Parasites behavioural changes...

Interestin parasite behaviour changes in humans, allergies...

the strange interactions of our living world.....

Biological modifications of the host

The parasite itself can cause various effects on the host body, some of which are not fully understood.
Reproductive changes

A recent study has indicated toxoplasmosis correlates strongly with an increase in boy births in humans.[18] According to the researchers, "depending on the antibody concentration, the probability of the birth of a boy can increase up to a value of 0.72 ... which means that for every 260 boys born, 100 girls are born." The study also notes a mean rate of 0.608 (as opposed to the normal 0.51) for Toxoplasma-positive mothers. The study explains that this effect may not significantly influence the actual sex ratio of children born in countries with high rates of latent toxoplasmosis infection because "In high-prevalence countries, most women of reproductive age have already been infected for a long time and therefore have only low titres of anti-Toxoplasma antibodies. Our results suggest that low-titre women have similar sex ratios to Toxoplasma-negative women."[18]
Behavioral changes

It has been found that the parasite has the ability to change the behaviour of its host: infected rats and mice are less fearful of cats.in fact, some of the infected rats seek out cat-urine-marked areas. This effect is advantageous to the parasite, which will be able to proliferate as a cat could eat the infected rat and then reproduce. [19] The mechanism for this change is not completely understood, but there is evidence that toxoplasmosis infection raises dopamine levels and concentrates in the amygdala in infected mice[citation needed].

The findings of behavioural alteration in rats and mice have led some scientists to speculate that Toxoplasma may have similar effects in humans, even in the latent phase that had previously been considered asymptomatic. Toxoplasma is one of a number of parasites that may alter their host's behaviour as a part of their life cycle.[20] The behaviors observed, if caused by the parasite, are likely due to infection and low-grade encephalitis, which is marked by the presence of cysts in the human brain, which may produce or induce production of a neurotransmitter, possibly dopamine,[21] therefore acting similarly to dopamine reuptake inhibitor type antidepressants and stimulants.

Correlations have been found between latent Toxoplasma infections and various characteristics:[22]

* Decreased novelty-seeking behaviour[23]
* Slower reactions
* Lower rule-consciousness and greater jealousy (in men)[23]
* Less frigidity and greater conscientiousness (in women)[23]

The evidence for behavioral effects on humans is controversial (see a collection of research papers at http://natur.cuni.cz/flegr/publ.php).[citation needed] No prospective research has been done on the topic, e.g., testing people before and after infection to ensure that the proposed behavior arises only afterwards. Although some researchers have found potentially important associations with Toxoplasma, the causal relationship, if any, is unknown, i.e., it is possible that these associations merely reflect factors that predispose certain types of people to infection. However, many of the neurobehavioral symptoms that are postulated to be due to toxoplasmosis correlate to the general function of dopamine in the human brain, and the fact that toxoplasmosis upregulates the production of dopamine-stimulating tyrosine hydroxylase enzymes makes it likely that neurobehavioral symptoms can result from infection.

Studies have found that toxoplasmosis is associated with an increased car accident rate in people with Rh-negative blood. The chance of an accident relative to uninfected people is increased roughly 2.5 times.[21][24][25]

This may be due to the slowed reaction times that are associated with infection.[24] "If our data are true then about a million people a year die just because they are infected with Toxoplasma," the researcher Jaroslav Flegr told The Guardian.[26] The data shows that the risk decreases with time after infection, but is not due to age.[21] Ruth Gilbert, medical coordinator of the European Multicentre Study on Congenital Toxoplasmosis, told BBC News Online these findings could be due to chance, or due to social and cultural factors associated with Toxoplasma infection.[27] However there is also evidence of a delayed effect which increases reaction times.[28]

Other studies suggest that the parasite may influence personality. There are claims of Toxoplasma causing antisocial attitudes in men and promiscuity[29] (or even "signs of higher intelligence"[30] ) in women, and greater susceptibility to schizophrenia and bipolar disorder in all infected persons.[29] A 2004 study found that Toxoplasma "probably induce[s] a decrease of novelty seeking." [31]

According to Sydney University of Technology infectious disease researcher Nicky Boulter in an article that appeared in the January/February 2007 edition of Australasian Science magazine, Toxoplasma infections lead to changes depending on the sex of the infected person. [32][33]

The study suggests that male carriers have shorter attention spans, a greater likelihood of breaking rules and taking risks, and are more independent, anti-social, suspicious, jealous and morose. It also suggests that these men are deemed less attractive to women. Women carriers are suggested to be more outgoing, friendly, more promiscuous, and are considered more attractive to men compared with non-infected controls. The results are shown to be true when tested on mice, though it is still inconclusive. A few scientists have suggested that, if these effects are genuine, prevalence of toxoplasmosis could be a major determinant of cultural differences.[22][33][34]
Toxoplasma's role in schizophrenia

