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Infectious Disease

Chronic Disease, Immunology, Infectious Disease, Neuroscience, Research, Stanford News

ME/CFS/SEID: It goes by many aliases, but its blood-chemistry signature is a giveaway

ME/CFS/SEID: It goes by many aliases, but its blood-chemistry signature is a giveaway

signature

It’s the disease that dare not speak its name without tripping over one of its other names. Call it what you will – chronic fatigue syndrome (CFS), myalgic encephalomyelitis (ME) or its latest, Institute of Medicine-sanctioned designation, systemic exertion intolerance disease (SEID). It’s very real, affecting between 1 million and 4 million people in the United States alone, according to Stanford infectious-disease sleuth Jose Montoya, MD, who has closely followed more than 200 SEID patients for several years and done extensive testing on these patients in an effort to find out what’s causing their condition.

Different authorities have quoted different numbers regarding those with SEID. The name-calling and number-assigning squishiness stems from the fact that beyond its chief defining symptom – overwhelming, unremitting exhaustion lasting for six months or longer – it’s tough to pin down. Additional symptoms can range from joint and muscle pain, incapacitating headaches or food intolerance to sore throat, lymph-node enlargement, gastrointestinal problems, abnormal blood-pressure or hypersensitivity to light, noise or other sensations.

Research into the hows and whys of SEID has been plagued by the inability to establish any characteristic biochemical or neuroanatomical underpinnings of the disorder. Although many viral suspects have been interrogated, no accused microbial culprit has been indicted. To this day, there are no valid laboratory tests for diagnosing SEID.

But a burst of insight into SEID’s physiological substrate came only months ago when Stanford neuroradiologist Mike Zeineh, MD, PhD, working with patients from Montoya’s registry, found that they shared a pattern of white-matter loss in specific parts of the brain. The discovery drew a great deal of attention in the press as well as the CFS community. (See our news release about that study for details.)

Now a high-profile, multi-institution team including Montoya has published a study in Science Advances showing yet another physiological basis for a diagnosis of SEID: a characteristic pattern, or “signature,” consisting of elevated levels of various circulating immune-signaling substances in the blood.

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Cancer, Evolution, Genetics, Infectious Disease, Microbiology, Research, Stanford News

Bubble, bubble, toil and trouble – yeast dynasties give up their secrets

Bubble, bubble, toil and trouble - yeast dynasties give up their secrets

yeasty brew

Apologies to Shakespeare for the misquote (I’ve just learned to my surprise that it’s actually “Double, double, toil and trouble“), but it’s a too-perfect lead-in to geneticist Gavin Sherlock’s recent study on yeast population dynamics for me to be bothered by facts.

Sherlock, PhD, and his colleagues devised a way to label and track the fate of individual yeast cells and their progeny in a population using heritable DNA “barcodes” inserted into their genomes. In this way, they could track the rise and fall of dynasties as the yeast battled for ever more scarce resources (in this case, the sugar glucose), much like what happens in the gentle bubbling of a sourdough starter or a new batch of beer.

Their research was published today in Nature.

From our release:

Dividing yeast naturally accumulate mutations as they repeatedly copy their DNA. Some of these mutations may allow cells to gobble up the sugar in the broth more quickly than others, or perhaps give them an extra push to squeeze in just one more cell division than their competitors.

Sherlock and his colleagues found that about one percent of all randomly acquired mutations conferred a fitness benefit that allowed the progeny of one cell to increase in numbers more rapidly than their peers. They also learned that the growth of the population is driven at first by many mutations of modest benefit. Later generations see the rise of the big guns – a few mutations that give carriers a substantial advantage.

This type of clonal evolution mirrors how a bacterium or virus spreads through the human body, or how a cancer cell develops mutations that allow it to evade treatment. It is also somewhat similar to a problem that kept some snooty 19th century English scientists up at night, worried that aristocratic surnames would die out because rich and socially successful families were having fewer children than the working poor. As a result, these scientists developed what’s known as the “science of branching theory.” They described the research in a paper in 1875 called “On the probability of extinction of families,” and Sherlock and his colleagues used some of the mathematical principles described in the paper to conduct their analysis.

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Big data, Genetics, Global Health, Infectious Disease, Research, Science

The benefit of mathematical models in medicine

The benefit of mathematical models in medicine

1024px-Free_range_chicken_flockTheoretical modeling sounds like it has, at best, a distant connection to the day-to-day concerns of medical professionals who care for or research the needs of patients. But when I spoke recently with Noah Rosenberg, PhD, a population geneticist at Stanford and editor of the scientific journal Theoretical Population Biology, he pointed out that modeling can offer distinct benefits to those in medical fields like epidemiology and genetics.

