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Infectious Disease

Infectious Disease, Medicine and Society, Parenting, Public Health, Research, Stanford News

California’s vaccination exemptions cluster in white, affluent communities

California's vaccination exemptions cluster in white, affluent communities


California’s measles epidemic was no fluke; between 2007 and 2013 the percentage of kindergarteners using a “personal belief” exemption to enroll in school without vaccinations doubled.

In that year, 3 percent of kindergarteners entered school unvaccinated. In some schools, the percentage of vaccinated children was so low that it threatened herd immunity, or the ability for a population to keep a pathogen at bay, according to Stanford health-policy researcher Michelle Mello, PhD, JD.

To understand the rapid increase, Mello worked with a team led by Tony Yang, ScD, with George Mason University. Their research is published today in the American Journal of Public Health.

They found the highest resistance to vaccinations among white, affluent communities. In contrast to previous studies, however, they did not find a correlation between higher levels of education and vaccine exemptions.

“Beliefs about vaccination risk tend to be more entrenched among certain communities of mothers,” Mello said. The study didn’t investigate reasons for seeking exemption, but other studies suggest some mothers in affluent communities may believe they can adequately protect their children through “intensive parenting techniques” such as an organic diet and restricting contact with sick children, Mello said.

Although California eliminated the personal belief exemption this summer in a broad-reaching law that requires all medically eligible school students to be vaccinated, the study speaks to how other states might approach the problem of vaccine exemptions, Mello said.

Similar clusters of vaccine resistance exist elsewhere and the findings could help public health agencies refine outreach methods, she said. For example, by specifically targeting local groups and reaching out to community leaders, officials may have more success providing education about vaccine risks and benefits, Mello said.

The results are particularly striking given the history of vaccination efforts, she said. In the first half of the twentieth century, public health officials struggled to ensure vaccines reached disadvantaged communities. Now, as fear of the targeted diseases has paled, parents may be more fearful of vaccines, leaving the entire population vulnerable.

Previously: Infectious disease expert discusses concerns about undervaccination and California’s measles outbreak, Stanford researchers analyze California’s new vaccine law and The earlier the better: Study makes vaccination recommendations for next flu pandemic
Photo by woodleywonderworks

Chronic Disease, Infectious Disease, Microbiology, Research, Science, Stanford News

Bad actors: Viruses, pathogenic bacteria co-star in health-horrific biofilms

Bad actors: Viruses, pathogenic bacteria co-star in health-horrific biofilms

biofilmA group under the direction of Stanford infectious disease investigator Paul Bollyky, MD, PhD, has uncovered a criminal conspiracy between two microbial lowlifes that explains how some of medicine’s most recalcitrant bacterial infections resist being expunged.

In a study published today in Cell Host & Microbe, Bollyky and his associates reveal that bacterial pathogens responsible for a big chunk of chronic infections can team up with a type of virus that bacteria ordinarily consider their worst enemies to form biofilms, which, our news release on the study explains, are “slimy, antiobiotic-defying aggregates of bacteria and organic substances that stick to walls and inner linings of infected organs and to chronic wounds, making infections excruciatingly hard to eradicate.” More from that release:

Biofilms factor into 75 to 80 percent of hospital-acquired infections, such as those of the urinary tract, heart valves and knee-replacement prostheses, Bollyky said. “A familiar example of a biofilm is the plaque that forms on our teeth,” he said. “You can brush twice a day, but once that plaque’s in place you’re never going to get rid of it.”

The study first focused on Pseudamonas aeruginosa, which accounts for one in ten hospital-acquired infections, many chronic pneumonia cases and much of the air-passage obstruction afflicting cystic-fibrosis patients.

Cystic fibrosis is deadly mainly because of biofilms formed by P. aeruginosa, Bollyky told me. “These biofilms fill up all the air spaces, and antibiotics can’t seem to penetrate them,” he said.

But he and his colleagues found that P. aeruginosa forms biofilms only when it’s been infected itself.

