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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

Aging, Genetics, Immunology, Infectious Disease, Research, Stanford News

In human defenses against disease, environment beats heredity, study of twins shows

In human defenses against disease, environment beats heredity, study of twins shows

Pfc. Lane Higson and Pfc. Casey Higson, identical twins serving in Iraq with the Enhanced Combat Aviation Brigade, 1st Infantry Division. The twins, natives of Myrtle Beach, S.C., joined the Army together and have not separated since.I’m one of those people who’ve paid to have their genomes analyzed for the purpose of getting a handle on susceptibility to this or that disease as time goes by. So it was with great interest that I came across a new study of twins conducted by immunologist Mark Davis, PhD, and fellow Stanford investigators. The study, published in CELL, shows that our environment, more than our heredity, plays the starring role in determining the state of our immune system, the body’s primary defense against disease. This is especially true as we age.

Improving gene-sequencing technologies have focused attention on the role of genes in diseases. But the finding that the environment is an even greater factor in shaping our immune response should give pause to anyone who thinks a whole-genome test is going to predict the course of their health status over a lifetime.

“The idea in some circles has been that if you sequence someone’s genome, you can tell what diseases they’re going to have 50 years later,” Davis told me when I interviewed him for a news release I wrote on the study. But, he noted, the immune system has to be tremendously adaptable in order to cope with unpredictable episodes of infection, injury and tumor formation.

Davis, who heads Stanford’s Institute for Immunity, Transplantation and Infection, is worth taking seriously. He’s made a number of major contributions to the field of immunology over the last 30 years or so.  (Not long ago, I wrote an article about one of those exploits for Stanford Medicine.)

To find out whether the tremendous differences observed between different people’s immune systems reflec tunderlying genetic differences or something else, Davis and his colleagues compared members of twin pairs to one another. Identical twins inherit the same genome, while fraternal twin pairs are no more alike genetically than regular siblings, on average sharing 50 percent of their genes. (Little-known fun factoid: The percentage can vary from 0 to 100, in principle, depending on the roll of the chromosomal dice. But it typically hovers pretty close to 50 percent, just as rolling real dice gives you a preponderance of 6s, 7s, and 8s. Think of a Bell curve.)

Because both types of twins share the same in utero environment and, usually, pretty close to the same childhood environment as well, they make great subjects for contrasting hereditary versus environmental influence. (If members of identical-twin pairs are found to be no more alike than members of fraternal-twin pairs with respect to the presence of some trait, that trait is considered to lack any genetic influence.)

In all, the researchers recruited 78 identical-twin pairs and 27 pairs of fraternal twins and drew blood from both members of each twin pair. That blood was hustled over to Stanford’s Human Monitoring Center, which houses the latest immune-sleuthing technology under a single roof. There, the Stanford team applied sophisticated laboratory methods to the blood samples to measure more than 200 distinct immune-system cell types, substances and activities.

Said Davis: “We found that in most cases – including your reaction to a standard influenza vaccine and other types of immune responsiveness – there is little or no genetic influence at work, and most likely the environment and your exposure to innumerable microbes is the major driver.”

It makes sense. A healthy human immune system has to continually adapt to its encounters with hostile pathogens, friendly gut microbes, nutritional components and more.

“The immune system has to think on its feet,” Davis said.

Previously: Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology’s Holy Grail, Deja vu: Adults’ immune systems “remember” microscopic monsters they’ve never seen before and Immunology escapes from the mouse trap
Photo by DVIDSHUB

CDC, Chronic Disease, Health Policy, In the News, Infectious Disease, Public Health

To screen or not to screen for hepatitis C

Hep CIn the past few years, newer, more effective treatments have been introduced for hepatitis C – a disease that can lead to chronic liver problems and in the worst cases, liver cancer. In 2012, the Centers for Disease Control and Prevention recommended screening for the disease in anyone born between 1945-1965, since about three-quarters of cases occur in this age group, the Baby Boomers. Last year, the World Health Organization also called for more screening for the disease.

