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Ebola, Ethics, Global Health, Stanford News

The Ebola crisis: an ethical balancing act

The Ebola crisis: an ethical balancing act

Ebola in GuineaShould Ebola patients in West Africa be given unproven treatments? How should clinicians decide which patients to treat, given the limited availability of some drugs? Should Ebola patients who are dying be given palliative care to relieve pain and suffering?

These are among the ethical questions addressed in a special issue of the American Journal of Bioethics, devoted to the many challenges involved in caring for patients with Ebola.

“Obviously, the Ebola crisis galvanized lots of different health care professionals and academics, but it was very important to the bioethics community,” David Magnus, PhD, director of the Stanford Center for Biomedical Ethics, told me. “From the very beginning, there were the usual public health ethics. But when the time came to give the scarce drug, ZMapp, to a small number of health care workers, there was a huge amount of controversy.”

“That also led to a major debate on the conduct of clinical trials and whether we should give unproven treatments to patients,” he said. “There’s a very big split in the biomedical ethics community.”

Magnus is editor-in-chief of the monthly journal, which is housed at Stanford. He said the special edition of the journal is particularly relevant now, given the recent launch by the NIH of a clinical trial involving ZMapp. The experimental drug, manufactured by a San Diego, Ca. company, was given to a very small number of clinicians in the United States who had been exposed to Ebola in West Africa.

In the journal, a group of ethicists led by New York University’s Arthur Caplan, PhD, argue that the gold standard in drug testing – the randomized, placebo-controlled trial – may not be the most practical and morally defensible approach in an emergency like the Ebola crisis.

A conventional trial is hard to justify, given that patients in the West were given the drug without any placebo controls; West Africans should be treated no differently. Nor can it be justified if the drug is compared against the usual standards of care in Africa, which may be ineffective and carry a high probability of death. That approach could just engender further mistrust in West African communities, they say. Rather, Caplan and his colleagues argue for an alternative approach – a side-by-side comparison of various experimental drugs to see which one is superior in helping rescue patients.

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

Spread of drug-resistant HIV in Africa and Asia is limited, Stanford research finds

Spread of drug-resistant HIV in Africa and Asia is limited, Stanford research finds

In the last decade, millions more people in the developing world have gained access to anti-viral drugs to treat HIV, with nearly 12 million now on this life-giving treatment. But with more people on medication, there’s concern about the spread of drug-resistant strains of the virus, which can be transmitted from one individual to the next.

A new, multi-center study led by Stanford researchers offers some good news on this front: The transmission of drug-resistant strains thus far has been fairly limited in the hard-hit regions of Africa and Asia. The research involved more than 50,000 patients in 111 countries.

It is inevitable that transmitted drug resistance will increase further, so we need to continue ongoing monitoring to ensure successful, long-term treatment outcomes

“What we are showing is that the rates of transmitted drug-resistant HIV in the low- and middle-income countries most affected by HIV have increased modestly,” Stanford infectious disease expert Robert Shafer, MD, principal investigator on the study, told me. “The rate of increase in sub-Saharan Africa has been low, and an increase has not been detected in south Asia and Southeast Asia.”

Shafer is nonetheless cautious, as drug resistance remains a problem in these regions, where patients are prescribed drug regimens that are not as effective as those used in the West. And adhering to a daily regimen can be challenging for these patients, as transportation, drug supply and other issues may get in the way. Resistance can occur when there is a gap in treatment.

“It is inevitable that transmitted drug resistance will increase further, so we need to continue ongoing monitoring to ensure successful, long-term treatment outcomes for the millions of people on therapy worldwide,” Shafer said.

In the study, he and his colleagues identified four mutations that were linked to resistance to two HIV drugs, nevirapine and efavirenz. That result points to the possibility of creating a simple test that could be used to detect these mutations, he said. Clinicians then could tailor their treatment accordingly.

Another key finding was that the drug-resistant strains that did occur were not from a single line of resistant viruses, but were quite distinct. That means they developed independently, not as a result of a single transmission chain. That differs from some other microbes, such as malaria and tuberculosis, where resistant strains can move very quickly through the population.