“We see a lot of occasions in public discussions of areas like the spread of epidemics, the demography of aging populations, and big data analysis in genomics where part of the backdrop arises from theoretical population biology work,” Rosenberg said. “We hope to spread the word that there is a place for the kinds of theoretical and mathematical insights that can contribute to those important topics.”

Rosenberg noted that papers in the journal often span the divide between mathematics and biology, but they have a few things in common. In an editorial he published last month in the journal, Rosenberg describes an ideal study for the journal – namely that first, “the mathematical work is motivated by a genuine problem in biology, and there’s a need for theory to resolve the problem,” he said. Secondly, the mathematical work is substantial enough that it uncovers new potential relationships or new explanations for a phenomenon, and lastly, that the advances contribute to our understanding of biology – though some of the best papers in the field can also have a big impact on the field of mathematics, too.

When I asked him to talk about what that would mean for studies that touch on health research, he pointed me to a couple of fascinating papers. One is a paper by Shai Carmi, PhD, and colleagues that explains a new way to look at shared DNA strands between people in order to understand their relatedness and the amount of overlap in their genomes. This has implications for how we think about “the way in which genes descend within families, including genes that may be related to a disease.” It’s one of the journal’s most downloaded papers, Rosenberg told me.

The second is a study by Maciej Boni, PhD, and colleagues that incorporates how decisions that poultry farmers in Southeast Asia make about market conditions might affect the spread of avian influenza in their flocks. When avian flu is identified in a region, poultry flocks are usually culled. It’s an interesting example of how human behavior can affect disease dynamics.

Rosenberg noted that the studies and models that are able to incorporate human behavioral patterns are among the most interesting that he sees. Nailing down how people’s decisions affect the course of an outbreak is notoriously difficult, but like the avian influenza paper demonstrates, mathematical models make it possible to explore the consequences of different assumptions about these decisions.

Rosenberg says that it’s even possible to make mathematical models of cultural practices (like deciding not to immunize your children) and how they spread among groups of people. One public laboratory this interaction is currently playing out in is the measles outbreak that got its start at Disneyland in December. The outbreak topped 100 cases nationwide, mostly among families that refuse to vaccinate their children. “It’s the intersection between human behavior and dynamics of disease,” he said. “Putting those together in a mathematical model to predict what might happen is the kind of work that appears in Theoretical Population Biology.”

Previously: Stanford physician Sanjay Basu on using data to prevent chronic disease in the developing world and Facebook app models how viruses spread through human interaction
Photo by Woodley Wonderworks

Immunology, Infectious Disease, Public Health, Research

Is honey the new antibiotic?

Is honey the new antibiotic?

3535805377_807788e3e1_z…Well, not quite. But recent research shows that honey does have infection-fighting properties surprisingly similar to the common antibiotic ampicillin. And even more importantly, honey worked just as well against bacteria that had developed a resistance to ampicillin, which is good news as the medical community raises awareness about antibiotic resistance.

The study, which was recently published in PLOS ONE, compared the effects of Canadian honey and ampicillin on E. coli bacteria. The most common kind of antibiotics – beta-lactams, which includes ampicillin – work by destroying the cell wall of a bacterium. This prohibits the bacterium from surviving, growing, and reproducing. In the experiment, the researchers used scanning electron microscopy to visualize the changes in the bacterial cultures’ cell structures. They saw that honey and ampicillin had similar effects on the shapes of the E. coli, that they affected it to a similar degree, and that honey had equal effects on normal and antibiotic-resistant E. coli.

As reported on the PLOS blog:

While scientists have yet to confirm the exact compounds responsible, the results of the above study support the idea that honey and ampicillin may have similar antibacterial efficacies, with possibly different mechanisms of attack.

But before you start smothering your toast with gooey goodness each morning or adding heaping spoonfuls to your tea, keep in mind that more research is needed to better understand the potential for honey’s medicinal use.

Previously: A look at our disappearing microbes
Photo by bionicgrrl

Events, Immunology, Infectious Disease, Microbiology, Public Health

A look at our disappearing microbes

A look at our disappearing microbes

8146322408_5312e9deb2_zCould obesity, asthma, allergies, diabetes, and certain forms of cancer all share a common epidemiological origin? NYU microbiologist Martin Blaser, MD, thinks so – he calls these “modern plagues” and traces them to a diminished microbial presence in our bodies, caused by the overuse of antibiotics and the increased incidence of caesarian sections.

