HAHF-Truths, HAHF-Measures, Full Price (Part 3)

29 Aug 2012

Complaining of the impacts of free-roaming cats on wildlife and the environment, along with a range of public health threats, dozens of veterinarians in Hillsborough County, Florida, have banded together to fight TNR. Evidence suggests, however, that their real concern has nothing to do with the community, native wildlife, or, indeed, with cats. What the Hillsborough Animal Health Foundation is most interested in protecting, it seems, is the business interests of its members.

In Part 3 of this five-part series, I discuss some of the science surrounding Toxoplasma gondii, and challenge HAHF’s claim that TNR increases the exposure risk for toxoplasmosis.

Cats and Toxoplasma gondii
As recently as last week, the Hillsborough Animal Health Foundation was insisting that cats are the only source of Toxoplasma gondii—essentially that without cats, there’s no toxoplasmosis. It looks like they’ve done some editing in the past few days, and the particular statement I’m recalling has been removed.

In any case, it’s not quite that simple. Read more

Less Toxo, More Hype

7 Mar 2012

“As human populations continue to expand farther out into natural areas,” warns The Wildlife Society in a February 17 blog post, “domesticated animals will continue to be at risk for exposure to diseases carried by their wild relatives.” Considering the domesticated animals in question are cats, the organization’s apparent concern is almost touching. Almost.

Actually, TWS is, not surprisingly, much more concerned about cats transferring disease from “their wild relatives” to humans. Results of a recent study, published a month ago in the online, open-access journal PLoS ONE, suggests TWS blogger “policyintern,” illustrate “the importance of keeping domesticated cats close to home to prevent disease transmission among cats and to humans.”

Among those diseases is one that’s been getting lots of attention recently in the mainstream media: toxoplasmosis.

And just how likely is it that your cat will give you toxoplasmosis?

Not very—at least according to this latest research. (The study also looked at bartonellosis and Feline Immunodeficiency Virus, but I’ll save those for another post.) To begin with, “feral, free ranging domestic cats were targeted in this study” [1, emphasis mine], not pets. And, despite what TWS and others would have us believe, contact with these cats is relatively uncommon.

Then there’s the unexpectedly low infection rate reported by the authors of the study: just 1 percent for domestic cats, as compared to 75 percent for pumas and 43 percent for bobcats. Based on previous studies, one would expect seroprevalence rates of 62–80 percent for feral cats. [2] (Even “owned” cats* were found to have rates of 34–36 percent. Interestingly, the highest rate of seroprevalence was found among cats living on farms: 41.9–100 percent.)

Seroprevalence, with bars representing 95 percent confidence intervals, of T. gondii IgG,** for domestic cats, bobcats, and pumas at all study locations (FR = Front Range, CO; WS = Western Slope, CO; OC = Orange County, CA; SDRC = San Diego/Riverside Counties, CA; VC = Ventura County, CA). Sample sizes are listed above columns.

This should be big news for TWS.

At the very least, the low infection rates found in feral cats—combined with the much higher rates in bobcats and pumas—raise serious questions about domestic cats’ role in environmental contamination of T. gondii. Just a year ago, an article published in a special section of The Wildlife Professional called “The Impact of Free Ranging Cats,” was unambiguous: “the science points to [domestic] cats.” [3]

“Based on proximity and sheer numbers, outdoor pet and feral domestic cats may be the most important source of T. gondii oocysts in near-shore marine waters. Mountain lions and bobcats rarely dwell near the ocean or in areas of high human population density, where sea otter infections are more common.” [3]

And, over the past several months, TWS Executive Director/CEO Michael Hutchins has used the TWS blog to hammer the point home, arguing (and twisting the facts along the way), for example, that a 2011 NIH study provided “further evidence that feral cats are a menace to our native wildlife and should be controlled.”

In July, it was the grave threat to humans:

“T. gondii infection has recently been correlated with the incidence of Parkinson’s disease, autism, and schizophrenia in humans, and it has long been known to cause fetal deformities and spontaneous abortions in pregnant women… Let’s hope that public health officials, including the CDC, begin to take note of these growing concerns about cats and their implications for human health.”

In fact, this latest study suggests that such concerns may not be growing at all, at least where toxoplasmosis is concerned. On the other hand, the simpler, scarier story—cats as a menace to both wildlife and humans—is certainly an easier sell for TWS.

* I assume this refers to indoor/outdoor cats, but have not chased down the individual studies to confirm this.

** Refers to immunoglobulin, or antibody, G (IgG), “which is detectable for ≥52 weeks after infection,” as compared to immunoglobulin M (IgM), “which indicates recent infections and is usually detectable ≤16 weeks after initial exposure.” [1]

Literature Cited
1. Bevins, S.N., et al., “Three Pathogens in Sympatric Populations of Pumas, Bobcats, and Domestic Cats: Implications for Infectious Disease Transmission.” PLoS ONE. 2012. 7(2): p. e31403. http://dx.doi.org/10.1371%2Fjournal.pone.0031403

2. Dubey, J.P. and Jones, J.L., “Toxoplasma gondii infection in humans and animals in the United States.” International Journal for Parasitology. 2008. 38(11): p. 1257–1278. http://www.sciencedirect.com/science/article/B6T7F-4S85DPK-1/2/2a1f9e590e7c7ec35d1072e06b2fa99d

3. Jessup, D.A. and Miller, M.A., “The Trickle-Down Effect.” The Wildlife Professional. 2011. 5(1): p. 62–64.

Crazy Is As Crazy Does

14 Feb 2012

An article in The Atlantic describes fascinating research into the effects of Toxoplasma gondii infection, but what role do domestic cats really play?