“We are finding that the strains being detected in low-income countries are pretty much unrelated to one another,” Shafer said. “So that suggests these have not yet gained a foothold in the population and are less often being transmitted among people who have never received the drugs before.”

The study appears online today in PLoS Medicine.

Cancer, Global Health, Patient Care, Stanford News

New global cancer map aims to improve care in developing countries

New global cancer map aims to improve care in developing countries

cancer map2

Most people don’t associate cancer with the developing world, yet 60 percent of new cancer cases and 70 percent of cancer deaths occur in less developed parts of the world, according to the World Health Organization. Now, the nonprofit Global Oncology, Inc. has launched a Global Cancer Project Map, a first-of-its-kind resource that will connect cancer experts around the world in an effort to advance cancer research and care in low-resource areas.

The interactive map includes more than 800 projects on six continents. With a few simple clicks, users can search for cancer experts and research projects and then contact the investigators and program managers. The goal is to spur collaboration among people in the field and enable experts to share their collective knowledge.

“Before it was difficult or often impossible to find information about cancer projects or experts, especially in limited-resource settings,” said Ami S. Bhatt, MD, PhD, an assistant professor of medicine and genetics at Stanford and co-founder of Global Oncology, Inc. “The map now makes it possible to connect colleagues in the global cancer community with a maximum of six clicks of a computer mouse.”

Bhatt, who directs global oncology for Stanford’s Center for Innovation in Global Health, and GO co-founder Franklin Huang, MD, PhD, have been working with the National Cancer Institute on ways to bring multidisciplinary teams together to solve complex problems in cancer. While there are many dedicated scientists and caregivers doing innovative work in cancer in the developing world, there’s been no single place where they could share knowledge or reference the work of their colleagues, she said. The cancer map is a first step in this process.

“We have the ambitious goal of providing access to every cancer research, care and outreach program in the world through the map,” said Huang, who is an instructor at the Dana-Farber Cancer Institute.

A collaboration with the NCI, the map was developed by GO volunteers, who are scientists, policymakers, public health experts, lawyers and other highly skilled individuals. It covers a wide range of projects, from prevention and screening to clinical programs and palliative care. For instance, it includes a project in Turkey to improve diagnostic accuracy of mammograms to detect breast cancer; development of an early screening test for gastric cancer in Mexico; and use of supplements to prevent arsenic-induced skin cancer in Bangladesh.

“The map is an important and innovative step forward in our effort to reduce health disparities and strengthen human capital in underserved areas of the world,” said Michele Barry, MD, director of Stanford’s Center for Innovation in Global Health. “With cancer rates rapidly increasing in low-resource settings, the map creates a place where the global cancer community can share and access information that is critical to providing better treatment and care.”

Bhatt and Huang unveiled the new map today at the Symposium on Global Cancer Research, being held in Boston. The symposium is co-sponsored by the NCI, the Consortium of Universities for Global Health and the Dana-Farber Cancer Institute.

Image from Global Oncology, Inc.

Behavioral Science, In the News, Medicine and Society, Research

Research prize for helping make mice comfy – and improving science

Research prize for helping make mice comfy - and improving science

OLYMPUS DIGITAL CAMERAA Stanford researcher has won accolades for a research paper that could help ease the lives of millions of laboratory mice – and improve the outcomes of research studies.

Joseph Garner, PhD, an associate professor of comparative medicine, and his colleagues observed that mice are routinely housed in cold conditions, which put stress on the animals. The mice compensate with physiologic changes that can skew the results of laboratory studies. For instance, temperature has been shown to affect immune function and tumor development in mice, among other factors. So cold stress in mice raises concerns not only for animal welfare but also for science.

Garner and his colleague, Briana Gaskill, PhD, proposed a simple solution: Give the animals some nesting material, and they’ll build a cozy home to regulate their temperatures. These comfy mice would be more physiologically comparable to humans, making them better research subjects, the researchers said. But one obstacle to adopting this simple solution was the question of how much nesting material is enough? In their prize-winning experiment, the researchers asked the mice how much nesting material they needed to give up a warm cage for a cold cage with a nest. The scientists found that between 6 and 10 grams of nesting material could effectively reduce cold stress in the animals – a standard now starting to be adopted in labs around the world.

