial hair in adolescence and, finally, the loss of head hair later in life. By making its host lose his head hair prematurely, the Malassezia pathogen reassigns him to a class of older men who, except for the rich and powerful, deal with sexual dissatisfaction not by divorcing and remarrying (or by finding a mistress) but rather by frequenting prostitutes. The possibilities for transmission to a new host are thus increased many times over.

Stranger things have happened

A fungal infection may actually cause sexual dissatisfaction. This kind of behavioral manipulation is not as fantastic as it may seem. Fungi are champions of such manipulation, both in overall prevalence and in sophistication:

The observation that, as a Kingdom, Fungi have many parasitic taxa [...] does not distinguish them from other major groups. Parasitism is a very common mode of life that has evolved repeatedly and probably more times than predation as a life history strategy [...]. What is notable is the apparently high frequency of parasitic fungi that have evolved not just to infect animals but also to adaptively manipulate animal behavior in ways that increase the fitness of the fungus. (Hughes et al. 2016)

You have probably heard about "zombie ants": a fungus infects an ant and reprograms its brain, causing it to leave its nest, climb up a plant, lock its jaws into the plant tissue, and die. A fruiting body then emerges from the ant's head and rains down spores on the forest floor below. There are other examples. In one case, the fungus keeps its host alive and controls its flight behavior so that the insect becomes a moving vehicle for spore release (Hughes et al. 2016).

What about humans? Greg Cochran has argued that an unknown pathogen can alter a man’s sexual orientation as a means to increase its opportunities for spreading to other hosts: "One possible route would be sexual, whereby homosexual behavior could facilitate spread because of the larger numbers of partners homosexual males may have on average, relative to heterosexual males" (Cochran et al. 2000).

Similarly, there may exist a pathogen that reverses male jealousy and makes its host desire cuckoldry, thereby gaining access to many more hosts (Frost 2013). Although many sexual fetishes are attested in the writings of ancient civilizations, cuckold envy does not seem to be one of them. The oldest references date back to 17th century England (Kuchar, 2011, pp. 18-19). The cause may thus be a sexually transmitted pathogen that entered England during the early days of the slave trade. Such a pathogen could have evolved in West Africa, where most women were in polygynous marriages, and where cuckoldry was the main route for transmission from one household to another.

We have never identified such pathogens largely because we have never bothered to look. They are also hard to find, given the delay between infection and behavioral change.

References

Ainsworth, G.C. (1958). Pathogenic yeasts. In A.H. Cook (Ed.) The Chemistry and Biology of Yeasts (pp. 587-602). New York: Academic Press.

http://krishikosh.egranth.ac.in/bitstream/1/23082/1/IVRI%20OB%201816.pdf#page=593

Arash, J., F. Sorour, and A.M. Mokhtari. (2002). Evaluation of the coincidence of Male Pattern Baldness and Pityrosporum group of fungus in Iran. Indian Journal of Dermatology 47(4): 224-226.

http://www.e-ijd.org/article.asp?issn=0019-5154;year=2002;volume=47;issue=4;spage=224;epage=226;aulast=Javanbakht;type=0

Cochran, G.M., P.W. Ewald, and K.D. Cochran. (2000). Infectious causation of disease: an evolutionary perspective. Perspectives in Biology and Medicine 43(3): 406-448.

https://doi.org/10.1353/pbm.2000.0016

Dawson, T.L. (2007).  Malassezia globosa and restricta: Breakthrough Understanding of the Etiology and Treatment of Dandruff and Seborrheic Dermatitis through Whole-Genome Analysis. Journal of Investigative Dermatology Symposium Proceedings 12(2): 15-19

https://doi.org/10.1038/sj.jidsymp.5650049 

Dawson, T.L., C. Leong, J. Goh, and A. Irudayaswamy. (2018). Geographical and ethnic differences in Malassezia species distribution on healthy skin. Congress of the International Society for Human and Animal Mycology

https://www.morressier.com/article/5ac39997d462b8028d89a224

Frost, P. (2013). First, sexual transmissibility and then ...? Evo and Proud, January 5

http://evoandproud.blogspot.com/2013/01/first-sexual-transmissibility-and-then.html

Hughes, D.P., J.P.M. Araujo, R.G. Loreto, L. Quevillon, C. de Bekker, and H.C. Evans. (2016). Chapter Eleven - From So Simple a Beginning: The Evolution of Behavioral Manipulation by Fungi. Advances in Genetics 94: 437-469.

https://doi.org/10.1016/bs.adgen.2016.01.004

Khadar, R.K., F. Cherif, R. Ben Hadid, M. Mokni, and A. Ben Osman. (2008). Penile shaft involvement in pityriasis versicolor. Acta Dermatovenerol Alp Pannonica Adriat. 17(2):86-9.

https://pdfs.semanticscholar.org/eaa2/e73dccf5b7cc31d8b0aa346e2d7b2db9837f.pdf

Kuchar, G. (2001). Rhetoric, Anxiety, and the Pleasures of Cuckoldry in the Drama of Ben Jonson and Thomas Middleton. Journal of Narrative Theory 31(1): 1-30.

