13 June 2012

Parasites can cause schizophrenia?!

Everyone's heard of parasites, how can you not have? They are everywhere - infecting billions of animals, plants and bacteria worldwide and are found in almost every ecosystem imaginable. In fact, parasitism is the most successful form of life on the planet and countless species choose to live in this manner; having evolved over millions of years to take advantage of their hosts and to avoid their defensive capabilities.

Unfortunately parasites also exploit humans and tens of millions of individuals die each year as a result of parasites, with countless more suffering from chronic and debilitating diseases. Probably the most well-known deadly parasites of  man are those from the genus Plasmodium, which affect over half the world's population and are responsible for causing malaria - a disease that kills a person every 12 seconds and has killed more humans throughout our history than all of our wars combined! Of course many other parasites prey on man as well, with other fairly well-known examples including African sleeping sickness (which is caused by African trypanosomes) and the debilitating disease leishmaniasis (which is caused by Leishmania parasites).

A child suffering from leishmaniasis, a protozoan parasite that inhabits macrophages - the same type of white blood cell that the AIDS virus (HIV) lives in. Depending on the strain of the parasite this lesion will either disappear by itself or, without medical intervention, could continue to grow until the child's death.

However many of these diseases occur in hot and distant countries, such as Africa which is plagued by the examples mentioned above, and it is easy to forget that parasites regularly effect us here in Europe, the United Kingdom and the USA as well. In fact, anyone who's ever had an itch in a rather private place knows that we can catch 'worms' - intestinal nematode parasites that latch onto the walls of our gut and shed their eggs through our faeces. However, although unpleasant, catching 'worms' is rarely life threatening and can even help to alleviate the symptoms of asthma and other inflammatory diseases as the body shifts the dominance of its immune response away from the inflammatory causing Th1 response to a Th2 response, which is more suitable for killing worms in the gut! Cases such as this, where parasites can to help reduce the symptoms of 'modern diseases' that have only recently appeared in the civilised world, have led many scientists to believe that our hygiene and healthcare is now so good it it actually harming us in some ways as with less infection our leucocyctes (white blood cells) have nothing to fight and actually begin to harm our own bodies!

However, many of the parasites that can effect us in Europe are much more sinister and do not have such helpful side effects. One such parasite is Toxoplasma gondii, an intracellular protozoan that is arguably the most successful parasite in the world as it can effect almost any warm blooded animal (most parasites can only inhabit one or a very small number of specific species) and is found on every continent of the globe. The parasite is spread through cat  faeces, by ingesting under-cooked meat or across a mother's placenta to her unborn baby (which is known as congenital or 'vertical' transmission) and can affect up to 80% of human populations depending on where you live. For example, the incidence of T. gondii is about 16% in the UK where eating rare meat is unpopular; yet in France, where rare meat and blue meats are in high demand, 8 in every 10 people are infected by the parasite!

While all felids can contract T. gondii and pass sporolating oocysts (which are essentially just 'bags' of membrane that contains multiple parasites) with their faeces, is the domestic cat (Felis catus) that mainly transmits them to humans. This is usually when their owner has changed their litter or stroked them near to their tail and then prepared food without first washing their hands.

It may be confusing then, why so few people have heard of T. gondii or about toxoplasmosis (the disease that it causes) and even more so, why we do not have a vaccine against the parasite. The answer however, is fairly mundane - it is because the parasite does not cause any symptoms in individuals with a normally functioning immune system meaning that healthcare organisations around the world largely ignore the parasite. In fact, healthcare institutions only bother worrying about the parasites in patients in a state of  immunodeficiency, such as AIDS or chemotherapy patients; and during pregnancy, as congenital infection can result in the baby being born  blind, deformed or even in a miscarriage (don't worry - the parasite is checked for during routine baby checks throughout pregnancy and can be killed safely by the antibiotic Spiramycin, which builds up and persists for long periods of time in placental tissue).

The lack of symptoms that T. gondii parasites cause has led many scientists to believe for years that the parasite is safe and doesn't merit further study, despite the parasite forming life-long cysts in our brains that contain bradyzoites (parasites that become active by turning into tachyzoites when the cyst is eaten by another organism. Obviously, this is a 'dead end' for the parasites in humans since we are only rarely eaten). However, recent research suggests that the parasites are in fact harmful to us - slowing down our reaction times, altering our behaviour and inducing many psychotic diseases like the infamous schizophrenia (which despite popular belief, is NOT a split-personality disorder!).

Toxoplasma gondii tachyzoites can be seen here, after absorbing an intracellular blue/purple dye. The parasites can enter almost any nucleated cell and illicit a strong Th1 immune response. Oddly, they want this response from their host and even promote it by secreting their own chemicals! These chemicals can also be beneficial for their host in other ways, helping them to overcome long-established intestinal worm infections and even develop immunity to Leishmania parasites!

It is still not clear exactly how the parasites alter our behaviour, with the outcome appearing to be dependent on gender and personality-type in humans but the changes are believed to be similar to those altered in rodents, where the animals become more likely to take risks; have delayed reaction times; become less able to learn; spend more time in open spaces; and lose their fear of cats - one of their major natural predators! Amazingly, the behavioural changes are so profound that infected mice have been seen to start running in circles with their eyes closed whenever they see a cat! It is believed that these changes are induced in rodent behaviour to increase the changes of them being eaten by a felid - a fact that is highly beneficial to the parasite as T. gondii can only enter the sexual stage of its life cycle inside a cat! Thus, cats are its definitive host and the parasites effectively spend their entire lives trying to get inside a cat. The changes in human behaviour are not believed to be aimed at us directly, but are thought to take place due to the similarities that our brains have to those of rodents.

Research has found that individuals infected with T. gondii are 2.65 times more likely to be involved in a car crash. This is not surprising really, given that the parasites slow down our reaction times and make us more likely to take risks.

Although inducing changes in our behaviour is undesirable and no-one wants to think that they are being manipulated by a parasite so that they get eaten by a cat, it may not really matter in the grand scheme of things - are most of us ever going to be in a position where a cat could eat us? The most worrying problem that is caused by T. gondii then, is the fact that they alter our brain chemistry. Studies have found that the parasite increases the production of the neurotransmitter dopamine in our brains and that this in turn, can lead to schizophrenia - a debilitating disease that is characterised by a range of symptoms including social withdrawal, delusions, self neglect, hallucinations and altered perception and thinking patterns. Schizophrenia is the ninth most prevalent cause of disability worldwide and frequently leaves its sufferers unable to function normally in society. Furthermore, the parasites have been found to be positively correlated with the risk of having a stroke, developing Alzheimer's disease, epilepsy and depression!

Thus, catching and living with T. gondii may not be as unproblematic as previously thought, especially because once you've been infected with the parasites, you will unfortunately have them for the rest of your life. To further complicate matters, it is unlikely that a drug can be developed against T. gondii parasites because once they switch to bradyzoites and form cysts throughout brain and muscle tissue, killing them becomes more trouble than its worth - killing that many parasites at once could release huge amounts of toxins into the host's bloodstream, causing them to die very rapidly from anaphylactic shock. Therefore, the only real protection against T. gondii is to prevent yourself from catching it in the first place. The easiest way you can do this is to ensure that you cook all meat thoroughly at temperatures above 65C for a least 10 minutes, even if the meat has been frozen as the parasites can survive for very long periods of time in temperatures as low as -12C!

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