A new study led by St. Jude Children’s Research Hospital investigators disproves reports that well-fed children are more vulnerable to the dengue virus. Mosquitoes spread the virus, which can cause severe flu-like symptoms and sometimes lethal complications.

Malnourished children are just as likely as their well-fed counterparts to develop life-threatening complications following repeated infections with the dengue virus, according to work from researchers at St. Jude and Hospital Nacional de Niños Benjamin Bloom in El Salvador.

Although infectious diseases often pose the greatest threat to children with an inadequate diet, study lead author Gabriela Maron, M.D., a St. Jude Infectious Diseases clinical fellow, said earlier reports from health providers in regions of the world where dengue is common suggested that the infection hit well-nourished children the hardest. Researchers have noted that one possible explanation is that even mild malnutrition blocks the immune system from launching the strong inflammatory response linked to severe dengue infection.

“There must be subtle differences between patients, possibly related to their immune response,” Maron said. St. Jude investigators are now collaborating with colleagues in El Salvador to see if differences in gene expression might identify those at high risk for severe infection.

The study was published in a recent issue of the American Journal of Tropical Medicine and Hygiene.

Health officials estimate about one-third of the world’s population is at risk for infection with one of the four dengue viruses, including a high percentage of children living in the Caribbean, Central and South America. “Even in the U.S., cases are reported along the southern border with Mexico,” Maron said. “Without a vaccine to prevent infection, international flights and the overall shrinking of the planet mean it could become an even more important problem for U.S. health officials.”

An individual’s first dengue infection typically produces mild symptoms. But later infections can lead to life-threatening dengue hemorrhagic fever and dengue shock syndrome, which are associated with internal bleeding and a dangerous reduction in the platelets that help blood clot. The challenge for health providers, especially those in countries where resources are scarce, is to rapidly identify patients at higher risk for complications.

In this study, researchers compared the height, weight and body-mass index (BMI) of three groups of children, ages 5 through 12. The groups were youngsters hospitalized for dengue fever and dengue hemorrhagic fever who were compared with healthy classmates living in the same neighborhoods. BMI is a measurement of body mass based on a person’s weight and height.

Those results were compared with an international sample of children of the same age compiled in the World Health Organization’s standardized database. Roughly the same proportion of children in each of the study’s groups qualified as either underweight, overweight or stunted, a possible sign of chronic malnutrition. There was also no difference in the average BMI of study participants, whether healthy or ill.

WHAT: National Institutes of Health (NIH) scientists investigating how prion diseases destroy the brain have observed a new form of the disease in mice that does not cause the sponge-like brain deterioration typically seen in prion diseases. Instead, it resembles a form of human Alzheimer’s disease, cerebral amyloid angiopathy, that damages brain arteries.

The study results, reported by NIH scientists at the National Institute of Allergy and Infectious Diseases (NIAID), are similar to findings from two newly reported human cases of the prion disease Gerstmann-Straussler-Scheinker syndrome (GSS). This finding represents a new mechanism of prion disease brain damage, according to study author Bruce Chesebro, M.D., chief of the Laboratory of Persistent Viral Diseases at NIAID’s Rocky Mountain Laboratories.

Prion diseases, also known as transmissible spongiform encephalopathies, primarily damage the brain. Prion diseases include mad cow disease or bovine spongiform encephalopathy in cattle; scrapie in sheep; sporadic Creutzfeldt-Jakob disease (CJD), variant CJD and GSS in humans; and chronic wasting disease in deer, elk and moose.

The role of a specific cell anchor for prion protein is at the crux of the NIAID study. Normal prion protein uses a specific molecule, glycophosphoinositol (GPI), to fasten to host cells in the brain and other organs. In their study, the NIAID scientists genetically removed the GPI anchor from study mice, preventing the prion protein from fastening to cells and thereby enabling it to diffuse freely in the fluid outside the cells.

The scientists then exposed those mice to infectious scrapie and observed them for up to 500 days to see if they became sick. The researchers documented signs typical of prion disease including weight loss, lack of grooming, gait abnormalities and inactivity. But when they examined the brain tissue, they did not observe the sponge-like holes in and around nerve cells typical of prion disease. Instead, the brains contained large accumulations of prion protein plaques trapped outside blood vessels in a disease process known as cerebral amyloid angiopathy, which damages arteries, veins and capillaries in the brain. In addition, the normal pathway by which fluid drains from the brain appeared to be blocked.

