Posts Tagged ‘infection’

By Richard Kemeny

According to much of the scientific literature, dominance in social animals goes hand-in-hand with healthier lives. Yet leaders of the pack might not be healthier in all aspects, and according to a study published last week (February 26) in Scientific Reports, they are more at risk of parasite infection.

“While high-ranking animals often have the best access to food and mates, these advantages appear to come with strings attached,” says study coauthor Elizabeth Archie, a behavioral and disease ecologist at the University of Notre Dame, in an email to The Scientist. “These strings take the form of higher parasite exposure and susceptibility.”

Lower social status is usually linked to poorer health, according to previous studies. Animals towards the bottom of hierarchies have to struggle more for resources, and are often subjected to aggressive behavior from their superiors. In many species of birds, mice, and nonhuman primates, for instance, poorer physical condition is more common for subordinates. Female macaques of low social status, for example, have been shown to have lower bone density and an increased risk of developing inflammatory diseases.

Yet the relationship between social subordination and infectious disease risk hasn’t been clearly measured, according Archie and her coauthors. To look at the relationship between social status and one particular malady—parasite infections—they carried out a meta-analysis of 39 studies spanning 31 species, searching for patterns of parasitism.

In the majority of studies, those individuals in dominant positions—in particular, dominant males—were found to be more at risk of being infected. The effect was strongest in mammals, and in ordered hierarchical societies where social status is correlated with sexual activity.

These findings support two previous hypotheses about the links between social status and parasitism. One relates infection risk to resource access: exposure to infection is more common when animals feed and mate more. Dominant reindeer, for example, spend more time eating than subordinate individuals, and are more likely to become infected by nematodes. And greater sexual activity brings more risk of transmitted infections. Take, for instance, dominant feral cats, whose sexual proclivity increases the chances of developing Feline Immunodeficiency Virus.

The other hypothesis proposes a trade-off between reproductive effort and immunity to disease. In other words, those in dominant positions expend more energy on mating, and therefore invest less into costly immune defences.

“When you put it in the context [of these hypotheses], it does make a lot of sense,” says Jennifer Koop, a biologist at the University of Massachusetts-Dartmouth, who was not involved in the study.

Archie doesn’t think that individuals will deliberately opt for lower status in order to avoid infection. “High status comes with so many other advantages that the cost of a few more parasites might not be enough for individuals to shun high social status,” she says.

It’s also conceivable that there are benefits to both parasite and host in this relationship, says Nicole Mideo, an evolutionary biologist at the Univeristy of Toronto, who was not involved in the study. “The parasites are exploiting the resources of the host, so if you have a host that doesn’t get access to much food, then the parasite isn’t going to get access to much food,” she says.

This study mostly focused on parasitic worms, a limitation the researchers want to expand beyond. Additionally, the toll on dominant animals’ health of the increased risk of parasite infections was not explored. Mideo explains that there could be subtle advantages here, as research has shown worms can alter immune systems, and might protect against other infections. “It’s entirely possible that having worm infections does confer some sort of advantage in the context of other potential diseases,” she says.

Habig et al., “Social status and parasitism in male and female vertebrates: a meta-analysis,” Scientific Reports, doi:10.1038/s41598-018-21994-7, 2018.


by Jennifer Brown

The recent Ebola outbreak in West Africa has claimed more than 11,300 lives—a stark reminder of the lack of effective options for treating or preventing the disease.

Progress has been made on developing vaccines, but there is still a need for antiviral therapies to protect health care workers and local populations in the event of future outbreaks.

Now, a new study suggests that gamma interferon, an FDA-approved drug, may have potential as an antiviral therapy to prevent Ebola infection when given either before or after exposure to the virus.

The findings, published in the journal PLOS Pathogens, show that gamma interferon, given up to 24 hours after exposure, inhibits Ebola infection in mice and completely protects the animals from death.

Ebola infection appears to be a stepwise process. First, the virus targets and infects macrophages or dendritic cells, two types of immune system cells found in the liver, spleen, and lymph nodes. Ebola then replicates in those cells. Following this initial infection, which happens at day 3 or 4 in non-human primates, Ebola virus is released into the blood and infects a plethora of other different cell populations.

“It goes from an early stage with a very targeted infection of only these few cell types, to everything being infected,” says Wendy Maury, professor of microbiology at the University of Iowa.

“We think what’s happening with gamma interferon is that it’s targeting macrophages and blocking the infection of those initial cell targets so you don’t get the second round of infection.”