Although we’re not even halfway through February, an article in the March issue of The Atlantic is already getting a lot of attention. But with a title like “How Your Cat Is Making You Crazy,” that’s no surprise. (Don’t get me wrong: the article is a great read.)

What is surprising is that the story hasn’t been picked up by the American Bird Conservancy or, more likely, The Wildlife Society.

Not yet, anyhow. Surely, it’s only a matter of days before ABC, TWS, and others (mis)use the article to stir up their witch-hunt against free-roaming cats. A careful read, however, suggests such a move would be both premature and misguided (as if that makes any difference).

Excerpts
At the center of “How Your Cat Is Making You Crazy” is the intriguing research* of Jaroslav Flegr, an evolutionary biologist at Charles University in Prague, who’s spent the past 20 years or so exploring the possible connections between infection with Toxoplasma gondii, a parasite cats can pass in their feces, and human behavior.

“Healthy children and adults,” explains writer Kathleen McAuliffe, “usually experience nothing worse than brief flu-like symptoms before quickly fighting off the protozoan, which thereafter lies dormant inside brain cells—or at least that’s the standard medical wisdom.”

But if Flegr is right, the ‘latent’ parasite may be quietly tweaking the connections between our neurons, changing our response to frightening situations, our trust in others, how outgoing we are, and even our preference for certain scents. And that’s not all. He also believes that the organism contributes to car crashes, suicides, and mental disorders such as schizophrenia.

As I say, it’s just a matter of time—and not much of it, I suspect—before TNR opponents jump all over this, shaping it to fit their (tired) message.

I expect to see the lengthy quote from Joanne Webster, a parasitologist at Imperial College London, parsed very carefully, for example. Webster and her colleagues discovered that Toxo-infected rats are actually attracted to cat urine, a phenomenon they dubbed “fatal feline attraction.” Commenting on Flegr’s research, Webster is, in McAuliffe’s words, “more circumspect, if not downright troubled.”

I don’t want to cause any panic. In the vast majority of people, there will be no ill effects, and those who are affected will mostly demonstrate subtle shifts of behavior. But in a small number of cases, [Toxo infection] may be linked to schizophrenia and other disturbances associated with altered dopamine levels—for example, obsessive-compulsive disorder, attention-deficit hyperactivity disorder, and mood disorders. The rat may live two or three years, while humans can be infected for many decades, which is why we may be seeing these severe side effects in people. We should be cautious of dismissing such a prevalent parasite.

I imagine those first two sentences will be among the first to be dropped from any ABC or TWS reference to the article. As will this response from Robert Sapolsky, a professor of biology and neurology at Stanford:

…I’m not too worried, in that the effects on humans are not gigantic. If you want to reduce serious car accidents, and you had to choose between curing people of Toxo infections versus getting people not to drive drunk or while texting, go for the latter in terms of impact.

Infection in Humans
“Humans,” explains McAuliffe, “are exposed not only by coming into contact with litter boxes, but also, he found, by drinking water contaminated with cat feces, eating unwashed vegetables, or, especially in Europe, by consuming raw or undercooked meat. According to the Centers for Disease Control and Prevention, the infection rate in the U.S. among those 12 and older is estimated to be 22.5 percent.

And while Toxoplasmosis “can come from cats,” the CDC points out that “people are more likely to get it from eating raw meat or from gardening.”

Nowhere in McAuliffe’s article does she mention the proportion of people infected through contact with cat feces, as compared to those infected from eating raw or undercooked meat. For the purposes of Flegr’s work, the source is largely immaterial. (And, virtually impossible to know, I gather—which would explain why I’ve never seen so much a guess.)

Infection in Cats
In the infamous “University of Nebraska-Lincoln paper,” published in 2010, the authors report—correctly, according to their source—that “most feral cats (62 percent to 80 percent) tested positive for toxoplasmosis.” [1] Trouble is, testing positive—seroprevalence—is simply not a useful measure of their ability to infect other animals or people.

“Most cats only shed oocysts for about one week in their life” (Note: The Atlantic suggests a three-week duration, as noted below) and seroconvert afterward. [2] “Thus, it is a reasonable assumption that most seropositive cats have already shed oocysts.” [2] “Testing positive,” in this case, is nothing more than the detection of antibodies resulting from seroconversion. Furthermore, because “most seronegative cats shed millions of oocysts after exposure to T. gondii… seropositive cats are likely to be less of a public health risk than seronegative cats.” [3]

Environmental Contamination
Because Flegr’s work doesn’t involve environmental contamination, McAuliffe only touched on the subject (“the parasite is typically picked up from the soil by scavenging or grazing animals—notably rodents, pigs, and cattle…”). For many TNR opponents, however, this is a hot topic—as some have suggested a direct connection between the presence of domestic cats and toxo-related infections in other animals, primarily land and marine mammals. (See, for example, my post from May 17 of last year.)

