Published by
Stanford Medicine

Category

Infectious Disease

Aging, Immunology, Infectious Disease

Found: A molecule mediating memory meltdown in aging immune systems

Found: A molecule mediating memory meltdown in aging immune systems

persistence of memoryEven perfectly healthy older people don’t always remember names as quickly as they did when they were younger. So what. They also don’t walk as fast. Big deal.

A bigger deal: Older immune systems don’t respond as quickly or as well to invasions by pathogens. That’s in large part because they fail to remember previous encounters with pathogens (or their defanged doppelgängers, which we call vaccines). Why do they forget? Stanford immunologist Jorg Goronzy, MD, may have a handle on part of the reason.

In a study published in Cell Reports, Goronzy and his colleagues have shown that immune cells of a particular type are more likely to be marked, in older people, by a surface protein that sparks apoptosis, or cellular suicide. As a result, the immune system’s memory of pathogens or vaccinations of yore gets cloudy, leaving the door open to a repeat attack by intruders that a more adept immune system would have summarily squelched.

A healthy immune system bulks up vigorously in response to pathogens or vaccines. Different types of immune cells that are skilled at recognizing and/or warring with the foreign body start to multiply and morph. Many of these cells effectively become front-line warriors, throwing themselves into battle against the invading pathogen (or its harmless vaccine lookalike). Others are more like archers lobbing darts that can knock off the bad guys while sparing innocent bystanders (the body’s own tissues). Still others, known as CD4 cells, coordinate the whole counterattack, sending chemical signals to other cells, or rubbing up against them at close range to whisper secret instructions.

Continue Reading »

Global Health, HIV/AIDS, Infectious Disease

Growing resistance to vital HIV drug raises concern

Growing resistance to vital HIV drug raises concern

tablets-193666_1280HIV resistance to the antiviral tenofovir, one of the mainstays of HIV treatment and prevention, is increasingly common following therapy, particularly in low and middle-income countries, according to a new, multi-national study.

“Public health organizations and global funders have been very effective at expanding antiretroviral drug therapy to increasing proportions of patients in need,” said Robert Shafer, MD, professor of medicine and co-author of the work. “This study highlights the need for efforts to ensure that the regimens used to treat HIV retain their effectiveness for as long as possible.”

Researchers studied 1,926 patients in 36 countries who developed virological failure after taking a first-line regimen containing tenofovir. In this group, tenofovir-resistant strains were found in 60 percent of the patients in sub-Saharan Africa, compared with fewer than 30 percent in Europe and North America. Patients most at risk for tenofovir resistance were those who started therapy late in the progression of the disease or who received tenofovir in combination with drugs less commonly used in upper-income countries.

About two-thirds of the patients with tenofovir-resistant strains also had become resistant to the other two drugs in their regimens, suggesting their treatment had become largely ineffective.

Resistance may develop when patients don’t take their medication regularly, although it may also occur in adherent patients on some of the regimens used in the developing world. People carrying resistant strains can pass them along to others, so that HIV resistance could become even more widespread, the researchers note.

“Tenofovir is a critical part of our armamentarium against HIV, so it is extremely concerning to see such a high level of resistance to this drug,” said lead author Ravi Gupta, MD, at University College London. “It is a very potent drug with few side effects, and there aren’t any good alternatives that can be deployed using a public health approach. Tenofovir is used not only to treat HIV but also to prevent it in high-risk groups, so we urgently need to do more to combat the problem of emerging resistance.”

The researchers say the results reinforce the need for increased drug resistance surveillance in both untreated and treated HIV-positive individuals. They are now working to better understand how these resistant viruses develop and spread.

The study, which involved dozens of researchers and institutions, appears today in the journal Lancet Infectious Diseases. It was co-authored by scientists at the London School of Hygiene and Tropical Medicine and funded by the Wellcome Trust.

Previously: Spread of drug-resistant HIV in Africa and Asia is limited, Stanford research finds, HIV study in Kenyan women: Diversity in a single immune-cell type flags likelihood of getting infected and Study: Chimps teach people a thing or two about HIV resistance
Image by bigblockbobber

Biomed Bites, Infectious Disease, Microbiology, Research, Videos

Improving infection recovery

Improving infection recovery

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative biomedical researchers. 

Think back on the last time you came down with something. First you were sick, acutely ill. But then, days or hours later, you were no longer ill, but also not well, stuck in the grey zone of recovery.

That’s the stage of illness that most interests David Schneider, PhD, an associate professor of microbiology and immunology, and those in his lab. As Schneider explains in the video above:

It looks like recovery is a different sort of process than getting sick. So we’re trying to take this apart first by working with fruit flies, then by working with mice and eventually by working with people.

