Researchers Discover How Noroviruses Cause Repeated Outbreaks Of "Stomach Flu"
Norovirus, a common cause of gastroenteritis ("stomach flu"), could potentially be controlled by a vaccine. But because the virus evolves to avoid the immune system, the vaccine might have to be modified from year to year, according to new research published in PLoS Medicine by Ralph Baric of the University of North Carolina, Chapel Hill, and colleagues.
Noroviruses, which are highly contagious, cause nausea, vomiting, and diarrhea. While most people recover within a few days, the very young and old may experience severe disease. Although maintaining hydration is essential, there is no specific treatment for infection. As with influenza, epidemics of norovirus infection occur periodically (often in closed communities such as cruise ships), and most people have several norovirus infections during their lifetime. This winter the UK has seen almost twice as many norovirus cases compared to the same period last year.
Noroviruses infect cells after attaching to molecules called histo-blood group antigens (HBGA) present on the cell surface. HBGAs comprise a family of complex sugar molecules that exist in great variety among human beings. The researchers found that this variety provides the key to understanding how norovirus outbreaks continue to occur, even in populations that have previously been exposed to noroviruses and therefore harbor antibodies against them.
By analyzing noroviruses isolated from several outbreaks, the researchers found that the viruses evolved to avoid attack by antibodies the hosts developed against them. Over time, some viruses selected in this way attain a shape that enables them to bind to one of the other forms of HBGA, and thereafter are not only resistant to previously existing antibodies, but are also able to infect cells carrying that particular form of HBGA. These viruses can then cause a new outbreak, and the cycle repeats itself.
This continuing evolution of new replacement strains suggests that vaccines could be designed to protect against norovirus infection, but that, as with influenza vaccines, ongoing epidemiologic surveillance and reformulations of norovirus vaccines will be needed.
In a related perspective article, Ben Lopman and colleagues at the UK Health Protection Agency, who were not involved in the study, discuss the evolution of noroviruses and the implications of this research for the control of future outbreaks.
Night-Time Acid Reflux Can Impact Sleep, New Studies Reveal
According to results of a survey presented at the 72nd Annual Scientific Meeting of the American College of Gastroenterology, nighttime acid reflux, along with some of the less typical manifestations or symptoms of gastroesophageal reflux disease (GERD), is associated with significant sleep impairment.
In a recent national survey, researchers assessed the prevalence of sleep impairment among people with GERD and people without GERD based on response to an Internet survey of a general population of U.S. adults. Using a validated GERD screening tool, 701 respondents were identified with GERD and the remaining were controls. Bonnie Dean, MPH, PhD, of Cerner LifeSciences, Ronnie Fass, MD of the University of Arizona and their research team found that sleep impairment was more common among people with GERD (41.9 percent) than those without GERD (19.4 percent). Researchers found that 49.5 percent of respondents with nighttime GERD reported sleeping poorly often or most of the time, compared to 36.7 percent of people with daytime GERD.
Using the survey, researchers also assessed sleep impairment among patients experiencing frequent nighttime atypical manifestations of GERD. In this case, Dr. Dean and her colleagues evaluated the subgroup of respondents with GERD, as identified using the validated GERD screener. They found that atypical manifestations or symptoms of GERD (i.e. coughing, sore throat, snoring, wheezing, choking, and chest pain) were common among those with acid reflux. Of GERD patients, 74 percent had at least one nighttime atypical manifestation. For almost every daytime and nighttime atypical manifestation assessed, more than 20 percent of GERD patients reported their occurrence as frequent (more than 2 days or nights per week). Researchers also found that sleep impairment was more common among GERD patients with atypical manifestations compared to GERD patients with only typical or classic symptoms such as heartburn and acid regurgitation. For eight of the nine nighttime atypical manifestations assessed, the proportion of GERD cases reporting sleep impairment was significantly higher for GERD cases with the atypical manifestation compared with GERD cases without the atypical manifestation.
"Awareness of nighttime reflux, atypical manifestations, and associated sleep complaints should allow more complete evaluation and treatment of GERD patients," said Dr. Dean about this project.
Tips for Calming Nighttime Acid Reflux Heartburn and other gastroesophageal reflux disease (GERD) symptoms experienced during the night commonly cause sleep disturbances, including arousal from sleep, increased wakefulness and overall poor sleep quality.