Ludwig, E. (1968). The role of sexual hormones in pattern alopecia. In A. Baccaredda-Boy, G. Moretti G, and J.R. Frey (Eds). Biopathology of Pattern Alopecia. International Symposium, Rapallo, July 1967: Proceedings. Basel, Karger, pp 50-60.

https://doi.org/10.1159/000387745

Saad, M., T. Sugita, H. Saeed, and A. Ahmed. (2013). Molecular Epidemiology of Malassezia globosa and Malassezia restricta in Sudanese Patients with Pityriasis Versicolor. Mycopathologia 175(1-2): 69-74.

https://doi.org/10.1007/s11046-012-9587-y

Ben Salah, S., F. Makni, S. Marrakchi, H. Sellami, F. Cheikhrouhou, S. Bouassida, A. Zahaf, A. Ayadi (2005). Identification of Malassezia species from Tunisian patients with pityriasis versicolor and normal subjects. Mycoses 48(4): 242-245

https://doi.org/10.1111/j.1439-0507.2005.01091.x

Sansone, G., and R.M. Reisner. (1971). Differential Rates of Conversion of Testosterone to Dihydrotestosterone in Acne and in Normal Human Skin—a Possible Pathogenic Factor in Acne. Journal of Investigative Dermatology 56(5): 366-372.

https://doi.org/10.1111/1523-1747.ep12261252

Sastry, P.S.R.K. (2004). Occult fungal infection is the underlying pathogenic cause of atherogenesis. Medical Hypotheses 63(4): 671-674.

https://doi.org/10.1016/j.mehy.2003.12.050 

Spinillo, A., L. Carratta, G. Pizzoli, G. Lombardi, C. Cavanna, G. Michelone, and S. Guaschino. (1992). Recurrent vaginal candidiasis. Results of a cohort study of sexual transmission and intestinal reservoir. Journal of Reproductive Medicine 37(4): 343-347.

Szasz, T.S., and A.M. Robertson. (1950). A theory of the pathogenesis of ordinary human baldness. Archives of Dermatology and Syphilology 61(1):34-48. https://doi.org/10.1001/archderm.1950.01530080040004   

Waldo, H. (1883). The causes and treatment of baldness. Bristol Med. Chir. J. 23(88): 107-113.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043940/

Zarei-Mahmoudabadi, A., M. Zarrin, and F. Mehdinezhad (2013). Seborrheic dermatitis due to Malassezia species in Ahvaz, Iran. Iranian Journal of Microbiology 5(3): 268-271.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895566 

Yes, demons do exist

 

Chlamydia infection rate, by country (WHO 2004, Wikicommons). Sub-Saharan Africa has been a natural laboratory for the evolution of sexually transmitted pathogens, including strains that can manipulate their hosts.

 

Are we being manipulated by microbes? The idea is not so whacky. We know that a wide range of microscopic parasites have evolved the ability to manipulate their hosts, even to the point of making the host behave in strange ways. A well-known example is Toxoplasma gondii, a protozoan whose life cycle begins inside a cat. After being excreted in the cat's feces, it is picked up by a mouse and enters the new host's brain, where it neutralizes the fear response to the smell of cat urine. The mouse lets itself be eaten by a cat, and the protozoan returns to a cat's gut—the only place where it can reproduce (Flegr, 2013).

T. gondii can also infect us and alter our behavior. Infected individuals have longer reaction times, higher testosterone levels, and a greater risk of developing severe forms of schizophrenia (Flegr, 2013). But there is no reason to believe that T. gondii is the only such parasite we need to worry about. We study it in humans simply because we already know what it does in a non-human species.