As a recent paper reports, bluntly: “Cats are the definitive host: the disease only occurs when cats are present.” [4] In fact, this claim is contradicted by a number of studies:

High levels (75 percent) of congenital transmission of T. gondii, for example, in a “wild population of mice,” led UK researchers to conclude “that this phenomenon might be more widespread than previously thought.” [5] Infections in sheep also point to congenital transmission, which “may be more important than previously considered.” [6]
The “high incidence of T. gondii found, among others, in free-living ruminants suggests a possibility of other, so far unknown, paths of transmission of this protozoan.” [7] “Due to the fact that they are widespread, and tick-bites occur frequently both in humans and in animals, ticks might play an important role in toxoplasmosis transmission.” [7]
Of particular interest are studies in the Arctic, where the prevalence of T. gondii infection in arctic foxes, Svalbard reindeer, sibling voles, walruses, kittiwakes, barnacle geese, and glaucous gulls “indicates that infection by oocysts is not an important mode of transmission on Svalbard.” [8] “T. gondii most likely is brought to Svalbard by migratory birds that become infected in temperate agricultural areas in the winter. However, marine sources of infection may exist. The high seroprevalence of T. gondii in the arctic fox population on Svalbard may be due to: (1) infection from migratory bird species through predation; (2) vertical transmission; and (3) tissue cyst transmission within the Svalbard ecosystem through scavenging and cannibalism. Together, these transmission routes cause a surprisingly high seroprevalence of T. gondii in a top predator living in an ecosystem with very few cats.” [8] Researchers studying infection rates in polar bears concluded: “It would… be inconceivable to assume that the few cats would play a major role in the epidemiology of T. gondii in the vast high Arctic. This is apparently the case in East Greenland as well.” [9]

In the Spring 2011 issue of The Wildlife Professional’s special section, “The Impact of Free Ranging Cats,” the authors argue: “Based on proximity and sheer numbers, outdoor pet and feral domestic cats may be the most important source of T. gondii oocysts in near-shore marine waters. Mountain lions and bobcats rarely dwell near the ocean or in areas of high human population density, where sea otter infections are more common.” [10] What the fail to acknowledge is that the most common type of T. gondii found to be infecting sea otters is the Type X strain, [11] which has yet to be traced to domestic cats, [12] or that “dual infections of T. gondii and S. neurona were more frequently associated with mortality and protozoal encephalitis than single infections, indicating a role for polyparasitism in disease severity.” [13]

Now What?
So, what are we to make of all this?

Or, as McAuliffe poses the question: “Given all the nasty science swirling around this parasite, is it time for cat lovers to switch their allegiance to other animals?”

Even Flegr would advise against that. Indoor cats pose no threat, he says, because they don’t carry the parasite. As for outdoor cats, they shed the parasite for only three weeks of their life, typically when they’re young and have just begun hunting. During that brief period, Flegr simply recommends taking care to keep kitchen counters and tables wiped clean. (He practices what he preaches: he and his wife have two school-age children, and two outdoor cats that have free roam of their home.)

Certainly, there’s still plenty we don’t know about T. gondii. A May 2011 article in Scientific American, for example, concedes simply: “The exact link between T. gondii and psychiatric diseases is tantalizing but remains murky.” [14]

Most telling of all may be the reaction of the pharmaceutical industry. Or, lack of a reaction, to be more precise. “Until solid proof exists that Toxo is as dangerous as some scientists now fear,” observes McAuliffe, “pharmaceutical companies don’t have much incentive to develop anti-Toxo drugs.” And if Big Pharma doesn’t think there’s money to be made here, how worried should we really be?

• • •

If history is any indication, “How Your Cat Is Making You Crazy” will be badly misrepresented by some TNR opponents, used to further vilify free-roaming cats as a public health threat. Not that they’ll offer anything in the way of a solution , of course—just more fear-mongering.

Now, if ABC, TWS, and all the rest are really concerned about toxo, why not propose a meat-free diet? OK, now that’s crazy.

*As opposed to, say, the unconvincing claims attempting to link T. gondii to brain cancer, published in a paper last summer. As expected, TWS took the bait.

Literature Cited
1. Hildreth, A.M., Vantassel, S.M., and Hygnstrom, S.E., Feral Cats and Their Management. 2010, University of Nebraska-Lincoln Extension: Lincoln, NE. elkhorn.unl.edu/epublic/live/ec1781/build/ec1781.pdf

3. Vollaire, M.R., Radecki, S.V., and Lappin, M.R., “Seroprevalence of Toxoplasma gondii antibodies in clinically ill cats in the United States.” American Journal of Veterinary Research. 2005. 66(5): p. 874–877. http://dx.doi.org/10.2460/ajvr.2005.66.874

4. Duffy, D.C. and Capece, P., “Biology and Impacts of Pacific Island Invasive Species 7. The Domestic Cat (Felis catus).” Pacific Science. 2011. 66(2 (Early View)): p. 000–000. http://pacificscience.files.wordpress.com/2011/09/pac-sci-early-view-66-2-6.pdf

5. Marshall, P.A., et al., “Detection of high levels of congenital transmission of Toxoplasma gondii in natural urban populations of Mus domesticus.” Parasitology. 2004. 128(01): p. 39–42. http://dx.doi.org/10.1017/S0031182003004189

6. Hide, G., et al., “Evidence for high levels of vertical transmission in Toxoplasma gondii.” Parasitology. 2009. 136(Special Issue 14): p. 1877-1885. http://dx.doi.org/10.1017/S0031182009990941

7. Sroka, J., Szymańska, J., and Wójcik-Fatla, A., “The occurrence of Toxoplasma gondii and Borrelia burgdorferi sensu lato in Ixodes ricinus ticks from eastern Poland with the use of PCR.” Annals of Agricultural and Environmental Medicine. 2009. 16(2): p. 313–319.

