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Infectious Disease

Biomed Bites, Immunology, Infectious Disease, Research, Stanford News

Figuring out a parasite’s secrets – insights from studying Toxoplasma gondii

Figuring out a parasite's secrets - insights from studying Toxoplasma gondii

Welcome to Biomed Bites, a weekly feature that highlights some of Stanford’s most innovative research and introduces Scope readers to innovators in a variety of disciplines. 

You’ve probably heard that pregnant women shouldn’t get near the litter box. The reason is that many kitties carry a parasite called Toxoplasma gondii, which is transmitted through their feces. The parasite infects about 2 billion people worldwide, according to Stanford microbiologist John Boothroyd, PhD.

Boothroyd, who also serves as the associate vice provost for graduate education, directs a lab that has uncovered some of the basic biology of this single-celled protozoan parasite. Here’s Boothroyd in the video above:

Most of the time, this causes no significant disease, very few symptoms and probably something that most of these people will never know they were infected with. Occasionally, however, this parasite can cause devastating disease. It can affect the brain of the unborn child, it can cause severe neurological problems, it can even kill the developing fetus.

Toxoplasmosis, or infection with the parasite, can also cause serious complications in immunocompromised individuals. Boothroyd said he was drawn to the study of the T. gondii because it is clinically significant — he has the opportunity to help millions of people: “I wanted something where I felt the work we were doing was worth the many, many hours that I and the people I worked with put in to the daily effort.” T. gondii is also related to the Plasmodium parasites that cause malaria and some of the work from Boothroyd’s lab has been translated into insights into malaria.

Boothroyd’s team also identified the T. gondii protein that triggers the immune response in humans. With that knowledge, the investigators were able to insert the gene coding for that protein into yeast, letting the yeast produce the protein, “instead of having to grow the parasite in literally hundreds of thousands of mice a year and then killing those mice to get the parasite,” Boothroyd said. He went on to explain:

The situation in which Toxoplasma presents the most significant problem for the doctor and for the patient is in the pregnant woman. The challenge becomes first, is she infected, and if so, has the parasite crossed the placenta and reached the fetus. And third, what is the consequence of the infection in the fetus? All three of those we have addressed through our work.

Although much about the parasitic diseases remains unknown, Boothroyd is glad he picked T. gondii to focus on: “I think we’ve been able to do some real good with this work.”

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

Previously: Stanford microbiologist’s secret sauce for disease detection, Cat guts, car crashes and warp-speed Toxoplasma infections and Patrick House discusses Toxoplasma gondii, parasitic mind control and zombies

Infectious Disease, Research, Stanford News

Stanford scientist Lucy Shapiro: “It never occurred to me to question the things I wanted to do”

Stanford scientist Lucy Shapiro: "It never occurred to me to question the things I wanted to do"

Lucy ShapiroIn the mid-1920s, Pearl Meister Greengard died giving birth to her son, the Nobel prize-winning scientist Paul Greengard, PhD. Decades later, Greengard and his wife established a prize to honor the very best female scientists, named after his missing mother. Although prizes abound in science, this is one of those prizes that scientists hold in the highest esteem. Today, Stanford developmental biologist Lucy Shapiro, PhD, will be awarded the 2014 Pearl Meister Greengard Prize. Shapiro revolutionized the understanding of the bacterial cell as an engineering paradigm whose cell division leads to the generation of diversity, a phenomenon fundamental to all life. She spoke recently about this award.

Like other accomplished scientists, you’ve won many awards. How does this one stack up?

It is very special. It’s the only big deal award for a woman  – I’m just so tremendously honored. Paul Greengard felt that women do not get their just due as real leaders in science, so the whole point of this award is to recognize women scientists with significant achievements, or breakthroughs in science.

It’s not just a prize for women in science, it’s a prize for actually doing something transformative in the field of biomedical sciences.

Did you have role models?