The University of Iowa does not have a specializing BioSafety Level 4 (BSL4) lab that is required for experiment using Ebola virus, so the researchers made their initial findings using a surrogate virus, which targets and infects the same cells as Ebola, but does not cause the disease.

This Ebola lookalike—a sheep in wolf’s clothing—consists of a less dangerous vesicular stomatitis virus (VSV) that expresses Ebola glycoproteins on its surface.

All of the results found using the surrogate virus were then repeated using mouse-adapted Ebola virus in the BSL4 lab of Maury’s longtime collaborator Robert Davey at Texas Biomedical Institute in San Antonio, Texas.

Gamma interferon inhibits the virus’s ability to infect human and mouse macrophages, in part by blocking virus replication in the cells. Pre-treating mice with interferon gamma 24 hours before exposure protects the animals from infection and death. The researchers were surprised to find that treatment up to 24 hours after what would have been a lethal exposure also completely protected the animals from death, and they could no longer detect any Ebola virus in the mouse’s cells.

The findings suggest that interferon gamma may be useful both as a prophylaxis and post-exposure treatment against Ebola. The team still has to determine how late gamma interferon can be given to the mice and still prevent infection. However, the results suggest a window of time after exposure when gamma interferon may be an effective antiviral therapy.

“My guess is that if you delay the gamma interferon too much, you miss this window of opportunity to block the infection in macrophage cells and the gamma interferon can no longer provide protection,” Maury says.

Maury and colleagues investigated how gamma interferon might be helping the cells fight off the Ebola virus. They identified that the expression of more than 160 genes in human macrophages is stimulated by gamma interferon. Introduction of some of these genes into cells was sufficient to prevent Ebola infection.

“This mechanistic information might suggest more precise drug targets rather than the broad effects, including adverse side-effects, that are produced by gamma-interferon,” she says.

Gamma interferon is already approved by the FDA to treat chronic granulomatous disease (an immune disease) and severe malignant osteopetrosis.

In addition to moving the studies into larger animal models, Maury next plans to study the ability of gamma interferon to inhibit Ebola infection in conjunction with other developing antivirals.

“Right now, there are no FDA-approved antiviral therapies for Ebola, but there are some being developed that target virus entry,” she says. “We know that gamma interferon blocks replication but not entry into cells. So combining an entry inhibitor with gamma interferon may allow us to reduce amount of gamma interferon needed and target two different steps in the virus’s life cycle, which has been shown in HIV to be critically important for controlling the virus.”


A one thousand year old Anglo-Saxon remedy for eye infections which originates from a manuscript in the British Library has been found to kill the modern-day superbug MRSA in an unusual research collaboration at The University of Nottingham.

Dr Christina Lee, an Anglo-Saxon expert from the School of English has enlisted the help of microbiologists from University’s Centre for Biomolecular Sciences to recreate a 10th century potion for eye infections from Bald’s Leechbook an Old English leatherbound volume in the British Library, to see if it really works as an antibacterial remedy. The Leechbook is widely thought of as one of the earliest known medical textbooks and contains Anglo-Saxon medical advice and recipes for medicines, salves and treatments.

Early results on the ‘potion’, tested in vitro at Nottingham and backed up by mouse model tests at a university in the United States, are, in the words of the US collaborator, “astonishing”. The solution has had remarkable effects on Methicillin-resistant Staphylococcus aureus (MRSA) which is one of the most antibiotic-resistant bugs costing modern health services billions.

The team now has good, replicated data showing that Bald’s eye salve kills up to 90% of MRSA bacteria in ‘in vivo’ wound biopsies from mouse models. They believe the bactericidal effect of the recipe is not due to a single ingredient but the combination used and brewing methods/container material used. Further research is planned to investigate how and why this works.

The testing of the ancient remedy was the idea of Dr Christina Lee, Associate Professor in Viking Studies and member of the University’s Institute for Medieval Research. Dr Lee translated the recipe from a transcript of the original Old English manuscript in the British Library.

The recipe calls for two species of Allium (garlic and onion or leek), wine and oxgall (bile from a cow’s stomach). It describes a very specific method of making the topical solution including the use of a brass vessel to brew it in, a straining to purify it and an instruction to leave the mixture for nine days before use.

The scientists at Nottingham made four separate batches of the remedy using fresh ingredients each time, as well as a control treatment using the same quantity of distilled water and brass sheet to mimic the brewing container but without the vegetable compounds.