Their study, Dr. Chesebro says, indicates that prion diseases can be divided into two groups: those with plaques that destroy brain blood vessels and those without plaques that lead to the sponge-like damage to nerve cells. Dr. Chesebro says the presence or absence of the prion protein anchor appears to determine which form of disease develops.

The new mouse model used in the study and the two new human GSS cases, which also lack the usual prion protein cell anchor, are the first to show that in prion diseases, the plaque-associated damage to blood vessels can occur without the sponge-like damage to the brain. If scientists can find an inhibitor for the new form of prion disease, they might be able to use the same inhibitor to treat similar types of damage in Alzheimer’s disease, Dr. Chesebro says.

A research project in the Academy of Finland’s Research Programme on Nutrition, Food and Health (ELVIRA) has brought new knowledge on the hereditary nature of gluten intolerance and identified genes that carry a higher risk of developing the condition. Research has shown that the genes in question are closely linked with the human immune system and the occurrence of inflammations, rather than being connected with the actual breakdown of gluten in the digestive tract.

“Some of the genes we have identified are linked with human immune defence against viruses. This may indicate that virus infections may be connected in some way with the onset of gluten intolerance,” says Academy Research Fellow Päivi Saavalainen, who has conducted research into the hereditary risk factors for gluten intolerance.

Saavalainen explains that the genes that predispose people to gluten intolerance are very widespread in the population and, as a result, they are only a minor part of the explanation for the way in which gluten intolerance is inherited. However, the knowledge of the genes behind gluten intolerance is valuable in itself, as it helps researchers explore the reasons behind gluten intolerance, which in turn builds potential for developing new treatments and preventive methods. This is essential, because the condition is often relatively symptom-free, yet it can have serious complications unless treated.

Researchers have localised the risk genes by using data on patients and on entire families. The material in the Finnish study is part of a very extensive study of thousands of people with gluten intolerance and control groups in nine different populations. The research will be published in a coming issue of Nature Genetics.

Research into hereditary conditions has made great progress over the past few years. Gene researchers now face their next challenge, as a closer analysis is now needed of the risk factors in the genes that predispose people to gluten intolerance. It is important to discover how they impact on gene function and what part they play in the onset of gluten intolerance.

Gluten intolerance is an autoimmune reaction in the small intestine. Roughly one in a hundred Finns suffer from this condition. The gluten that occurs naturally in grains such as wheat, barley and rye causes damage to the intestinal villi, problems with nutrient absorption and potentially other problems too. Gluten intolerance is an inherited predisposition, and nearly all sufferers carry the genes that play a key part in the onset of the condition. The only known effective treatment is a lifelong gluten-free diet.

Why does an apple a day keep the doctor away? New research published in the open access journal BMC Microbiology contributes to our understanding of why eating apples is good for you.

Microbiologists from the National Food Institute at the University of Denmark fed rats on a diet that was rich in whole apples, apple juice, purée or pomace, or put them on a control diet. They then analysed the microbial content of the rats’ digestive systems to see if eating apples had any impact on the numbers of presumed ‘friendly’ bacteria in the gut. “Certain bacteria are believed to be beneficial for digestive health and may influence the risk for cancer. We faced a well-known problem though – many types of bacteria cannot be easily cultured in the lab”, said research leader Professor Tine Rask Licht. The team therefore used genetics instead of culture techniques to examine the microbiology of the intestines. 16S rRNA is a molecule that is only found in bacteria and its make up is unique to each species or strain. “By working out the sequences of 16S rRNA molecules in the rats’ intestines and matching these to known bacterial profiles of 16S rRNA, we could determine which microorganisms were abundant in each group of rats”, explained Licht.

So what was the verdict? “In our study we found that rats eating a diet high in pectin, a component of dietary fiber in apples, had increased amounts of certain bacteria that may improve intestinal health”, said co-researcher Andrea Wilcks. “It seems that when apples are eaten regularly and over a prolonged period of time, these bacteria help produce short-chain fatty acids that provide ideal pH conditions for ensuring a beneficial balance of microorganisms. They also produce a chemical called butyrate, which is an important fuel for the cells of the intestinal wall”.

Of course, further research is needed to determine whether the digestive system of humans responds to apples in the same way as rats, but these findings certainly suggest that Europe’s favourite fruit has a well-deserved place in our 5-a-day.

A randomised controlled trial of fish oil given intravenously to patients in intensive care has found that it improves gas exchange, reduces inflammatory chemicals and results in a shorter length of hospital stay. Researchers writing in BioMed Central’s open access journal Critical Care investigated the effects of including fish oil in the normal nutrient solution for patients with sepsis, finding a significant series of benefits.