8. Prestrud, K.W., et al., “Serosurvey for Toxoplasma gondii in arctic foxes and possible sources of infection in the high Arctic of Svalbard.” Veterinary Parasitology. 2007. 150(1–2): p. 6–12. http://www.sciencedirect.com/science/article/B6TD7-4PYR4P2-2/2/fcc91fcf1d1426cd1b750bd3840bdb31

9. Oksanen, A., et al., “Prevalence of Antibodies Against Toxoplasma gondii in Polar Bears (Ursus maritimus) From Svalbard and East Greenland.” Journal of Parasitology. 2009. 95(1): p. 89–94. http://dx.doi.org/10.1645/GE-1590.1

10. Jessup, D.A. and Miller, M.A., “The Trickle-Down Effect.” The Wildlife Professional. 2011. 5(1): p. 62–64.

11. Conrad, P.A., et al., “Transmission of Toxoplasma: Clues from the study of sea otters as sentinels of Toxoplasma gondii flow into the marine environment.” International Journal for Parasitology. 2005. 35(11-12): p. 1155-1168. http://www.sciencedirect.com/science/article/B6T7F-4GWC8KV-2/2/2845abdbb0fd82c37b952f18ce9d0a5f

12. Miller, M.A., et al., “Type X Toxoplasma gondii in a wild mussel and terrestrial carnivores from coastal California: New linkages between terrestrial mammals, runoff and toxoplasmosis of sea otters.” International Journal for Parasitology. 2008. 38(11): p. 1319-1328. http://www.sciencedirect.com/science/article/B6T7F-4RXJYTT-2/2/32d387fa3048882d7bd91083e7566117

13. Gibson, A.K., et al., “Polyparasitism Is Associated with Increased Disease Severity in Toxoplasma gondii-Infected Marine Sentinel Species.” PLoS Neglected Tropical Diseases. 2011. 5(5): p. e1142. http://dx.doi.org/10.1371%2Fjournal.pntd.0001142

14. Koch, C., “Protozoa Could Be Controlling Your Brain.” Scientific American. 2011. http://www.scientificamerican.com/article.cfm?id=fatal-attraction

More Cats, Less Brain Cancer

28 Jul 2011

“Evidence continues to pile up,” writes Michael Hutchins, Executive Director and CEO of The Wildlife Society, in yesterday’s blog post, “that Toxoplasmosis, a disease caused by a parasite (Toxoplasma gondii) that lives in the guts of cats, may be responsible for serious human health problems.”

Hutchins was referring to a recent study in which researchers found “Infection with T. gondii was associated with a 1.8-fold increase in the risk of brain cancers across the range of T. gondii prevalence in our dataset (4–67 percent).” [1]

True to form, Hutchins used the opportunity to call for “doing away with managed cat colonies and TNR (trap-neuter-release) management practices for feral cats,” making a public plea to “public health officials, including the CDC.”

But what exactly does this latest study contribute to Hutchins’ “pile of evidence”?

The Study
According to a news release from the U.S. Geological Survey, “the study analyzed 37 countries for several population factors” and “showed that countries where Toxoplasma gondii is common also had higher incidences of adult brain cancers than in those countries where the organism is not common.”

“The study does not prove that Toxoplasma gondii directly causes cancer in humans, and the study does not imply that an infected person automatically has high cancer risk,” says [Kevin] Lafferty, who is based at the USGS Western Ecological Research Center. “However, we do know that Toxoplasma gondii behaves in ways that could stimulate cells towards cancerous states, so the discovery of this correlation offers a new hypothesis for an infectious link to cancer.”

According to the study’s abstract (I’ve been unable to access the paper), the authors took into account several factors:

“We corrected reports of incidence for national gross domestic product because wealth probably increases the ability to detect cancer. We also included gender, cell phone use and latitude as variables in our initial models. Prevalence of T. gondii explained 19 per cent of the residual variance in brain cancer incidence after controlling for the positive effects of gross domestic product and latitude among nations.” [1]

It will be interesting to compare—once I’m able to review the study in detail—these findings with those published earlier this year in the Journal of the National Cancer Institute (a collaborative effort involving several agencies, including, as it happens, the CDC):

“The relatively low variation in incidence and death rates for cancer of the brain and [other nervous system] nationally and internationally suggests that environmental risk factors do not play a major role in this disease. In fact, other than hereditary tumor syndromes and increased familial risk without a known syndrome, the only known modifiable causal risk factor for brain tumors is exposure to ionizing radiation.” [2, in-line citations removed for readability]

Correlation ≠ Causation
To illustrate the critical difference between correlation and causation, author Charles Seife uses the dramatic example of the mid-1990s NutraSweet scare—which, incredibly, was also linked brain cancer (falsely, as it turns out).