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Global Health, Health Policy, Infectious Disease, Research, Stanford News

Building the case for a national hepatitis B treatment program in China

Building the case for a national hepatitis B treatment program in China

An estimated 100 million people in China are living with chronic hepatitis B infection, making it the most prevalent life threatening disease in the country. If left untreated, hepatitis B can lead to serious liver damage and is the leading cause of liver-related cancer and deaths in China. Despite the availability of effective therapies, there is no national policy in place to cover hepatitis B treatment and many patients, particularly those with rural health plans, can’t afford it.

Now, in the first comprehensive, independent study of its kind, researchers at Stanford and the University of Michigan have published a cost-effective analysis of all available treatments – branded and generic – for chronic hepatitis B in China. The analysis, published today in PLOS ONE, quantifies the economic value and potential life-saving benefits of implementing a national treatment strategy in China.

If China can successfully treat hepatitis B, the rest of the world will follow

The paper is also the first to provide cost thresholds, meaning the specific price point at which a particular drug would be cost-effective or offer cost-savings.

“Health insurance programs in China don’t always cover the most effective medications,” said Stanford research associate Mehlika Toy, PhD, lead author of the study. “In comparing the potential cost-effectiveness of all available treatments, we aim to provide policy-makers in China with the evidence to support the development and implementation of a viral hepatitis treatment program, and information to help support drug pricing negotiations.”

In their analysis, the researchers compared eight different treatment strategies using a statistical model to simulate disease progression and long-term health outcomes. The analysis evaluated chronic hepatitis B patients who had not received prior treatment, but would be eligible for treatment under current international and World Health Organization guidelines.

Costs were determined based on estimated medical management and related costs associated with disease complications, such as cirrhosis (scarring of the liver) and liver cancer, as well as generic and brand drug costs.

The findings showed that certain therapies performed better than others and that not treating at all resulted in the highest health care costs and the worst health outcomes, compared to other strategies. For example, it was shown that 65 percent of non-cirrhotic patients with active hepatitis associated with high virus concentrations (HBeAg positive) would die of hepatitis B-related liver disease in their lifetime if not treated. Alternately, approximately 60 percent of those deaths could be averted if treated with one of two highly potent, low-resistance drugs, entecavir and tenofovir.

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Evolution, Infectious Disease, Microbiology, Pediatrics, Pregnancy, Research, Stanford News

Mastermind or freeloader? Viral proteins in early human embryos leave researchers puzzled

Mastermind or freeloader? Viral proteins in early human embryos leave researchers puzzled

and_virus_makes_four_fullI’m filing this finding firmly under the category of “Things I’m glad I didn’t know when I was pregnant.” (Other items include the abject terror of letting your teen get behind the steering wheel of a car for the first time, and the jaw-dropping number of zeros that can appear in a college financial aid package.) Recently, Stanford researchers found that the earliest stages of human development – those that occur within days of fertilization – may take place in a stew of viral proteins that lie in wait tucked inside the human genome. What do the viral proteins do? Who knows! Why are they popping up when we’re (arguably) at our most vulnerable? No idea!

Ugh. Like there’s not enough to worry about while growing another human inside your body.

I’m not being entirely fair here. Developmental biologist Joanna Wysocka, PhD, and graduate student Edward Grow, were some of the first researchers to show that ancient viral DNA sequences abandoned in our genome after long-ago infections can and do make viral proteins early in human development. I wrote about their finding on this blog earlier this year.

My article in the most recent issue of Stanford Medicine magazine expands on this story, describing how they made their finding and their future plans to learn more about our viral co-pilots. As I explain:

The finding raises questions as to who, or what, is really pulling the strings during human embryogenesis. Grow and Wysocka have found that these viral proteins are well-placed to manipulate some of the earliest steps in our development by affecting gene expression and even possibly protecting the embryo’s cells from further viral infection.

I’m often struck by how much parenting is like research. It’s a (seemingly) never-ending, but very rewarding, job. And for both, there’s clearly always lots to learn. As I write:

So, who’s in charge here? Us or the viruses? Or is there no longer any distinction? There’s certainly been plenty of evidence showing that humans are far from free operators when it comes to, well, pretty much anything. Our bodies are teeming masses of bacteria, viruses and even fungi that are collectively known as the microbiome. Many of these microorganisms, which are 10 times more numerous than our own cells, are essential to a healthy life, such as the gut bacteria that help us digest our food.