I attended a recent public lecture sponsored by UC Santa Cruz’s Microbiology and Environmental Toxicology department, during which the charismatic Blaser cited statistics about antibiotic use in childhood. Alarmingly, American children receive on average seventeen courses of antibiotics before they are twenty years old, taking a progressively bigger toll on their internal microbial ecosystems. We also have an unprecedented rate of c-sections – at nearly 33 percent. Babies delivered this way are deprived of contact with their mothers’ vaginal microbes, which in vaginal deliveries initiates the infant’s intestinal, respiratory, and skin flora. Breastfeeding has implications for beneficial bacterial transfer, too.

It’s not news that antibiotics are being overused – Stanford Medicine hosts an Antimicrobial Stewardship Program dedicated to this cause, and the CDC has been hosting a campaign for awareness about appropriate antibiotic use for several years, including their use in farm animals. (Seventy to eighty percent of antibiotic use takes place on farms to promote growth – that is, not for veterinary reasons.)

Overuse leads to antibiotic resistance, a serious problem. Meanwhile, research by Blaser and others – notably Stanford microbiologist David Relman, MD – has shown that abundant bacterial and viral life is essential to healthy bodies, and that imbalances in the microbial ecosystems that inhabit our gut play an important role in the chronic diseases of the modern age. Blaser said he is concerned that we’re going down a path where each generation has fewer and fewer species of microbes; part of his research is to compare human gut biodiversity in different parts of the globe, and people in remote areas of New Guinea have far more variety than those in Western nations.

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Global Health, Health Policy, In the News, Infectious Disease

President Obama and Indian Prime Minister praise partnership that led to rotavirus vaccine

President Obama and Indian Prime Minister praise partnership that led to rotavirus vaccine

Barack_Obama_talks_with_Narendra_ModiDuring his three-day visit to India, President Barack Obama issued a joint statement with Indian Prime Minister Narendra Modi praising the “highly successful collaboration” that led to the availability of a newly developed Indian rotavirus vaccine, which is expected to save 80,000 children in India alone each year.

The vaccine was developed with support from the Indo-U.S. Vaccine Action Program, co-chaired since 2009 by Harry Greenberg, MD, senior associate dean for research at the Stanford School of Medicine. Greenberg was the lead inventor of the first-generation vaccine for rotavirus, a severe diarrheal disease that kills between 300,000 and 400,000 children each in the developing world.

“This is the VAP’s biggest accomplishment to date,” Greenberg told me from Taiwan, where he is attending a conference. “The program really helped support the development of a new safe and effective rotavirus vaccine from the start to finish. And it’s the first time ever that a new vaccine was developed in a less developed country by and for that country and became licensed.”

The vaccine initiative, funded by the U.S. Public Health Service and the Indian government, was created in 1987 to help advance the development of new vaccines of importance to India. The NIH manages research grants in the United States for the vaccine program.

“The VAP has been the most successful, continuous program we have with India,” Roger Glass, MD, PhD, director of the NIH’s Fogarty International Center, wrote in an email from India to top NIH officials. “It’s amazing to me that this little research project on rotavirus with Harry Greenberg and George Curlin (former deputy director of NIH’s Division of Microbiology and Infectious Diseases) has turned into a real product that is being launched and will be used.”

A low-cost version of the vaccine, known as Rotavac, is being manufactured in India and was launched into the marketplace on Jan. 23, Greenberg said. It was the result of an unusual team effort involving diverse multinational groups of investigators from 13 institutions seeking to create a vaccine that was not only safe and effective, but also affordable enough for use in India and other low-income countries, Greenberg said. The Indian government is negotiating to purchase the vaccine for public distribution. The vaccine also will compete in the private market against at least two other commercially available vaccines.

In the joint statement, the two world leaders pledged continued support for the vaccine program, and Greenberg, who recently stepped down from his chairmanship, made an argument for now focusing the attention of the vaccine partnership on respiratory syncytial virus (RSV), a potentially serious lung disease that is prevalent in children in India and in other regions as well.

“RSV is an incredibly important pediatric pathogen all over the world, and there is now potential for great progress,” Greenberg said. “I suggested to VAP that it think about RSV as a new target for research. It has a huge public impact and it may well be that there are great advances to be made in the near future. I think that idea resonated with the people. We will see.”