Philip Calder, from the University of Southampton, UK, worked with a team of researchers to carry out the study in 23 patients with systemic inflammatory response syndrome or sepsis in the Hospital Padre Américo, Portugal. He said, “Recently there has been increased interest in the fat and oil component of vein-delivered nutrition, with the realization that it not only supplies energy and essential building blocks, but may also provide bioactive fatty acids. Traditional solutions use soybean oil, which does not contain the omega-3 fatty acids contained in fish oil that act to reduce inflammatory responses. In fact, soybean oil is rich in omega-6 acids that may actually promote inflammation in an excessive or unbalanced supply”.

Calder and his colleagues found that the 13 patients in the fish oil group had lower levels of inflammatory agents in their blood, were able to achieve better lung function and left hospital earlier than the 10 patients who received traditional nutrition. According to Calder, “This is the first study of this particular fish oil solution in septic patients in the ICU. The positive results are important since they indicate that the use of such an emulsion in this group of patients will improve clinical outcomes, in comparison with the standard mix”.

Retroviruses such as HIV and HTLV-1 don’t hit-and-run, they hit-and-hide. They slip into host cells and insert their own DNA into the cell’s DNA, and from this refuge they establish an infection that lasts a lifetime.

But that infection might be much less troublesome and much more manageable if the immune system could mount a strong response to the virus during its first few days in the body, according to a new study by cancer researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James).

The animal study, published online in the journal Blood, examined the human T-lymphotropic virus type 1 (HTLV-1), which causes adult T-cell leukemia and several inflammatory diseases in some people.

“Our findings indicate that if the immune system could respond strongly to HTLV-1 and kill infected target cells early, it may inhibit the virus’s ability to establish reservoirs of infected cells and make the infection more manageable later,” says principal investigator Michael Lairmore, a professor and chair of veterinary biosciences and a cancer researcher at OSUCCC-James.

“This study tells us that the more we know about the earliest events of infection, the more it will help us develop vaccines and might block those events.”

Lairmore and his colleagues examined HTLV-I infection in rabbits that were treated with the drug cyclosporin A, which is commonly used to suppress the immune system in people following organ transplantation. The researchers compared animals treated with this drug prior to viral infection with those given the drug one week after infection.

This study builds on earlier work by Lairmore and his colleagues showing that HTLV-I produces proteins that activate infected immune cells and causes them to divide, thereby increasing the number of infected cells in the body. The researchers found that cyclosporin A blocked that activation.

In this new study, the researchers used cyclosporin A to learn whether modifying the immune response – by providing fewer immune cells for the virus to attack – at a critical time, after the first week of infection when the virus needs to spread, would influence the extent of the infection weeks later.

In animals given the immune-suppressing drug first, the virus flourished. The number of virus copies jumped to 200 per 10,000 immune cells (lymphocytes), compared with 40 per 10,000 immune cells in control animals (these were infected with the virus but not given the drug). After a week or two, the number of virus copies fell, ranging from 113 to 160 for remainder of the 10-week experiment.

In the animals that were given the virus first and then the immune-suppressing drug a week later, on the other hand, the virus languished. The number of virus copies in these animals was lower than the controls, and it remained that way throughout the 10-week experiment. At week four after infection, for example, the immune-suppressed animals had on average nine virus copies per 10,000 immune cells, compared with 40 copies in control samples. At week 10, they had 10 virus copies compared with 30 in controls.

“The first experiment told us that if the immune system is suppressed, the viral load goes up – and we expected that,” says Lairmore. “The second group was the surprise. Their viral load was low from the start, and it stayed that way. We didn’t expect that. We thought the virus would recover and come back up.

“Collectively, our findings indicate that the immune system plays a key role in controlling HTLV-1 spread during early infection, which has important implications for a vaccine against this virus and for therapy for HTLV-1-associated diseases,” says Lairmore.

A bacterial species that depends on cooperation to survive is discriminating when it comes to the company it keeps. Scientists from Indiana University Bloomington and Netherlands’ Centre for Terrestrial Ecology have learned Myxococcus xanthus cells are able to recognize genetic differences in one another that are so subtle, even the scientists studying them must go to great lengths to tell them apart.

The scientists’ report, which appears in a recent issue of Current Biology, also provides further evidence that cooperation in nature is not always a festival of peace and love. Rather, cooperation may be more of a grudging necessity, in which partners continually compete and undermine one another in a bid for evolutionary dominance.