“What we’re learning now is that our ‘junk DNA,’ including some viral genes, is recycled for development in the first few days and weeks of life,” says [study co-author and former Stanford stem cell researcher Renee Reijo-Pera], who is now on the faculty of Montana State University. “The question is, what is it doing there?”

Previously: Stanford Medicine magazine tells why a healthy childhood mattersMy baby, my…virus? Stanford researchers find viral proteins in human embryonic cells and Species-specific differences among placentas due to long-ago viral infection, say Stanford researchers
Photo of Joanna Wysocka by Misha Gravenor

Dermatology, Genetics, Infectious Disease, Microbiology, Research, Stanford News

Inside job: Staphyloccus aureus gets critical assist from host-cell protein accomplice

Inside job: Staphyloccus aureus gets critical assist from host-cell protein accomplice

bank heistStaphylococcus aureus is a bacterium that colonizes the skin (and, often, the noses) of about one in three people, mostly just hanging out without causing symptoms. But when it breaches the skin barrier, it becomes a formidable pathogen.

S. aureus not only accounts for the majority of skin and soft-tissue infections in the U.S. and Europe, but can spread to deeper tissues leading to dangerous invasive infections in virtually every organ including the lungs, heart valves, and bones. These complications cause an estimated 11,000 deaths in the U.S. annually.

Making matters worse, antibiotic-resistant strains of S. aureus are becoming increasingly prevalent and even more difficult and costly to treat. All of which makes it crucial to understand the factors that control the bug’s virulence: What turns a common colonizer into a pathogen?

The answers that typically spring to mind involve molecules the pathogen produces that enable damage to cells of the host organism. Certainly S. aureus is no slouch in that arena. Prominent among the many virulence factors it produces, one called α-toxin aggregates on host cell surfaces to form pores that injure the cells’ outer membranes, often killing the cells.

But it turns out that forming pores appears not to be enough, by itself, for lethal host-cell injury. In a study published in Proceedings of the National Academy of Sciences, a team directed by Stanford microbe sleuths Manuel Amieva, MD, PhD, and Jan Carette, PhD, identified several hitherto-unsuspected molecules produced within host cells themselves that determine whether the cells live or die after α-toxin-induced pore formation.

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Immunology, Infectious Disease, Precision health, Research, Stanford News, Transplants

A blood test that monitors for post-lung-transplant rejection and infection

A blood test that monitors for post-lung-transplant rejection and infection

lungsA team under the direction of Stanford bioengineer Steve Quake, PhD, has shown that a noninvasive blood test can accurately diagnose lung-transplant rejection. The test also simultaneously detects infections by patient-imperiling microbes.

About 3,500 lung transplant procedures are performed annually worldwide. But median survival after the graft barely exceeds five years, trailing the outcomes for kidney, heart, liver and other solid organ transplants. Chronic organ rejection is the biggest single factor. Infection (for which recipients are at high risk due, ironically, to their post-transplant regimen of immune-suppressing drugs given to reduce the likelihood of organ rejection) is another leading contributor.

In a study published in Proceedings of the National Academy of Sciences, Quake and his associates demonstrated that the test, which involves high-throughput sequencing of DNA, flags organ rejection by detecting increasing amounts of donor DNA in a recipient’s blood. The relatively low-cost test doesn’t require the highly invasive removal of lung tissue, and it can also screen for myriad bacterial, viral and fungal pathogens.

In another study in 2014, Quake and Stanford colleagues had come up with a similar blood test to determine whether a heart-transplant recipient was headed for organ rejection. The new study expands the test’s applicability to lung transplantation – and suggests that its utility may extend to solid organs in general, including more-frequently performed procedures such as kidney transplantation (more than 17,000 in the United States alone in 2014).

