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Infectious Disease

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

Our aging immune systems are still in business, but increasingly thrown out of balance

Our aging immune systems are still in business, but increasingly thrown out of balance

business as usual

Stanford immunologist Jorg Goronzy, MD, told me a few years ago that a person’s immune response declines slowly but surely starting at around age 40. “While 90 percent of young adults respond to most vaccines, after age 60 that response rate is down to around 40-45 percent,” he said. “With some vaccines, it’s as low as 20 percent.”

A shaky vaccine response isn’t the only immune-system slip-up. With advancing age, we grow increasingly vulnerable to infection (whether or not we’ve been vaccinated), autoimmune disease (an immune attack on our own tissues) and cancer (when a once well-behaved cell metamorphoses into a ceaselessly dividing one).

A new study led by Goronzy and published in Proceedings of the National Academy of Sciences, suggests why that may come about. The culprit he and his colleagues have fingered turns out not to be the most likely suspect: the thymus.

This all-important organ’s job is to nurture an army of specialized  immune cells called T cells. (The “T” is for “Thymus.”) T cells are capable of recognizing and mounting an immune response to an unbelievably large number of different molecular shapes, including ones found only on invading pathogens or on our own cells when they morph into incipient tumor cells.

Exactly which feature a given T cell recognizes depends on the structure of a receptor molecule carried in abundance on that T cell’s surface.  Although each T cell sports just one receptor type, in the aggregate the number of different shapes T-cells recognize is gigantic, due to a high rate of reshuffling and mutation in the genes dictating their receptors’ makeup. (Stanford immunologist Mark Davis, PhD, perhaps more than any other single individual,  figured out in the early 1980s how this all works.)

T cells don’t live forever, and their generation from scratch completely depends on the thymus. Yet by our early teens the organ,  situated  in front of the lungs at the midpoint of our chest, starts shriveling up and replaced by (sigh – you knew this was coming)  fat tissue.

After the thymus melts away,  new T-cells come into being only when already-existing ones undergo cell division, for example to compensate for the attrition of their neighbors in one or another immune-system dormitory (such as bone marrow, spleen or a lymph node).

It’s been thought that the immune-system’s capacity to recognize and mount a response to pathogens (or incipient tumors) fades away because with age-related T-cell loss comes a corresponding erosion of diversity:  We just run out of T-cells with the appropriate receptors.

The new study found otherwise.  “Our study shows that the diversity of the human T-cell receptor repertoire is much higher than previously assumed, somewhere in the range of one billion different receptor types,” Goronzy says. “Any age-associated loss in diversity is trivial.” But the study also showed an increasing imbalance, with some subgroups of T cells (characterized by genetically identical  receptors)  hogging the show and other subgroups becoming vanishingly scarce.

The good news is that the players in an immune response are all still there, even in old age. How to restore that lost balance is the question.

Previously: How to amp up an aging immune response, Age-related drop in immune responsiveness may be reversible and Deja vu: Adults’ immune systems “remember” microscopic monsters they’ve never seen before
Photo by Lars Plougmann

Global Health, Infectious Disease, Public Health, Public Safety, Stanford News

Biosecurity experts discuss Ebola and related public health concerns and policy implications

Biosecurity experts discuss Ebola and related public health concerns and policy implications

ebola_081214

More than 1,800 people in the West African nations of Liberia, Sierra Leone and Guinea have contracted the Ebola virus since March and the death toll has surpassed 1,000, according to the latest figures from the World Health Organization. As the number of cases and death continue to climb many are concerned about what can be done to curtail the outbreak and the likelihood of it spreading to the United States.

In a Q&A recently published by the Center for International Security and Cooperation and The Freeman Spogli Institute for International Studies, Stanford biosecurity experts David Relman, MD, and Megan Palmer jointly answer these questions and others related to the public health concerns and policy implications of the outbreak. On the topic of broader lessons about the dynamics and ecology of emerging infectious diseases that can help prevent or respond to outbreaks now and in the future, they respond:

These latest outbreaks remind us that potential pathogens are circulating, replicating and evolving in the environment all the time, and human action can have an immense impact on the emergence and spread of infectious disease.

