Is latent Toxoplasmosis worth doing something about?

[jsalvatier]

Toxoplasmodi gondii is a parasitic protozoa who’s primary host is cats but also infects other mammals, primarily mice and rats but including humans, as part of its life cycle. Infection by Toxoplasmodi gondii is called Toxoplasmosis and may be acute (flu like symptoms) or latent.

Toxoplasmosis is extremely common. Worldwide, about 30% (US 11%; France 88%!) of people about of people have Toxoplasmosis.

Toxoplasmosis is known to cause behavioral changes in rats:

It has been found that the parasite has the ability to change the behaviour of its host: infected rats and mice are less fearful of cats—in fact, some of the infected rats seek out cat-urine-marked areas. This effect is advantageous to the parasite, which is able proliferate if a cat eats the infected rat and thereby becomes a carrier.

Observational studies suggest that latent Toxoplasmosis may also cause behavioral changes in humans (source paper). The observed differences between infected people and non-infected people include:

• Decreased novelty seeking behavior

• Slower reactions

• Lower rule-consciousness and greater jealousy (in men)

• Greater warmth, conscientiousness and moralistic behavior (in women)

It’s also suspected by some of being a cause of Schizophrenia.

Obviously some or all these may be due to unobserved 3rd causes.

There haven’t been any randomized studies yet, as far as I know. It seems like such studies would be easy to conduct rigorously since a high fraction of the population is already infected. For example, by finding people who are already infected and randomly cure some of them. This kind of experiment is even pretty close to how you would expect the information to be used.

I’ve been around cats a fair amount and the base rate is high in the US, so my chances of having latent Toxoplasmosis seem fairly high. Thus I am curious whether this is worth doing something about. Diagnosis sounds like it is fairly simple (PCR on blood samples). It’s easy enough so that it can be done in large scale studies at least. Treatment is done with atovaquone and clindamycin, which appear to be relatively inexpensive.

I’d expect the effects to be net negatives (most random changes are detrimental) and even if the behavioral effects are smallish, the effects over a lifetime will add up. Has anyone else gotten tested and/​or treated for latent Toxoplasmosis? Is it worth it?

[printing-spoon]

Is there any research on whether curing the infection actually undoes the damage?

[Logos01]

http://​​www.davidbrin.com/​​givingplague.htm

That is all.

[MBlume]

Thanks for that, hadn’t seen it before.

[Morendil]

My wife got a routine test for toxo during her first pregnancy, and we had a bit of a scare when that came back positive; she needed an amnio, months of antibiotics, regular monitoring. Of course being French we already had a high base rate, but we were also cat people back then.

Just how large are those statistically significant effects, would be my first question. How well replicated the studies, my second. I wouldn’t bother doing much about something that is small or somewhat anecdotal.

[jsalvatier]

From this paper

Consistent and significant differences in Cattell’s personality factors were found between Toxoplasmainfected and -uninfected subjects in 9 of 11 studies, and these differences were not the same for men and women.

and

Those with latent infection performed significantly more poorly (analysis of covariance, P = 0.011) and appeared to lose their concentration more quickly, although the effect of the infection was modest and explained less than 10% of the variability in performance. Similar results were recently obtained in 2 (unpublished) studies performed on 439 blood donors and 623 military servicemen.

Explaining ~10% of the variance actually seems fairly high to me.

[Morendil]

Explaining ~10% of the variance actually seems fairly high to me

How high is the sky? That is, 10% of the variance might be a lot, but what is the variance like? In other words, what magnitude of effect should you expect from getting cured of toxo? How many IQ points would that get you? (Or whatever scale matters to you...)

[jsalvatier]

That’s true, I’m not sure.

[Kevin]

I did a lot of research into this, and the answer is sadly no. There is no good, safe treatment for toxoplasmosis. The current best treatment is simulataneous dosing of two ultra-strong antibiotics for two months. Such a course wreaks havoc on the body, and is properly only recommended in severely immuno-compromised individuals (late-stage HIV, etc.).