With better than half of all lung-transplant patients suffering organ rejection in just the first year after their operation, this advance holds great clinical potential. Quick, accurate diagnosis is the first step toward appropriate treatment.

Previously: A simple blood test may unearth the earliest signs of heart transplant rejection, Step away from the DNA? Circulating *RNA* in blood gives dynamic information about pregnancy, health and Might kidney-transplant recipients be able to toss their pills?
Photo by Lorraine Santana

Infectious Disease, Public Health, Stanford News

Experts and 8-year-olds agree: It’s worth getting a flu shot

Experts and 8-year-olds agree: It's worth getting a flu shot

smiley faceIf you’re around my young daughters these days and happen to mention the flu shot, you’re likely to get an earful. “We got ours too late last year and got really sick,” they’ll tell you (as I look down in embarrassment). “It’s really important to get one.” They also, not surprisingly, were not at all upset when I made an appointment – nice and early! – for them to get vaccinated a few weeks ago. They knew it would hurt, but in the words of my 8-year-old, “it’s worth it.”

My girls – the walking pro-flu shot billboards that they are – were the first people I thought of when I came across a Stanford BeWell article this week on – you guessed it – the importance of flu shots. In the piece, infectious disease expert Cornelia L. Dekker, MD, answers questions about influenza and last year’s flu vaccine (which failed to protect people against several strains of the flu), and she reminds local readers that shots are being offered on campus for students, staff and faculty for free.

Previously: How one mom learned the importance of the flu shot – the hard way and Ask Stanford Med: Answers to your questions about seasonal influenza
Photo by cignoh

Infectious Disease, Microbiology, Research, Stanford News

Why C. difficile-defanging mouse cure may work in people, too

Why C. difficile-defanging mouse cure may work in people, too

CdiffI wrote a news release last week about a study just published in Science Translational Medicine. The study, despite it having been conducted in mice, not humans, received a fair amount of coverage – by The Washington Post, Yahoo!, Fox News, NBC, CBS and Reuters, among other places – and deserved the attention it got. It demonstrated the efficacy of a small-molecule drug that can disable the nasty intestinal pathogen C. difficile without killing it – and, importantly, without decimating the “good” bacteria that populate our gut by the trillions.

That’s a big deal. If you want to see a lot of ugly weeds pop up, there’s no better way to go about it than letting your lawn go to hell.

C. difficile – responsible for more than 250,000 hospitalizations and 15,000 deaths per year in the United States and a $4 billion annual health-care tab in the U.S. alone – is typically treated by antibiotics, which have the unfortunate side effect of wiping out much of our intestinal microbe population. That loss of carpeting, ironically, lays the groundwork for a dangerous and all-too-common comeback of C. difficile infection.

A question worth asking about this study, conducted by what-makes-pathogens-tick expert Matt Bogyo, PhD, and a team of Stanford associates: Why should we think that what works in mice is going to work in people?

The only sure answer isn’t a torrent of language but a clinical trial of the drug, ebselen, in real, live people with C. difficile infections or at risk for them. (Bogyo has already started accumulating funding to initiate a trial along those lines.)

But there’s also reassurance to be drawn from the fact that ebselen isn’t an entirely exotic newcomer to the world of medical research. As I noted in my release:

Bogyo and his associates focused on … ebselen because, in addition to having a strong inhibitory effect, ebselen also has been tested in clinical trials for chemotherapy-related hearing loss and for stroke. Preclinical testing provided evidence that ebselen is safe and tolerable, and it has shown no significant adverse effects in ensuing clinical trials.

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Bioengineering, Cancer, Infectious Disease, Precision health, Research, Stanford News

Stanford scientists co-opt viral machinery to create medical delivery system

Stanford scientists co-opt viral machinery to create medical delivery system

James Swartz

Stanford engineering researcher James Swartz, PhD, and his colleagues have remodeled a hepatitis B virus to turn it into a microscopic taxi for medical therapies. The team stripped the virus of its pathogenic DNA and modified an outer shell so that they could “hang” molecular tags on the outside to help deliver vaccines or other therapies to specific cells. The researchers reported their findings in a paper in the scientific journal Proceedings of the National Academy this week.