Researchers are starting to look at manipulation by another human parasite, a sexually transmitted bacterium called Chlamydia trachomatis. Zhong et al. (2011) have found that it synthesizes proteins that manipulate the signalling pathways of its human host. These proteins seem to facilitate reinfection, although there may be other effects:

Despite the significant progresses made in the past decade, the precise mechanisms on what and how chlamydia-secreted proteins interact with host cells remain largely unknown, and will therefore still represent major research directions of the chlamydial field in the foreseeable future. (Zhong et al., 2011)

What else would a sexually transmitted pathogen do to its host? For one thing, it could cause infertility: 

While several nonsexually transmitted infections can also cause infertility (e.g., schistosomiasis, tuberculosis, leprosy), these infections are typically associated with high overall virulence. In contrast, STIs tend to cause little mortality and morbidity; thus, the effect on fertility seems to be more "targeted" and specific. In addition, several STI pathogens are also associated with an increased risk of miscarriage and infant mortality (Apari et al., 2014)

Chlamydia is a major cause of infertility, and this effect seems to be no accident. Its outer membrane contains a heat shock protein that induces cell death (apoptosis) in placenta cells that are vital for normal fetal development. The same protein exists in other bacteria but is located within the cytoplasm, where it can less easily affect the host's tissues. Furthermore, via this protein, Chlamydia triggers an autoimmune response that can damage the fallopian tubes and induce abortion. This response is not triggered by the common bacterium Escherichia coli. Finally, Chlamydia selectively up-regulates the expression of this protein while down-regulating the expression of most other proteins (Apari et al., 2014).

But how would infertility benefit Chlamydia and other sexually transmitted pathogens? Apari et al. (2011) argue that infertility causes the host and her partner to break up and seek new partners, thus multiplying the opportunities for the pathogen to spread to other hosts. A barren woman may pair up with a succession of partners in a desperate attempt to prove her fertility and, eventually, turn to prostitution as a means to support herself (Caldwell et al., 1989). This is not a minor phenomenon. STI-induced infertility has exceeded 40% in parts of sub-Saharan Africa (Apari et al., 2011).

It gets kinkier and kinkier

Does the manipulation stop there? We know, for instance, that sexual promiscuity correlates with the risk of contracting different STIs, but is this a simple relationship of cause and effect? Could an STI actually promote infidelity by stimulating sexual fantasizing about people other than one's current partner?

Let's look at another pathogen, Candida albicans, commonly known as vaginal yeast, which can cause an itchy rash called vulvovaginal candidiasis (VVC). Reed et al. (2003) found no significant association between VVC and the woman's frequency of vaginal sex, lifetime number of partners, or duration of current relationship. Nor was there any association with presence of C. albicans in her male partner. But there were significant associations with the woman masturbating or practicing cunnilingus in the past month.

VVC is thus more strongly associated with increased sexual fantasizing, as indicated by masturbation rate, than with a higher frequency of vaginal intercourse. This does look like host manipulation, although one might wonder why it doesn't translate into more sex with other men, this being presumably what the pathogen wants. Perhaps the development of masturbation as a lifestyle (through use of vibrators and pornography) is making this outcome harder to achieve.

A sexually transmitted pathogen can also increase its chances of transmission by disrupting mate guarding. This is the tendency of one mate, usually the male, to keep watch over the other mate. If mate guarding can be disabled or, better yet, reversed, the pathogen can spread more easily to other hosts. This kind of host manipulation has been shown in a non-human species (Mormann, 2010).

Do we see reversal of mate guarding in humans? Yes, it's called cuckold envy—the desire to see another man have sex with your wife—and it's become a common fetish. Yet it seems relatively recent. Greco-Roman texts don't mention it, despite abundant references to other forms of alternate sexual behavior, e.g., pedophilia, cunnilingus, fellatio, bestiality, etc. The earliest mentions appear in 17th century England (Kuchar, 2011, pp. 18-19). This was when England was opening up to world trade and, in particular, to the West African slave trade.

Sub-Saharan Africa has been especially conducive to sexually transmitted pathogens evolving a capacity for host manipulation. Polygyny rates are high, in the range of 20 to 40% of all adult males, and the polygynous male is typically an older man who cannot sexually satisfy all of his wives. There is thus an inevitable tendency toward multi-partner sex by both men and women, which sexually transmitted pathogens can exploit ... and manipulate.

What about sexual orientation?

A pathogen can also become more transmissible by giving its host a new sexual orientation. This strategy would disrupt the existing pair bond while opening up modes of transmission that may be more efficient than the penis/vagina one. Some vaginal strains of Candida albicans have adapted to oral sex by becoming better at adhering to saliva-coated surfaces (Schmid et al., 1995). Certain species that cause bacterial vaginosis, notably Gardnerella vaginalis and Prevotella, seem to specialize in female-female transmission (Muzny et al., 2013; Sobel, 2012).

Finally, there is the hypothesis that exclusive male homosexuality has a microbial origin (Cochran et al., 2000). Its main shortcomings are that (a) there is no candidate pathogen and that (b) exclusive male homosexuality has been observed in social environments with limited opportunities for pathogen transmission, such as small bands of hunter-gatherers across pre-Columbian North America (Callender & Kochems, 1983). On the other hand, there seems to have been a relatively recent shift in European societies from facultative to exclusive male homosexuality, so something may have happened in the environment, perhaps the introduction of a new pathogen (Frost, 2009).