Here are several tips to help reduce nighttime acid reflux so you can sleep better:
* Sleep with your head and shoulders elevated
* Wear loose-fitting clothes
* Wait 2 to 3 hours after eating to go to sleep
* Avoid foods that trigger heartburn
Why Persistent Acid Reflux Sometimes Turns Into Cancer
New research from scientists at UT Southwestern Medical Center and the Dallas Veterans Affairs Medical Center underscores the importance of preventing recurring acid reflux while also uncovering tantalizing clues on how typical acid reflux can turn potentially cancerous.
In research published in July and August, scientists discovered that people with acid reflux disease, particularly those with a complication of acid reflux called Barrett's esophagus, have altered cells in their esophagus containing shortened telomeres, the ending sequences in DNA strands. Combined with related research to be published this month, the findings indicate that the shortened sequences might allow other cells more prone to cancer to take over.
"The research supports why it is important to prevent reflux, because the more reflux you have and the longer you have it, the more it might predispose you to getting Barrett's esophagus. So you want to suppress that reflux," said Dr. Rhonda Souza, associate professor of internal medicine at UT Southwestern and lead author of the paper which appeared in the American Journal of Physiology -- Gastrointestinal and Liver Physiology.
Heartburn occurs when acid splashes back up from the stomach into the esophagus, the long feeding tube that connects the stomach and throat, causing a burning sensation.
Over time, the persistent acid bath can cause normal skin-like cells in the esophagus to change into tougher, more acid-resistant cells of the type found in the stomach and intestine, a condition called Barrett's esophagus, explained Dr. Stuart Spechler, professor of internal medicine and senior author of the paper. "Unfortunately, those acid-resistant cells are also more prone to cancer," Dr. Spechler said.
Adenocarcinoma of the esophagus, the cancer that is especially associated with Barrett's esophagus, is currently the most rapidly rising cancer in the U.S., with a sixfold increase in cases during the past 30 years, according to the National Cancer Institute.
Understanding how and why the cells change in some cases and not others has been a major challenge for investigators.
Researchers compared telomere length and telomerase activity in biopsy specimens from 38 patients with GERD and 16 control patients. This new line of research suggests that the continuous acid bath affecting esophageal cells causes them to divide more frequently in order to regenerate the damaged lining. However, each time the cells divide, the telomeres at the end of DNA become shorter. When they become too short, the aging cell can no longer divide, Dr. Souza said.
Scientists suspect that when cells can no longer divide, other cells might infiltrate the area to make up for the loss. And those cells may be more likely to generate the acid-resistance that makes them more likely to turn cancerous.
"If the telomeres get short enough, maybe the cells can't regenerate any more and maybe that's why you start to see this change," said Dr. Spechler. "Perhaps the esophagus can't regenerate the normal skin-like squamous cells, and instead, it has to recruit cells from somewhere else and that's why you start getting these changes to intestinal-like cells."
Other studies by this group of UT Southwestern digestive disease specialists suggest the alternate cells that eventually take over might be bone-marrow cells.
"There could be cells circulating from the bone marrow that wouldn't ordinarily end up in the esophagus. But if you shorten the telomeres enough and the esophagus can't regenerate anymore, perhaps these bone-marrow cells might have to replace that tissue, and bone-marrow cells can turn into intestinal tissue," Dr. Spechler said. "This hasn't been proven, but we have some data that supports that."
In research available online prior to printing this month in Diseases of the Esophagus, Drs. Souza, Spechler and colleagues demonstrate that bone-marrow cells come into play to regenerate the esophageal lining in rats that have heavy reflux.
"So the first paper shows that the telomeres are short, suggesting that the normal squamous cells might not be able to divide anymore, so they die out," Dr. Spechler said. "The second paper suggests that the bone-marrow cells may then come and take their place, giving rise to the intestinal cells instead of the normal, skin-like cells."
Further research will be needed to confirm that hypothesis, Dr. Souza said.
"It's an interesting series of experiments," she said. "None of them absolutely prove that this is what's going on, but it's an interesting concept, and it certainly supports the theory that your normal cells poop out and eventually they can't replace the damaged ones, and maybe that's why you get Barrett's esophagus."
If confirmed, the research might also help scientists find a way to prevent the bone-marrow cells from invading or to identify markers that would allow an earlier diagnosis for Barrett's esophagus, which doesn't usually have symptoms.