Our goal is to be able to take someone suffering from an infection and really help them improve their recovery.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: Immune cell linked to surgery recovery time, Stanford scientists find, Stanford team develops a method to prevent the viral infection that causes dengue fever and Shrugging off bugs: there’s more to beating infections than just fighting them

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

Precision health: A blood test that signals need for antibiotics

Precision health: A blood test that signals need for antibiotics

antibioticsGo to your doctor with a sinus infection and the first thing she’ll likely ask you is how long you’ve been sick. If it’s been less than two weeks, chances are she’ll say you probably have a viral infection and won’t prescribe an antibiotic. If you say it’s been three or four weeks, she’ll probably give you a prescription, assuming viral infections typically resolve in two weeks. But this rule of thumb is more educated guess than science.

In a nice example of precision health, a new blood test being developed at Stanford could indicate whether you have a bacterial infection or a viral infection and tell you and your doctor whether an antibiotic would help.

So if you have a bacterial infection that an antibiotic could cure, you won’t have to wait days or weeks to get treatment. And if you don’t need a prescription, you won’t damage your body’s microbiome with a round of antibiotics you don’t need.

The test, developed by Purvesh Khatri, PhD, assistant professor of medicine, and a team of six other researchers at Stanford, is based on changes in the way human immune cells express their genes.

It seems almost like science fiction, but Khatri’s team has found that cells don’t just respond differently to bacterial infections and viral infections; they also respond differently to different kinds of viral infections, so it’s possible to tell whether someone has a cold versus the flu as much as 24 hours before they even show symptoms.

The same test could have other uses, including quickly showing whether a vaccine is working and, someday, telling if someone is infected with Ebola or other deadly and contagious viruses.

You can read more details in our press release and even more in the paper (subscription required), which was published online today in the journal Immunity.

Previously: Study means an early, accurate, life-saving sepsis diagnosis could be coming soon
Photo by Sheep purple

Infectious Disease, Patient Care, Pediatrics, Public Health

Should doctors give up their white coats?

Should doctors give up their white coats?

14445634744_b7caf10f5f_k_flickr_NEC_560x373

When you google ‘doctor,’ virtually every image shows a person in a long-sleeved white coat. The crisp white coat with a stethoscope around the neck has long symbolized the profession. However, there is controversy about whether doctors should give up their classic uniform, as described in a recent story in the Boston Globe.

Britain’s National Health Service banned white coats several years ago, requiring doctors to be bare below the elbows to avoid spreading infections. Many clinical departments in the United States have done the same. The argument goes something like this:

  • The sleeves of white coats are germ magnets.
  • Doctors don’t launder their white coats very often, so deadly infections can be spread from one patient to another.
  • Therefore, doctors shouldn’t wear long-sleeved white coats.

As a pediatric infectious disease specialist at Stanford, Charles Prober, MD, supports this theory. He told me during a recent interview: “In terms of the infectious disease risk, there is little question that one can carry bacteria or viruses on your clothing — whether it’s a white coat or the sleeve of your shirt, and one way to lessen that is to wash up to the elbows, especially when you’re going into high-risk environments like the ICU or nursery. Obviously you can only wash up to your elbows if they aren’t covered with something.

William Benitz, MD, division chief of neonatal and developmental medicine, agrees:

I find the summary reports highly credible and accept the contention that the long sleeves of white coats harbor infectious agents and carry them from patient to patient. We banned white coats in our NICU about 5 years ago, along with a mandate for baring arms to the elbow and hand cleansing upon entering any patient room. Part of the reason for the former is to reinforce and provide active visual evidence of the latter. We used to hear ‘but I won’t touch anything’ a lot, but that was often not so. Not an issue now.

Continue Reading »

Health Policy, Infectious Disease, Microbiology, Public Health, Research, Stanford News

Excessive antibiotic use in flu season contributes to resistance

Excessive antibiotic use in flu season contributes to resistance

addiction-71573_1280The cold and flu season is upon us — and with that comes the potential overuse of antibiotics. All too often, physicians prescribe antibiotics for viral infections, which typically is ineffectual and can even be dangerous for elderly Medicare patients.

An estimated 2 million Americans are infected with drug-resistant organisms each year, resulting in 23,000 deaths and more than $20 billion in excess costs, according to the Centers for Disease Control and Prevention.

Excessive antibiotic use in cold and flu season is not only costly, but it also contributes to antibiotic resistance, writes Marcella Alsan, MD, PhD, and her co-authors in a study published in the December edition of Medical Care. The study’s objective was to develop an index of excessive antibiotic use in cold and flu season and determine its correlation with other indicators of clinically appropriate or inappropriate prescribing.

