Good news on Toxoplasmosis Treatment

ResearchBlogging.orgToxoplasmosis is a disease caused by Toxoplasma gondii, a protozoan. It is very common in cats, but also known in humans. This is the disease people worry about when they have children and cats in the same house. Don’t let your child eat cat poop! Pregnant women should avoid this disease, as there are especially bad outcomes for the offspring.The good news is this: A new drug currently in testing phase for treating malaria is very effictrive against T. gondii. This new drug, a form of triazine, goes by the memorable name JPC-2067-B.This finding is recently reported in PLoS Neglected Tropical Diseases (an On Line Open Access Journal).Here is the more or less comprehensible “author’s summary” (essentially, an “abstract” written in somewhat more understandable English) from the paper:

Toxoplasmosis is a neglected tropical disease, an emerging disease as well as a significant problem in developed countries causing a substantial health burden. Better medicines with less toxicity are greatly needed. Herein, we found that a novel triazine currently being advanced to clinical trials for malaria, JPC-2067-B, is highly effective against T. gondii. We demonstrate that JPC-2067-B inhibits T. gondii growth in culture (IC50 20 nM), inhibits the purified enzyme (IC50 6.5 nM), is more efficacious than pyrimethamine, and is cidal in vitro. JPC-2067-B administered parenterally and the orally administered pro-drug (JPC-2056) are also effective against T. gondii tachyzoites in vivo. A molecular model of T. gondii DHFR-TS complexed with JPC-2067-B was developed. We found that the three main parasite clonal types and isolates from South and Central America, the United States, Canada, China, and Sri Lanka have the same amino acid sequences preserving key binding sites for the triazine. Toxicology data are presented. JPC-2056/JPC-2067-B have potential to be more effective and less toxic treatments for toxoplasmosis than currently available medicines.

A triazine is an organic chemical with properties that make it useful in a number of different areas, from use in insecticides to use in dyes. “Cidal” means it can kill stuff. Like homicidal. To be administered parenterally means to be administered in a way other than by eating it, like into tissue or into the blood. In other words, administered in a way that does not subject the drug (or whatever) to the slings and arrows of the digestive system.Here’s a picture of the drug:i-21301b6dc7687afe3e8e21eaa5de4627-toxoplasmosis_drug.jpgThis drug works by inhibiting the activity of the enzyme dihyrofolate reductase, which is apparently unique to this kind of portozoan (including the malaria parasite). There is a similar enzyme in humans, of course, we do all descend from a common ancestor, after all. But since we descended with modification, as discussed by Darwin, these enzymes are not exactly the same. So this new drug affects the version of the enzyme in the parasite but not (much) the version of the enzyme in humans.According to one of the study authors (McLeod), toxoplasma infection is

…probably the most common parasitic infection in the world, causing very significant disease in those who have immature immune systems or who are immune-compromised….An infected cat can excrete up to 20 million oocysts over two weeks…Even a single oocyst is infectious and they can remain infectious in water for up to six months and in warm moist soil for up to a year.


University of Chicago Medical Center Press Release

Mui, E.J., Schiehser, G.A., Milhous, W.K., Hsu, H., Roberts, C.W., Kirisits, M., Muench, S., Rice, D., Dubey, J.P., Fowble, J.W., Rathod, P.K., Queener, S.F., Liu, S.R., Jacobus, D.P., McLeod, R., Matlashewski, G. (2008). Novel Triazine JPC-2067-B Inhibits Toxoplasma gondii In Vitro and In Vivo. PLoS Neglected Tropical Diseases, 2(3), e190. DOI: 10.1371/journal.pntd.0000190

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13 thoughts on “Good news on Toxoplasmosis Treatment

  1. This is for treatment in humans right?Also, what makes it a tropical disease? Not sure why this term applies here. It’s really a lot more widespread than that.

  2. Good questions!!!Yes, this for people.Why is it a tropical disease? Now you are opening a can of worms. Why is Malaria a tropical disease? Because mainly people in the tropics get it. But 100 years ago, it was very very common in Mediterranean climates and frequent/occasional in temperate climates. So malaria is a tropical disease because we’ve trimmed it out of the temperate regions.I was in a grant review meeting once where someone noted that a particular proposal for work in Afghanistan would be better off submitted to the “South of the Equator” committee. I noted that Afghanistan is north of the equator. I was told this was not the point … Still working on that one.This might be a parasite that evolved and emerged in cats. Cats are tropical: there are far more species of cats in the tropics than temperate regions.But there are still many species of Mediterranean and temperate cats, and some of the “tropical” cats are only tropical because we’ve wiped out the temperate populations (like lions!)P:erhaps there is special funding for tropical diseases?

  3. Cats, well domestic cats, are more of a Mediterranean species, having been domesticated in the Levant during the neolithic. Also, there is some thought, mirrored in Zimmer’s book on parasites, that Toxoplasma may also reflect an earlier human interaction with cats (ie food for them), which I am not quite sure would necessarily be tropical either.I assumed it was something relatively arbitrary, which seems to be your take on it at least.

  4. The domestic cat comes from a wild species that is not Levantine specifically. In the Levant, yes, but that would be like calling Americans “people from Paramus New Jersey”There are about 15 genera of cats, about 9 are mainly tropical and 2-3 are tropical extending into temperate regions. By species, way more cats are tropical than not.On the other hand, just as the term “tropical” is a bit strange here, the idea that Toxoplasma spp are generally found in cats is being taken for granted here. I’m not sure everyone has checked all the cats.

  5. While no cat is immune, and pregnant women need to be extravigilant, it’s useful to know that toxoplasmosis is mostly a disease of cats that frequent the outdoors. If Puss is a strictly indoor cat, the chances she’ll have it are very low.