“In some social microbes, cooperation is something that happens primarily among identical or very similar cells, as a way of competing against relatively unrelated individuals in other cooperative units,” said IU Bloomington biologist Gregory Velicer, who led the research. “This is unlike humans, who are more likely to cooperate with unrelated individuals as well as with close kin. In the bacteria we study, cooperation appears to be highly restricted.”

Myxococcus xanthus is a predatory bacterium that swarms through soil, killing and eating other microbes by secreting toxic and digestive compounds. When food runs out, cells aggregate and exchange chemical signals to form cooperative, multi-cellular “fruiting bodies.” Some of the cells create the fruiting body’s structure, while other cells are destined to become hardy spores for the purpose of surviving difficult conditions.

Previously, experiments by Velicer and Ph.D. student Francesca Fiegna showed that when different Myxococcus strains isolated from around the globe were mixed together, the number of spores produced was much reduced. This indicated that this social bacterium had diverged into many socially conflicting types. Michiel Vos, then a Ph.D. student with Velicer at the Max Planck Institute for Developmental Biology in Tübingen, Germany, set out to find whether Myxococcus bacteria sharing the same centimeter-scale soil patch were still capable of efficiently forming fruiting bodies together, or whether these close neighbors would already engage in social conflict.

As part of the experimental design for their Current Biology study, Velicer and Vos paired Myxococcus strains isolated from soil samples taken just centimeters apart to see whether they would behave cooperatively or competitively.

The scientists found that some pairs of strains, inhabiting the same patch of soil and almost identical genetically, had nevertheless diverged enough to inhibit each other’s ability to make spores.

In general, however, the scientists found competition was less intense among centimeter-scale pairings than for pairings of more distantly related bacteria isolated from distant locations. These results indicate that social divergence can evolve rapidly within populations, but this divergence can be augmented by geographic isolation.

Another set of experiments revealed that different strains actively avoid each other prior to starvation-induced fruiting body formation. Velicer and Vos argue that this type of exclusion within diverse populations — in which the probability of social conflict among neighbors is high — may serve to direct the benefits of cooperation to close kin only.

Velicer says he plans to conduct an exhaustive search for specific genetic differences that lead to antagonism and social exclusion in pairing of closely related strains. “We’ve got lots of candidate genes,” he said.

A long-term goal, Velicer explains, is to understand how new species of social bacteria might evolve sympatrically, that is, in a geographical area shared with a parental species.

“If strong social incompatibilities evolve rapidly, that has implications for understanding how interacting strains diverge over long periods of time,” Velicer said.

After Mimivirus, Mamavirus and the virophage, the group of giant viruses now has a new member called Marseillevirus. Discovered in an amoeba by the team led by Didier Raoult at the Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes research group (CNRS/Université Aix-Marseille 2), a description of this new virus was published this week on the website of the Proceedings of the National Academy of Sciences (PNAS). These findings suggest the exchange of genes in amoebae that may lead to the constitution of different gene repertoires that could be a source of new pathogens.

Amoebae are single-cell, eukaryote (possessing a nucleus) living organisms, some of which are human or animal parasites and may cause a variety of pathologies. Most amoebae live in water, damp soils or mosses. They are mobile and capable of ingesting a wide variety of different organisms (for example, viruses or bacteria with extraordinarily broadly ranging sizes and lifestyles). Thus amoebae provide a site for numerous exchanges of genetic material arising from the many organisms that “colonize” them.

The team led by Didier Raoult at URMITE (CNRS/Université Aix-Marseille 2)(1) has recently discovered, in an amoeba, a member of a new family of giant viruses, which it has called the Marseillevirus, smaller than Mimivirus, which is the largest giant virus known at present. With a chimeric genome (containing both DNA and RNA) of 368,000 base pairs, Marseillevirus is indeed the fifth largest viral genome to be sequenced. It has an icosahedral shape and a diameter of about 250 nanometers (or 250 millionths of a millimeter). In addition, the researchers discovered that it contained genes from markedly differing sources, i.e. of bacterial, viral or eukaryote origin, or arising from Archae(2). The genome of Marseillevirus, a mosaic of genes from very different organisms, thus demonstrates the exchange of genes between the organisms that “colonize” amoebae. These studies have also revealed the role of amoebae, and more generally phagocytic protists (or single-cell eukaryotes) that feed on microbes in the environment, in the constitution of new gene “repertoires” which may be capable of generating new agents that will be pathogenic to multicellular organisms such as animals, plants or humans.

A vascular surgical technique pioneered at UT Southwestern Medical Center and designed to replace infected aortic grafts with the body’s own veins has proved more durable and less prone to new infection than similar procedures using synthetic and cadaver grafts.