“Lots of people… don’t eat foods that contain the artificial sweetener NutraSweet for fear of developing brain cancer,” writes Seife, tracing the mythical connection to “a bunch of psychiatrists led by Washington University’s John Olney.”

“These scientists noticed that there was an alarming rise in brain tumor rates about three or four years after NutraSweet was introduced in the market.

Aha! The psychiatrists quickly came to the obvious conclusion: NutraSweet is causing brain cancer! They published their findings in a peer-reviewed journal, the Journal of Neuropathology and Experimental Neurology, and their paper immediately grabbed headlines around the world.

But a closer look at the data shows how unconvincing the link really is. Sure, NutraSweet consumption was going up at the same time brain tumor rates were, but a lot of other things were on the rise, too, such as cable TV, Sony Walkmen, Tom Cruise’s career. When Ronald Reagan took office in 1981, government spending increased just as dramatically as brain tumor rates… The correlation between government overspending and brain cancer is just as solid as the link between NutraSweet and brain cancer.” [3]

Sounds eerily familiar, doesn’t it?

Given the numerous factors and interrelationships involved in developing brain cancer—some of which, of course, we don’t even know—Hutchins’ eager indictment of cats is, at the very least, premature. In fact, Hutchins is going to have a difficult time connecting the dots in light of recent research.

More Cats, Less Brain Cancer
If brain cancer is more common where T. gondii is more common, then one might expect rates of brain cancer to increase over time as the prevalence of T. gondii increases. Which would seem to be the case here in the U.S., if cats are indeed the culprit.

According to data compiled last year in Conservation Biology, the population of pet cats tripled over the past 40 years, from approximately 31 million in 1971 to more than 90 million today. [4]

What Conservation Biologists Can Do--Chart_590px

So what about brain cancer?

In 2006, researchers using data from the Surveillance, Epidemiology, and End Results Program for 1973–2001 were surprised to find incident rates decreasing. Following an increase of 1.68 percent between 1973 and 1987, the incident rate began to drop off by 0.44 percent annually (as indicated in the chart below; EAPC = estimated annual percentage of change).

Trends in brain cancer incidence and survival in the United States (590px)

“The cause for this decline,” suggest the study’s authors, “is unclear because of the paucity of definitive knowledge on the risk factors of brain cancer, but solace can be taken from the fact that brain cancers are not rising in this era of increasing environmental toxic exposures.” [5]

More recently, a report published by the Central Brain Tumor Registry of the United States (PDF) found “no statistically significant trend in incidence rates of all primary brain tumors from 2004 through 2007.” [6]

• • •

Lafferty and his colleagues concede that their work is “correlational,” a jumping-off point for further investigation. Again, I haven’t been able to read the paper yet, but I’m skeptical that their line of inquiry is headed anywhere productive. Cast a net as wide as they did—surveying the prevalence of T. gondii and incidence of brain cancer across 37 countries—and you’re bound to catch something.

Of course, something is all Michael Hutchins needs for his witch-hunt.

Hutchins refers to piles of evidence without taking the trouble to examine any of it, simply ignoring what doesn’t fit neatly into his narrative—declining brain cancer rates in the U.S., for example. Or, some rather interesting comments from Lafferty himself (which, strangely, were omitted from USGS’s news release, but were mentioned by several other news outlets, including LiveScience and Fox News):

“…one shouldn’t be panicking about owning cats… The risk factors for getting Toxoplasma are really hygiene and eating undercooked meat. One should be more concerned about those than pets.”

That sounds familiar, too. It’s the same advice the CDC provides on its Website.

Literature Cited
1. Thomas, F., et al., “Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common.” Biology Letters. 2011.

2. Kohler, B.A., et al., “Annual Report to the Nation on the Status of Cancer, 1975, Featuring Tumors of the Brain and Other Nervous System.” Journal of the National Cancer Institute. 2011. http://jnci.oxfordjournals.org/content/early/2011/03/31/jnci.djr077.abstract

3. Seife, C., Proofiness: The Dark Arts of Mathematical Deception. 2010: Viking Adult.

4. Lepczyk, C.A., et al., “What Conservation Biologists Can Do to Counter Trap-Neuter-Return: Response to Longcore et al.” Conservation Biology. 2010. 24(2): p. 627–629. www.abcbirds.org/abcprograms/policy/cats/pdf/Lepczyk-2010-Conservation%2520Biology.pdf

5. Deorah, S., et al., “Trends in brain cancer incidence and survival in the United States: Surveillance, Epidemiology, and End Results Program, 1973 to 2001.” Neurological Focus. 2006. 20(April): p. E1. thejns.org/doi/pdf/10.3171/foc.2006.20.4.E1

6. n.a., CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2004-2007. 2011, Central Brain Tumor Registry of the United States: Hinsdale, IL. www.cbtrus.org/2011-NPCR-SEER/WEB-0407-Report-3-3-2011.pdf

Close Enough?