Food Safety Begins As Vegetables Grow
Monitoring vegetables while they are growing is crucial in the prevention of contamination of fresh produce with harmful bacteria such as E. coli and Salmonella, say plant pathologists who are members of The American Phytopathological Society (APS).
There have been outbreaks of E. coli and Salmonella for at least the past decade, and the incidences of vegetable contamination are increasing in frequency. "We've studied plant pathogens on plants for a long time, but haven't studied human pathogens on plants until recently," said Jeri D. Barak, research microbiologist with the U.S. Department of Agriculture's Agricultural Research Service (ARS) in Albany, Calif.
"What we've found up to this point is that most contamination is occurring while the plants are still growing in the field," said Barak. "The most successful way to prevent contamination of fresh produce is to intervene before the harvest, not after," she said.
Her research has shown that pathogens like Salmonella use specific genes to colonize plants, creating an active interaction with the plant surface. "When this happens, the bacteria become almost inseparable from the vegetable," she said.
Barak and other APS members will present their latest food safety research and describe future research needs at a symposium titled "Cross Domain: Emerging Threats to Plants, Humans, and Our Food Supply" on Monday, July 30 from 1 to 5 p.m. These experts from across the United States will discuss the environmental biology of bacteria in fresh produce and the link between plants and bacteria associated with human infections, such as the recent E. coli outbreaks from California spinach.
A Stomach Microbe Linked To Asthma Prevention
The stomach bacterium Helicobacter pylori, which causes stomach cancer and peptic ulcers, may not be all bad. According to a new study, it may help protect kids from asthma.
The study, based on an analysis of a health survey of 7,663 adults, showed that a virulent strain of H. pylori was especially associated with being asthma-free before the age of 15. People who carry the strain were 40 percent less likely to have had asthma at an early age than those who didn't carry the strain. The study also found that the microbe was associated with protection against ragweed and other allergies due to pollens and molds particularly among younger adults.
The study is published in the Archives of Internal Medicine.
"Ultimately, the potentially protective properties of Helicobacter are consistent with one another," explains Martin J. Blaser, M.D., the Frederick H. King Professor of Internal Medicine, Chairman of the Department of Medicine, and Professor of Microbiology at NYU School of Medicine, who has been studying H. pylori for more than 20 years.
"These properties point toward a much more complex view of the organism - not just as ulcer-pathogen or cancer-pathogen, but as an organism that has its costs and benefits to us," says Dr. Blaser. "The relative costs and benefits clearly differ among individuals."
Dr. Blaser performed the study with Yu Chen, Ph.D., MPH, assistant professor in the Department of Environmental Medicine at NYU School of Medicine, a new faculty member with expertise in epidemiology.
H. pylori lives in the mucous layer lining the stomach where it persists for decades. It is acquired usually before the age of 10, and is transmitted mainly in families. Dr. Blaser's previous studies have confirmed the bacterium's link to stomach cancer and elucidated genes associated with its virulence, particularly a gene called cagA.
Over recent years, Dr. Blaser began to suspect that the organism, the dominant bacteria in the stomach, may play a role in human health as well as disease. This observation, he says, is consistent with a theory called the hygiene hypothesis. It suggests that exposure to microbial infections in early childhood prevents or diminishes the development of allergies and asthma.
Dr. Blaser has proposed that H. pylori may protect against diseases of the upper gastrointestinal tract, such as gastroesophageal reflux disease (GERD), which may lead to Barrett esophagus, a premalignant condition, and adenocarcinoma of the esophagus. All of these conditions have become more common in developed countries - esophageal cancer of this type is the fastest rising cancer in the United States - as H. pylori has become far less common due to improved sanitation and widespread use of antibiotics, says Dr. Blaser. (At the same time, the incidence of peptic ulcers and gastric cancer has declined in developed countries.)
Today, less than 10 percent of children carry the organism in industrialized countries, while some 90 percent of children are infected usually by age 5 in developing countries. "This bacterium has been the dominant organism in our stomach for tens of thousands of years, and it can't disappear from us without consequences," says Dr. Blaser. He says that a substantial body of work now shows that H. pylori helps protect against GERD and the conditions it leads to in the esophagus.
"The hypothesis that colonization of H. pylori, especially cagA strain, is protective of asthma risk needs to be tested by prospective studies. The findings from our study and others will collectively provide evidence," says Dr. Chen.