Previously: Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial and Trials, and tribulations, of a rotavirus vaccine
Photo courtesy of The White House

In the News, Infectious Disease, Pediatrics, Public Health

Infectious disease expert discusses concerns about undervaccination and California’s measles outbreak

Infectious disease expert discusses concerns about undervaccination and California's measles outbreak

3480352546_ab985b66a6_zStanford’s Yvonne Maldonado, MD, who heads up Lucile Packard Children’s Hospital Stanford infectious disease team, weighed in on California’s measles outbreak last week on KQED’s Forum program.

The state reported 59 confirmed measles cases following an outbreak at Disneyland in December and fueled by high rates of under-vaccination.

“Measles is one of the most infectious viruses in humans that we know of,” Maldonado said. Spread by tiny droplets, measles remains contagious in a room for up to two hours after an infected person has left, she said.

At first, the disease appears like a lot of childhood diseases with three primary symptoms, what doctors call the “3 c’s,” — cough, coryza (runny nose) and conjunctivitis (red, watery eyes). The disease also produces fever, the charactoristic rash and in rare cases, pneumonia or other complications.

“It is not a simple, easy disease to deal with,” Maldonado said.

All children should receive two doses of the vaccine, which is 99 percent effective at preventing the disease, Maldonado said.

Adults who are born after 1957 and do not believe they have had measles, or a vaccine, should also be checked. Although measles has been basically eliminated in the U.S., it is prevalent in other countries and under-vaccination  can lead to outbreaks, the researchers said.

Previously: Measles is disappearing from the Western hemisphere, Measles are on the rise; now’s the time to vaccinate, says infectious-disease expert and A look at the causes and potential cost of the U.S. measles outbreaks 
Photo by Dave Haygarth

Infectious Disease, Parenting, Pediatrics, Pregnancy, Public Health

Cocooning newborns against pertussis

Cocooning newborns against pertussis

Grandparent hand with babyAt my last prenatal visit, I got a booster shot for whooping cough (sometimes called pertussis). The Centers for Disease Control and Prevention recommends women get a booster in the third trimester of every pregnancy. Whooping cough has been on the rise for years, and there’s an outbreak happening in California, where we live.

Newborns are especially vulnerable to severe complications from the disease, so doctors suggest that anyone who’s going to be in close contact with newborns and isn’t up-to-date also get a booster: fathers, siblings and even visiting grandparents. The strategy is called “cocooning.”

But what do you do when a grandparent doesn’t want to get a shot? A lot of people don’t like getting vaccinations, either because they want to avoid the discomfort of a shot in the arm or they don’t believe vaccines are effective. (They are.) It’s a question that comes up more often than I expected in online communities. Many pregnant women insist that grandparents who won’t get pertussis shots won’t be allowed to see the new grandchild. Others argue that you can’t force a medical decision like that on someone else. Throw in the added complication that if you’re a first-time parent, it might be the first time you’ve had to confront your parents about how you plan to raise your child. What a mess.

I’m lucky that most of my daughters’ grandparents are already vaccinated for pertussis: My parents and my mother-in-law came to stay and help us with the baby a few years ago and all got vaccinated at the time. But with all the things occupying us as new parents, we didn’t even think to ask my father-in-law, who lives nearby but didn’t have any extended stays in our home. As it turns out, he’s not a fan of vaccinations, and he insists that he got the flu from his last flu shot. (He didn’t.) Obviously, he hadn’t gotten the pertussis booster.

For this baby, we’re planning on bringing up the shot with him, but we’re not expecting him to actually get one. So what will we do? I surprised myself by deciding that I won’t insist he get one in order to see the baby, as long as he doesn’t have any cold symptoms when he visits. (Pertussis usually starts as a mild cold that gets progressively worse; by the time most people are diagnosed, they’ve been sniffling and shedding pertussis bacteria for weeks since they first showed symptoms.) But, who knows? Maybe Grandpa Lesko will surprise us and get the shot for the baby’s sake – or just to avoid the sniffle quarantine policy.

We’ll see.

Previously: Failure to vaccinate linked to pertussis deathsCDC: More U.S. adults need to get recommended vaccinations, and Whooping cough vaccine’s power fades faster than expected
Photo by Ashley Grant

Infectious Disease, SMS Unplugged

The bacteria that nearly killed my grandmother

The bacteria that nearly killed my grandmother

SMS (“Stanford Medical School”) Unplugged is a forum for students to chronicle their experiences in medical school. The student-penned entries appear on Scope once a week; the entire blog series can be found in the SMS Unplugged category.

Staphylococcus aureauMagnification 20,000“Hefur þú lært um Staphylococcus aureus?” I almost don’t recognize the bacteria name because my grandmother pronounces it differently in Icelandic.

“Já–” I’m about to translate my microbiology flashcard for her when she interrupts, her hands busy kneading the cookie dough and her eyes on my little sister near the oven.

