Brain parasite may strip away rodents' fear of predators—not just of cats - Science Magazine

Posted: 14 Jan 2020 08:20 AM PST

By Kelly ServickJan. 14, 2020 , 11:20 AM

Toxoplasma gondii exerts a strange sort of mind control on rodents: Once infected with the brain parasite, they seem to lose their fear of cats and become more likely to get eaten. When they are, the microbe can make its way into the feline intestine to reproduce. But a new study argues that T. gondii's effects on rodents aren't cat specific; instead, the parasite simply makes mice more eager to explore and less fearful of any species that might gobble them up.

"It doesn't make the parasite look to be this genius that many people thought it was," says William Sullivan, a microbiologist at the Indiana University School of Medicine, Indianapolis, who was not involved in the new work.

T. gondii can infect any warm-blooded vertebrate, including people, but its relationship with cats is special. Only in the feline gut can it reproduce sexually and assume a hardy, infectious form called an oocyst, which gets excreted to infect more animals.

Some researchers suspect the parasite tweaks a rodent's brain to change how it perceives cats. And some lab tests have revealed infected mice prefer to explore cat urine over that of other potential predators.

But that's not what parasitologist Dominique Soldati-Favre at the University of Geneva found. When she and colleagues allowed T. gondii-infected mice to explore chambers containing four smells—those of themselves, bobcats, foxes, and guinea pigs (a nonpredator)—the rodents didn't give the bobcat smell special treatment. Indeed, infected mice spent the most time investigating the guinea pig and fox smells, the team concludes today in Cell Reports. The mice were also willing to venture into a chamber containing a live, anesthetized rat (another potential predator), whereas uninfected control mice almost invariably stayed away.

In several other behavioral tests, the team found that infected mice showed less anxiety and a stronger tendency to explore. For example, they spent more time in the arms of a maze that were open and exposed—areas that mice typically find threatening.

"We realized it wasn't just about having lost fear against the cat," Soldati-Favre says. "Really, these mice are very open-minded, and they go everywhere."

Other studies have found similar changes in anxiety and exploration, notes Joanne Webster, a parasitologist at the Royal Veterinary College, Hawkshead, who was not involved with the work. And the new research hasn't convinced her that the cat-focused effect of T. gondii is a myth. "I don't think they've got the power to dispute that here." The researchers, she notes, report the odor preferences of the mice over 10 minutes, whereas some previous odor tests have tracked mice for several hours. She suspects the new test was too short to pick up a subtle tendency to explore the bobcat odor more intently than the others.

Other experts embrace the new finding. T. gondii "clearly manipulates the crap out of the host," says Laura Knoll, a parasitologist at the University of Wisconsin, Madison, and there's no evolutionary reason this manipulation needs to focus on cats. Sexual reproduction may depend on the cat, but the parasite is transmitted any time an animal eats infected prey. A generally bold, curious mouse is "more likely to be out and about and get eaten. And every time it's eaten—whether it's [by] a fox or a bobcat—[T. gondii] does get passed on."

Knoll's team recently published a method to get T. gondii to reproduce in laboratory mice. Like that study, she says, this new one supports the idea that "there's nothing that special about the cat."

Soldati-Favre and colleagues propose that an immune response provoked by T. gondii cysts in the brain underlies the behavior changes. Unlike some previous studies suggesting the cysts concentrate in particular regions and may act on specific brain circuits, this one finds a roughly even distribution of cysts across the mouse cortex—the brain's outer layer. And genetic analysis of brain tissue revealed certain markers of inflammation. Both cyst number and level of inflammation correlated with the degree of behavior change in infected mice, they report.

Up to one-third of humans are thought to harbor a T. gondii infection, known as toxoplasmosis, and some research has linked it to schizophrenia and other mental illness. Soldati-Favre speculates that, because the parasite seems to produce fewer and smaller cysts in healthy humans than in mice, it may drive less inflammation and very minor behavioral change in people. The authors propose future studies to test whether infected humans show signs of inflammation, which is thought to contribute to certain neurodegenerative diseases.

If researchers ever decide they do want to combat the effect of T. gondii infection in the human brain, the new results suggest reducing inflammation might help, Sullivan says. His team recently found that dosing T. gondii-infected mice with an anti-inflammatory drug could reverse some of their behavioral changes.

