Posts tagged infection
Articles and news from the latest research reports.
Toxoplasma infection permanently shifts balance in cat-and-mouse game
The toxoplasma parasite can be deadly, causing spontaneous abortion in pregnant women or killing immune-compromised patients, but it has even stranger effects in mice.
Infected mice lose their fear of cats, which is good for both cats and the parasite, because the cat gets an easy meal and the parasite gets into the cat’s intestinal tract, the only place it can sexually reproduce and continue its cycle of infection.
New research by graduate student Wendy Ingram at the University of California, Berkeley, reveals a scary twist to this scenario: the parasite’s effect seem to be permanent. The fearless behavior in mice persists long after the mouse recovers from the flu-like symptoms of toxoplasmosis, and for months after the parasitic infection is cleared from the body, according to research published today (Sept. 18) in the journal PLoS ONE.
“Even when the parasite is cleared and it’s no longer in the brains of the animals, some kind of permanent long-term behavior change has occurred, even though we don’t know what the actual mechanism is,” Ingram said. She speculated that the parasite could damage the smell center of the brain so that the odor of cat urine can’t be detected. The parasite could also directly alter neurons involved in memory and learning, or it could trigger a damaging host response, as in many human autoimmune diseases.
Ingram became interested in the protozoan parasite, Toxoplasma gondii, after reading about its behavior-altering effects in mice and rats and possible implications for its common host, the domesticated cat, and even humans. One-third of people around the world have been infected with toxoplasma and probably have dormant cysts in their brains. Kept in check by the body’s immune system, these cysts sometimes revive in immune-compromised people, leading to death, and some preliminary studies suggest that chronic infection may be linked to schizophrenia or suicidal behavior.
Pregnant women are already warned to steer clear of kitty litter, since the parasite is passed through cat feces and can cause blindness or death in the fetus. One main source of spread is undercooked pork, Ingram said.
With the help of Michael Eisen and Ellen Robey, UC Berkeley professors of molecular and cell biology, Ingram set out three years ago to discover how toxoplasma affects mice’s hard-wired fear of cats. She tested mice by seeing whether they avoided bobcat urine, which is normal behavior, versus rabbit urine, to which mice don’t react. While earlier studies showed that mice lose their fear of bobcat urine for a few weeks after infection, Ingram showed that the three most common strains of Toxoplasma gondii make mice less fearful of cats for at least four months.
Using a genetically altered strain of toxoplasma that is not able to form cysts and thus is unable to cause chronic infections in the brain, she demonstrated that the effect persisted for four months even after the mice completely cleared the microbe from their bodies. She is now looking at how the mouse immune system attacks the parasite to see whether the host’s response to the infection is the culprit.
“This would seem to refute – or at least make less likely – models in which the behavior effects are the result of direct physical action of parasites on specific parts of the brain,” Eisen wrote in a blog post about the research.
“The idea that this parasite knows more about our brains than we do, and has the ability to exert desired change in complicated rodent behavior, is absolutely fascinating,” Ingram said. “Toxoplasma has done a phenomenal job of figuring out mammalian brains in order to enhance its transmission through a complicated life cycle.”
(Source: newscenter.berkeley.edu)
Tapeworm-Linked Seizures May Be Rising in U.S.
Tapeworm infection in the brain that can trigger seizures is a growing health concern, doctors say.
But the infection, which leads to swelling in the brain, is usually treatable with medication, according to a leading association of neurologists.
Estimated cases of neurocysticercosis, as the tapeworm infection is called, range from 40,000 to 160,000 each year in the United States, said Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine in Houston. “It’s been around a long time, affecting people living in severe poverty, but the disease is not well-studied or understood,” Hotez said.
Texas is one area of the country with many cases. “The disease has now become a leading cause of epilepsy in Houston,” Hotez said. “Every [week], we have patients come into our tropical medicine clinic with it.”
Concerns about an apparent increase of neurocysticercosis within the United States led the American Academy of Neurology to issue treatment guidelines for doctors and patients in the April 9 issue of the journal Neurology.
The recommendations are based on a review of 10 studies published between 1980 and 2010 that evaluated so-called cysticidal drugs for treatment of tapeworm infections. The infection involves infestation of the brain with the larvae of the Taenia solium tapeworm. In severe cases, it can cause death.
Tapeworm infection is common in Third World countries because of inadequate sanitation and hygiene, and an estimated 2 million people worldwide have epilepsy as a result. The good news is that good hygiene and food preparation can prevent it.