The possibility that toxoplasmosis is one cause of schizophrenia has been studied by scientists since at least 1953.[35] These studies had attracted little attention from U.S. researchers until they were publicized through the work of prominent psychiatrist and advocate E. Fuller Torrey. In 2003, Torrey published a review of this literature, reporting that almost all the studies had found that schizophrenics have elevated rates of Toxoplasma infection.[35] A 2006 paper has even suggested that prevalence of toxoplasmosis has large-scale effects on national culture.[36] These types of studies are suggestive but cannot confirm a causal relationship (because of the possibility, for example, that schizophrenia increases the likelihood of Toxoplasma infection rather than the other way around).[35]

* Acute Toxoplasma infection sometimes leads to psychotic symptoms not unlike schizophrenia.
* Some anti-psychotic medications that are used to treat schizophrenia, such as haloperidol, also stop the growth of Toxoplasma in cell cultures.
* Several studies have found significantly higher levels of Toxoplasma antibodies in schizophrenia patients compared to the general population.[37]
* Toxoplasma infection causes damage to astrocytes in the brain, and such damage is also seen in schizophrenia

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Parasitic worms are usually bad news, but perhaps not if you have allergies. Matt Kaplan reports on a radical new therapy

HOOKWORMS, whipworms, pinworms, flukes: mere mention of the panoply of parasitic worms that plague humans is enough to make most of us shudder. Not John Turton. In the mid-1970s, while working at the UK.s Medical Research Council Laboratories in Surrey, he intentionally infected himself with hookworms in an attempt to relieve his chronic hay fever. It worked. For two summers while he harboured the parasites, his allergy abated, only to return when he was free of them (The Lancet, vol 308, p 686).

Turton.s grim experiment came at a time when it was emerging that people living in regions where parasitic worm infections are rife tend to have fewer allergies. Nevertheless, he might have thought twice. In 1913, W. Herrick, a doctor from Columbia University in New York, noticed a very different link between parasitic worms, or helminths, and allergy. Lab workers whose duties included dissecting the gut-dwelling roundworm Ascaris often developed tenderness and swelling in their fingers, and more severe allergies after longer exposure, especially asthma.

Since the 1970s, researchers have been trying to make sense of these conflicting findings in the hope of being able to harness the power of parasites to help relieve allergies without making things worse. They know they are playing with fire . after all, helminths are responsible for some truly horrible diseases and cause great suffering around the world. Yet, as the effects of helminths on the human body become clearer, it looks as though their healing potential may be unleashed.

Not surprisingly, few researchers have been willing to take the risk of deliberately infecting themselves as Turton did. Instead, most studies are based on populations in countries where people are already infected. This research tends to focus on the three most commonly diagnosed allergic conditions: asthma, eczema and hay fever. The results have been confusing, but now researchers are beginning to understand why.

One study conducted in Taiwan, for example, showed that people infected with Enterobius vermicularis, a pinworm that is one of the most common gut parasites in the world, were less likely to have hay fever than the general population (Clinical Experimental Allergy, vol 32, p 1029). However, results from Ecuador tell a different story. Noting that hay fever was significantly more common in children living in urban than rural settings, researchers looked for a correlation between the allergy and levels of infection with the roundworm Ascaris lumbricoides. The parasite was equally common in both groups, so they concluded that something else must be responsible for the prevalence of hay fever (Clinical Experimental Allergy, vol 34, p 845).

The findings on eczema have proved just as difficult to interpret. For example, a study in Uganda found that eczema was less common among infants whose mothers had been infected with helminths while pregnant (JAMA, vol 294, p 2032). However, another study, this time in Ethiopia, discovered that children with Trichuris worms, whipworms that infest the large intestine, were more likely to have eczema than uninfected children (Journal of Allergy and Clinical Immunology, vol 115, p 370).

.Hookworms potential to protect against asthma may be related to its lung migration phase.

As for asthma, Herrick.s finding that it can be triggered merely by contact with Ascaris was confirmed in the 1970s. However, hookworms reduced the severity of asthma in a group of Ethiopians (The Lancet, vol 358, p 1493) and similar benefits have been noted in Brazilian asthma sufferers infected with Schistosoma mansoni, the flatworm responsible for schistosomiasis, which damages internal organs.

What are we to make of all this? The crucial link between allergies and parasites is the human immune system. Allergies are triggered by an overactive immune response, and helminths have strategies to damp down our immune response to promote their survival; after all, they have evolved in lockstep with humans for millennia.