I had many role models. When I started out a whole bunch of years ago, there were woman at Albert Einstein College of Medicine that had an enormous effect on my life. Really smart, accomplished women with families who were full professors. It made a difference in the trajectory of my career.

Another role model was Barbara McClintock, PhD. She never married, never had any children, and she was an unbelievably brilliant scientist. She was my role model not necessarily because she was a woman, her influence was simply being a great scientist.

There’s another part to this, one that’s hard to write about, but is critical. It’s particularly critical for women to be extremely confident. You have to know what you are good at and to not feel in any way threatened. One of the major things my parents instilled in me was a sense of confidence and a feeling that I can do anything.

It never occurred to me to question the things I wanted to do. Other people’s remarks rolled off like rainwater – I didn’t care. One of the things I tell my women students and postdocs is to act confident, even if you don’t feel confident.

It’s hard to be a female scientist -

That’s not always true. It depends on your goals and your mindset and how you’re willing to live your life. I think that to be a good scientist, you have to have a deep passion for it that supersedes all kinds of stuff. Were there roadblocks or difficulties? Of course. I know that for all top scientists, the unchanging, deep passion, the central core of their life, is their science. That doesn’t mean that we are not mothers and grandmothers and part of society and complete people. But the real core, the passion is our lab.

You have to stay true to what you know to be the core of your life. Do more obstacles get thrown at women? I suppose that’s true. But I haven’t had a life of that.

I don’t want to make this award all about women. Yes, of course, it’s been given because I’m a woman scientist. But it’s also because I’ve done something meaningful as a scientist.

Continue Reading »

Global Health, History, HIV/AIDS, Infectious Disease

A doctor’s dilemma: to help or hold back from treating dangerous infections

If, like me, you’ve wondered why a doctor or nurse would decide to volunteer to help patients with often fatal infectious diseases like Ebola, The New York Times Magazine ran an essay today by Stanford physician and author Abraham Verghese, MD, MACP, in which he addresses, among other issues, the tension for clinicians between self-preservation and the impulse to help.

We doctors feel the pull. But each of us has reasons to stay back, reasons that get bigger as we age

He begins with his time treating patients in a hospital in India, detailing his encounters with tuberculosis, malaria, and filariasis among other diseases, but his description of his fear of and his reflections of his encounter with his first rabies patient is poignant:

I felt terribly sorry for this man who was old enough to be my father. Squatting by his mat, I was ashamed of my earlier fear and hesitation. I was glad to spend some time with him. By the next morning he was comatose and convulsing. By nightfall, he’d transcended the mortal world.

He  goes on to discuss his work with HIV patients in the 1980s, and the fear that surrounded the disease at the time. Many physicians donned full protective gear, even though researchers had determined, even in the early days of the epidemic, that the disease wasn’t spread via casual contact. Verghese connects these fears to current fears about Ebola, but doesn’t blame physicians who are cautious. He also documents his own impulses:

I have the urge to sign up, to head to Liberia or Sierra Leone; the call for doctors seems personally addressed to me. When I tell my mother, who is in her 90s, that I am thinking of volunteering in West Africa, she clutches my hand and says: “Oh, no, no, no. Don’t go!” I’m secretly pleased.

….

We doctors feel the pull. But each of us has reasons to stay back, reasons that get bigger as we age: children, partners, parents, grants.

Verghese captures the conundrum facing doctors and nurses who want to help, but who are – for a  variety of reasons – pulled away.

Previously: Ebola: This outbreak is differentStanford physician shares his story of treating Ebola patients in Liberia and Dr. Paul Farmer: We should be saving Ebola patients

Ebola, Global Health, In the News, Infectious Disease

Ebola: This outbreak is different

Ebola: This outbreak is different

15038945315_7613c40e54_zMisinformation about Ebola blankets the web. To clarify priorities, and spur action, Stanford global health specialist Michele Barry, MD, penned a strongly worded essay published today in Boston Review:

In the United States, the few cases imported have incited irrational fear which is not only unwarranted but actually undermines an appropriate response to the outbreak. By focusing on quarantine, we are ignoring the need for centralized public health systems and training to deal with inevitable cases of Ebola.