The paper, published in 2012 in PLoS One, won a high commendation recently from the National Centre for the Replacement, Refinement & Reduction of Animals in Research, a leading, UK-based scientific organization that supports research which aims to minimize the need for animals in research and improve animal welfare.

The group said that the research results “have the potential to positively impact the welfare of millions of laboratory mice all over the world.”

Garner and Gaskill both traveled to London to receive the prize.

Previously: Stanford students design “enrichments” for lions, giraffe and kinkajou at the San Francisco Zoo, Nesting improves mouse well-being, could aid research studies and Stanford researcher’s easy solution to problem of drug testing in mice
Photo, which originally appeared in Stanford Medicine magazine, by Brianna Gaskill

Global Health, Health Policy, Infectious Disease

“Made-in-India” vaccine could save thousands of children

"Made-in-India" vaccine could save thousands of children

5559524166_510ebb57a0_zIndia reached a milestone this week with the introduction of a novel rotavirus vaccine, the first vaccine designed entirely in the developing world. The vaccine is not only safe and effective, but also affordable; the manufacturer, Bharat Biotech, has pledged to make it available for $1 to governments in low-income countries.

The vaccine, known as ROTAVAC, will be used to fight a disease that kills 80,000 children a year in India alone. On a global scale, rotavirus, which causes severe diarrheal disease, is responsible for some 450,000 childhood deaths and 2 million hospitalizations.

The vaccine was developed through a unique partnership supported by the Indo-U.S. Vaccine Action Program, which was chaired until recently by Harry Greenberg, MD, senior associate dean for research at the School of Medicine. Greenberg was a lead inventor of the first-generation vaccine for rotavirus.

“The ROTAVAC project is a beautiful example of the great power of team science,” Greenberg told me. “The vaccine is a culmination of a very large and disparate group of people and organizations, all working together for a common goal: to produce a safe, effective and affordable vaccine to prevent severe, rotavirus-associated diarrhea in Indian children.”

During a three-day visit to India in January, U.S. President Barack Obama and Indian Prime Minister Narendra Modi had praised the “highly successful collaboration” that lead to the development of the vaccine. Prime Minister Modi was on hand for ceremonies Monday announcing the launch of the vaccine, which the Indian government will make available in public clinics across the country.

The vaccine originated from a weakened strain of rotavirus that was isolated from an Indian child in the mid-1980s. It went through a long development process which included investigators from 13 institutions and culminated in a randomized, double-blind clinical trial involving nearly 6,800 infants in India. The results, published in the Lancet in 2014, showed it was as effective as two other licensed, commercial oral rotavirus vaccines.

The vaccine was developed with support from the National Institutes of Health and the U.S. Centers for Disease Control and Prevention, among others.

“The impact of this vaccine to improve child survival is enormous,” said Roger Glass, MD, PhD, director of the Fogarty International Center at the NIH. “Our groups at the CDC and NIH are proud to be an integral part of this longstanding and enormously successful collaboration with our Indian colleagues.”

Previously: President Obama and Indian Prime Minister praise partnership that led to rotavirus vaccine, Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial and Trials, and tribulations, of a rotavirus vaccine
Photo by The Bill and Melinda Gates Foundation

Emergency Medicine, Medicine and Society, Patient Care, Public Safety, Stanford News

A young child, a falling cabinet, and a Life Flight rescue

A young child, a falling cabinet, and a Life Flight rescue

ticktockLife in the air rescue business is highly unpredictable. You can spend many hours idling away the time in an obscure, basement office. But when an emergency call comes, you literally don’t have a second to grab a pen on the way out the door.

So it was on one November day, when I did a ride-along with Stanford’s illustrious Life Flight air ambulance service, the oldest in California. The team graciously agreed to let me accompany them on a flight for a story for Stanford Medicine magazine, whose current issue is focused on the role of time in medicine. Life Flight, I figured, would give me a sense of the split-second timing that can sometimes make a difference between life and death in an emergency situation. I was scheduled to fly with the crew in late October, but instead I spent that day learning about the service in what proved to be a leisurely day with no calls.