The new results suggest the parasite has found a "sweet spot," he says: invading the brain enough to provoke an immune response that drives the animal toward predators, but not enough to kill its host right away. It may not be an ultraprecise tweak to the perception of cats, but it's still "a very smart strategy," he says. "In a way, that is kind of mad genius."

Global Worming - Sporting Post

Posted: 14 Jan 2020 03:37 AM PST

Ascarids (photo: supplied)

The fact that the majority of horse owners the world over are still deworming horses as they did 40 years ago – by the calendar – regardless of need or species affecting the horse, may have grave consequences, writes Dr Karl van Laeren of Worm-Ex Lab.

There are four major groups of parasites that need to be considered:

1. Small Strongyles or Cyathostomins;

Strongyles (photo: supplied)

These worms live in the gut wall of the cecum (the very large equivalent of a human's appendix but designed to digest grass) before maturing and migrating into gut lumen or cavity They often occur in numbers exceeding 100,000 worms in the gut wall. As adults they migrate out of the wall into the intestinal cavity where they live on bacteria and protozoa and cause little harm. This is where reproduction and egg production occurs and is the principle egg seen in horse's dung. If a rare mass emergence of larvae from the gut wall occurs, this could be fatal in young horses.

2. Large Strongyles;

These worms are the real "bad boys" of yesteryear. They migrate beyond the gut wall and into the arteries of the abdomen, or in the liver and other abnormal sites like the testicular arteries in stallions or the aorta, before it splits into the leg arteries. Left untreated, they form masses, called thromboses, which can break loose, leading to a blockage of the arterial tree and starving the

intestine of blood supply, which causes areas of the intestine to die off, resulting in colics and other complications. Fortunately, nowadays Large Strongyles are a lot more rare, thanks to the deworming efficacy on many studs.

3. Non strongylid Gastrointestinal nematodes (parasites) or GIN's

Pinworms (left) vs Ascarids (right) (photo: supplied)

These include Parascaris equorum (Ascarids), Habronema sp. and Draschia megastoma (Summer sore worms), Oxyuris equi (pinworms), Trichostrongylus axei (stomach bankrupt worms contracted from cattle and sheep especially in winter rainfall areas. This is the only parasite horses and ruminants share in common) and Strongyloides westerii (transmitted in mare's milk to foals). On studs and racing stables the Ascarid worm that develops after passing through the lungs of horses is the most spectacular due to its large pencil-like size. The eggs of this GIN are thick walled and very well designed to survive in the environment for years, overcoming freezing cold or hot dry spells. Because these parasites pass through the horse's respiratory system, left uncontrolled, they can result in respiratory issues like "the snots" as well as intestinal blockages, leading to colics and associated complications. Ascarids developed resistance 20 years ago to the newest generation of dewormers.

4. Tapeworms

Tapeworms (photo: supplied)

Tapeworms undergo an indirect life cycle, needing a forage mite to complete the life cycle.

Parasite control is effected by the administration of anthelmintics (a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either paralysing or killing them and without causing significant damage to the host).

Most studs deworm all horses willy-nilly two to four to even eight times a year, regardless of age or immunity.

Anthelmintic Resistance

The more we, as humans, get exposed to antibiotics the more likely a bacterium will mutate into a super bug. The same principle applies to our horses' parasites or GIN's. The more dewormers used per year, the greater the likelihood of resistance occurring and the faster it is likely to happen. A dewormer is a tool to rid horses of GIN's but it is also a selector for hardy resistant worms as what's left alive after a deworming have been specifically selected to withstand that particular dewormer.

Anthelmintic resistance (termed AR in the scientific literature) occurs when worms get exposed to an effective dewormer, but fail to respond satisfactorily. A satisfactory response is a reduction of at least 95% on the pre-worming worm egg count. So, if a horse shows 1000 eggs per gram of dung pre-deworming, they should have 50 or less eggs two weeks after deworming to meet the 95% acceptance level. If not, they are showing signs of AR.