[gwern]

Seems to be correct. From The Atlantic:

As concerns about the latent infection mount, however, experts have begun thinking about more-aggressive steps to counter the parasite’s spread. Inoculating cats or livestock against T. gondii might be one way to interrupt its life cycle, offers Johns Hopkins’ Robert Yolken. Moving beyond prevention to treatment is a taller order. Once the parasite becomes deeply ensconced in brain cells, routing it out of the body is virtually impossible: the thick-walled cysts are impregnable to antibiotics. Because T. gondii and the malaria protozoan are related, however, Yolken and other researchers are looking among antimalarial agents for more-effective drugs to attack the cysts. But for now, medicine has no therapy to offer people who want to rid themselves of the latent infection; and until solid proof exists that Toxo is as dangerous as some scientists now fear, pharmaceutical companies don’t have much incentive to develop anti-Toxo drugs.

[dlthomas]

Obviously some or all these may be due to unobserved 3rd causes.

Cat people vs. dog people?

[jsalvatier]

Yes, the one that really catches my attention is “slower reactions”, though since that’s something that’s observed in rats as well and explained 10% of the variance in reaction times (see the paper).

[dlthomas]

Agreed—my comment was about ²⁄₃ in jest.

[Broggly]

According to Peter Watt’s blog toxoplasmosis doesn’t actually reduce fear in rats, but instead causes the odor of cat urine to activate sexual arousal pathways as well as fear pathways. The overall effect causes them to approach the smell of cat urine.

[gwern]

Phenotype screens off genotype, as the genetic saying goes. Infection reduces Openness? Well, do you have some reason to want to increase your Openness? (Are you also looking into acquiring some psilocybin, which might actually be cheaper than treatment if Morendil is generalizable about it taking ‘months’ ?)

Slower reactions—would that significantly improve your life? I’m a cat person so I may be infected, but I can’t say I often think (outside of taekwondo) ‘I wish I had 10% faster reflexes!’

The greater jealousy thing may be an issue.

[roystgnr]

Car crashes are still responsible for a million deaths and something like a trillion dollars in damages every year. Reducing the number of people on the road with slowed reaction times would only have to make a very small relative dent in that to have a very large absolute effect.

On the other hand, toxoplasmosis treatment is almost certainly not the low-hanging fruit here—better cultural attitudes and vehicle safety features already make driving much safer in some places than in others, and self-driving cars may make the very concept of driver reaction time moot in a generation.

[gwern]

Treatment on a large scale presents different concerns than on a small scale.

1. Specifically, what about reinfection? AFAIK human-to-human infection is not how toxo is spreading, and so a mass treatment plan would not affect the reinfection rate or give people any sort of immunity. So either the benefit will be temporary as people are reinfected by their cats, or this is a perpetual ongoing public health commitment on the scale of vaccinations.

2. And the treatment uses antibiotics. I suspect more lives are saved every year by antibiotics than are taken by cars, many more lives. (IIRC, there’s around 50k car deaths annually in the US; I’d guess there are way more infections cured than that.) What’s the risk of developing antibiotic resistance in toxo or anything people might have? (We’re not risking any of the last-resort antibiotics are we?) And antibiotics aren’t perfect, they can have serious side-effects.

So, I’m saying this is very far from a no-brainer on an individual basis, and it’s even worse on a population level.

[MBlume]

Self-driving cars look like an excellent lever point to increase standard of living and economic productivity. Unfortunately, I strongly suspect they will be regulated out of existence for about a decade after the technology is up to snuff.

[MattTagg]

I strongly suspect they will be regulated out of existence for about a decade after the technology is up to snuff.

I wouldn’t be so sure about that.

Self-Driving Cars Approved By California Legislature

http://​​www.huffingtonpost.com/​​2012/​​08/​​30/​​self-driving-cars_n_1845018.html

[DanielLC]

It explains 10% of the variance. It can take you from the 45th percentile to the3 55th. It’s probably decreases it by less than 10%.

[CronoDAS]

‘I wish I had 10% faster reflexes!’

That would probably make me better at video games...

[Peter_de_Blanc]

Sounds like you should do more Tae Kwon Do.

[gwern]

Yeah. But thinking about it some more, TKD was probably not the best example—I actually have thought, quite a few times, during fencing that ‘man I wish I had faster reflexes, he’s ridiculous’. (Weapons are a lot faster than legs.)

[Peter_de_Blanc]

My fencing coach emphasizes modeling your opponent more accurately and setting up situations where you control when stuff happens. Both of these skills can substitute somewhat for having faster reflexes.

[Multipartite]

Depending on the cost, it at least seems to be worth knowing about. If one doesn’t have it then one can be assured on that point, whereas if one does have it then one at least has appropriate grounds on which to second-guess oneself.