Alsan, a core faculty member at Stanford Health Policy, and senior author, Dartmouth economist Jonathan Skinner, PhD, concluded that flu-related antibiotic use was correlated with prescribing high-risk medications to the elderly.

“These findings suggest that excessive antibiotic use reflects low-quality prescribing,” the authors wrote. “They imply that practice and policy solutions should go beyond narrow, antibiotic specific, approaches to encourage evidence-based prescribing for the elderly Medicare population.”

To better understand patterns of antibiotic overuse and whether such patterns reflect prescribing quality, the authors developed a measure that isolates antibiotic prescribing in response to state-by-state influenza activity. They focused on the elderly, as national data on antibiotic use are readily available and because the interactions between multiple prescriptions are particularly important for this population.

Continue Reading »

Global Health, Infectious Disease, Public Health, Public Safety

Stanford team develops a method to prevent the viral infection that causes dengue fever

Stanford team develops a method to prevent the viral infection that causes dengue fever

327708441_433edf50d4_zDengue fever is the most widespread and fastest growing mosquito-borne virus in the world. It infects an estimated 390 million people each year — nearly twice the number of people infected annually by malaria — and unlike malaria, there is no vaccine or treatment.

Despite the severity and worldwide frequency of the disease, dengue fever receives relatively little press in the United States. But soon this trend may change. Just recently an outbreak of dengue fever struck Hawaii’s Big Island and the reach of this tropical disease is expected to spread.

Now, a team of Stanford researchers led by Judith Frydman, PhD, have developed a new way to target the disease by using a drug compound that tinkers with a critical cellular pathway in the host, blocking the virus at multiple steps. Frydman is a professor of biology and of genetics.

A Stanford News story explains:

Frydman’s group focused on Hsp70, a type of protein found in most organisms and known as a “chaperone.” Hsp70’s main job is to help other proteins fold into their functional shape, and to then protect them from damage by environmental stresses. DENV (dengue fever), like many other viruses, also relies on Hsp70, to help replicate the viral genome, and ultimately produce the viral proteins it needs to take control of the host cells and spread infection.

Frydman’s team discovered that using a specific compound to inhibit Hsp70 in human blood cells blocks the virus without harming the cells. This compound is effective against different strains and types of dengue fever and it blocks other insect-borne diseases, including West Nile virus, yellow fever and tick-borne encephalitis.

“Our findings have major implications for our understanding of the interface between viral and chaperone biology, and provide a new way of thinking about strategies to develop a novel class of antivirals,” Frydman said.

Previously: Exploiting insect microbiomes to curb malaria and dengueFighting fire with fire? Using bacteria to inhibit the spread of dengue and Dengue fever in New Caledonia
Photo by Andy Simonds

Global Health, Infectious Disease

Chikungunya is on its way to a neighborhood near you

Chikungunya is on its way to a neighborhood near you

8143929538_78a76a9b23_z (1)Very embarrassing confession: When I heard this piece on the radio yesterday, I thought it was about a chicken virus. Wow, I remember thinking, that’s strange I haven’t heard of this new debilitating chicken virus.

Oh, dear. The virus, of course, is actually chikungunya, a mosquito-borne pathogen that, according to a new study in Neurology, can lead to memory problems, dementia or even death.

“As it spreads across the world, we’re realizing that it’s not so benign,”  Desiree LaBeaud, MD, associate professor of pediatrics, told NPR.

The study highlighted by All Things Considered examined the aftermath of a 2005 epidemic on an island off Madagascar — sparked by storing water during a drought — that affected 300,000 people. “It was horrible,” investigator Patrick Gérardin, MD, PhD, told NPR.

Usually, chikungunya strikes with a fever, aches, and joint pain. Sometimes, however, it progresses to encephalitis, or inflammation of the brain. Why some people are hit hard, and others experience a relatively minor illness, remains a mystery, LaBeaud said.

This isn’t just a tropical disease that afflicts people in far-off lands. Chikungunya has been spotted in dozens of states, brought back by travelers. And there’s no treatment. No vaccine. This is no chicken virus.

For more on LaBeaud’s work, check out this video.

Previously: All hands on deck: Doctor answers call to work on largest Ebola epidemic in history, Why are viruses so wily? One researcher thinks she knows — and is working to thwart them and Should we worry? Stanford’s global health chief weighs in on Ebola
Photo by John Tann

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

2908834379_de34b5c780_o

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.

Continue Reading »

Stanford Medicine Resources: