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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

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

Discovered: Why so many people with schistosomiasis (there’s a lot of them) are so vulnerable to bacterial co-infection

Discovered: Why so many people with schistosomiasis (there's a lot of them) are so vulnerable to bacterial co-infection

More than a billion people worldwide – almost all of them in developing countries – are infected by worm-like parasitic organisms called helminths. Organisms making up just a single genus of helminth, Schistosoma, account for one-quarter of those infections, which damage different body parts depending on what schistosomal species is doing the infecting. Some go for the lung. Others (card-carrying members of the species Schistosoma haematobium) head for the urinary tract, with one in ten infected patients suffering severe physical consequences.

People with schistosomiasis of the urinary tract are especially vulnerable to bacterial co-infections. Worse, these co-infections exacerbate an already heightened risk of bladder cancer in infected individuals, it’s believed. Unfortunately, considering the massive numbers of cases, surprisingly little is understood about the molecular aspects of the infection’s course.

A big reason for that relative ignorance has been the absence of an effective animal model enabling the detailed study of urinary-tract schistosomiasis. A couple of years ago, Stanford schistosomiasis expert Mike Hsieh, MD, PhD, developed the world’s first decent mouse model for the disease, allowing him to explore the molecular pathology that occurs early in the course of infection. Now, in a just-published study in Infection and Immunity, Hsieh has put that mouse model to work in coaxing out the cause of the curious collegiality of S. haematobium and co-infecting bacteria.

The secret, the scientists learned, is that S. haemotobium infection induces a spike in levels of a circulating immune-system signaling protein, or cytokine, called IL-4. That excess, in turn, results in a drop in the number and potency of a subset of immune cells that are important in fighting off bacterial infections. The discovery opens a pathway toward the development of new, non-antibiotic drug treatments for co-infected patients that won’t wreak havoc with their microbiomes, as antibiotics typically do.

Previously: Is the worm turning? Early stages of schistosomiasis bladder infection charted, Neglected story of schistosomiasis in Ghana, as told in a  sand animation and A good mouse model for a bad worm

Global Health, HIV/AIDS, Infectious Disease, Stanford News

Stanford study: South Africa could save millions of lives through HIV prevention

Stanford study: South Africa could save millions of lives through HIV prevention

South Africa could save the lives of some 4.5 million people over the next 20 years by using a double-barreled approach to HIV prevention.

That’s the result of a new study by Stanford researchers who looked at two methods for helping contain the epidemic in South Africa. According to the latest figures from the United Nations Joint Programme on HIV/AIDS, South Africa is the world’s hardest-hit country with 6.1 million people infected with HIV and most new infections happening via heterosexual transmission.

Effectively targeting people who don’t use condoms and have many sexual partners would prevent many infections and avert the costs of having to treat people down the road

One way to prevent sexual transmission of the disease is to give antiretroviral therapy to individuals as soon as they are found to be HIV-positive, said Sabina Alistar, PhD, first author of the new study. The World Health Organization now recommends that people go on ARV treatment when their CD4 counts – a measure of their immune system function – fall below 500. But a landmark study, published in 2011, showed that if infected individuals are effectively taking ARV treatment, the chance of their passing on the virus falls by a staggering 96 percent. So the greater the number of infected people on treatment, the less the virus will spread through the population.

“It’s much more cost-effective to put people in treatment as you find them, regardless of how far along they’ve progressed, rather than wait until they get really sick and put them on treatment,” said Alistar, who did the study while a PhD candidate in Management Science and Engineering at Stanford.

That idea isn’t new, but in this latest study from Stanford, the researchers examined the benefits of combining that universal approach to therapy with another tool, creating a powerful, cost-effective strategy for preventing millions of infections over time. The added tool, known as pre-exposure prophylaxis, or PrEP, involves daily use of a pill containing an antiretroviral drug. The pill is taken by people who may be at risk for HIV but are not infected. A landmark 2010 trial found that PrEP, if used faithfully, can reduce the risk of acquiring the virus by up to 73 percent.