Both male and female homosexuality seem to have multiple causes, but it’s likely that various pathogens have exploited this means of spreading to other hosts.

Conclusion

This is a fun subject when it concerns silly mice or zombie ants. But now it concerns us. And that's not so funny. Can microbes really develop such demonic abilities to change our private thoughts and feelings?

It does seem hard to believe. Perhaps this is an argument for intelligent design. After all, only an all-knowing designer could have made creatures that are so small and yet capable of so much ... things like inducing abortion, breaking up marriages, and altering normal sexual desires. Yes, such an argument could be made.

But I don't think anyone will bother.

 

References

Apari, P., J. Dinis de Sousa, and V. Muller. (2014). Why Sexually Transmitted Infections Tend to Cause Infertility: An Evolutionary Hypothesis. PLoS Pathog 10(8): e1004111.

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1004111

Caldwell, J.C., P. Caldwell, and P. Quiggin. (1989). The social context of AIDS in sub-Saharan Africa, Population and Development Review, 15, 185-234.

https://www.soc.umn.edu/~meierann/Teaching/Population/Readings/Feb%209%20Caldwell.pdf

Callender, C. and L.M. Kochems. (1983). The North American Berdache, Current Anthropology, 24, 443-470.

http://www.jstor.org/discover/10.2307/2742448?uid=3739448&uid=2&uid=3737720&uid=4&sid=21104311299061 

Cochran, G.M., P.W. Ewald, and K.D. Cochran. (2000). Infection causation of disease: an evolutionary perspective, Perspectives in Biology and Medicine, 43, 406-448.

http://www.isteve.com/infectious_causation_of_disease.pdf

Flegr, J. (2013). Influence of latent Toxoplasma infection on human personality, physiology and morphology: pros and cons of the Toxoplasma-human model in studying the manipulation hypothesis, The Journal of Experimental Biology, 216, 127-133. http://jeb.biologists.org/content/216/1/127.full 

Frost, P. (2009). Has male homosexuality changed over time, Evo and Proud, March 5

http://evoandproud.blogspot.ca/2009/03/has-male-homosexuality-changed-over.html

Kuchar, G. (2001). Rhetoric, Anxiety, and the Pleasures of Cuckoldry in the Drama of Ben Jonson and Thomas Middleton, Journal of Narrative Theory, 31 (1), Winter, pp. 1-30. 

Mormann, K. (2010). Factors influencing parasite-related suppression of mating behavior in the isopod Caecidotea intermedius, Theses and Disserations, paper 48

http://via.library.depaul.edu/etd/48 

Muzny, C.A., I.R. Sunesara, R. Kumar, L.A. Mena, M.E. Griswold, et al. (2013). Correction: Characterization of the vaginal microbiota among sexual risk behavior groups of women with bacterial vaginosis. PLoS ONE 8(12):

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0080254 

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.

http://online.liebertpub.com/doi/abs/10.1089/154099903322643901 

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.

http://jcm.asm.org/content/33/11/2920.short 

Sobel, J.D. (2012). Bacterial vaginosis, Wolters Kluwer, UpToDate

http://www.uptodate.com/contents/bacterial-vaginosis 

Zhong, G., L. Lei, S. Gong, C. Lu, M. Qi, and D. Chen. (2011). Chlamydia-Secreted Proteins in Chlamydial Interactions with Host Cells, Current Chemical Biology, 5, 29-37

http://www.ingentaconnect.com/content/ben/ccb/2011/00000005/00000001/art00004

Brainwashed by a microbe?

Toxoplasma gondii (source: A.J. Cann)

It’s long been known that many organisms are parasites, i.e., they survive by living off a host. In recent years we’ve learned that some of them can improve on their life strategy by manipulating their host’s behavior. A fungus, Ophiocordyceps unilateralis, will invade an ant’s brain and direct its host to go to the right height above ground, lock itself into position … and die (Ophiocordycepsunilateralis, 2013). A tapeworm, Schistocephalus solidus, will infect a fish and cause its host to turn white and prefer the water surface, thereby making it an easy prey for a passing bird—the next stage in the worm’s life cycle (Fish diseases and parasites, 2013). A protozoan, Toxoplasma gondii, after being excreted in cat feces and then picked up by a mouse, will infiltrate the brain of its new host and neutralize the fear response to the smell of cat urine. The host thus becomes a way to get back into a cat’s gut—the only place where this protozoan can sexually reproduce (Ingram et al., 2013). 

Ants, fish, mice … The sequence is troubling. What about us? Have some microbes evolved to manipulate our brains? Perhaps, but it would be hard to prove. For one thing, we’re continually being infected by seemingly benign microbes that trigger no symptoms of infection, i.e., fever, pus formation, immune response, etc. They go about their business without our knowing they’re inside us.