People develop the tapeworm infection when they consume improperly cooked meat, such as pork, or any food or drink that contains the tapeworm eggs or larvae (also known as cysts). Touching the fecal matter of an infected person is another means of transmission. The larvae then transform into full-sized tapeworms, which can grow to several feet, Hotez said.
In pigs, tapeworm larvae travel to the brain and await transmission to another animal (a human, for instance) when the pigs are eaten, he said. The parasites do the same thing in humans, but there’s nowhere to go from the human brain. Ultimately, the larvae die, and that’s when the trouble begins.
As the larvae die, they lose the ability to hide from the body’s immune system. The immune system responds by causing inflammation, which leads to epileptic seizures and brain swelling, Hotez said.
The guidelines for children and adults recommend using the medication albendazole to kill the cysts if they’re alive and treating brain swelling with corticosteroid drugs that dampen the immune system. The study found that albendazole (Albenza), used with or without the corticosteroids, reduced seizure frequency and the number of brain lesions seen in imaging scans. Not enough data was available to evaluate another drug, praziquantel, the researchers said.
Only limited evidence exists to support specific treatment approaches, however, and the treatments may produce side effects, such as abdominal complaints, according to the guidelines. It’s also unclear whether anti-epileptic medications may help prevent the seizures caused by the inflammation.
For now, the key is physician awareness, said Dr. Karen Roos, a professor of neurology at the Indiana University School of Medicine and lead author of the guidelines. “Physicians from areas of the world where this infection is endemic are very knowledgeable about this infection,” she said. “They know more than U.S. physicians.”
Infection with the tapeworm is preventable through proper sanitation, good hygiene and thorough cooking of meat.
(Source: nlm.nih.gov)
How herpesvirus invades nervous system
Northwestern Medicine scientists have identified a component of the herpesvirus that “hijacks” machinery inside human cells, allowing the virus to rapidly and successfully invade the nervous system upon initial exposure.
Led by Gregory Smith, associate professor in immunology and microbiology at Northwestern University Feinberg School of Medicine, researchers found that viral protein 1-2, or VP1/2, allows the herpesvirus to interact with cellular motors, known as dynein. Once the protein has overtaken this motor, the virus can speed along intercellular highways, or microtubules, to move unobstructed from the tips of nerves in skin to the nuclei of neurons within the nervous system.
This is the first time researchers have shown a viral protein directly engaging and subverting the cellular motor; most other viruses passively hitch a ride into the nervous system.
"This protein not only grabs the wheel, it steps on the gas," says Smith. "Overtaking the cellular motor to invade the nervous system is a complicated accomplishment that most viruses are incapable of achieving. Yet the herpesvirus uses one protein, no others required, to transport its genetic information over long distances without stopping."
Herpesvirus is widespread in humans and affects more than 90 percent of adults in the United States. It is associated with several types of recurring diseases, including cold sores, genital herpes, chicken pox, and shingles. The virus can live dormant in humans for a lifetime, and most infected people do not know they are disease carriers. The virus can occasionally turn deadly, resulting in encephalitis in some.
Until now, scientists knew that herpesviruses travel quickly to reach neurons located deep inside the body, but the mechanism by which they advance remained a mystery.
Smith’s team conducted a variety of experiments with VP1/2 to demonstrate its important role in transporting the virus, including artificial activation and genetic mutation of the protein. The team studied the herpesvirus in animals, and also in human and animal cells in culture under high-resolution microscopy. In one experiment, scientists mutated the virus with a slower form of the protein dyed red, and raced it against a healthy virus dyed green. They observed that the healthy virus outran the mutated version down nerves to the neuron body to insert DNA and establish infection.
"Remarkably, this viral protein can be artificially activated, and in these conditions it zips around within cells in the absence of any virus. It is striking to watch," Smith says.
He says that understanding how the viruses move within people, especially from the skin to the nervous system, can help better prevent the virus from spreading.
Additionally, Smith says, “By learning how the virus infects our nervous system, we can mimic this process to treat unrelated neurologic diseases. Even now, laboratories are working on how to use herpesviruses to deliver genes into the nervous system and kill cancer cells.”
Smith’s team will next work to better understand how the protein functions. He notes that many researchers use viruses to learn how neurons are connected to the brain.
"Some of our mutants will advance brain mapping studies by resolving these connections more clearly than was previously possible," he says.