But in a recent analysis piece in The BMJ (formerly the British Medical Journal), several scientists, including Stanford epidemiologist John Ioannidis, MD, DSc, lay out the case that universal screening in this age group may not be warranted. A story in the San Francisco Chronicle today quotes Ioannidis:

“The question is whether these aggressive screening policies are justified and whether they would result in more benefit than harm,” said Dr. John Ioannidis...“We know very little about the potential harms of these drugs, especially in the long-term. And we don’t know how they will translate into long-term benefits.”

Ioannidis and his colleagues suggest that instead of rolling out widespread screening programs, researchers, as soon as possible, start a randomized trial to test the usefulness of screening and who may benefit from it.

On top of the medical uncertainties of the new treatments, they’re expensive, costing about $84,000 for the 12-week treatment. But they’ve been shown to cure patients of their hepatitis C infections at the end of that 12 week stint. Not all people who contract the disease will develop chronic infections, but a majority – two-thirds -will. Twenty percent of those cases will go on to develop severe liver disease.

Advocates of universal screening say that the new screening strategy could identify many people who don’t know they’re sick – symptoms from hepatitis C chronic infections can take years to manifest. But Ioannidis and his colleagues note that many people will get unnecessary treatment and that the long-term uncertainties of the treatment should be taken into consideration.

Previously: Despite steep price tag, use of hepatitis C drug among prisoners could save money overallA primer on hepatitis CFor patients with advanced hepatitis C, benefits of new drugs outweigh costsDrugs offer new hope for hepatitis C and Program examines hepatitis C, the “silent epidemic”
Photo of hepatitis C virus by AJ Cann

Infectious Disease, otolaryngology, Public Health, Research, Science, Stanford News

New version of popular antibiotic eliminates side effect of deafness

New version of popular antibiotic eliminates side effect of deafness

About five years before he died, my father was prescribed gentamycin, one of the most commonly used class of antibiotics called aminoglycosides, for a heart infection of unknown origins. The antibiotic successfully cured him of the life-threatening infection, but it also left him with a life-changing side effect, one with the strange-sounding name of oscillopsia.

Oscillopsia is a balance disorder that creates the illusion of an unstable visual world in its patients that can be quite disabling. For my father, it messed with his tennis game in the remaining years of his life and forced him to sit on the couch when he would rather have been running around with his grandchildren. But he was lucky. In addition to balance disorders, side effects from these cheap and extremely effective antibiotics that have been used for decades worldwide, include high rates of deafness and kidney damage.

ChengNow, Stanford researchers led by otolaryngologoist Alan Cheng, MD, (pictured at left) and Tony Ricci, PhD, have made a modified version of these drugs that successfully treats infections without the side effects of deafness and kidney damage. In a press release on the study, which was published Friday in the Journal of Clinical Investigation, I wrote about a boy (whose story is also told in this Stanford-produced video) who lost his hearing from these antibiotic treatments during his battle with cancer:

On Christmas Eve, 2002, Bryce Faber was diagnosed with a deadly cancer called neuroblastoma. The 2-year-old’s treatment, which, in addition to surgery, included massive amounts of radiation followed by even more massive amounts of antibiotics, no doubt saved his life. But those same mega-doses of antibiotics, while staving off infections in his immunosuppressed body, caused a permanent side effect: deafness.

“All I remember is coming out of treatment not being able to hear anything,” said Bryce, now a healthy 14-year-old living in Arizona. “I asked my mom, ‘Why have all the people stopped talking?’ He was 90 percent deaf.

These are extremely important life-saving drugs, Ricci, a basic scientist and expert on the biophysics of the inner ear, told me. But they could be so much better if patients didn’t have to risk their toxic side effects. So far, the new versions of the drug that he and colleagues developed have only been tested in mice, but the hope is to conduct clinical trials as soon as is safely possible. “If we can eventually prevent people from going deaf from taking these antibiotics, in my mind, we will have been successful,” Ricci said. “Our goal is to replace the existing aminoglycosides with ones that aren’t toxic.”

The new drugs have not yet been tested as to whether they still cause balance disorders. That’s on the docket for the future. But my article describing this wedding of basic science with clinical treatment is a hopeful reminder of the importance of modern-day scientists to public health.

Previously: Listen to this: Research upends understanding of how humans perceive sound; Stanford developed probe aids study of hearing and Studying the inner ear and advancing research in developmental biology

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