For another thing, a microbe can permanently alter our mental wiring and then be removed from our body. The culprit vanishes from the scene of the crime and leaves only a few ambiguous clues. This is the conclusion of a recent study on Toxoplasma gondii. When mice were infected with a weakened strain of this protozoan, they were able to overcome the infection and clear all traces of it from their brains. Yet the behavioral change remained:

[…] our data indicate that infection with all three major North American T. gondii clonal lineages results in loss of innate, hard-wired aversion to feline predator urine in mice. […] permanent interruption of mouse innate aversion to feline urine is a general trait of T. gondii infection that occurs within the first three weeks, independent of parasite persistence and ongoing brain inflammation. (Ingram etal., 2013)

It seems that T. gondii moves around the host’s brain and alters many neurons without actually taking up residence in them, apparently by injecting specific proteins through the cell wall.

Although we’re not a natural host, T. gondii does appear to alter human behavior: 

Toxoplasma-infected subjects differ from uninfected controls in the personality profile estimated with two versions of Cattell’s 16PF, Cloninger’s TCI and Big Five questionnaires. Most of these differences increase with the length of time since the onset of infection, suggesting that Toxoplasma influences human personality rather than human personality influencing the probability of infection. Toxoplasmosis increases the reaction time of infected subjects, which can explain the increased probability of traffic accidents in infected subjects reported in three retrospective and one very large prospective case-control study. […] Toxoplasma-infected male students are about 3 cm taller than Toxoplasma-free subjects and their faces are rated by women as more masculine and dominant. These differences may be caused by an increased concentration of testosterone. Toxoplasma also appears to be involved in the initiation of more severe forms of schizophrenia. At least 40 studies confirmed an increased prevalence of toxoplasmosis among schizophrenic patients. Toxoplasma-infected schizophrenic patients differ from Toxoplasma-free schizophrenic patients by brain anatomy and by a higher intensity of the positive symptoms of the disease. (Flegr, 2013)

T. gondii is being studied for possible behavioral effects mainly because it has attracted so much attention. But we’re probably being manipulated by other parasites. “A large number of parasitic organisms probably exist in helminths, protozoa, fungi, bacteria, archea and viruses that may influence the phenotype of their human host even more than the Toxoplasma. These organisms are, however, still waiting for research teams to engage in a systematic study of their influence on the human host” (Flegr, 2013).

Where to look? Cherchez la femme. Sexually transmitted diseases have much to gain from altering host behavior. I would especially look at bacterial vaginosis, chlamydia, and vaginal yeast.

References 

Fish diseases and parasites. (2013). Wikipedia

http://en.wikipedia.org/wiki/Fish_diseases_and_parasites

Flegr, J. (2013). Influence of latent Toxoplasma infection on human personality, physiology and morphology: pros and cons of the Toxoplasma–human model in studying the manipulation hypothesis, The Journal of Experimental Biology, 216, 127-133. http://jeb.biologists.org/content/216/1/127.full 

Ingram, W.M., L.M. Goodrich, E.A. Robey, and M.B. Eisen (2013). Mice infected with low-virulence strains of Toxoplasma gondii lose their innate aversion to cat urine, even after extensive parasite clearance. PLoS ONE 8(9): e75246. doi:10.1371/journal.pone.0075246

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0075246

Ophiocordyceps unilateralis. (2013). Wikipedia

http://en.wikipedia.org/wiki/Ophiocordyceps_unilateralis#Anti-zombie-fungus_fungus 

The demon within. Part III

Sir John Hawkins (1532-1595) was instrumental in bringing England into the slave trade. Was this trade a source of new pathogens for the English population?

Some vaginal strains of Candida albicans have become better at sexual transmission, such as through improved adhesion to saliva-coated surfaces and through displacement of non-vaginal strains in a new host.

But the adaptations don’t stop there. In my last two posts, I argued that these strains have also become better at sexual transmission by manipulating host behavior. They can cross the blood/brain barrier. We know this. Once inside the control room, why not go one step farther?

C. albicans is an ideal candidate for such evolution. First, It’s common. There’s a large pool of genetic variants for natural selection to act upon.

Second, C. albicans has developed the capacity to spread from one host to another through intimate contact. It thus has every reason to enhance this capacity by rewiring its host’s neural circuits, even at the cost of doing much harm.

As biologist Paul Ewald observed:

For decades medical science was dominated by the doctrine of "commensalisms' - the notion that the pathogen-host relationship inevitably evolves toward peaceful coexistence, and the pathogen itself toward mildness, because it is in the germ's interest to keep its host alive. This sounds plausible, but it happens to be wrong.