Aortic graft infections are one of the most serious complications in patients undergoing aortic grafting procedures for peripheral arterial disease (PAD) and aortic aneurysms. PAD reduces blood circulation in the pelvis and lower extremities, and aortic aneurysms result in a weakening of the aortic wall that can cause lethal rupture of the aorta, the largest artery in the body. Patients with PAD and aortic aneurysms often require surgery, and aortic grafting procedures using synthetic grafts are typically the first line of treatment.

For patients with PAD, the procedure restores blood circulation to the legs, and for patients with aneurysm, it replaces the weakened aortic wall and prevents rupture. Synthetic grafts made of Dacron, a polyester material, are placed in the aorta and femoral arteries in the abdomen and groin, which feed blood to the legs. But in about 1 percent to 2 percent of these patients, the grafts become infected a complication that causes amputation and death if left untreated.

Dr. G. Patrick Clagett, chief of vascular surgery at UT Southwestern, pioneered a technique called the neo-aortoiliac system (NAIS) that repairs these aortic-graft infections. The procedure involves removing the infected graft and replacing it with sections of femoral-popliteal veins harvested from the patient’s thighs, rather than another synthetic graft or vessels harvested from human cadavers.

In a recent study published in the Journal of Vascular Surgery, Dr. Clagett and his team reported on 187 patients at UT Southwestern treated for aortic graft infections who underwent the NAIS procedure from 1990 to 2006. It is the largest group of such patients ever studied, and the researchers found that the incidence of re-infection was lower and the procedure resulted in superior durability with much lower long-term amputation rates when compared with other operations to treat this condition.

“This operation has gained favor worldwide in the treatment of this devastating condition,” said Dr. Clagett. “Since performing the first operation here in the 1990s, we have accumulated data over the years and have found this procedure to be far superior in overall patient outcomes.”

Simply replacing the old Dacron graft with a new synthetic graft can result in devastating infection of the new one, said Dr. Clagett, who is immediate past president of the Society for Vascular Surgery. His team and others also have found that the new synthetic or cadaver grafts tend to develop clots and new blockages.

“When we use the patient’s own tissue to construct a new graft, it provides an advantage because they are less likely to form clots within the graft and less likely to develop new blockages,” Dr. Clagett said. “Patients also need fewer subsequent procedures, a common problem with the other treatments for this complication.”

He added that patients who have the NAIS procedure don’t need to be on lifelong antibiotic therapy. Because the aortic reconstruction is fashioned with the patient’s own tissue, there is no foreign material that is prone to re-infection.

Brazilian researchers have performed the first-ever autopsy study to examine the precise causes of death in victims of the H1N1 swine flu.

“The lack of information on the pathophysiology of this novel disease is a limitation that prevents better clinical management and hinders the development of a therapeutic strategy,” said lead author, Thais Mauad, M.D., Ph.D., associate professor of the Department of Pathology at São Paulo University, in Brazil.

The results of their study will be published in the January 1 issue of the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

The researchers examined 21 patients who had died in São Paulo with confirmed H1N1 infection in July and August, 2009. Most were between the ages of 30 and 59. They found that three-quarters (76 percent) of the patients had underlying medical conditions such as heart disease or cancer, but there was no clear complicating medical condition in the remaining quarter. All presented a progressive and rapidly fatal form of the disease.

While previous data has shown that most patients with a non-fatal infection have fever, cough and achiness (myalgia), Dr. Mauad noted that “most patients with a fatal form of the disease presented with difficulty breathing (dyspnea), with fever and myalgia being less frequently present.”

All patients died of severe acute lung injury, but there were three distinct patterns of the damage to their lungs, indicating that the infection killed in distinct ways. “All patients have a picture of acute lung injury,” said Dr. Mauad. “In some patients this is the predominant pattern; in others, acute lung injury is associated with necrotizing bronchiolitis (NB); and in others there is a hemorrhagic pattern.”

“Patients with NB are more likely to have a bacterial co-infection. Patients with heart disease and cancer are more likely to have a hemorrhagic condition in their lungs. It is important to bear in mind that patients with underlying medical conditions must be adequately monitored, since they are at greater risk of developing a severe H1N1 infection,” said Dr. Mauad. In these patients, H1N1 infection may present as a potential fatal disease, requiring early and prompt intensive care management, including protective ventilation strategies and adequate hemodynamic management. “We found that 38 percent of these patients had a bacterial infection (bronchopneumonia). This has important consequences because these patients need to receive antibiotic therapy, in addition to antiviral therapy.”