They call the engineered product a virus-like particle (as opposed to a real virus with infectious material) or a smart particle. “We make it smart by adding molecular tags that act like addresses to send the therapeutic payload where we want it to go,” Swartz said in a Stanford News story.

The smart particle is a novel way to deliver vaccines or cancer therapies by teaching the body’s immune cells to recognize pathogens or cancer cells. Alternatively, the smart particle can deliver medicine specifically to the cells that need it.

Swartz and his colleagues’ effort is part of a larger field of targeted therapies that aims to precisely deliver therapies to the cells that need them and avoid damaging nearby healthy cells. Current cancer therapies, for example, are effective at fighting malignant cells, but also kill off healthy cells. That’s why cancer therapies often have such devastating side effects. But previous attempts to create virus-sized delivery systems have not been successful. In fact, Swartz’s team had a hard time getting funding for the early stages of this project because of previous failed efforts by other scientists.

So far, Swartz and colleagues have created the self-assembling shell that is invisible to the body’s natural immune defenses and strong enough to weather conditions in the blood stream and get its packaged contents to its destination inside the body. Next, they’ll work on putting specific cancer-fighting tags on the shell.

The most challenging task will be to pack the shell with a tiny dose of medicine. But Swartz sounded optimistic about his team’s goals. “I believe we can use this smart particle to deliver cancer-fighting immunotherapies that will have minimal side effects,” he said.

Previously: A less toxic, targeted therapy for childhood brain cancerIs cancer too complex for targeted therapies? and Working to create a universal flu vaccine
Photo, of Swartz holding an enlarged replica of a virus-like particle, by Linda Rice

Global Health, Health Policy, HIV/AIDS, Infectious Disease

From Bollywood actress to social activist

From Bollywood actress to social activist

TeachAIDS classDuring a recent trip to India, I had the great fortune to spend the day with Amala Akkineni, a beloved south Indian actress who is using her celebrity to advance the greater public good.

A trained dancer and once a major Bollywood star, Akkineni has turned her attentions in the last few decades to the nonprofit world, where she works on behalf of women and girls, people with HIV/AIDS and other vulnerable members of society.

She is still a widely recognized movie idol, attracting gawkers and autograph seekers wherever we went in Hyderabad, a south Indian city of some 7 million people. Despite her fame, she is a modest woman, who dressed simply that day in a blue cotton sari, delicate necklace and no make-up as she took us on a tour of some of the many social projects that are dear to her heart.

I met Akkineni through a friend at Stanford, Piya Sorcar, PhD, who founded a remarkably successful project, TeachAIDS, which began as her graduate thesis in the School of Education. The nonprofit disseminates video materials around the globe, using animated figures of well-known celebrities to convey simple messages about transmission, treatment and prevention of HIV/AIDS. The videos are now available in 81 countries and in 14 languages, including 7 dialects common in India, where AIDS is still a major public health problem.

Akkineni first took us to her nonprofit, Blue Cross of Hyderabad, an animal shelter that she founded in 1992 after her garage had filled up with disabled and abused creatures she had rescued from streets and homes in Hyderabad. Akkineni works regularly at the shelter and is not afraid to get her hands dirty as she comforts dogs with missing legs or feeds camels rescued from the slaughterhouse.

As she became known in Hyderabad for her work with animals in the 1990s, she was approached by Karl Sequeira, an activist in the world of AIDS and addiction, who wanted her help in starting a hospice for AIDS patients. “I was already known as this notorious ex-actress who was running this hospice for animals. So he thought I was a kindred soul,” she told me in an interview in her small office at the shelter. At the time, HIV/AIDS was such a stigmatized condition that people with full-blown disease were literally being tossed in the trash, she said. “AIDS was everywhere but nobody knew how to deal with it. It was spreading like wildfire,” she told me. She, Sequeira and other activists raised enough in one evening to open an AIDS hospice run by the Freedom Foundation, which offers a wide range of HIV services today (Sequeira died in 2004).

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