[…] If you're a germ that can travel from person to person by way of a "vector," or carrier, such as a mosquito or a tsetse fly, you can afford to become very harmful. This is why, Ewald argues, insect borne diseases such as yellow fever, malaria, and sleeping sickness get so ugly. Cholera uses another kind of vector for transmission: it is generally waterborne, travelling easily by way of faecal matter shed into the water supply. And it, too, is very ugly. (Hooper, 1999)

An infectious organism will thus try to turn its host into a launching pad for infection of other hosts. The long-term survival of any one host no longer matters.

Avenues for future enquiry

Where from?

If a pathogen is responsible for cuckold envy, and if the first recorded mention of this fetish comes from 17th-century England, the point of origin is probably extra-European. Specifically, it would have been a society that came into contact with England through that country’s expansion of foreign trade, exploration, and colonization from the 16th century onward. We’re probably looking at the West Indies, West Africa, the eastern American seaboard, or the territories of the Hudson’s Bay Company.

One of my commenters, Jim Bowery, suggested that the pathogen could have entered England via the West African slave trade. Indeed, an argument can be made that sexually transmitted diseases are most likely to develop in high-polygny societies, such as exist among the ‘female-farming’ peoples of sub-Saharan Africa. On the one hand, the polygynous male cannot sexually satisfy all of his wives. On the other, many young males are locked out of the marriage market, the result being a lot of sex on the sly.

As anthropologist Pierre van den Berghe pointed out:

The temporary celibacy of young men in polygynous societies is rarely absolute, however. While it often postpones the establishment of a stable pair-bond and the procreation of children, it often does not preclude dalliance with unmarried girls, adultery with younger wives of older men, or the rape or seduction of women conquered in warfare. Thus, what sometimes looks like temporary celibacy is, in fact, temporary promiscuity. (van den Berghe, 1979, pp. 50-51).

Do other STDs manipulate human sexual behavior?

Is manipulation of sexual behavior a logical adaptation for STDs? If so, have other human STDs evolved in this direction? No one seems to have asked the question. Admittedly, cause and effect are hard to tease apart. Do STDs correlate with sexual promiscuity solely because a promiscuous person is more likely to catch one? Which is the chicken and which is the egg?

Research on insects has turned up several cases of an STD manipulating host behavior in order to facilitate sexual transmission.

Behavioural changes associated with parasitic infection are well known, and at least some of these appear to be adaptations on the part of the parasite to increase transmission (Moore, 1993, 2001; Poulin, 1994a, b, 1998a, 2000). Four recent studies of insect STDs are relevant here. McLachlan (1999) showed that male midges (Paratrichocladius rufiventris) infected with the mite Unionicola ypsilophora were more likely to be in mating pairs than uninfected males. As discussed earlier, the mites rely on female midges to return them to water to complete their life cycle. If they find themselves on a male midge, therefore, they are effectively dead unless their host mates with a female […].

Raina et al. (2000) found that Hz-2V infected female corn earworm moths Helicoverpa zea produce two to three times more sex pheromone than uninfected female moths, possibly enhancing their ability to attract male moths, although they also reported that these animals vigourously resisted mating. Abbot & Dill (2001) found that male Labidomera clivicollis beetles infected with the mite Chrysomelobia labidomera were more likely to displace other males from mating pairs, which again could be interpreted as being adaptive manipulation of the host by the parasite to increase transmission. Webberley et al. (2002), by contrast, found that infection of Adalia bipunctata with Coccipolipus hippodamiae did not have any effect on the mating behaviour of the host. (Knell & Webberley, 2004)

References

Hooper, J. (1999). A new germ theory, The Atlantic Journal, February

http://gc.homeunix.net/

Knell, R.J., and K.M. Webberley. (2004). Sexually transmitted diseases of insects: distribution, evolution, ecology and host behaviour, Biol. Rev., 79, 557–581.

van den Berghe, P.L. (1979). Human Family Systems. An Evolutionary View, New York: Elsevier.

The demon within. Part II

Preferential binding by Candida albicans to various types of cells in a macaque brain (Denaro et al., 1995).

In my last post, I examined the relationship between sexual behavior and vulvovaginal candidiasis (VVC), a condition that occurs when certain strains of vaginal yeast (Candida albicans) become highly virulent. Clearly, the relationship is not a simple one of cause and effect. Occurrence of VVC correlates not with vaginal sex but rather with non-vaginal sex, i.e., fellatio, cunnilingus, and masturbation. There is also no significant association between VVC and the presence of C. albicans in the male partner, including his oral cavity.

The evidence suggests that the direction of causality runs in the opposite direction. These strains of C. albicans do not enter a woman’s vagina via fellatio, cunnilingus, or masturbation, at least not primarily. Instead, they may be manipulating the host’s behavior by weakening her sexual inhibitions and inciting her to maximize contact between vaginal fluids and colonizable sites on her partner’s body.