We are starting to see common factors that may be contributing to the frequency and severity of outbreaks. Increasing human intrusion into zoonotic disease reservoir habitats and natural ecosystems, increasing imbalance and instability at the human-animal-vector interface, and more human population displacement all are likely to increase the chance of outbreaks like Ebola.

The epicenter of this latest outbreak was Guéckédou, a village near the Guinean Forest Region. The forest there has been routinely exploited, logged, and neglected over the years, leading to an abysmal ecological status quo. This, in combination with the influx of refugees from conflicts in Guinea, Liberia, Sierra Leone, and Cote d’Ivoire, has compounded the ecological issues in the area, potentially facilitating the spread of Ebola. There seems to be a strong relationship between ecological health and the spread of disease, and this latest outbreak is no exception.

While forensic analyses are ongoing, unregulated food and animal trade in general is also a key factor in the spread of infectious diseases across large geographic regions. Some studies suggest that trade of primates, including great apes, and other animals such as bats, may be responsible for transit of this Ebola strain from Central to Western Africa.

Overall, Relman and Palmer remind the public, “It’s important that we not lose sight of more chronic, but less headline-grabbing diseases that will be pervasive, insidious long-standing challenges for Africa and elsewhere.”

Previously: Stanford global health chief launches campaign to help contain Ebola outbreak in Liberia and Health workers use crowdsourced maps to respond to Ebola outbreak in Guinea
Photo by European Commission DG ECHO

From August 11-25, Scope will be on a limited publishing schedule. During that time, you may also notice a delay in comment moderation. We’ll return to our regular schedule on August 25.

Global Health, Infectious Disease, Stanford News

Stanford global health chief launches campaign to help contain Ebola outbreak in Liberia

Stanford global health chief launches campaign to help contain Ebola outbreak in Liberia

A Medical Officer at Lacor hospital in Gulu, 360 kilometers (224 miles) north of the Ugandan capital, Kampala examines a child suspected of being infected with the Ebola virus Tuesday, Oct.17, 2000. Only days after it was announced that an outbreak of Ebola, the world's most feared virus, had struck in northern Uganda the death toll rose to 35 and according to health officials 38 other people have been affected by the virus. (AP Photo/Sayyid Azim)Michele Barry, MD, director of Stanford’s Center for Innovation in Global Health, has launched a fundraising campaign to help combat the Ebola outbreak in Liberia, which has claimed the life of a colleague who mentored residents in the Yale/Stanford Johnson & Johnson Scholars Program.

Samuel Brisbane, MD, was the first Liberian doctor to die in the outbreak, which the World Health Organization says is responsible for more than 700 deaths in West Africa and is by far the largest outbreak in the history of the disease. Brisbane was an internist who treated patients at the John F. Kennedy Memorial Hospital in the capital city of Monrovia, the country’s largest hospital. A second medical officer has become ill at the hospital, one of the sites for the scholars’ program, Barry told me.

Through the program, Brisbane mentored physicians from Stanford and other institutions who volunteer for six-week stints in resource-limited countries. He quarantined himself after showing signs of illness but died on July 26 after being transferred to a treatment center, Barry said.

Like HIV, the Ebola virus is spread through direct contact with blood or body fluids from an infected individual. Barry said Liberia is in desperate need of personal protective equipment for health care workers, such as masks, gowns and gloves, as well as trained personnel who can do contact tracing and isolation of infected individuals. The Ebola virus has a 21-day incubation period, during which time an infected individual can transmit the virus.

Barry joined an informal fundraising campaign with her colleagues on Tuesday to help Liberian health-care workers contain the spread of the disease, raising $11,000 in 48 hours. Today, she broadened the appeal in an e-mail sent to all Stanford medical school faculty.

Barry has had experience fighting Ebola in Uganda, where she said outbreaks have been limited by isolating patients in outdoor, tented hospitals and where physicians and nurses have had access to good protective gear. In the past, she said the disease typically has had “hot spots” that last a month and then subside.

But the latest epidemic, which has affected patients in Guinea, Sierra Leone and Nigeria, as well as Liberia, has followed a somewhat different path.

“I think we are doing a better job of taking care of patients and keeping them alive longer, so they become more viremic — meaning the virus has spread through their bloodstream — and more infectious,” she said. “And with globalization, there is more traffic across borders so spillover to other countries occurs.”

She said she does not see the disease as a major threat to the United States, where effective infection control methods are widespread.

“I think we need to be vigilant, but I don’t think there needs to be any true concern that this is going to spread to the United States,” she said. “There’s always a risk of a patient coming in unknown to the hospital, but we practice good universal precautions because we have the equipment and we’ve been trained to treat HIV.”

Donations to the health-care project can be made online here.

Photo, from 2000 outbreak in Uganda, by ASSOCIATED PRESS

Immunology, In the News, Infectious Disease, Parenting, Pediatrics, Public Health

Side effects of childhood vaccines are extremely rare, new study finds

Side effects of childhood vaccines are extremely rare, new study finds

Pneumococcus-vaccineAs you may have heard about elsewhere, a new paper published today on the safety of childhood vaccines provides reassurance for parents and pediatricians that side effects from vaccination are rare and mostly transient. The paper, a meta-analysis appearing in Pediatrics, updates a 2011 Institute of Medicine report on childhood vaccine safety. It analyzed the results of 67 safety studies of vaccines used in the United States for children aged 6 and younger.

“There are no surprises here; vaccines are being shown over and over again to be quite safe,” said Cornelia Dekker, MD, medical director of the vaccine program at Lucile Packard Children’s Hospital Stanford, who chatted with me about the study earlier today. “The safety record for our U.S.-licensed vaccines is excellent. There are a few vaccines for which they document that there are indeed adverse events, but the frequency is quite rare, and in almost all cases they are very easy to manage and self-limited.”

A Pediatrics commentary (.pdf) accompanying the new study puts the value of immunization in context:

Modeling of vaccine impact demonstrates that routine childhood immunizations in the 2009 US birth cohort would prevent ~42,000 deaths and 20 million cases of disease and save $13.5 billion in direct health care costs and $68.8 billion in societal costs.

The commentary goes on to contrast the risks of vaccines with the potential complications of vaccine-preventable diseases:

The adverse events identified by the authors were rare and in most cases would be expected to resolve completely after the adverse event. This contrasts starkly with the natural infections that vaccines are designed to prevent, which may reduce the quality of life through permanent morbidities, such as blindness, deafness, developmental delay, epilepsy, or paralysis and may also result in death.

The study found evidence against suspected links between vaccines and several acute and chronic diseases. For instance, the researchers found high-quality evidence that several different vaccines are not linked to childhood leukemia and that the measles, mumps and rubella (MMR) vaccine is not linked to autism. The DTaP vaccine is not linked to diabetes mellitus, and the Hepatitis B vaccine is not connected to multiple sclerosis, according to moderate-quality evidence.

The evidence does connect a few vaccines to side effects. For instance, the MMR, pneumococcal conjugate 13 and influenza vaccines are linked to small risks of febrile seizures, with the risk of such seizures increasing slightly if the PCV-13 and flu vaccines are given together.

“A febrile seizure can be quite alarming, but fortunately it does not have long-lasting consequences for child,” Dekker said, noting that the risk of such seizures from vaccines is around a dozen per 100,000 doses of vaccine administered.

The rotavirus vaccine is linked to risk of intussusception, an intestinal problem that can also occur with rotavirus infection itself. But the benefits of rotavirus vaccination “clearly outweigh the small additional risk,” Dekker said.

The study confirmed earlier research showing that some vaccines, including MMR and varicella, cause problems for immunocompromised children, such as kids who have HIV or who have received organ transplants. Since they can’t safely receive vaccines, this group of children relies on the herd immunity of their community to protect them.

“It’s not as if the parents of immunocompromised kids have a choice about whether to vaccinate,” Dekker told me. “They have to depend on others to keep immunization levels high, and that starts breaking down when more people hold back from having their healthy kids fully immunized.”

Dekker hopes the new findings will encourage more parents to have their healthy kids fully vaccinated.

Previously: Measles is disappearing from the Western hemisphere, Measles are on the rise; now’s the time to vaccinate, says infectious-disease expert and Tips for parents on back-to-school vaccinations
Photo by Gates Foundation

Big data, Global Health, Infectious Disease, Videos

Discussing the importance of harnessing big data for global-health solutions

Discussing the importance of harnessing big data for global-health solutions

The 2014 Big Data in Biomedicine conference was held here last month, and interviews with keynote speakers, panelists, moderators and attendees are now available on the Stanford Medicine YouTube channel. To continue the discussion of how big data can be harnessed to benefit human health, we’ll be featuring a selection of the videos this month on Scope.

At this year’s Big Data in Biomedicine conference, Michele Barry, MD, FACP, senior associate dean and director of the Center for Innovation in Global Health at Stanford, moderated a panel on infectious diseases. During the discussion, she raised the point that the lines between infectious disease and non-communicable disease are becoming increasingly blurred.

In the above video, Barry expands on this point and offers her point of view on the role big data can play in advancing global health solutions. “Big Data is clearly important these days to get a larger picture of population health,” say says. “What I’m concerned about, and would love to see happen, is for big data surveillance to happen in developing countries and under-served areas, particularly in Sub-Saharan Africa.” Watch Barry’s interview to understand how harnessing big data to improve preventative care for large populations could benefit all of us.

Previously: Stanford statistician Chiara Sabatti on teaching students to “ride the big data wave”, Using Google Glass to help individuals with autism better understand social cues, Rising to the challenge of harnessing big data to benefit patients and U.S. Chief Technology Officer kicks off Big Data in Biomedicine

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

Microbial mushroom cloud: How real is the threat of bioterrorism? (Very)

Microbial mushroom cloud: How real is the threat of bioterrorism? (Very)

Dr. Milana Trounce, M.D. teaches a class on the the risks of bioterror at the Stanford School of Medicine. Photo taken on Monday, April 21, 2014. ( Norbert von der Groeben/ Stanford School of Medicine )

“What if nuclear bombs could reproduce? Get your hands on one today, and in a week’s time you’ve got a few dozen.”

That’s the lead sentence of a feature article I just wrote for Inside Stanford Medicine. The answer is, bombs can’t reproduce. But something just as potentially deadly – and a whole lot easier to come by – can, and does.

What I learned in the course of writing the feature, titled “How contagious pathogens could lead to nuke-level casualties” (I encourage you to take a whack at it), was bracing. Stanford surgeon Milana Trounce, MD, who specializes in emergency medicine, has been teaching a course that pulls together students, faculty and outside experts from government, industry and academia. Her goal is to raise awareness and inspire collaborations on the thorny multidisciplinary problems posed by the very real prospect that somebody, somewhere, could very easily be producing enough killer germs to wipe out huge numbers of people – numbers every bit as large as those we’ve come to fear in the event of a nuclear attack.

Among those I quote in the article are infectious-disease expert David Relman, MD, and biologist/applied physicist Steven Block, PhD, both of whom have sat in on enough closed-door meetings to know that bioterrorism is something we need to take seriously.

Not only do nukes not reproduce. They don’t leap from stranger to stranger, or lurk motionless in midair or on fingertips. Nor can they be fished from soil and streams or cheaply conjured up in a clandestine lab in someone’s basement or backyard.  One teaspoon of the toxin produced by the naturally occurring bacterial pathogen Clostridium botulinum is enough to kill several hundreds of thousands of people. That’s particularly scary when you consider that this toxin – better known by the nickname “Botox” -  is already produced commercially for sale to physicians who inject it into their patients’ eyebrows.

As retired Rear Adm. Ken Bernard, MD, a former special assistant on biosecurity matters to Presidents Bill Clinton and George W. Bush and a guest speaker for Trounce’s Stanford course, put it: “Who can be sure there’s no off-site, illegal production? Suppose a stranger were to say, ‘I want 5 grams — here’s $500,000’?

That’s five grams, as in one teaspoon. As I just mentioned, we’re talking hundreds of thousands of people killed, if this spoonful were to, say, find its way into just the right point in the milk supply chain (the point where loads of milk from numerous scattered farms get stored in huge holding tanks before being parsed out to myriad delivery trucks). That’s pretty stiff competition for a hydrogen bomb. For striking terror into our hearts, the only thing bioweapons lack is branding – nothing tops that mushroom-cloud logo.