17 May 2011

Among the findings of a recent study:

Five of 18 cats trapped “between the spring and fall of 2008 and 2009” in central Illinois’ 1,500-acre Robert Allerton Park tested positive for Toxoplasma gondii antibodies. Five of the seropositive cats were trapped at the same site; there, one white-footed mouse (of 21 trapped) also tested positive, and a gray squirrel tested negative. The site where the sixth seropositive cat was trapped revealed similar results among the “small home range” (SHR) mammals found there: one of 34 white-footed mice was seropositive; a fox squirrel was negative.

All of which means… what, exactly?

Although there were five times as many “infected” cats at the first site, infection rates among SHR mammals were only about one-and-a-half times as high as those at the second site. Put another way: given the infection rate among SHR mammals at the second site, one would have expected three seropositive SHR mammals at the first site.

In fact, a press release put out last week put a very different spin on Shannon Fredebaugh’s thesis work (downloadable PDF):

One third of the cats sampled were infected with T gondii, as were significant numbers of the wild animals found at every site. Animals that inhabit or range over territories of 247 acres (100 hectares) or more, such as raccoons and opossums, were more likely to be infected than those with smaller ranges.

But these animals “could have acquired T. gondii infection somewhere outside of the park,” said Nohra Mateus-Pinilla, a wildlife veterinary epidemiologist at the University of Illinois Prairie Research Institute and leader of the study. Animals with smaller home ranges likely picked up the infection close to where they were trapped, she said. This makes these animals good sentinels of disease in a natural area. “The small animals are screening the environment for us,” she said. “So when we sample one of those animals, we are really sampling their lifestyle.”

The absence of bobcats in the park combined with the occurrence of domestic cats and T. gondii infection in wildlife that inhabit small territories strongly suggest that feral, free-ranging or abandoned house cats are the source of the infection, Mateus-Pinilla said. Cats are vital for the survival of the parasite, and so they are—either directly or indirectly—spreading T. gondii to the wildlife in the park. “There’s no other option,” she said.

Well, “one third of the cats” certainly sounds more impressive than “six of 18.” And “significant numbers of the wild animals found at every site” had an undeniable allure to it—though, in fact, the statement applies only to the park’s “large home range” (LHR) mammals (mostly raccoons and opossums).

Far more troubling, though, is the alleged connection between cats, T. gondii, and infected SHR mammals.

Environmental Contamination
“If one infected cat defecates there, any area can become infected,” Fredebaugh said in the press release. “It just takes one cat to bring disease to an area.”

But, as Fredebaugh points out, “environmental detection of oocysts is difficult and was not evaluated in this study.” [1] She simply assumes a causal link between “infected” cats and environmental contamination: more seropositive cats means more contaminated soil.

In fact, Fredebaugh goes further, assuming that the mere presence of cats—seropositive or not—is the key factor in SHR infection rates. In addition to trapping data, she uses data from scent stations and motion detection cameras (which proved largely ineffective, capturing photos of just four cats over the course of the research) to designate each of the eight sites as either high or low “cat occurrence,” as indicated in the following table (please forgive the tiny type):

Fredebaugh acknowledges that “scent stations should only be used to identify trends in animal populations and as a supplemental tool in conjunction with other population estimates,” [1] thereby raising serious questions about their use in her study. (She’s not interested in trends, her scent station and trapping data correlate quite poorly, and her use of scent station data is hardly “supplemental.”)

But back to the environmental contamination.

Cats (both domestic and wild) are T. gondii’s definitive host—the animal in which the parasite reproduces sexually. Cats pass the mature, infective form of T. gondii in their feces—a process called “shedding oocysts.”

Although oocysts can survive in soil for up to 18 months, and are resistant to disinfectants, cats typically “shed oocysts only once in their life.” [see discussion in 2] Indeed, according to Dubey and Jones, “Most cats seroconvert after they have shed oocysts. Thus, it is a reasonable assumption that most seropositive cats have already shed oocysts.” [2]

So, who’s to say that the “infected” cats Fredebaugh trapped shed oocysts in the area where they were found? Indeed, we don’t even know that these cats shed oocysts in the park. It’s been suggested (based on a small sample of cats monitored closely from 1974 to 1977) that home ranges of unsterilized feral females can exceed 500 acres, while those of unsterilized feral males may approach 2,500 acres. (Even house-based males, which were also unsterilized, had large home ranges: 865–939 acres.) [3]

What’s more, Fredebaugh points out that, given their “relatively good physical condition,” some of these cats might have been “recently abandoned at RAP.” [1] In which case, they wouldn’t have been “contributing” any oocysts to the park’s soil—assuming they were seropositive to begin with.

Odds Ratios
Fredebaugh expresses her results using odds ratios, a measure easy enough to calculate but rather difficult to grasp intuitively (especially for those of us, myself included, unfamiliar with the measure). A page on the Children’s Mercy Hospital (Kansas City, MO) Website explains odd ratios this way:

“An odds ratio of 1 implies that the event is equally likely in both groups. An odds ratio greater than one implies that the event is more likely in the first group. An odds ratio less than one implies that the event is less likely in the first group.”

(Some examples are discussed in detail here.)

