杏吧原创

HAVE you been acting out of character lately? Are you having trouble concentrating? Don鈥檛 blame late nights or old age 鈥� you might be at the mercy of a mind-altering parasite. A microscopic beast lying low in your brain may be exercising a subtle form of thought control, turning you into somebody slightly different.

This might sound pretty far-fetched, but evidence is growing that Toxoplasma gondii 鈥� a relative of the malaria parasite 鈥� can change the way you think. And you might already be infected without knowing it.

Why haven鈥檛 you heard any of this before? Because medical opinion insists that Toxoplasma is nearly always harmless, a cause for concern only to pregnant women and people with a weakened immune system. The case for the mind-control hypothesis is far from proven. But if it鈥檚 true, the parasite will become a public health nightmare overnight.

Toxoplasma 鈥� or toxo as it is informally known 鈥� is one of the most common human parasites in the world, infecting between 30 and 60 per cent of the global population. Any mammal can be infected, but it鈥檚 only in cats that toxo can sexually reproduce. It releases eggs that are spread in cat faeces, and if these end up in moist soil they can remain infective for 18 months. A passing rat or mouse might pick up the infection from the contaminated soil and if a cat kills and eats them the life cycle continues.

Toxo鈥檚 danger to pregnant women comes from the parasite鈥檚 ability to cross the placenta and trigger a miscarriage or damage the baby鈥檚 brain. But such cases are fairly rare, with only a handful a year in Britain and similar levels in other developed countries such as the US and Australia. So apart from warning prospective mothers against emptying the cat鈥檚 litter tray, dealing with toxo has never been a public health priority.

Risk factors vary between countries; most people get toxo from eating undercooked meat 鈥� pigs, cattle and sheep can all carry the parasite. You can also catch toxo by accidentally ingesting soil traces contaminated with cat faeces. So always wash your hands after doing the gardening.

In the initial phase of infection, called acute toxoplasmosis, the parasite is present in the blood. Typically, it causes little more than a headache and sore throat, although in rare cases it can lead to serious eye damage. Even if you do visit the doctor, it is almost always dismissed as a viral infection.

After this initial assault, the parasite hides from the immune system by forming resistant cysts on muscle and nerve tissue, including the brain 鈥� a stage known as latent toxoplasmosis. For most people, this disappearing act is the end of the story. Once the parasite has gone to ground it almost never re-emerges, unless your immune system is suppressed, if you get AIDS, for example. You keep the latent infection for the rest of your life 鈥� there are no drugs to cure it 鈥� but the received medical wisdom is that it is harmless.

So why the cause for concern? Well, researchers already know that toxo can manipulate rodents, its natural 鈥渋ntermediate host鈥�. Remarkably, rats and mice behave more recklessly when they are infected (see 鈥淔atal attraction鈥�). Joanne Webster and her team at Oxford University have found that the hapless rodents are more active and less scared of new things. They are even attracted to cat urine. And research by Jaroslav Flegr and colleagues at Charles University in Prague has shown that rats have slowed reaction times. All this makes them much more vulnerable to a feline pounce, which is exactly what the parasite wants. After all, toxo needs to infect a cat (the 鈥渄efinitive host鈥�) to complete its life cycle and spread its genes.

So could humans be subject to the same parasitic puppeteering? True, toxo would have little evolutionary incentive to influence our actions, as prehistoric humans were probably not eaten by big cats often enough to make it pay off. But rat and human brains are very similar. They have many of the same bits and are run by the same collection of chemicals. No one really knows how toxo subverts rat behaviour but it鈥檚 likely that it interacts with a chemical in the brain. The chances are that the same substance is in our brains too, so it鈥檚 perfectly feasible that humans experience side effects.

Flegr and his team decided to find out if this were actually happening. They carried out a series of tests on volunteers, some of whom had a latent infection, as revealed by antibodies to toxo in their blood.

The results from personality tests were complicated and showed confusing gender differences, but men at least seemed to mimic one aspect of rat manipulation. Infected men tended to be more independent and inclined to break rules, although infected women tended to go the other way. Could it be that males are being made more reckless, like the rats, while for some reason the mind-control chemical has the opposite effect in females? At this stage it鈥檚 still unclear, and of course, there鈥檚 not necessarily a causal relationship 鈥� certain personalities could simply be more prone to picking up infections.

But one test, measuring reaction times and attention span, gave more consistent results (Parasitology, vol 122, p 515). Both men and women who had a latent infection took longer to press a computer key after a prompt from the monitor. People without an infection took about 250 milliseconds to react, but those with a latent infection reacted about 8 per cent slower. What鈥檚 more, toxo-positive subjects did worse as the experiment went on, suggesting that they have shorter attention spans. Again, the effects in humans seem to be mimicking those in rats.

Until recently, few people have taken Flegr鈥檚 results very seriously. So what if toxo causes a few strange lab results, what difference does that make in the real world? What made people sit up and take notice was research published in August by Flegr鈥檚 team showing that humans with a latent infection are 2.7 times more likely to be involved in a car accident (BMC Infectious Diseases, ).

Dangerous driving

The researchers tested blood samples from 146 people involved in car crashes for which they were at least partly responsible, and 446 control subjects. There were more toxo carriers in the 鈥渁ccident鈥� group. It didn鈥檛 matter whether the subject was a driver or a pedestrian, having the parasite makes you more of a danger to other road users. Worryingly, there鈥檚 an obvious link with Flegr鈥檚 reaction time results. And if toxo slows our reaction times, what other effects is it having? Could it contribute to other transport accidents or industrial mishaps?