Previously: Stanford bioterrorism experts comments on new review of anthrax case and Show explores scientific questions surrounding 2001 anthrax attacks
Photo of Milana Trounce by Norbert von der Groeben

Applied Biotechnology, Events, Infectious Disease, Research, Stanford News, Videos

Stanford microbiologist’s secret sauce for disease detection

Stanford microbiologist's secret sauce for disease detection

Last week, John Boothroyd, PhD, kicked off Stanford’s first Disease Detective lecture series with a fascinating tale about how his lab invented a simple biochemical “secret sauce” that revolutionized the detection of viral and bacterial infections like HIV, Hepatitis C and gonorrhea.

“It mostly started as a sketch on a piece of paper, then later became Gen-Probe’s core technology, which won them the 2004 National Medal of Technology,” explained Boothroyd, a Stanford professor of microbiology and immunology.

What Boothroyd invented, in collaboration with postdoctoral researchers James Burg and Philippe Pouletty, is called Transcription-Mediated Amplification.

Before this discovery, detecting a snippet of disease-specific DNA in a sample of cells was like finding a needle in a haystack. To increase a test’s accuracy, a lab technician would try to coax the target DNA into replicating itself through hours of tedious time-and- temperature-sensitive steps.

Boothroyd and his team’s new process consisted of a simple recipe of primers and enzymes that, after optimization by Gen-Probe, tricked a target snippet of DNA into automatically creating 10 billion copies of itself in less than an hour. This ultimately enabled the development of cheaper and faster disease tests.

In 2012 Boothroyd was ushered into the Stanford Inventor’s Hall of Fame because of this patent, which is among the top-ten revenue-generating inventions Stanford. He has six other patented inventions, including one that makes antigen production for the testing of toxoplasmosis infections far more efficient. Another detects toxoplasmosis in the amniotic fluid of pregnant women. He describes this research in the video above.

Looking back on his career choices, one thing that Boothroyd is grateful for is being able to combine his two loves at Stanford — basic research and teaching — while leaving the business of running a company to his patent licensees.

To the lecture hall filled with student researchers worried about the “postdocalypse,” the shortage of tenure-track research positions in academia, he gave this advice:

“I think the [postdocalypse] negativity is overstated. You have to have faith in yourself. You have to do what you want to do. If you’re enjoying your work and it’s a stepping stone to where you’re going, relax and see what happens.”

The next Disease Detective lecture will be held during fall quarter 2014. Watch for details on the Stanford Predictives and Diagnostics Accelerator webpage.

Previously: Patrick House discusses Toxoplasma gondii, parasitic mind control and zombies, Cat guts, car crashes, and warp-speed Toxoplasma infections, and NIH study supports screening pregnant women for toxoplasmosis

Global Health, Health Costs, Infectious Disease, Public Health, Research, Stanford News

The earlier the better: Study makes vaccination recommendations for next flu pandemic

The earlier the better: Study makes vaccination recommendations for next flu pandemic

no fluIn 2009, the H1N1 flu virus circled the globe, sickening and killing thousands of people. Though the World Health Organization announced that the virus was a pandemic in June 2009, in the U.S., widespread vaccination campaigns didn’t occur until about nine months later. By that time, many people had already spent a week coughing on the couch, recovered, and developed immunity to the virus.

After observing these delays, Stanford researchers Nayer Khazeni, MD, and Douglas K. Owens, MD, wanted to know when is the best time to vaccinate to save lives, reduce infections and lower health-care costs. They used the U.S. response to the 2009 pandemic to create a computer model that simulated how a more deadly flu pandemic would move through a metropolis like New York City.

In their paper, which appears in Annals of Internal Medicine, the researchers found that if a city could vaccinate its residents six months after the start of an outbreak, instead of nine, it could stop more than 230,000 infections and prevent the deaths of 6,000 people. The city could also save $51 million in hospital bills for infected individuals.

It takes about six months for scientists, public health officials and vaccine companies to create and distribute a new flu vaccine. Most vaccines are still grown in chicken eggs! But newer technologies that use cell cultures or genetic engineering to create vaccines may soon shorten the wait to just four months. Shaving off those two months would almost double the savings, in terms of both lives and health-care dollars, they found.

