A recent paper about toxoplasmosis in the journal Biology Letters (Thomas et al. 2011) has attracted a lot of attention because it reports a possible link between this cat-associated parasite and brain cancer in people.

Toxoplasma gondii is a protozoal parasite. Cats are the natural host and can (but rarely do) pass the parasite oocysts (eggs) in their feces. People can be infected by ingestion of Toxoplasma oocysts that have been outside of the cat long enough (24 hours or more) to develop into an infectious form. Human Toxoplasma exposure is common, although this is typically not acquired directly from pet cats.  Adult cats rarely shed oocysts, whereas exposure from contaminated soil (e.g. from working in a garden and not washing ones hands afterward) or undercooked meat of various kinds are also important sources in different areas. Almost always, when a person gets infected, disease does not occur. Rather, the immune system contains the parasite, but is unable to kill it completely.  The parasite therefore often enters a dormant state forming small cysts in various body tissues, including in the brain.

Most concern regarding Toxoplasma involves pregnant women who have not been previously exposed to the parasite (and therefore have no antibodies to fight it off quickly). If they become infected during pregnancy, serious infection of the fetus can occur. Another problem in people is Toxoplasma encephalitis, a severe brain condition that occurs most commonly in people with compromised immune systems (e.g. HIV patients), typically from re-activation of dormant Toxoplasma. 

The recent paper by Thomas et al raises an additional concern: brain cancer. The basic premise of the paper is that some types of persistent infections might be able to induce mutations at the cellular level, resulting in cancer. Since Toxoplasma can cause longterm but dormant infection in the brain, they investigated a possible linkage.

The researchers took international statistics about malignant brain cancer from the International Agency for Research on Cancer database to determine brain cancer rates in different countries. They then compared these to Toxoplasma antibody rate data from 37 countries (from a 2006 paper that collected data from other papers). They found that the prevalence of antibodies against Toxoplasma in a country was related to the prevalence of brain cancer in the country (that’s an oversimplification of what they did, since they did various kinds of statistical analyses, but that was their basic conclusion).

Some things to consider, though, before you ask for an MRI because you’re a cat owner:

• This is a pretty superficial study. When I started reading it, I assumed they had done a case-control study, whereby they took a group of people with brain tumours and an equivalent group of people without brain tumours, and compared Toxoplasma antibody rates. That’s not what was done. Rather, what they are essentially saying is that the incidence of brain tumours is higher in countries with a higher incidence of Toxoplasma antibodies in people. There are potentially a lot of other factors that might be involved. For example, they also showed that the incidence of brain cancer increased with increased gross domestic product (GDP) of the country, i.e. brain cancer rates are higher in wealthier countries. This could be because brain cancers are most often diagnosed as a result of more advanced medical care or that there are other lifestyle issues that might be risk factors for cancer. Toxoplasma antibody rates may be higher in high GDP countries (possibly because more people own cats, or for a number of other reasons) and thus the statistics shown an association between brain cancer and Toxoplasma antibodies.  It does NOT mean that Toxoplasma infection is necessarily causing brain cancer.  As the authors say, "This leaves open the possibility that brain cancers and T. gondii are both affected by a third correlated factor."
• This study included all brain tumours. It’s hard to believe that Toxoplasma would be a risk factor for all of the various brain tumour types, if there is actually an association.
• The Toxoplasma prevalence data weren’t obtained in a standard manner by the researchers. Rather, they took data from a paper written in 2006. That paper obtained the data from various other published papers, some decades old. It doesn’t mean that the data are not valid, but using data from studies that collected the information in different ways and from vastly different time periods creates some weaknesses.
• Studies that are looking at a subject from a high level don’t necessarily tell you what the risk is at the individual level. As the authors state "…analyses of data aggregated at the population level may not pertain to individual risk." (In epidemiology, this is called the ecological fallacy.)
• A large percentage of the human population (~1/3) has antibodies to Toxoplasma, indicating previous infection. That’s a huge number, yet the incidence of brain cancer is very low overall. Certainly, even if there is a true association, the likelihood of an individual developing cancer from Toxoplasma is very low.
• Pet cats rarely shed Toxoplasma. They usually only shed for a couple of weeks of their life, typically when they’re kittens. Also, the Toxoplama oocysts must live in the environment for 24 hours or longer to become infectious and a person has to ingest them to get infected. Therefore basic hygiene practices should reduce the chance of exposure even if a cat is shedding oocysts.

This is an example of a study that is great for generating questions that need to be answered, but not answering the questions. They’ve shown a crude association between toxoplasmosis and brain cancer. What that means is more detailed study is needed to see if the association is real (i.e. not the result of some other correlated factor) and furthermore to try to determine if the association is actually causative. Unfortunately, the press and internet don’t understand that aspect and freak people out with statements such as "Cat parasite linked to brain cancer. A parasite spread by cats could almost double their owner’s chance of developing brain cancer, research suggests."

One of the paper’s concluding statements sums it up nicely: "Clearly, further research is necessary to determine the proximate links between T. gondii and different types of brain tumours and to investigate a mechanism of action." That means we need to work to determine what the true nature of the association is, and not panic at the possibilities.