If the relationship between H. pylori and asthma is confirmed in other studies, which is always the yardstick of scientific validity, then it raises the question about whether "we should be trying to eliminate Helicobacter from children," says Dr. Blaser. "This is probably the first time in human history that we have children who are growing up without Helicobacter guiding their immune responses," he says. "By the repeated courses of antibiotics given to children, we are changing human microecology and we don't know what we are doing."
In the new study, Drs. Blaser and Chen evaluated whether H. pylori's protective effect against GERD could play a role in asthma, another condition sometimes associated with GERD. They used data from the Third National Health Nutrition Examination Survey (NHANES III), which was conducted from 1988 to 1994, and originally involved nearly 40,000 people. The survey included questions about a medical history of asthma, allergic rhinitis, and allergy symptoms. Nearly 8,000 of the participants were tested for antibodies to H. pylori and the cagA protein in their blood. This subgroup formed the basis of the study.
Drs. Blaser and Chen found no overall association between the presence of the cagA strain of H. pylori and current asthma status in the individuals they studied, but found an inverse association with ever having had asthma. Those with the virulent strain were 20 percent less likely to have ever had asthma compared with participants without H. pylori. In addition, the association differed quite strikingly by age of onset. It was strongest among participants who had the cagA strain of H. pylori and had had asthma before the age of 15. This result was statistically significant, meaning that the results were not likely due to chance. Those with the virulent strain were 40 percent less likely to have had asthma at a young age.
In another part of the study, they analyzed the results of allergy skin testing to six allergens, including ragweed, rye grass, and Russian thistle, among a subgroup of 2,386 adults who had the skin tests. They correlated the results with participants' H. pylori status and found the strongest association for these allergens among the younger people in the group who carried the bug. This suggested that H. pylori is involved in protection from sensitivity to pollens and molds, says Dr. Blaser.
"No one would have predicted that the presence or absence of bacteria in your stomach is associated with your sensitivity to pollens and molds," says Dr. Blaser. "But now we have that observation and we can begin to construct a model. One hypothesis is if you have H. pylori in your stomach, you have an inflammatory process that is on-going for decades, and this is skewing the immune response in a particular direction."
Smoking Influences Crohn's Disease - Effect Seen On Location, Severity Of The Disease In The Gastrointestinal Tract
A new study in The American Journal of Gastroenterology suggests that smoking may determine which part of the intestinal tract is attacked in those who suffer from Crohn's disease. Where the disease is located often determines whether the patient will eventually require surgical treatment.
"In patients who smoke, Crohn's disease tends to appear more frequently in the small intestine, rather than the colon," says study author Dr. Marian Aldhous. "Our data shows that when Crohn's disease is located here, it tends to cause more penetrating or obstructive damage, which would have to be treated by surgery."
The results of this study raise interesting questions about why smoking would affect different parts of the intestine in different ways. "Fundamental differences in small and large bowel physiology may explain the differences in location of Crohn's disease in smokers," says Aldhous. "The effects of smoking should be further investigated, to understand why smoking has a differential effect on different parts of the bowel."
Pain Affecting Older People Being Researched By The University Of Nottingham
A little-understood medical condition - which affects millions of older people in Britain - is to be studied at The University of Nottingham. David Humes of the Division of Gastroenterology, in The School of Medical and Surgical Sciences, has gained funding from Help the Aged and the Royal College of Surgeons to explore how the pain caused by diverticular disease can be reduced. The condition is formed by pouching in the lower gut - which can be painful, and, if infection sets in, can also be life-threatening.
Dr David Humes, said: "Our aim is to discover whether inflammation of the bowels causes the pain of diverticular disease. We will test new anti-inflammatory drugs to see if they could become a valuable treatment for this condition, which in varying degrees affects as many as two-thirds of the older people in our society."
Dr Lorna Layward, Research Manager for Help the Aged, said: "We are delighted to be supporting David Humes alongside the Royal College of Surgeons. This study is elegant and clear-sighted, with the potential quickly to produce real treatments for people with diverticular disease. That would be fantastic news for older people and another great success for researchers at The University of Nottingham."
The project is one of 20 new studies across the UK that have been awarded funding this year by the Help the Aged biomedical Research into Ageing programme, all of which are helping bring better health and independence to older people.