The remedy was tested on cultures of the commonly found and hard to treat bacteria, Staphylococcus aureus, in both synthetic wounds and in infected wounds in mice.

The team made artificial wound infections by growing bacteria in plugs of collagen and then exposed them to each of the individual ingredients, or the full recipe. None of the individual ingredients alone had any measurable effect, but when combined according to the recipe the Staphylococcus populations were almost totally obliterated: about one bacterial cell in a thousand survived.

The team then went on to see what happened if they diluted the eye salve – as it is hard to know just how much of the medicine bacteria would be exposed to when applied to a real infection. They found that when the medicine is too dilute to kill Staphylococcus aureus, it interfered with bacterial cell-cell communication (quorum sensing). This is a key finding, because bacteria have to talk to each other to switch on the genes that allow them to damage infected tissues. Many microbiologists think that blocking this behaviour could be an alternative way of treating infection.

Dr Lee said: “We were genuinely astonished at the results of our experiments in the lab. We believe modern research into disease can benefit from past responses and knowledge, which is largely contained in non-scientific writings. But the potential of these texts to contribute to addressing the challenges cannot be understood without the combined expertise of both the arts and science.

“Medieval leech books and herbaria contain many remedies designed to treat what are clearly bacterial infections (weeping wounds/sores, eye and throat infections, skin conditions such as erysipelas, leprosy and chest infections). Given that these remedies were developed well before the modern understanding of germ theory, this poses two questions: How systematic was the development of these remedies? And how effective were these remedies against the likely causative species of bacteria? Answering these questions will greatly improve our understanding of medieval scholarship and medical empiricism, and may reveal new ways of treating serious bacterial infections that continue to cause illness and death.”

University microbiologist, Dr Freya Harrison has led the work in the laboratory at Nottingham with Dr Steve Diggle and Research Associate Dr Aled Roberts. She will present the findings at the Annual Conference of the Society for General Microbiology which starts on Monday 30th March 2015 in Birmingham.

Dr Harrison commented: “We thought that Bald’s eyesalve might show a small amount of antibiotic activity, because each of the ingredients has been shown by other researchers to have some effect on bacteria in the lab – copper and bile salts can kill bacteria, and the garlic family of plants make chemicals that interfere with the bacteria’s ability to damage infected tissues. But we were absolutely blown away by just how effective the combination of ingredients was. We tested it in difficult conditions too; we let our artificial ‘infections’ grow into dense, mature populations called ‘biofilms’, where the individual cells bunch together and make a sticky coating that makes it hard for antibiotics to reach them. But unlike many modern antibiotics, Bald’s eye salve has the power to breach these defences.”

Dr Steve Diggle added: “When we built this recipe in the lab I didn’t really expect it to actually do anything. When we found that it could actually disrupt and kill cells in S. aureus biofilms, I was genuinely amazed. Biofilms are naturally antibiotic resistant and difficult to treat so this was a great result. The fact that it works on an organism that it was apparently designed to treat (an infection of a stye in the eye) suggests that people were doing carefully planned experiments long before the scientific method was developed.”

Dr Kendra Rumbaugh carried out in vivo testing of the Bald’s remedy on MRSA infected skin wounds in mice at Texas Tech University in the United States. Dr Rumbaugh said: “We know that MRSA infected wounds are exceptionally difficult to treat in people and in mouse models. We have not tested a single antibiotic or experimental therapeutic that is completely effective; however, this ‘ancient remedy’ performed as good if not better than the conventional antibiotics we used.”

Dr Harrison concludes: “The rise of antibiotic resistance in pathogenic bacteria and the lack of new antimicrobials in the developmental pipeline are key challenges for human health. There is a pressing need to develop new strategies against pathogens because the cost of developing new antibiotics is high and eventual resistance is likely. This truly cross-disciplinary project explores a new approach to modern health care problems by testing whether medieval remedies contain ingredients which kill bacteria or interfere with their ability to cause infection”.—a-medieval-remedy-for-modern-day-superbugs.aspx



The many documented cases of strange delusions and neurological syndromes can offer a window into how bizarre the brain can be.

It may seem that hallucinations are random images that appear to some individuals, or that delusions are thoughts that arise without purpose. However, in some cases, a specific brain pathway may create a particular image or delusion, and different people may experience the same hallucination.

In recent decades, with advances in brain science, researchers have started to unravel the causes of some of these conditions, while others have remained a mystery.