It seems to me that, in this case at least, odds ratios obscure more than they reveal. When Fredebaugh reports “a significant difference in the seroprevalence of T. gondii for SHR mammals at sites with a high frequency of cat occurrence,” we know nothing of sample size or the overall fit of the data (which, ranges from pretty good—for LHR mammals—to pretty lousy—for SHR mammals).

A simple x-y graph illustrates this point:

By (mis?)representing the data in odds ratios, Fredebaugh suggests a connection that’s not actually supported by her research findings.

That said, she’s is hardly the first to imply causation where nothing more than correlation has been demonstrated (and, again, even that is dicey). In “The Impact of Free Ranging Cats,” a special section of the Spring Issue of The Wildlife Professional, for example, David Jessup and Melissa Miller argue that “the science points to cats,” but provide little more than “proximity” and “sheer numbers” to support their claim that “outdoor pet and feral domestic cats may be the most important source of T. gondii oocysts in near-shore marine waters.” [4]

(No?) Other Options
The fact that the researchers are so certain of their conclusions—that the only explanation for T. gondii in Robert Allerton Park is the presence of cats—is telling. I can’t help but think that they knew going in what they would find (a perception reinforced by what’s included in, and omitted from, Fredebaugh’s literature review, as described below).

In fact, Mateus-Pinilla’s comment—“There’s no other option.”—is challenged by several recent studies.

“Among white-footed mice,” writes Fredebaugh, “I found a 6 percent seroprevalence of T. gondii antibodies, which was high, compared to other studies… Mice have a short life span, thus the findings that mice, including some juveniles, were seropositive implies an active infection and recent T. gondii contamination in RAP.” [1]

Actually, researchers at the University of Salford’s Centre for Parasitology and Disease Research found an overall prevalence of 59 percent among the “200 mice… trapped from within houses in the Cheetham Hill area of Manchester.” [5] More important, they observed “high levels of congenital transmission… with 75 percent of female mice transmitting parasites to foetuses prior to birth” (emphasis added), leading them to conclude:

“These high levels of congenital transmission in this wild population of mice, taken together with other recent data on congenital transmission in sheep, suggests that this phenomenon might be more widespread than previously thought.” [5]

Fredebaugh, by contrast, mentions congenital transmission only in passing.

In another paper, researchers from the Centre for Parasitology and Disease Research challenge the conventional wisdom surrounding the transmission of T. gondii (note: I’ve removed several in-text citations for the sake of readability):

“The life cycle is well understood and three principal routes are recognised: ingestion of infective oocysts shed by the cat, consumption of undercooked meat containing Toxoplasma cysts and congenital transmission. Traditionally, the main route of infection is considered to be infection by oocysts deposited in faeces by the definitive host, the cat. This would imply that a high degree of contact with cats would be required to explain the very high prevalences found in many animal and human populations. Toxoplasma gondii has been reported in a very wide range of species. However, this also includes some species that would not normally come into contact with cats.” [6]

“Congenital transmission,” suggest Hide et al., “offers another possible mode of parasite transmission in the absence of cats.” [6]

“One way of determining the importance of transmission routes is to investigate transmission in a system where one of the routes of transmission is absent or minimal. For example, the carnivorous route could be excluded as a source of transmission in a herbivorous species such as sheep.” [6]

On the basis of multiple studies (see [7] and [8] for details of the study with sheep), Hide and his colleagues make a compelling argument that congenital transmission “may be more important than previously considered.” [6]

Researchers working in “the remote, virtually cat-free, high arctic islands of Svalbard” (the northern-most part of Norway) [9] came to similar conclusions. Among the “arctic foxes (n = 594), Svalbard reindeer (n = 390), sibling voles (n = 361), walruses (n = 17), kittiwakes (n = 58), barnacle geese (n = 149), and glaucous gulls (n = 27),” tested, Prestrud et al. found T. gondii only in the arctic foxes (257, or 43 percent), geese (11, or 7 percent), and walruses (1, or 6 percent). [10]

“The finding of no seropositive reindeer or sibling voles,” they argue, “indicates that infection by oocysts is not an important mode of transmission on Svalbard.” [10] (Also of interest is their suggestion that the seropositive walrus demonstrates “that T. gondii is present in the marine food chain.” [10])

So where does the T. gondii come from?

“…we suggest that T. gondii most likely is brought to Svalbard by migratory birds that become infected in temperate agricultural areas in the winter. However, marine sources of infection may exist. The high seroprevalence of T. gondii in the arctic fox population on Svalbard may be due to: (1) infection from migratory bird species through predation; (2) vertical transmission; and (3) tissue cyst transmission within the Svalbard ecosystem through scavenging and cannibalism. Together, these transmission routes cause a surprisingly high seroprevalence of T. gondii in a top predator living in an ecosystem with very few cats.” [10]

A study of polar bears is further evidence that “other options” do indeed exist:

“In Svalbard cats are banned by the Norwegian authorities; however, a few cats may exist in Russian mining communities. Thus, the possibility of cats as a source of infection for polar bears cannot totally be excluded. Nonetheless, the existing cat population is very limited and local, and the proportion of seropositive polar bears is rather high, indicating that polar bears are commonly infected with T. gondii. It would, therefore, be inconceivable to assume that the few cats would play a major role in the epidemiology of T. gondii in the vast high Arctic. This is apparently the case in East Greenland as well.” [11]

As with the single seropositive walrus discussed above, the results of the polar bear study indicates “that there might be marine sources of T. gondii in the region.” [9]

And finally, in a paper published in 2009, Polish researchers proposed yet another possibility. The “high incidence of T. gondii found, among others, in free-living ruminants,” write Sroka et al., “suggests a possibility of other, so far unknown, paths of transmission of this protozoan.”