(I have been horrified in the past by tales of {people who may or may not have inherited a dominant gene for definite early disease-related death} who all refused to be tested, thus dooming themselves to a lives of fear and uncertainty. If they were going to have entirely healthy lives then they would have lived in fear and uncertainty instead of being able to enjoy them, and if they were giong to die early then they would have lived in fear and uncertainty (and stressful, gradually-increasing denial/​acceptance) rather than quickly getting used to the idea, resetting their baseline, getting their loose ends in order and living as appropriate for their expected remaining lifespan. Whether or not one does (or can do) anything about one’s state doesn’t change that oneself having more information about oneself can (in most circumstances?) only be helpful.)

[gwern]

...Their findings suggest that this microbe is particularly insidious-the changes it makes may be permanent.

To replicate, Toxoplasma must invade a cell. Stanford parasitologist John C. Boothroyd has dubbed this process “kiss and spit.” The parasite first attaches to the host cell (the kiss) and then releases an arsenal of foreign proteins into that cell (the spit). Toxoplasma then enters the host cell, and the injected proteins help it redecorate its new home. The parasite’s first act is establishing a protective bubble in which it can divide in peace without attacks from host cell proteins. (Later, during the infection’s dormant stage, these bubbles thicken to become tissue cysts.) The parasite then moves the mitochondria, which serve as the cell’s powerhouses, to be adjacent to the protective bubble. It also acts on the cell’s DNA, inhibiting the expression of some host genes while activating others. Finally, Toxoplasma modifies host proteins to alter their function and inhibit the immune response.

Altogether, these modifications ensure that the host cell will live a long time and supply energy to the parasite, without alerting immune cells that a parasite has moved in. Although these findings have principally been made with rodents, work with human cell cultures suggests that the same changes probably take place in the human body. In our labs, we are studying how Toxoplasma replicates and interacts with its host in an effort to develop new drugs to treat this infection.

Remarkably, a study that Boothroyd’s group published in 2012 showed that Toxoplasma not only spits into the cells it invades but also spits into cells that it does not infect. This behavior-spitting proteins in passing without lingering in the cells-is a recent discovery in the microbial world. Consequently, cells that are not harboring Toxoplasma contain parasite proteins that can co-opt and reprogram that cell. In the brains of infected mice, cells that have been spat into but not invaded are even more common than ones containing parasites. This widespread scattering of proteins means Toxoplasma can affect its host at a global level, making it easier to imagine how the parasite might manipulate the activity of an entire animal. In 2013 biologist Michael Eisen of the University of California, Berkeley, and his colleagues found that a rodent’s strange attraction to cat odors may be permanent, even if there are no longer signs of infection. In one study, Eisen exposed mice to a mutant strain of the parasite that does not appear to form brain cysts. Four months later the infected mice had no detectable parasites in the brain, yet they were still attracted to cat odors instead of repelled.

--”Common Parasite Could Manipulate Our Behavior: Toxoplasma gondii, a parasite inhabiting the brains of an estimated three billion people, could tweak its host’s behavior”, SciAm

[gwern]

More coverage: http://​​www.theatlantic.com/​​magazine/​​archive/​​1969/​​12/​​how-your-cat-is-making-you-crazy/​​8873/​​?single_page=true

[leo_gri]

Might not be so bad after all. (Personal hypothesis : however the trial was only made in New Zealand, so the parasite might not be exactly the same that in other parts of the world . I’m also wondering if the opposite effect on males and females could cancel each other out on a large scale study.)

Before reading this article, I was thinking of an “animal urine blind test” as a prediagnosis. An absence of disgust for cat urine could mean you’re likely to be infected (however, in this article, the monkey were the natural prey of Leopard whereas humans in western regions are obviously not cat’s preys). What do you think of it ? Any testimonies from people who know whether they are infected or not ? (I realize it’s not very useful, because there is no good way to get rid of Latent Toxoplasmis and because it’s probably not a very big deal. I wanted to do this mostly out of curiosity and my main interest is to know whether it could be a real instrument of diagnosis)

[jsalvatier]

http://​​www.doctortipster.com/​​10789-recent-study-links-t-gondii-parasite-to-suicidal-attempts.html

[RHollerith]

It would be a mistake to assume that worthwhile tests and treatments are available.

Prevention usually has better bang for the buck for things like this.