In people who don.t have allergies, foreign material entering the body prompts the release of cytokines, molecules that sound the alarm to get the attention of other immune cells. As immune cells rally to attack the intruder, a second set of molecules is released to prevent the immune response from overreacting. One of the key molecules responsible for keeping reactions in check is interleukin-10, which inhibits the release of certain cytokines. People with allergies tend to have lower than normal levels of interleukin-10, so immune responses frequently get out of hand. Conversely, people infected with helminths have above-average levels of the molecule, and research on schistosomiasis patients indicates that this is at least partially because the worms release chemicals that stimulate the production of interleukin-10 in their host.

The mystery, then, is not so much that helminthic infections can damp down hay fever and other allergies, but that in some cases parasites do not. Clearly, different helminths interact with the immune system in different ways. "Parasitic worms are often treated as having the same effect on the body, but they probably do not," says Carsten Flohr at the University of Nottingham, UK, who recently published an article on the subject (Clinical Experimental Allergy, vol 39, p 20). What is not clear is the mechanism that sends the immune response in either direction.

One possible explanation is the helminths. lifespan. A short-lived worm, such as E. vermicularis, will not have much of a chance to tinker with the immune system and is less likely to be able to suppress the response than a hookworm, for example, a parasite that.s in for the long haul. Worms responsible for chronic infections would be unlikely to survive without evolving mechanisms that allow them to strike up an immunological balance with their host.

In addition, different species may have specific effects on immunity depending on the areas of the body they inhabit. Trichuris, for example, is ingested and stays in the gut, escaping the intense immune response that schistosomes encounter as they burrow their way through the skin, which is heavily monitored by cytokines and highly reactive, explains Flohr. Hookworm larvae also enter through the skin and make their way through the bloodstream to the lungs, where they pass through the thin-walled blood vessels. They then travel up from the lungs into the trachea, only to be coughed up and swallowed, allowing them to reach the small intestine where they develop into adult worms. "The potential protective effects of hookworm infections on asthma may be related to these parasites. lung migration phase," Flohr says.

Hookworm.s potential to protect against asthma may be related to its lung migration phase

It is this specificity that makes parasitic worms attractive as a potential treatment for allergic conditions. "The nice thing about a worm is it does the work of entering the body and interacting with the immune system for you. It has evolved excellent techniques that allow it to get to where it wants to go and lower the ensuing immune response," says immunologist Klaus Erb from Boehringer Ingelheim Pharmaceuticals in Germany.

Could there really ever be a demand for worm therapy? With a growing understanding of which parasites have the most potential to alleviate allergies, some researchers are convinced worms have a future. That.s partly because allergies are a huge and increasing problem, particularly in the developed world where they affect around 1 in 5 children, and partly because there is no treatment that resolves the underlying problem of an overreactive immune system. The choice is antihistamine tablets, which only work as long as you keep taking them, or a painful and time-consuming course of injections to desensitise you to the materials that prompt the immune system to overreact.

.Benefits occur when individuals are excreting at least 50 hookworm eggs per gram of faeces.

In an attempt to bring helminthic therapy a step closer, researchers at the University of Nottingham are testing the suitability of hookworms as a treatment for asthma. First they infected healthy people with the worms and discovered that a dose of 10 larvae resulted in a high enough level of infection to confer immune benefits; studies in Ethiopia indicate that this occurs when infected individuals are excreting at least 50 hookworm eggs per gram of faeces. Side effects included itching and sometimes minor intestinal discomfort, but they were only mild. The researchers then recruited asthma sufferers to test the effectiveness of hookworm therapy. "We monitored airway responsiveness during the period when we knew the larvae were migrating through the airways to determine if the migration made respiratory disease worse," says Johanna Feary, a member of the Nottingham team. And, most recently, they have conducted a 16-week, placebo-controlled trial on 34 people with asthma.

Benefits occur when individuals are excreting at least 50 hookworm eggs per gram of faeces

The results of these ground-breaking studies have yet to be published. Even if the treatment proves highly effective, it may well be difficult to convince people that worm therapy is the way to go. Many doctors find the idea repellant. "These things are disgusting. People are never going to allow themselves to be infected with them," says clinical immunologist Asif Rafi at the University of California, Los Angeles. "You really don.t want to treat people with worms if you don.t have to," adds Erb.

Aside from the yuck factor, there is another problem: helminths could ultimately make patients more susceptible to other diseases. It is an oversimplification to suggest that worms just reduce the immune response, says Rafi. What they are doing is changing the type of activity the immune system engages in. When reacting to parasites, bacteria and viruses, the immune system must balance the release of molecules that sound the alarm and increase inflammation, against those that calm things down, reducing inflammation and repairing tissue. Parasitic worms are particularly adept at shifting the balance towards an anti-inflammatory state, as it.s the ability to control inflammation that allows them to survive for years in a human. That.s good for them, but may make their host vulnerable to other infectious diseases.