“Due to the fact that they are widespread, and tick-bites occur frequently both in humans and in animals, ticks might play an important role in toxoplasmosis transmission.” [12] (Note: the authors acknowledge both support for, and differing opinions about, the possibility of such a pathway.)

Fredebaugh mentions none of this work in her thesis; none of the author’s names appear in her lengthy list of references (which, to most people, probably appears comprehensive). And still, both she and Mateus-Pinilla (who chaired Fredebaugh’s thesis advisory committee) are committed to the proposition that, as Jessup and Miller suggest, “the science points to cats.”

Greater (Mis)Understanding
Fredebaugh concludes her thesis by suggesting that her results:

“provide a greater understanding of how feral cats and wildlife utilize natural areas in a highly fragmented landscape and how feral cat land use may impact wildlife parasite prevalence both directly and indirectly. With this information, I more clearly understand the association between wildlife and feral cats and can suggest better control strategies for feral cat populations. Using wildlife with small spatial scale habitat use as sentinels of parasite presence in the environment, I can gain a better understanding of the epidemiologic impact of T. gondii in different urban and rural settings to prevent human and wildlife infection. Further collaborative research is needed to determine the most effective management strategy for feral cat populations in natural areas and to evaluate the direct relationship between feral cats and their impacts on wildlife.” [1]

At the risk of being overly critical, I’m suggesting that Fredebaugh’s work has not only failed to clarify our understanding of feral cats, wildlife, and the transmission of T. gondii, but has—due to its problematic methodology and incomplete literature review—actually made matters worse (especially with regard to possible “control strategies”).

• • •

Not surprisingly, The Wildlife Society’s CEO/Executive Director Michael Hutchins immediately endorsed the study (his summary conveniently omits the small sample size involved, the inverse relationship between “infected” cats and “infected” SHR mammals, and several other important aspects of the research) and its misguided conclusions, pleading:

“How many more peer reviewed studies do we need to convince leaders to change the way that we are currently dealing with the feral cat population explosion in this country?”

I don’t want to suggest that Hutchins and I are on the same page here, but omit the word explosion, and that’s pretty much the same question I’ve been asking for a while now.

Literature Cited
1. Fredebaugh, S.L., Habitat Overlap and Seroprevalence of Toxoplasma Gondii in Wildlife and Feral Cats in a Natural Area. 2010, University of Illinois at Urbana-Champaign: Urbana-Champaign, IL. p. 88. http://www.ideals.illinois.edu/bitstream/handle/2142/16185/1_Fredebaugh_Shannon.pdf?sequence=6

3. Liberg, O., “Home range and territoriality in free-ranging house cats.” Acta Zoologica Fennica. 1984. 171: p. 283–285.

4. Jessup, D.A. and Miller, M.A., “The Trickle-Down Effect.” The Wildlife Professional. 2011. 5(1): p. 62–64.

7. Morley, E.K., et al., “Significant familial differences in the frequency of abortion and Toxoplasma gondii infection within a flock of Charollais sheep.” Parasitology. 2005. 131(02): p. 181–185. http://dx.doi.org/10.1017/S0031182005007614

8. Morley, E.K., et al., “Evidence that primary infection of Charollais sheep with Toxoplasma gondii may not prevent foetal infection and abortion in subsequent lambings.” Parasitology. 2008. 135(02): p. 169–173. http://dx.doi.org/10.1017/S0031182007003721

9. Prestrud, K.W., et al., “Direct high-resolution genotyping of Toxoplasma gondii in arctic foxes (Vulpes lagopus) in the remote arctic Svalbard archipelago reveals widespread clonal Type II lineage.” Veterinary Parasitology. 2008. 158(1-2): p. 121–128. http://www.sciencedirect.com/science/article/B6TD7-4TDK6Y8-2/2/1e5b02861f7a0c81f2277f65f42e6be9

10. Prestrud, K.W., et al., “Serosurvey for Toxoplasma gondii in arctic foxes and possible sources of infection in the high Arctic of Svalbard.” Veterinary Parasitology. 2007. 150(1-2): p. 6–12. http://www.sciencedirect.com/science/article/B6TD7-4PYR4P2-2/2/fcc91fcf1d1426cd1b750bd3840bdb31

11. Oksanen, A., et al., “Prevalence of Antibodies Against Toxoplasma gondii in Polar Bears (Ursus maritimus) From Svalbard and East Greenland.” Journal of Parasitology. 2009. 95(1): p. 89–94. http://dx.doi.org/10.1645/GE-1590.1

12. Sroka, J., Szymańska, J., and Wójcik-Fatla, A., “The occurrence of Toxoplasma gondii and Borrelia burgdorferi sensu lato in Ixodes ricinus ticks from eastern Poland with the use of PCR.” Annals of Agricultural and Environmental Medicine. 2009. 16(2): p. 313–319.