Virus and genes involved in causation of schizophrenia
For the first time, an international team of researchers has found that a combination of a particular virus in the mother and a specific gene variant in the child increases the risk of the child developing schizophrenia.
Viruses and genes interact in a way that may increase the risk of developing schizophrenia significantly. This happens already in the developing foetus.
An international team of scientists led by Aarhus University, Denmark, has made this discovery. As the first in the world, they scanned the entire genome of hundreds of sick and healthy people to see if there is an interaction between genes and a very common virus - cytomegalovirus - and to see whether the interaction influences the risk of developing schizophrenia.
And it does.
Women that have been infected by the virus - and around 70% has - will have a statistically significant increased risk of giving birth to a child who later develops schizophrenia if the child also has the aforementioned gene variant. This variant is found in 15 percent. The risk is five times higher than usual, the researchers report in Molecular Psychiatry.
No cause for alarm
People infected with cytomegalovirus most often do not know it, as the infection by the virus, which belongs to the herpes virus family, is usually very mild. But the researchers stress that there is no cause for alarm - even if both risk factors are present in mother and child, there may be a variety of other factors that prevents disease development in the child.
But as schizophrenia affects 1 per cent of the global population, this new knowledge is very important.
"In the longer term, the development of an effective vaccine against cytomegalovirus may help to prevent many cases of schizophrenia," says Professor of Medical Genetics at Aarhus University, Anders Børglum.
"And our discovery emphasizes that mental disorders such as schizophrenia may arise in the context of an interaction between genes and biological environmental factors very early in life."
(Source: eurekalert.org)
Malign environmental combination favours schizophrenia
The interplay between an infection during pregnancy and stress in puberty plays a key role in the development of schizophrenia, as behaviourists from ETH Zurich demonstrate in a mouse model. However, there is no need to panic.
Around one per cent of the population suffers from schizophrenia, a serious mental disorder that usually does not develop until adulthood and is incurable. Psychiatrists and neuroscientists have long suspected that adverse enviromental factors may play an important role in the development of schizophrenia. Prenatal infections such as toxoplasmosis or influenza, psychological, stress or family history have all come into question as risk factors. Nevertheless, until now researchers were unable to identify the interplay of the individual factors linked to this serious mental disease.
However, a research group headed by Urs Meyer, a senior scientist at the Laboratory of Physiology & Behaviour at ETH Zurich, has now made a breakthrough: for the first time, they were able to find clear evidence that the combination of two environmental factors contributes significantly to the development of schizophrenia-relevant brain changes and at which stages in a person’s life they need to come into play for the disorder to break out. The researchers developed a special mouse model, with which they were able to simulate the processes in humans virtually in fast forward. The study has just been published in the journal Science.
Can bacteria fight brain cancer?
The thinking behind an approach that has caused trouble in California.
Last week, the Sacramento Bee reported that two neurosurgeons at the University of California, Davis, had been banned from research on humans after deliberately infecting three terminally ill cancer patients with pathogenic bacteria in an attempt to treat them. All three died, two showing complications from the infection. Nature explores what happened and the science behind it.
New Compounds Inhibit Prion Infection
ScienceDaily (July 23, 2012) — A team of University of Alberta researchers has identified a new class of compounds that inhibit the spread of prions, misfolded proteins in the brain that trigger lethal neurodegenerative diseases in humans and animals.
U of A chemistry researcher Frederick West and his team have developed compounds that clear prions from infected cells derived from the brain.
"When these designer molecules were put into infected cells in our lab experiments, the numbers of misfolded proteins diminished — and in some cases we couldn’t detect any remaining misfolded prions," said West.
West and his collaborators at the U of A’s Centre for Prions and Protein Folding Diseases say this research is not yet a cure, but does open a doorway for developing treatments.
"We’re not ready to inject these compounds in prion-infected cattle," said David Westaway, director of the prion centre. "These initial compounds weren’t created for that end-run scenario but they have passed initial tests in a most promising manner."
West notes that the most promising experimental compounds at this stage are simply too big to be used therapeutically in humans or animals.
Human exposure to prion-triggered brain disorder is limited to rare cases of Creutzfeldt-Jakob or mad cow disease. The researchers say the human form of mad cow disease shows up in one in a million people in industrialized nations, but investigating the disease is nonetheless well worth the time and expense.
"There is a strong likelihood that prion diseases operate in a similar way to neurodegenerative diseases such as Alzheimer’s, which are distressingly common around the world," said West.
Source: Science Daily