Dr Layward adds: "Help the Aged is committed to funding high quality biomedical research through our Research into Ageing programme and we have funded 20 new projects in 2007. Unfortunately for each project we can fund a further four must be turned away, so we need more donations to enable us to fund as many of the best projects as possible. We must prevent a situation that sees much of this life-changing research being consigned to the scrapheap, never to happen."
This new funding enhances the existing partnership between Help the Aged and The University of Nottingham. The charity has funded numerous projects at the University over the last three decades and, in addition to the new study with David Humes, currently funds Dr Simon Conroy's project that may lead to new support programmes for older people known to be at risk from accidental falls.
The Help the Aged biomedical Research into Ageing programme exists to improve the health and independence of older people. This is very important for the wellbeing of our ageing population. The number of people in the UK aged over 75 is projected to rise by over 70 per cent in the next 15 years whereas the population of people under 16 is set to decline slightly (1).
¹Government Actuary Department website 2007, period life expectancy, based on mid-2004 population estimates.
More information about the Help the Aged biomedical Research into Ageing programme is available at http://research.helptheaged.org.uk/_research/
American College Of Gastroenterology Offers Esophageal Reflux Testing Recommendations
New, updated guidelines for esophageal reflux testing appear in The American Journal of Gastroenterology. Developed and approved by the American College of Gastroenterology, these guidelines summarize advances in gastroesophageal reflux disease (GERD) diagnostic testing and how they have modified the clinical management of esophageal disorders.
"Gastroenterologists are confronted with an increasing number of patients presenting symptoms of GERD that are unresponsive to drug therapy," says lead author Dr. Ikuo Hirano. "These patients may have typical reflux symptoms of heartburn and regurgitation but also may complain of chest pain, asthma, chronic cough and chronic laryngitis." This confusing list of symptoms, coupled with the fact that many of these patients do not have visible esophageal erosions, makes diagnosis and treatment of GERD a challenge. Furthermore, non-gastrointestinal entities, such as cardiac or pulmonary disease, may produce symptoms that are similar to those attributable to GERD.
Some new technologies offer opportunities for more accurate diagnoses. "Wireless capsule pH monitoring, bile acid reflux monitoring devices and esophageal impedance can all improve the detection of reflux," says Dr. Hirano. These technologies have helped gastroenterologists to discover new forms of reflux, and to better characterize traditional acid reflux.
Of course, all technologies have limitations, and the new guidelines highlight these as well. In addition, recommendations on the clinical applications of esophageal reflux testing are presented.
Limits Of The Reflux Disease Questionnaire In General Practice
A new study, published in the journal "Digestion", determined the diagnostic and therapeutic response of the Reflux Disease Questionnaire (RDQ) using the symptom association probability as reference. The symptom association probability objectively determines with a Fisher exact test whether symptoms are due to reflux events taking all symptom episodes and reflux events into account. In addition, the RDQ's construct validity and its relationship to quality of life were ascertained.
Seventy-four patients with gastro-oesophageal reflux disease (GORD) symptoms (age 51 years (22-78); male 62%) derived from primary care completed the RDQ, Gastrointestinal Rating Scale and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaires before and after a two-week course of esomeprazole, a proton pump inhibitor (40 mg daily). The symptom association probability was determined by a 24-hour pH recording before proton pump inhibitor treatment. The diagnostic abilities of the RDQ (total and 4 dimensions scores) were assessed with the area under the curve of a receiver operating curve. RDQ scores before and after proton pump inhibitor treatment were compared with Wilcoxon tests. Multiple linear regressions assessed the RDQ's construct validity (Gastrointestinal Rating Scale) and relationship to quality of life (QOLRAD).
The areas under the curve were low for all RDQ dimensions (<0.6). In patients positive for symptom association probability all RDQ dimensions improved (p < 0.0001) while the scores of those negative for symptom association probability did not (heartburn p < 0.01; GORD and total score p < 0.05; regurgitation and dyspepsia not significant). The RDQ was related to the total and reflux dimensions of the Gastrointestinal Rating Scale, while the food and drink quality of life dimension was linearly associated with the RDQ.
Therefore, the RDQ is a valid and reliable questionnaire with excellent construct validity and a good relationship to quality of life. The diagnostic value of the RDQ in primary care is limited, but combination with an additional proton pump inhibitor treatment course might improve the RDQ's ability to discriminate GORD patients according to their symptom association probability outcome.