On my second ride-along day, it appeared that history was about to repeat itself when, just as my shift was about to end, the emergency call came in at 3:39 p.m. I became an eye witness to the rescue of a toddler who suffered a serious head injury when a heavy, ill-secured cabinet at her preschool crashed down on her head during naptime. The story was so dramatic that it made the local news. The school was shut down several days later by local officials because of code violations.

Things could have gone poorly for little Aeshna, the 3-year-old victim of the accident, who was left dazed, not fully conscious and vomiting as a result of her injury – clear signs of head trauma. She could have suffered significant bleeding in the brain and permanent brain damage – a prospect that was a major concern for her parents and caregivers.

The two Life Flight nurses, who have a breathtaking array of skills, and their veteran U.S. Navy pilot made it to the scene at the Fremont, Ca. preschool across the bay within 23 minutes of the call and were able to bring Aeshna back to Stanford for quick assessment and treatment.

You can read the minute-by-minute scenario of Aeshna’s rescue in the the magazine, which came out last week.

Previously: Stanford Medicine magazine reports on time’s intersection with health, Comparing the cost-effectiveness of helicopter transport and ambulances for trauma victims, Stanford Life Flight celebrates 30 years and Ask Stanford Med: Answers to your questions about wildnerness medicine
Illustration by Lincoln Agnew

Immunology, In the News, Medicine and Society, Pediatrics, Public Health, Stanford News

A discussion of vaccines, “the single most life-saving innovation ever in the history of medicine”

A discussion of vaccines, "the single most life-saving innovation ever in the history of medicine”

vaccine and syringeIn a recent, in-depth interview with KCBS Radio, now available online, Stanford immunologist Mark Davis, PhD, called vaccines “the single most life-saving medical innovation ever in the history of medicine” and called not vaccinating children a real danger.

Davis was interviewed on air for 30 minutes following the announcement that he’ll direct a new, $50-million initiative at Stanford, funded by the Bill & Melinda Gates Foundation, which aims to speed discovery of vaccines for some of the world’s deadliest infectious diseases, such as malaria, tuberculosis and HIV.

Davis, who directs the Stanford Institute for Immunity, Transplantation and Infection, harked back to the time when cemeteries were filled with the graves of young children who fell victim to diseases such as measles and mumps that were virtually wiped out with the advent of vaccines. In the pre-vaccine era, about half of all children died of infectious diseases that are readily preventable today, he noted.

“One day I wandered through Union Cemetery in Redwood City, which started around 1850,” he said. “What was telling about the earlier graves is how many graves you have where they are two large headstones for the mother and father and a lot of little headstones for the children who died in infancy from measles and mumps and all these diseases that had also vanished with childhood vaccination but that are now coming back because people say, ‘I’ve heard something bad about these vaccines. So we are not going to give them to our kid.’”

Parents who chose not to vaccinate their children “are putting your kid at risk and also putting other young children at risk, as children don’t get vaccinated for measles until they are one year old. So kids die. Older people – a population we study here at Stanford – don’t respond very well. Their immune system often deteriorates with age… So even if they had a measles shot in their youth, they might still be vulnerable. So if you don’t vaccinate your child, you are putting your kid at risk, anyone with an immune deficiency at risk, little babies at risk, old people at risk. It just shouldn’t be permitted.”

Measles, he noted, is a “very ambitious” virus that spreads through the air, surviving on droplets of water vapor, so coughing can readily spread the disease. As a matter of public health, the disease can be controlled through the principle of “herd immunity” – the idea that if most people are vaccinated, a disease will be less likely to move through the population, he said.

“So it’s not just about you and your child. It’s about society… If more and more people are not vaccinated, it gives a virus, like the measles virus, an opportunity to run through the population very quickly, which it does, and endanger many more people,” he told listeners.

As to whether California should require parents to vaccinate their children, Davis was adamant on the subject:

I wouldn’t want unvaccinated kids in a classroom with my kids. I think it’s a danger. These are decisions made by parents that could affect the health of their children for the rest of their lives… The government is totally correct to say you should not kill your child, you should not starve your child, you should not beat your child, and you should not deprive your child of vaccines.