"There may well be a downside to worm infection," admits David Pritchard from the Nottingham team. "The great challenge we face is finding the correct balance between alleviating disease and propagating it."

There may be another way to exploit the healing powers of helminths, however. "What we really need, is to find useful compounds being produced by these worms, rather than trying to use the worms themselves," says Rafi.

That is exactly what William Harnett and colleagues are doing at the University of Strathclyde in Glasgow, UK. They have shown that a complex protein called ES-62 . produced by Acanthocheilonema viteae, a parasitic filarial nematode worm that infects rodents . dramatically reduces inflammation associated with allergic conditions in mice. Intriguingly, ES-62 affects multiple aspects of the immune system simultaneously. As well as inducing production of anti-inflammatory cytokines such as interleukin-10, it also inhibits production of pro-inflammatory cytokines and proliferation of lymphocytes . the immune system.s white blood cells . and blocks the activation of mast cells, which play a key role in promoting inflammation. Now Harnett and his team are attempting to create small drug-like molecules that mimic the effects of ES-62.

Treating allergies with "essence of parasite" might sound like an ambitious goal, but the ES-62 research could be just the start. Parasitologist Jan Bradley at the University of Nottingham points out that there is far more to helminths than just how they influence allergic reactions. For example, Murray Selkirk at Imperial College London has discovered that infection with parasitic worms gives animals some protection against pneumonia caused by influenza. "Things are going to get a whole lot more complicated when we start considering the effects generated by interactions between different parasites, and the interactions between parasites and certain viruses," says Bradley..

Who.s for worm therapy?

Some species of parasitic worm are better at suppressing allergies than others. Likewise, some people get greater benefits from worm infections than others. Researchers suspect that a person.s age, diet and the environment in which they became infected may make a difference. In rural settings in developing countries, for example, children are often repeatedly infected from an early age. "This leads to a degree of host immunity and is probably the reason why helminths such as hookworms can survive in the same host for years, often causing only mild symptoms," says Carsten Flohr of the University of Nottingham, UK. In this case, the parasites are more likely to help alleviate allergies. Where people are infected later in life, however, exposure to helminths can actually lead to allergies.

Another factor that seems to influence the link between parasites and allergies in different individuals is genes. "Genetics are known to play a role in whether people are susceptible to both allergies and parasites," says immunologist Padraic Fallon at Trinity College in Dublin, Ireland. "Both of these susceptibilities could be under common genetic control." It may be that people who are prone to allergies have immune systems that naturally respond more aggressively towards invading parasites. Such highly reactive immune systems would have been selected for in areas where infections from parasitic worms were high. In today.s developed world, where such infections are rare, these individuals will be more prone to allergies. However, they may also be more likely to respond to helminthic therapy.

Parasites

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Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii.[1] The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid (cat) family. Animals are infected by eating infected meat, by ingestion of faeces of a cat that has itself recently been infected, or by transmission from mother to fetus. Cats have been shown as a major reservoir of this infection.[2]

Up to one third of the world's human population is estimated to carry a Toxoplasma infection.[3] The Centers for Disease Control and Prevention notes that overall seroprevalence in the United States as determined with specimens collected by the National Health and Nutritional Examination Survey (NHANES) between 1999 and 2004 was found to be 10.8%, with seroprevalence among women of childbearing age (15 to 44 years) of 11%.[4]

During the first few weeks, the infection typically causes a mild flu-like illness or no illness. After the first few weeks of infection have passed, the parasite rarely causes any symptoms in otherwise healthy adults. However, people with a weakened immune system, such as those infected with advanced HIV disease or those who are pregnant, may become seriously ill, and it can occasionally be fatal. The parasite can cause encephalitis (inflammation of the brain) and neurologic diseases and can affect the heart, liver, and eyes (chorioretinitis).

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A study conducted in Vietnam has added further weight to the view that parasitic gut worms, such as hookworm, could help in the prevention and treatment of asthma and other allergies.

Led by Dr Carsten Flohr, a Clinical Scientist from The University of Nottingham, and Dr Luc Nguyen Tuyen from the Khanh Hoa Provincial Health Service in central Vietnam, the study is the largest double-blind placebo controlled clinical trial to date looking at the potential links between hookworm and other gut worm infections and allergic conditions such as asthma and eczema.

Thanks to improved hygiene practices parasitic worms have been mostly eradicated among human populations living in developed countries. However, experts believe that over millions of years of co-evolution worms have found methods to dampen down host immune responses to prolong their own survival inside humans. This relationship seems to have become so intertwined that without gut worms or other parasites, our immune system can become unbalanced, which in turn could contribute to the development of asthma and other allergies. At the same time, it is important to remember that gut parasites can cause severe disease and are a major cause of iron-deficiency anaemia in developing countries.