“If you could focus on getting PrEP to people who engage in risky behaviors, then you could get quite significant results,” Alistar said. “Effectively targeting people who do not use condoms and have many sexual partners would prevent many infections and avert the costs of having to treat people down the road.”

She and her colleagues calculated that combining the two strategies – universal therapy for all those with HIV and targeted PrEP therapy for uninfected, high-risk individuals – would cost $150 per quality-adjusted life year gained (a QALY is measure of how much health benefit is gained for every dollar invested). That is a highly valuable bargain for South Africa, she said, which has significant resources to invest in the epidemic.

Eran Bendavid, MD, an assistant professor of medicine at Stanford and senior author of the paper, said scientists are now developing an approach to PrEP that only requires an injection every three or four months, rather than a daily pill.

When that therapy becomes available, “That has the potential to become a game-changer, since the Achilles heel of PrEP is low adherence,” Bendavid said.

The paper appears online today in the journal BMC Medicine.

Previously: U.S. AIDS Czar tells Stanford audience that witnessing death is a powerful motivatorTask force recommends HIV screening for all people aged 15 to 65International AIDS conference ends on an optimistic note and Using family planning counseling to reduce number of HIV-positive children in Africa

Clinical Trials, Global Health, Infectious Disease, Pediatrics, Stanford News

Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial

Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial

dollar bill 2Nearly every child in the world has been infected with rotavirus at least once by the age of five. But kids in poor countries get the worst of it. Rotavirus mortality is low in the developed world, but in low-income countries it’s a killer, accounting for 85 percent of the estimated 180,000 to 400,000 annual deaths caused by the pathogen.

The disparity exists for at least two reasons.

First, widespread malnutrition results in a different epidemiology. For example, 70 percent of rotavirus hospitalizations in India happen the first year of life, compared with 40 percent in high- and middle-income countries.

Second, price. Vaccination is second only to gaining access to potable water as a low-cost, high-payoff  strategy for ensuring children’s health. But many vaccines are far too pricey for families living on incomes in the neighborhood of $1,500 per year. As a result, most childhood deaths from vaccine-preventable diseases happen in low-income countries. India has the most rotavirus deaths in the world, estimated at about 75,000-122,000 per year (close to a quarter of the worldwide total.)

So it’s great news that a new rotavirus vaccine developed by Indians for Indians has leaped the safety and efficacy thresholds of a late-stage clinical trial, in which more than 6,500 Indian infants were inoculated, and will likely become available in that country for less than a dollar a dose. (The full immunization procedure requires three separate doses.)

The results appear in a study just published in The Lancet and co-authored by a team including veteran rotavirus-vaccine developer Harry Greenberg, MD. An accompanying perspective piece co-written by Greenberg, who also directs the Stanford Center for Clinical and Translational Research and Education, states:

[P]roof of the efficacy of the… vaccine against a disease that affects almost every child in India, leads to millions of clinic visits and hundreds of thousands of hospital admissions, and kills roughly one child in every 175-200 born in India before their fifth birthday is cause for celebration.

The new vaccine was the first to be fully tested for efficacy in a randomized, double-blind, placebo-controlled clinical trial in India. Interestingly, its development began with the discovery, by an Indian pediatrician, that newborns were getting rotavirus infections in the hospital but not getting sick. The strain they were infected with turned out to be an attenuated mutant virus that turns on the body’s immune response without causing symptoms: in short, the ideal vaccine candidate.

Ultimately spearheaded by a young Indian biotechnology company, Bharat Biotech, the effort to capitalize on this promising episode of serendipity drew financial support from the Bill & Melinda Gates Foundation and technical assistance from the Government of India’s Department of Biotechnology, the United States’ Centers for Disease Control and Prevention, and Stanford, among others.  This international team of collaborators then spent more than 15 years turning the promise into a reality.

Previously: Trials, and tribulations, of a rotavirus vaccine
Photo by David Guo

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