Even if the city can’t vaccinate until nine months into an outbreak, residents can slow the virus’ spread by staying home when sick, wearing a face mask, hand washing, and in severe cases, even closing down schools and public transportation. These low-tech methods can buy the residents time while they are waiting for a vaccine to become available.

Patricia Waldron is a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously: Could self-administered flu vaccine patches replace injections? Text message reminders shown effective in boosting flu shot rates among pregnant women and Working to create a universal flu vaccine
Photo by itsv 

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

Using video surveillance to gain insights into hand washing behavior

Using video surveillance to gain insights into hand washing behavior

13715-handwashing_newsSimply washing your hands can reduce the reduce respiratory illnesses, such as colds, in the general public by 21 percent, cut the number of people who get sick with diarrhea by 31 percent and lower diarrheal illness in people with weakened immune systems by 58 percent, according to data from the Centers for Disease Control and Prevention.

Despite these compelling facts, and many years of global awareness campaigns, hand-cleaning rates remain far below full compliance — particularly in low-income, developing world settings. But using video surveillance to observe hygiene practices can offers insights that may help improve design, monitoring and evaluation of hand-washing campaigns, according to a new Stanford study.

For the study, researchers installed video cameras at the washing stations outside latrines of four public schools in the Kibera slum of Nairobi, Kenya. Teachers were informed in advance and parents and administrators granted their permission for the experiment. Their findings were highlighted in a Stanford News article published yesterday:

  • Both video observation and in-person observation demonstrated longer hand cleaning times for hand washing with soap as compared to rubbing with sanitizer.
  • Students at schools equipped with soap and water, instead of sanitizer, were 1.3 times more likely to wash their hands during simultaneous video surveillance and in-person observation when compared with periods of in-person observation alone.
  • Overall, when students were alone at a hand-cleaning station, hand cleaning rates averaged 48 percent, compared to 71 percent when at least one other student was present.

Based on their findings, study authors recommended the following approaches for boosting hand washing:

  • Placement of hand cleaning materials in public locations
  • Scheduling specific times for bathroom breaks between classes
  • Designating specific students to be hand hygiene “champions”
  • Formation of student clubs to demonstrate and promote hand hygiene to classmates

Previously: Examining the effectiveness of hand sanitizers, Survey outlines barriers to handwashing in schools, Examining hand hygiene in the emergency department, Good advice from Washyourhandsington and Hey, health workers: Washing your hands is good for your patients
Photo by Amy Pickering

Global Health, Infectious Disease, Technology

Health workers use crowdsourced maps to respond to Ebola outbreak in Guinea

Médecins Sans Frontières and other international aid organizations are furiously working to contain an outbreak of Ebola in Guinea and nearby African countries. Latest reports estimate that the virus has infected 157 people and killed 101 in Guinea alone.

A New Scientist story published today explains how health workers from Médecins Sans Frontières were initially at a disadvantage when they arrived in Guinea to combat the deadly virus because they only had topographic charts to use in pinpointing the source of the disease. Desperately in need of maps that would be useful in understanding population distribution, the organization turned to Humanitarian OpenStreetMap Team, which coordinated a crowdsourcing effort to produce the first digital map of Guéckédou, a city of around 250,000 people in southern Guinea. Hal Hodson writes:

As of 31 March, online maps of Guéckédou were virtually non-existent, says Sylvie de Laborderie of cartONG, a mapping NGO that is working with MSF to coordinate the effort with HOT. “The map showed two roads maybe – nothing, nothing.”

Within 12 hours of contacting the online group, Guéckédou’s digital maps had exploded into life. Nearly 200 volunteers from around the world added 100,000 buildings based on satellite imagery of the area, including other nearby population centres. “It was amazing, incredible. I have no words to describe it. In less than 20 hours they mapped three cities,” says de Laborderie.

Mathieu Soupart, who leads technical support for MSF operations, says his organisation started using the maps right away to pinpoint where infected people were coming from and work out how the virus, which had killed 95 people in Guinea when New Scientist went to press, is spreading. “Having very detailed maps with most of the buildings is very important, especially when working door to door, house by house,” he says. The maps also let MSF chase down rumours of infection in surrounding hamlets, allowing them to find their way through unfamiliar terrain.

Previously: Using crowdsourcing to diagnose malaria and On crowdsourced relief efforts in Haiti

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