Flegr鈥檚 study has certainly raised eyebrows among the small group of specialists in the field, including some public health officials. For example, Richard Holliman, a parasite researcher at St George鈥檚 Hospital Medical School in London, says that although the results need to be replicated: 鈥淭he implications could be huge.鈥�

Longer reaction times might not be the only neurological effect of toxo. Another controversial idea is that latent infection might trigger some forms of schizophrenia. Fuller Torrey at the Stanley Medical Research Institute in Maryland and his team has found that schizophrenics are more likely to be cat owners, and to have latent toxoplasmosis. What鈥檚 more, drugs used to relieve schizophrenia symptoms happen to harm the parasite, at least in the test-tube. Torrey believes this may be why the drugs work.

So what should we do if it turns out that significant fractions of the population are infected with a parasite that slows reactions and possibly causes serious mental health problems?

Holliman, for one, says that we would have to consider which professions we allow infected people to enter. Would we want someone with slowed reactions working as an airline pilot, for example, or driving a lorry? On the other hand, if we banned all infected people from jobs where fast reactions are important, we could lose a third of our workforce or more.

In any event, toxo is unlikely to be a problem for airline pilots. The licensing process usually involves rigorous aptitude testing, which is designed to weed out anyone with chronic impairments. Tony Evans, deputy chief medical officer at the UK Civil Aviation Authority says: 鈥淚f you鈥檙e performing below par, you鈥檙e not going to get through the course.鈥�

But what about all the other professions where reaction times matter? If it turns out that latent toxoplasmosis really slows you down should bus drivers or machinery operators be screened for the parasite? And if insurance companies decide that toxo-positive drivers are a greater risk, will they be justified in charging them higher premiums?

Cutting the number of people who become infected with toxo in the first place is clearly an important way forward. Unfortunately, the only animal species for which a vaccine is available is sheep, because acute infection has serious consequences for farmers. So-called 鈥渁bortion storms鈥�, when up to 50 per cent of ewes in a flock miscarry, occur because they鈥檙e exposed to the parasite.

But progress towards a human vaccine has been frustratingly slow. Researchers have identified components of the parasite that provide some protection against infection when injected into mice. But this early work has stalled through lack of funding. There is not much interest in the area because, although toxo is an important parasite, it doesn鈥檛 kill, says Fausto Araujo at the Palo Alto Medical Foundation in California who was involved in the mice studies. Perhaps if the Czech findings are substantiated, vaccine research will acquire a new urgency. In the meantime, the only option seems to be reducing the parasite鈥檚 spread through basic public health measures.

Many people pick up toxo from undercooked meat, so better kitchen hygiene and thorough cooking should go a long way to lowering infection rates. In a recent survey, Tanya Aspinall and colleagues at the University of Manchester Institute of Science and Technology found that 27 of 71 meat products from British supermarkets harboured toxo DNA, although they don鈥檛 know if the parasites were viable.

Holliman is adamant that tackling the parasite in meat is the best option for reducing human infection. 鈥淭here鈥檚 no good reason why food should be sold with viable Toxoplasma in it,鈥� he says. On that score, keeping cat faeces away from animal feed is fundamental.

In Britain, attitudes to the toxo public health threat vary from concern to indifference, often depending on how well informed the speaker is. A spokesman for the British government鈥檚 Department for Environment, Food and Rural Affairs said officials were unaware of the studies on human behaviour. But the government-funded Toxoplasma Reference Laboratory in Swansea has been monitoring this research. Clinical scientist Edward Guy says the findings aren鈥檛 yet strong enough to justify action, and he is keen to avoid public panic of the sort that surrounded unsubstantiated research linking the MMR vaccine to autism.

Down on the farm

The issue has also been discussed by the government鈥檚 Advisory Committee on Zoonoses, which reviews the dangers posed by animal diseases that can be passed to humans. It is already considering what new policies would be needed if toxo turns out to be more dangerous than we think, or if the public becomes more concerned about it. One option is tighter controls on farms to prevent animals picking up the parasite.

The public health implications of toxo seem to be a higher priority in America. The US Department of Agriculture has recently commissioned a three-year study of beef, chicken and pork going into the food chain to assess the risk to the consumer. The researchers will analyse 6000 meat samples. 鈥淭he study will provide the first risk assessment of the likelihood of exposure to Toxoplasma by ingesting raw or undercooked meat,鈥� a department spokesman says.

Pigs have traditionally been thought of as the most likely animals to pick up a toxo infection so the USDA is being advised by Elizabeth Wagstrom, director of veterinary science at the US National Pork Board, which represents producers. She says that US pork infection levels are falling because of more intensive, indoor farming, which keeps pigs away from cats. But such gains could be reversed if organic farming becomes more common. 鈥淚t鈥檚 a lot more difficult to control the parasitic disease with animals outside,鈥� says Wagstrom.

Ultimately we鈥檒l have to wait and see if the latest findings are backed up by more research. No one is suggesting drastic policy changes on the back of a handful of studies. But toxo researchers complain that the field is being held back by dogma. It鈥檚 hard to get funding because of the entrenched belief that latent toxoplasmosis is harmless. Holliman says that alternative theories are seen as 鈥渢oo off-the-wall鈥�.

Yet no one can give a good scientific reason why these effects couldn鈥檛 occur. After all, toxo profoundly changes rodent behaviour, so why not us as well? As Joanna Webster says: 鈥淚 definitely think there is something there. There鈥檚 no reason to think that the parasite could not manipulate humans.鈥