Previously: With a Gates Foundation grant, Stanford launches major effort to expedite vaccine discovery, Infectious disease expert discusses concerns about undervaccination and California’s measles outbreak and Side effects of childhood vaccines are extremely rare, new study finds
Photo by NIH

Global Health, Immunology, Research, Stanford News

With a Gates Foundation grant, Stanford launches major effort to expedite vaccine discovery

With a Gates Foundation grant, Stanford launches major effort to expedite vaccine discovery

Mark DavisThe vaccine field got a major boost today with the announcement that the Bill & Melinda Gates Foundation will invest $50 million in a new collaboration with Stanford’s School of Medicine to speed the development of vaccines for some of the world’s major scourges. The funds will support the new Stanford Human Systems Immunology Center, a multidisciplinary effort led by immunologist Mark Davis, PhD.

In recent decades, efforts to develop vaccines for major killers such as HIV and malaria have been stymied in part by the expense and time involved in conducting large-scale trials, which have often proved disappointing. Through the new initiative, scientists will use advanced immunological tools to better understand how vaccines provide protection and identify the most promising candidates to pursue in clinical trials.

What we need is a new generation of vaccines and new approaches to vaccination

“What we need is a new generation of vaccines and new approaches to vaccination,” said Davis, director of the Stanford Institute for Immunity, Transplantation and Infection. “This will require a better understanding of the human immune response and clearer predictions about vaccine efficacy for particular diseases.”

The 10-year initiative will involve multiple faculty from diverse fields, including medicine, engineering and computer science. It will capitalize on a range of technologies, some of which have been pioneered at Stanford, which can rapidly analyze individual cells and provide a detailed profile of the human immune response, with all of its various components.

“This grant will provide crucial support to Stanford’s world-class scientists as they collaborate with investigators around the globe to assess vaccines against some of the most formidable diseases of our time,” said Lloyd B. Minor, dean of Stanford’s medical school. “The Stanford Human Systems Immunology Center will help the most promising vaccine candidates to move quickly and efficiently from the lab to the front lines of treatment, impacting countless lives.”

Previously: Knight in lab: In days of yore, postdoc armed with quaint research tools found immunology’s Holy Grail
Photo of Mark Davis by Steve Fisch

Global Health, Health Policy, In the News, Infectious Disease

President Obama and Indian Prime Minister praise partnership that led to rotavirus vaccine

President Obama and Indian Prime Minister praise partnership that led to rotavirus vaccine

Barack_Obama_talks_with_Narendra_ModiDuring his three-day visit to India, President Barack Obama issued a joint statement with Indian Prime Minister Narendra Modi praising the “highly successful collaboration” that led to the availability of a newly developed Indian rotavirus vaccine, which is expected to save 80,000 children in India alone each year.

The vaccine was developed with support from the Indo-U.S. Vaccine Action Program, co-chaired since 2009 by Harry Greenberg, MD, senior associate dean for research at the Stanford School of Medicine. Greenberg was the lead inventor of the first-generation vaccine for rotavirus, a severe diarrheal disease that kills between 300,000 and 400,000 children each in the developing world.

“This is the VAP’s biggest accomplishment to date,” Greenberg told me from Taiwan, where he is attending a conference. “The program really helped support the development of a new safe and effective rotavirus vaccine from the start to finish. And it’s the first time ever that a new vaccine was developed in a less developed country by and for that country and became licensed.”

The vaccine initiative, funded by the U.S. Public Health Service and the Indian government, was created in 1987 to help advance the development of new vaccines of importance to India. The NIH manages research grants in the United States for the vaccine program.

“The VAP has been the most successful, continuous program we have with India,” Roger Glass, MD, PhD, director of the NIH’s Fogarty International Center, wrote in an email from India to top NIH officials. “It’s amazing to me that this little research project on rotavirus with Harry Greenberg and George Curlin (former deputy director of NIH’s Division of Microbiology and Infectious Diseases) has turned into a real product that is being launched and will be used.”

