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Global Health, In the News, Infectious Disease, Podcasts

Talking about the Zika virus

Talking about the Zika virus

The Zika virus has been reported in 23 countries and territories in the Americas. Brazil is the hardest hit nation so far with more than 1 million infections. In the continental U.S. the 35 known cases of Zika have been the result of people who have traveled to infected areas and returned to the U.S. No local mosquito-borne transmission has been reported.

Globalization has changed the rapid nature in which viruses spread. To that end, broad calls for action have been engaged. The World Health Organization has declared Zika an international health crisis, and the U.S. Centers for Disease Control and Prevention declared it a Level 1 alert – the highest activation. Earlier this week, President Obama asked Congress to allocate $1.8 billion in emergency finding to vaccine research, surveillance and rapid response programs. The request also includes foreign aid to countries most impacted by Zika.

While the virus is not known to be deadly and most people who contact it will have no symptoms at all, pregnant women are most at risk. To protect their babies, the CDC is warning pregnant women not to travel to areas affected by the virus. There is no vaccine to prevent the disease.

The New York Times yesterday provided an interesting detailed history of the virus’ path since its discovery in 1947, and new information about the virus is emerging every day. Just yesterday, CDC Director Thomas Frieden told the House Foreign Affairs Committee that the CDC has uncovered new evidence supporting the link between Zika and microcephaly, a birth defect in which infants are born with unusually small heads and incomplete brain development.

In this new 1:2:1 podcast I spoke with Stanford infectious disease expert Yvonne Maldonado, MD, about Zika and the latest on the virus. She’s a professor of pediatrics at the school of medicine and the chief of pediatric infectious disease at Stanford Children’s Health.

Previously: Zika outbreak shares key traits with Ebola crisis, Stanford experts point out

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

If you gum up a malaria parasite’s protein-chewing machine, it can’t do the things it used to do

If you gum up a malaria parasite's protein-chewing machine, it can't do the things it used to do

chewing gum“Life in the tropics” evokes images of rain forests, palm trees, tamarinds and toucans. It also has a downside. To wit: One-third of the Earth’s population – 2.3 billion people – is at risk for infection with the mosquito-borne parasite that causes malaria.

Thankfully, mortality rates are dropping because of large-scale global intervention efforts. But malaria remains stubbornly prevalent in sub-Saharan Africa and Southeast Asia, where hundreds of millions of people become infected each year and more than 400,000 of them – mostly children younger than 5 – still die from it.

The parasite has the knack of evolving rapidly to develop resistance to each new generation of drugs used to fend it off. Lately, resistance to the current front-line antimalarial drug, artemisinin, is spreading and has now been spotted in a half-dozen Southeast Asian countries.

So it’s encouraging to learn that Stanford drug-development pioneer Matt Bogyo, PhD, and his colleagues have designed a new compound that can effectively kill artemisinin-resistant malaria parasites. Better, exposure to low doses of this substances re-sensitizes them to artemisinin.

By exploiting tiny structural differences between the parasitic and human versions of an intercellular protein-recycling machine called the proteasome, the compound Bogyo’s team has created attacks the malaria parasite while sparing human cells.

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HIV/AIDS, Infectious Disease, Research, Science, Stanford News

“Unprecedented” approach for attempting to create an HIV vaccine

"Unprecedented" approach for attempting to create an HIV vaccine

Stanford’s 588732155_c05dda114e_zPeter S. Kim, PhD, was recently elected to the National Academy of Engineering, making him one of only 20 people who are members of all three National Academies (the other two are Medicine and Science). Stephen Quake, PhD, a bioengineer here, is also a member of all three academies.

This honor is particularly fitting for Kim, who joined Stanford in 2014 to be part of the new interdisciplinary institute Stanford ChEM-H, which bridges the schools of medicine, engineering and humanities & sciences for research in human health. Kim had spent a decade as president of Merck Research Laboratories and hopes that in his return to academic research his group will be able to help create a vaccine for HIV.

I talked to Kim recently about why he thinks he’ll succeed where so many have failed in their efforts to develop an HIV vaccine, and the importance of working across disciplines:

How is your approach to creating an HIV vaccine different from ones that haven’t been successful?

In over 30 years of intense work by many people to try and come up with a vaccine, none has succeeded. That’s in large part because the virus can mutate very quickly. It can change and therefore escape an antibody. The approach that we’re taking is to target a part of HIV that is normally buried but becomes exposed during the infection process. This region is highly conserved – it is 90 percent identical between all HIV strains.

If this region doesn’t mutate often why haven’t other people tried to target it?

It is unprecedented to make a vaccine against a region of a protein that is only exposed briefly. People are skeptical because the vaccine has to be there right at the moment that the virus is infecting the cell.

What gives you confidence the approach will work?

There’s an FDA-approved drug, called Fuzeon, that binds this same region and has been shown to be effective in people. That drug isn’t widely used because it has to be injected, but it validates our idea that targeting this transiently exposed part of the protein can be effective at fighting the virus in humans.

How far along are you?

We’ve shown that we can elicit antibodies in animals that are capable of inhibiting HIV in a lab dish. Thus, we know that our vaccine candidates can generate antibodies against the virus, and that those antibodies recognize and fight the virus. But, we still need to generate a much stronger inhibitory response before we test it in people.

You’re now a member of the three academies that also represent the academic interests of ChEM-H, which brought you to Stanford. Do you think spanning disciplines helps in your work?

The research that we do is greatly enhanced by having the proximity of engineering, medicine and science at Stanford. We study things as basic as the molecular structures of viral proteins. Ultimately, we need to understand how the human immune system creates antibodies against these proteins. This work is greatly facilitated by engineering methods to determine the DNA sequence of single immune cells. In the future, we would also love to see what is occurring at a single molecule level when a virus infects a cell. To do that will require bringing together world class engineering, science and medicine.

Previously: Research investment needed now, say top scientists and Stanford ChEM-H bridges chemistry, engineering and medicine
Image of an HIV particle by AJ Cann

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.

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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?

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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.

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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.

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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

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