Here is a look at seven odd hallucinations, which show that anything is possible when the brain takes a break from reality.

1. Alice-in-Wonderland syndrome
This neurological syndrome is characterized by bizarre, distorted perceptions of time and space, similar to what Alice experienced in Lewis Carroll’s “Alice’s Adventures in Wonderland.”

Patients with Alice-in-Wonderland syndrome describe seeing objects or parts of their bodies as smaller or bigger than their actual sizes, or in an altered shape. These individuals may also perceive time differently.

The rare syndrome seems to be caused by some viral infections, epilepsy, migraine headaches and brain tumors. Studies have also suggested that abnormal activity in parts of the visual cortex that handle information about the shape and size of objects might cause the hallucinations.

It’s also been suggested that Carroll himself experienced the condition during migraine headaches and used them as inspiration for writing the tale of Alice’s strange dream.

English psychiatrist John Todd first described the condition in an article published in the Canadian Medical Association Journal in 1955, and that’s why the condition is also called Todd’s syndrome. However, an earlier reference to the condition appears in a 1952 article by American neurologist Caro Lippman. The doctor describes a patient who reported feeling short and wide as she walked, and referenced “Alice’s Adventures in Wonderland” to explain her body image illusions.

2. Walking Corpse Syndrome
This delusion, also called Cotard’s Syndrome, is a rare mental illness in which patients believe they are dead, are dying or have lost their internal organs.

French neurologist Jules Cotard first described the condition in 1880, finding it in a woman who had depression and also symptoms of psychosis. The patient believed she didn’t have a brain or intestines, and didn’t need to eat. She died of starvation.

Other cases of Cotard’s syndrome have been reported in people with a range of psychiatric and neurological problems, including schizophrenia, traumatic brain injury and multiple sclerosis.

In a recent case report of Cotard’s syndrome, researchers described a previously healthy 73-year-old woman who went to the emergency room insisting that she was “going to die and going to hell.” Eventually, doctors found the patient had bleeding in her brain due to a stroke. After she received treatment in the hospital, her delusion resolved within a week, according to the report published in January 2014 in the journal of Neuropsychiatry.

3. Charles Bonnet syndrome
People who have lost their sight may develop Charles Bonnet syndrome, which involves having vivid, complex visual hallucinations of things that aren’t really there.

People with this syndrome usually hallucinate people’s faces, cartoons, colored patterns and objects. It is thought the condition occurs because the brain’s visual system is no longer receiving visual information from the eye or part of the retina, and begins making up its own images.

Charles Bonnet syndrome occurs in between 10 and 40% of older adults who have significant vision loss, according to studies.

4. Clinical lycanthropy
In this extremely rare psychiatric condition, patients believe they are turning into wolves or other animals. They may perceive their own bodies differently, and insist they are growing the fur, sharp teeth and claws of a wolf.

Cases have also been reported of people with delusional beliefs about turning into dogs, pigs, frogs and snakes.

The condition usually occurs in combination with another disorder, such as schizophrenia, bipolar disorder or severe depression, according to a review study published in the March issue of the journal History of Psychiatry in 2014.

5. Capgras delusion
Patients with Capgras delusion believe that an imposter has replaced a person they feel close to, such as a friend or spouse. The delusion has been reported in patients with schizophrenia, Alzheimer’s disease, advanced Parkinson’s disease, dementia and brain lesions.

One brain imaging study suggested the condition may involve reduced neural activity in the brain system that processes information about faces and emotional responses.

6. Othello syndrome
Named after Shakespeare’s character, Othello syndrome involves a paranoid belief that the sufferer’s partner is cheating. People with this condition experience strong obsessive thoughts and may show aggression and violence.

In one recent case report, doctors described a 46-year-old married man in the African country Burkina Faso who had a stroke, which left him unable to communicate and paralyzed in half of his body. The patient gradually recovered from his paralysis and speaking problems, but developed a persistent delusional jealousy and aggression toward his wife, accusing her of cheating with an unidentified man.

7. Ekbom’s syndrome
Patients with Ekbom’s syndrome, also known as delusional parasitosis or delusional infestations, strongly believe they are infested with parasites that are crawling under their skin. Patients report sensations of itching and being bitten, and sometimes, in an effort to get rid of the pathogens, they may hurt themselves, which can result in wounds and actual infections.

It’s unknown what causes these delusions, but studies have linked the condition with structural changes in the brain, and some patients have improved when treated with antipsychotic medications.