  6. Thanks for this Greg – a couple of commenters have asked me about Toxo-treatments and it’s good to now have somewhere to point them too. Incidentally, I would be interested to see what you made of this paper that came out in Biology Letters last year and suggested that Toxo infection could have a small but significant influence on human culture.Also: “…probably the most common parasitic infection in the world,” – presumably this means that it’s the most common parasitic infection in humans in the world? I would have thought that overall, arthropod pathogens like Wolbachia would be more common?

  7. Ed,Yes I read that when it came out. It makes sense. It is probably the case that more parasites manipulate their hosts than we realize as yet. Since this parasite is not really adapted to manipulating human behavior in a way, but is (if in fact it is) adapted to manipulate mice, or whatever, we would expect odd results that humans would then translate into meaningful things with labels (like “loyalty”) … because we translate everything into a form that can be described with meaningful labels.

  8. Toxoplasmosis is also becoming a problem for sea otters on the California coast, with as many as 40% being seropositive. (Dave Jessup has published on this). This really is a neglected disease, not only of domestic but of wild cats as well. Not only would a treatment be good, but so would a vaccine. I wonder if anyone could get the Gates Foundation interested in wildlife diseases?

  9. i am so happy to hear good news about toxoplasmosis treatment. I am not immunocompromised, actualy i do think i have quite a strong immune system, but since i was infected with tozxoplasmosis, i have episodes whan i prefer to b ded due to the complezity of the symptoms.Now, can anyone tell me where should i write in order to benefit of this kind of treatment?i would b a happy camper again!u can drop me an e-mail at vulcanneles@yahoo.com, or udarlunar@yahoo.comoh, i will pray for those guys all tha days of my life if i get cured!!!!!

  10. Hi Greg, i was reading a mes here on your blog, i don’t know what xacly this toxoplasma gondi’s doing, mabe is not able to manipulate the humans, but i want to share from my experience few things. whenever i am sick with god know’s what, flu or cold or .., i do experience another recurence episode from thoxoplasmosis. SO, what hap than? i’m like under hypnosis, i have no fear, i drive mechanical, my reactions are slow,can not focus enough, light sensitivity and i do not experience fear. Also than, my liver functions become unnormal, i feel intoxicated , tired, sleepy, joint pain ( actualy i thought that i might have some sort of hepatitis, i’m clear of any of those viruses anyway).i just thought that might be good to mention those things!cheers!and all the best!!

  11. Look what googling your old papers comes up with Greg.
    I contributed a little bit on the malaria end of things but you have done an excellent job summarizing this work. The JPC#### name is for Jacobus Pharmaceutical Company and they have made many different dihydrofolate reductase (DHFR) inhibitors over the years. When one hits the market I’m sure they’ll get a snazzier name.
    The combined DHFR-TS enzyme (dihydrofolate reductase-thymidilate synthase, as found in these parasites) is different enough from human DHFR (one function enzyme) that the protein sequences don’t bear any resemblance to each other and could have evolved separately to do the same function. As these are enzymes that help make nucleotide precursors, inhibiting the right ones can lead to the inability to properly make DNA which causes parasites to die.
    I’m not familiar with the actual numbers, but I think that the vast majority of cat owners have latent toxoplasmosis. A cat’s normal grooming techniques hit all the surface areas and, well, the bum. You spend a bit of time petting cats or changing infected litter boxes and then you end up with the parasite on you and then in you. Toxo persists in the environment for a long time as well so spread from cat to cat can be as easy as contacting an area another cat has been. Until the immune system beats a toxo infection into a latent stage the waves of sickness can put a good deal of stress on the body – which is one of the reasons pregnant women should be sure to avoid new toxo exposure while already established but latent infections are less deadly to the growing baby.
    As for the most recent postings from users, many, many people have toxo and it’s not just people with AIDS that experience runaway toxo infections, even a temporary immune deficiency like that after a strong sickness can allow toxo infections to become activated.
    Luckily, gates foundation funding has hit many tropical diseases and it currently funds investigations into toxo too. I think malaria still gets the majority of the funds but research into many other diseases are also funded through this organization.

  12. Look what googling your old papers comes up with Greg.
    I contributed a little bit on the malaria end of things but you have done an excellent job summarizing this work. The JPC#### name is for Jacobus Pharmaceutical Company and they have made many different dihydrofolate reductase (DHFR) inhibitors over the years. When one hits the market I’m sure they’ll get a snazzier name.
    The combined DHFR-TS enzyme (dihydrofolate reductase-thymidilate synthase, as found in these parasites) is different enough from human DHFR (one function enzyme) that the protein sequences don’t bear any resemblance to each other and could have evolved separately to do the same function. As these are enzymes that help make nucleotide precursors, inhibiting the right ones can lead to the inability to properly make DNA which causes parasites to die.
    I’m not familiar with the actual numbers, but I think that the vast majority of cat owners have latent toxoplasmosis. A cat’s normal grooming techniques hit all the surface areas and, well, the bum. You spend a bit of time petting cats or changing infected litter boxes and then you end up with the parasite on you and then in you. Toxo persists in the environment for a long time as well so spread from cat to cat can be as easy as contacting an area another cat has been. Until the immune system beats a toxo infection into a latent stage the waves of sickness can put a good deal of stress on the body – which is one of the reasons pregnant women should be sure to avoid new toxo exposure while already established but latent infections are less deadly to the growing baby.
    As for the most recent postings from users, many, many people have toxo and it’s not just people with AIDS that experience runaway toxo infections, even a temporary immune deficiency like that after a strong sickness can allow toxo infections to become activated.
    Luckily, gates foundation funding has hit many tropical diseases and it currently funds investigations into toxo too. I think malaria still gets the majority of the funds but research into many other diseases are also funded through this organization.

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