That’s the bacteria that almost killed her eleven years ago, she tells me. I can hear her words building up. This is a story that has been waiting to be told often enough to be reconciled.

They did not know what was wrong with her. They thought maybe cancer, maybe tuberculosis – and I almost interrupt her story to tell her about Pott disease. That’s when tuberculosis from the lungs goes through the blood to the vertebrae and causes back pain, fever, night sweats and weight loss. I memorized the flashcard a few weeks ago.

My little sister stops doing handstands in the middle of the kitchen and comes to stand next to my chair. Together we watch Grandma roll the cookie dough as she continues talking.

It took the doctors a whole long time to figure out what was wrong with her. In the meantime, she was in so much pain from her back that she had to be on high doses of morphine. Codeine.

She could hear them yelling at each other in the next room, my great uncle and the other doctor. The two internists had very different approaches. My great uncle wanted to identify what was going on before putting her up for surgery. The other doctor yelled at him that he was going to wait so long the woman would die.

My grandma stops her cookie cutting and sits across from me. She looks at me for a moment over her glasses and tells me how terrifying it is to know that your doctors don’t know what’s wrong with you.

My poor great uncle, I tell her – he was just trying to make sure that they didn’t make you worse by operating.

My grandma nods and describes how when they finally did agree to have her undergo surgery, my great uncle called the best surgeon in town and had him come back early from vacation to operate on her the next day. And good thing too, for when they did, they found that three of her vertebrae had been turned to dust.

With an infection like that, the surgeon said she was hours away from death.

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Ebola, Events, Infectious Disease, Stanford News

Physician at forefront of Ebola fight: “Ultimate award” is what you get back from survivors

Physician at forefront of Ebola fight: "Ultimate award" is what you get back from survivors

BauschWhen Lassa fever, a cousin of Ebola, was afflicting hundreds of thousands of people in West Africa in the late 90s, Daniel Bausch, MD, MPH & TM, worked with the federal Centers for Disease Control and Prevention in Guinea to set up a laboratory for study and testing of the rodent-borne disease. Unfortunately, the lab lost its international funding in 2003, as it could have proven useful in preventing the Ebola epidemic, which began in a remote village in Guinea just a few hours away, Bausch told a Stanford audience last week.

“I think back that if we had succeeded in keeping this lab going, how different it would have been if we’d been able to just send a sample down the road,” instead of losing valuable time in shipping the samples to Europe for testing, said Bausch, the keynote speaker at a day-long global health conference.

Today, Bausch, an associate professor at the Tulane School of Public Health and Tropical Medicine, is at the forefront of the Ebola fight, treating patients at an Ebola clinic in Sierra Leone that he helped establish and training and recruiting other clinicians. He is also consulting with the World Health Organization in the development and implementation of treatment guidelines and drug and vaccine testing for the disease.

In 1996, Bausch was working with the CDC in the Democratic Republic of Congo, where dozens of miners were being felled by a strange set of symptoms. The source was identified as Marburg virus, a cousin of Ebola that kills more than 80 percent of victims. While the usual course of spread is from one person to the next, these miners were harboring different variants of the virus, suggesting multiple sources, he said. The disease was traced back to the caves where miners unearthed their gold and where they were exposed to bats — the likely reservoir of the virus, Bausch said. He and colleagues published an article on their Marburg investigation in 2006 in the New England Journal of Medicine.

Because of his rare expertise with hemorrhagic fevers, Bausch was called upon early on to help fight in the latest Ebola outbreak, working alongside West African colleagues in Guinea and Sierra Leone who died of the disease.  He said one bright spot in the epidemic is the speed with which scientists have moved forward in developing new treatments and potential vaccines. “In the last six months, we’ve seen a process that’s unprecedented, with accelerated science and the launch of clinical trials that would normally take years,” he said.

And he said he cherishes the experience of seeing patients who have successfully fought off the disease. He showed a photo of a colleague, draped in white protective gear, alongside a young survivor: a smiling boy in striped pants who had lost his father to Ebola.

“That is the ultimate reward… It means something to you – what you get back from (the survivors),” he said.

The Stanford Global Health Research Convening Day was sponsored by Stanford’s Center for Innovation in Global Health.

Previously: Back home from Liberia, Stanford physician continues to help in fight against EbolaEbola: This outbreak is differentStanford physician shares his story of treating Ebola patients in Liberia and Ebola: A look at what happened and what can be done
Photo, of Daniel Bausch and others in Guinea, courtesy of Bausch

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