Small Strongyles are the most common parasites in horses and also the most commonly susceptible to AR. However, there are over 40 species of Small Strongyles and only one or two may initially have mutated into a resistant species. So, a count may only drop from 1000 eggs per gram of dung to say 150, which indicates only 85% reduction. This is an indication that some worm species are not being effectively destroyed and it may be worth trying another dewormer to rid the horse of the remaining worms. This war against parasites is won or lost by the accumulation of small victories and/or oversights.

As young horses carry the highest worm burdens and may be exposed to up to eight dewormings per year, this is the portion of the horse population that has shown the greatest tendency to develop resistance.

Breeding A Better Worm?

In essence, resistance is occurring in the Performance Horse and Thoroughbred studs and has the potential to spread to in contact horses. To date we have encountered no less than 60 such young Thoroughbreds that fail to clear fully after ivermectin dewormers. In such cases, we then advocate moxidectin dewormers which may reduce the burden some more. However, these horses never drop to the mandatory 95-99% reduction levels one would expect with macrocyclic lactone dewormers (the family of drugs containing ivermectin, abamectin, the cattle dewormer, doramectin, and moxidectin).

There is evidence of Macrocyclic lactone dewormer resistance in sheep, cattle and in horses. We diagnosed our first case in a horse from the Eastern Cape in 2016. A new molecule, monopantel, developed in New Zealand is now available for sheep and goats but alas, the first cases of resistance were reported in 2013 in NZ.

Horses, however, have no new "get out of jail solution" if resistance is encountered, as monopantel's safety in horses and in pregnant mares is not assured. We are having to revert to older families of drugs or a combination of deworming drugs to clear resistant parasites. Stomach tubing with up to three drugs has been required in some Ascarid infections.

As long as horse owners and even their veterinarians remain confused or unaware of the risk factors of repeated deworming with, moxidectin in particular, GINs, especially in young horses, are prone to encourage and select for resistant genes to evolve and disseminate to other horses sharing the same paddock space. Stud farms are breeding good equine genetics (bloodstock) through selecting strong compatible pedigrees, but inadvertently, excessive and unnecessary dewormings are breeding bad persisting parasite genes with a propensity to show resistance to drugs that previously proved highly effective.

Growing Problem

Anthelmintic resistance is now a worldwide phenomenon. Just think of the old days were one syringe of dewormer was truly BROAD SPECTRUM. This term is now a dream of the past as Ascarids, pinworms and now Small Strongyles all show signs of AR.

The Southern African evidence pertaining to AR has mainly come from the Thoroughbred studs producing stock for racing purposes. Usually this trend to AR is only noticed when these horses arrive at the few training establishments practicing selective deworming. Selective deworming is an evidence-based deworming protocol where only horses with over a predetermined threshold level are dewormed. Studs and racing stables should do worm egg counts (WEC) and especially feacal egg count reduction tests (FECRT) to establish the efficacy of their deworming drug of choice and whether AR is present in their herd. "Is our deworming achieving a 95% plus outcome post worming?" should be on every forward-thinking stud personnel's mind.

If doing these tests on the entire draft of yearlings and two year olds in one's care is initially unattractive, one should consider testing a sector of the stud to establish whether the drugs one is employing are producing the desired outcome. A reduction of 95% plus should be achievable on an individual basis and certainly on a stud basis to ensure that one's deworming protocol is effective.

Oddity

The one clear oddity about AR is that it never shows up in an entire draft of horses. One or more individuals may be affected, while other members of the herd may show no signs. So, throw one's net out as far as possible as the problem is still very selective in distribution. Only by looking critically at one's deworming methods are we likely to avert a looming disaster.

Trying new technologies, we tend to compare this in our minds with what we perceive to be a perfect solution, global across-the-board deworming. Unfortunately, the latter is far from a perfect solution and it behooves stud managers, racehorse trainers and veterinarians to realize that performing WEC is the gold standard in parasite diagnosis. Not doing this is leading to an already occurring dilemma of up to 10% of 2 year olds presenting with resistant worms arriving at the training yards.

Acknowledgements. The term "Global Worming" was coined by Dr Rose Nolen-Walston and cited in an article written by Ray Kaplan the Equine Parasitology scientist from the University of Georgia, USA .

An Inconvenient Truth: Global Worming and Anthelmintic Resistance.
Veterinary Parasitology, 2012: Vol 186 Issue 1 & 2 pgs. 70-78. Kaplan R et al.

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