This scenario is all the more likely because vaginal yeast is common and thus provides a large pool of organisms for natural selection to act upon. Vaginal strains of C. albicans also show evidence of adaptation to saliva-based transmission, i.e., they 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 (Schmid et al., 1993).

So these vaginal strains became better at spreading from a female host to a new male host. But what then?

Did they then evolve the capacity to make the male host more sexually promiscuous? Perhaps. But keep in mind that male-to-female transmission is much less effective than female-to-male transmission. Although VVC can develop on male body sites, the vagina is by far the primary site for C. albicans colonization and infection.

From the standpoint of C. albicans, the optimal scenario would be one where the female host goes on to infect other males. What can her regular male partner do to bring this about?

He could cease all mate-guarding behavior. In plain English, he could stop being jealous. He could even encourage her to have sex with other men.

This kind of parasite manipulation does occur in one organism, the isopod Caecidotea intermedius. A parasite, Acanthocephalus dirus, infects this isopod as an intermediate host in order to enter its final host, one of several freshwater fishes. When the parasite is still soft and immature, it cannot survive a fish eating its isopod host. It thus seeks to reduce this risk by suppressing conspicuous host behaviors, like mate guarding. Later, when the parasite becomes hard and mature, it can survive consumption of its host and, in fact, seeks this outcome. It now stimulates conspicuous behaviors, like mate guarding, and changes its host’s pigmentation to increase visibility (Mormann, 2010).

‘Cuckold envy’

In humans, suppression of mate guarding seems to match a behavior called “cuckold envy”—a sexual fetish where a man is not only indifferent to being cuckolded but actually derives pleasure from cuckoldry. How prevalent is this fetish? A Google search for the term “wife breeding” turned up 793,000 hits, many of which corresponded to videos that have been specially developed for this market.

Cuckold fetishists tend to center their fantasies on black men, perhaps because darker skin and heavier facial features help evoke the image of a rival male. In fact, some of these fetishists have rebranded themselves as members of the “interracial community,” presumably to gain social acceptance and to blend into the broader antiracist movement. Such individuals may be behind the apparent mainstreaming of interracial porn, as seen for example in the antiracist Swedish video Blanda Upp! (2010). One might draw parallels here between lesbian activists and the feminist movement …

This sexual fetish seems to be sufficiently common to foster speculation about a possible Darwinian (or pseudo-Darwinian) cause:

In his book Sperm Wars, biologist Robin Baker speculated that the excitement and stimulation of the cuckolding fetish emerges from the biology of sexuality and the effects of sexual arousal on the brain. According to his theory, when a man believes that his female mate may have been sexual with another man, he is prompted by biological urges to copulate with the female, in an effort to "compete" with the other man's sperm. (Cuckold – Wikipedia)

Baker’s theory fails to explain why most men have precisely the opposite emotional reaction, i.e., feelings of hurt, anger, and rage.

This seems to be true in all human societies. A search for the term ‘cuckold’ in the Human Relations Area Files (HRAF) turned up references to 32 cultures. All of the references indicated intensely negative feelings in the cuckolded men, as seen in the following examples:

Yanomamö (South America)
Discovery of liaisons by the cuckold inevitably leads to club fighting between the factions of the lover and the husband. The woman involved usually suffers more than either of the male principals in the fighting that follows, as women are severely punished by their husbands. The punishment usually consists of a beating with a club, but men frequently shoot their unfaithful wives with barbed arrows in a non-vital area of the body, such as the buttocks or leg. In one instance I witnessed, the enraged husband struck his wife in the face with a burning log, severely burning her mouth. Burning is a common punishment, and many women bear immense scars from wounds inflicted by enraged husbands. (Chagnon, 1967, pp. 91-92)

Tukano (South America)
Adultery or even flirting with a ceremonial friend’s spouse is a principal cause for a break in this otherwise very stable relationship. A ceremonial friend who has been wronged by his partner retaliates by entering the offender’s house to break or carry off everything belonging to him except the hammock. This act of vandalism declares the friendship broken. Eternal animosity succeeds it. (Goldman, 1963, p. 132).