A low-cost version of the vaccine, known as Rotavac, is being manufactured in India and was launched into the marketplace on Jan. 23, Greenberg said. It was the result of an unusual team effort involving diverse multinational groups of investigators from 13 institutions seeking to create a vaccine that was not only safe and effective, but also affordable enough for use in India and other low-income countries, Greenberg said. The Indian government is negotiating to purchase the vaccine for public distribution. The vaccine also will compete in the private market against at least two other commercially available vaccines.

In the joint statement, the two world leaders pledged continued support for the vaccine program, and Greenberg, who recently stepped down from his chairmanship, made an argument for now focusing the attention of the vaccine partnership on respiratory syncytial virus (RSV), a potentially serious lung disease that is prevalent in children in India and in other regions as well.

“RSV is an incredibly important pediatric pathogen all over the world, and there is now potential for great progress,” Greenberg said. “I suggested to VAP that it think about RSV as a new target for research. It has a huge public impact and it may well be that there are great advances to be made in the near future. I think that idea resonated with the people. We will see.”

Previously: Life-saving dollar-a-dose rotavirus vaccine attains clinical success in advanced India trial and Trials, and tribulations, of a rotavirus vaccine
Photo courtesy of The White House

Ebola, Events, Infectious Disease, Stanford News

Physician at forefront of Ebola fight: “Ultimate award” is what you get back from survivors

Physician at forefront of Ebola fight: "Ultimate award" is what you get back from survivors

BauschWhen Lassa fever, a cousin of Ebola, was afflicting hundreds of thousands of people in West Africa in the late 90s, Daniel Bausch, MD, MPH & TM, worked with the federal Centers for Disease Control and Prevention in Guinea to set up a laboratory for study and testing of the rodent-borne disease. Unfortunately, the lab lost its international funding in 2003, as it could have proven useful in preventing the Ebola epidemic, which began in a remote village in Guinea just a few hours away, Bausch told a Stanford audience last week.

“I think back that if we had succeeded in keeping this lab going, how different it would have been if we’d been able to just send a sample down the road,” instead of losing valuable time in shipping the samples to Europe for testing, said Bausch, the keynote speaker at a day-long global health conference.

Today, Bausch, an associate professor at the Tulane School of Public Health and Tropical Medicine, is at the forefront of the Ebola fight, treating patients at an Ebola clinic in Sierra Leone that he helped establish and training and recruiting other clinicians. He is also consulting with the World Health Organization in the development and implementation of treatment guidelines and drug and vaccine testing for the disease.

In 1996, Bausch was working with the CDC in the Democratic Republic of Congo, where dozens of miners were being felled by a strange set of symptoms. The source was identified as Marburg virus, a cousin of Ebola that kills more than 80 percent of victims. While the usual course of spread is from one person to the next, these miners were harboring different variants of the virus, suggesting multiple sources, he said. The disease was traced back to the caves where miners unearthed their gold and where they were exposed to bats — the likely reservoir of the virus, Bausch said. He and colleagues published an article on their Marburg investigation in 2006 in the New England Journal of Medicine.

Because of his rare expertise with hemorrhagic fevers, Bausch was called upon early on to help fight in the latest Ebola outbreak, working alongside West African colleagues in Guinea and Sierra Leone who died of the disease.  He said one bright spot in the epidemic is the speed with which scientists have moved forward in developing new treatments and potential vaccines. “In the last six months, we’ve seen a process that’s unprecedented, with accelerated science and the launch of clinical trials that would normally take years,” he said.

And he said he cherishes the experience of seeing patients who have successfully fought off the disease. He showed a photo of a colleague, draped in white protective gear, alongside a young survivor: a smiling boy in striped pants who had lost his father to Ebola.

“That is the ultimate reward… It means something to you – what you get back from (the survivors),” he said.

The Stanford Global Health Research Convening Day was sponsored by Stanford’s Center for Innovation in Global Health.

Previously: Back home from Liberia, Stanford physician continues to help in fight against EbolaEbola: This outbreak is differentStanford physician shares his story of treating Ebola patients in Liberia and Ebola: A look at what happened and what can be done
Photo, of Daniel Bausch and others in Guinea, courtesy of Bausch

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