Quechua (South America)
The two strongest insults that Saraguro males can fling at each other (or curse behind their backs) are maricón (homosexual) and cabrón (literally, he-goat, but meaning cuckold). (Belote, 1978, p. 79)

Pashtun (Asia)
[…] for daows (“cuckold” and by extension “dupe”) is the most serious curse and adultery rather than incest the crime of horror. Among the most serious offenses against Pakhtun social order, adultery causes more trouble, mobilizes more sanctions, and ramifies further than any other Pakhtun delict. (Anderson, 1982, p. 401)

Greeks (Europe)
Conversely, the act of disobedience by which she damages her husband most severely is adultery. In adultery she makes her husband a cuckold (κερατ□ς), one who wears a horn. ‘She puts horns on him’ (το□ βάζει κέρατα), it is said. The implication that the cuckold wears a horn may be an ironical allusion to the sexual potency which his wife's action suggests he does not possess (Campbell, 1964, p. 152)

Azande (Africa)
[…] he is certain that she has a lover and he broods in dark anger till he can discover who has made him a cuckold. (Evans-Pritchard, 1937, p. 268)

Men seem to tolerate cuckoldry the most in societies with low paternal investment, i.e., ‘female farming’ societies of sub-Saharan Africa and Papua-New Guinea. But I found no HRAF reference to men actually feeling pleasure at the idea of being cuckolded. The closest match was the custom of ‘wife exchange’ among the Inuit and some Amerindian peoples, like the Comanche:

In many cases, the levirate as practiced by the Comanches approximated polyandry, for brothers lent each other their wives. This “anticipatory levirate” reflected an attitude of camaraderie and denial of sexual jealousy between two brother-warriors.

[…] Women, however, were not free to initiate liaisons. Adulterous men could be sued for damages and customarily made payments in horses or other goods, but the women in question bore the brunt of the shame, and her punishment might include disfigurement (usually slitting of the nose) or death at the hands of her husband. When pressing his case, the cuckold would address his wife's lover as “brother,” an ironic reference to the proper conditions for wife sharing. (Gelo, 1986, pp. 29-30)

When I switched from a cross-cultural search to a cross-historical one, the oldest references to cuckold envy seemed to be in plays from 17th-century England. In these plays, the cuckold anxiety of earlier periods gives way to cuckold envy:

In A Mad World, My Masters Middleton fully realizes some of the subtle psycho/social details that Jonson develops with the potential cuckold Kitely in Every Man in His Humor. The perverse pleasure that Jonson's acquiescent cuckold derives from his subject position is latent, as Martin Semour-Smith notes, in the etymology of Kitely's name: "Mr. Sale draws attention in his edition to the dialect word 'kittle', meaning 'ticklish' ie. 'hard to deal with, touchy'; but he has missed the verb 'to kittle': 'to stir, with feeling or emotion, usually pleasurable.'" Seymour-Smith continues, noting that it "was also clear to Jonson that Kitely perversely enjoyed his wife less as a direct sexual object than as the indirect object by which he might be cuckolded" (xii, xiii). (Kuchar, 2001, p. 18)

In Every Man in His Humor, the lead character notes the strangeness of his fetish:

Who will not judge him worthy to be robbed,
That sets his doors wide open to a thief,
And shows the felon, where his treasure lies?
(Kuchar, 2001, p. 19)

If 17th-century England is the ground zero for cuckold envy, where was it beforehand? In some yet unknown human population? Or was it in a nonhuman species? Perhaps we are looking at an evolutionary trajectory similar to that of the AIDS virus, i.e., a lengthy period of co-adaptation in a nonhuman population followed by transfer to a human population and increased virulence.

References

Anderson, J.W. (1982). Social structure and the veil: comportment and the composition of interaction in Afghanistan, Anthropos, 77 (3/4), 397.

Belote, L. (1978). Prejudice and pride: Indian-White relations in Saraguro, Ecuador,
Ann Arbor, Michigan: University Microfilms International.

Campbell, J.K. (1964). Honour, family and patronage: a study of institutions and moral values in a Greek mountain community, Oxford: Clarendon Press.

Chagnon, N. (1967). Yanomamö warfare, social organization and marriage alliances,
Ann Arbor, Mich.: University Microfilms.

Cuckold – Wikipedia, http://en.wikipedia.org/wiki/Cuckold

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.

Evans-Pritchard, E.E. (1937). Witchcraft, oracles and magic among the Azande,
Publisher: Oxford: Clarendon Press.

Gelo, D. (1986). Comanche belief and ritual, Ann Arbor, Mich.: University Microfilms International.

Goldman, I. (1963). The Cubeo: Indians of the Northwest Amazon, Urbana, Illinois: University of Illinois Press.

Kuchar, G. (2001). Rhetoric, Anxiety, and the Pleasures of Cuckoldry in the Drama
of Ben Jonson and Thomas Middleton, Journal of Narrative Theory, 31 (1), Winter, pp. 1-30.

Mormann, K. (2010). Factors influencing parasite-related suppression of mating behavior in the isopod Caecidotea intermedius, Theses and Disserations, paper 48
http://via.library.depaul.edu/etd/48

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.

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.