Ebola is not spread through air, water or food, but end-stage sick patients can have over a billion viral particles in a cubic centimeter — or about a fifth of a teaspoon — of blood making contact with bodily fluids highly contagious.

This Ebola outbreak is different, she says. Previously, the virus stayed close to its forest reservoir in Central Africa. Now, it’s in large cities, spreading through heavily populated areas that have been decimated by poverty and conflict.

As the virus spread, the World Health Organization was slow to respond, Barry writes. “The WHO was alerted to the cluster of cases in Guinea by March, but did not sound the alarm until August. Why did this happen?”

And what, now, can be done?

In actuality, the solution to this Ebola crisis is not drugs, mass quarantine, vaccines or even airdrops of personal protective gear. The real reasons this outbreak has turned into an epidemic are weak health systems and lack of workforce; any real solution needs to address these structural issues.

We have the tools to spot emerging outbreaks and to stop them. We know how to prevent transmission of Ebola. Orchestrating an international response, however, one that considers the welfare of patients and healthcare workers, the resilience of healthcare systems and the triumph of reason — that needs some work.

Previously: Stanford physician shares his story of treating Ebola patients in Liberia, How to keep safe while operating on Ebola patients and Ebola: A look at what happened and what can be done
Photo from the European Commission DG ECHO

Global Health, Infectious Disease, Stanford News

Stanford physician shares his story of treating Ebola patients in Liberia

Stanford physician shares his story of treating Ebola patients in Liberia

P1030655For a month, emergency physician Colin Bucks, MD, found himself in the remote, dense jungle of northeast Liberia in the heat of the battle against Ebola. A clinical assistant professor of surgery at Stanford, Bucks was a volunteer with the International Medical Corps at a new tent-like unit hastily built to accept the continuing stream of Ebola patients in the hard-hit West African country.

The facility, a series of low, tin-roofed, concrete buildings, were primitive in design but had very effective methods for controlling infection, including spigots everywhere that dispensed virus-killing doses of chlorine and protective gear for covering the body head to toe. Aside from providing basic care, such as fluid and electrolyte replacement, Bucks said much of his time was spent comforting patients, who were physically isolated from family members because of the threat of infection.

P1030673“In this setting (in West Africa), there is an additional barrier because you have one physical degree of separation, as your head, your hands, your face are completely covered. But that doesn’t preclude the same level of connection to the patient and the same sense of responsibility and care,” said Bucks, who left Liberia Oct. 22 and is now isolated at his home in Redwood City, Calif. “There may be a higher percentage of sad cases because Ebola has a high-case fatality rate, so there is an added burden there. But there is a similarity to working a tough case in rural Liberia to working a tough case in a U.S. critical care unit.”

He said the unit received patients from a nearby hospital, as well as those brought in by makeshift ambulances that might travel as much as eight hours to retrieve ailing victims. “We would get these reports everyday from the ambulance – we have four cases and three flat tires. The roads would be blocked with trees. They would have to drive through dense jungles. The ambulance stories were by far the most riveting.”

Colin Trish PPEBucks said the caregivers at the unit, which included 125 Liberians, were able to save just under half the patients who came in, with each survivor serving as an important ambassador to the community.

“The public health message was blanketing the country, but there was still a lot of fear and misunderstanding,” he said. “People are scared to come to the hospital. People are scared to undergo treatment. It helped every time we had patients discharged as cured.”

Bucks, who is now following recommendations and Stanford requirements to remain in isolation for 21 days, says there is a desperate need for other U.S. volunteers like himself to help contain the spread of the virus. “There needs to be a rational policy that facilitates health-care workers going to and from the U.S. Policy should help this – not impede this. But you need an organized response on West Africa. Otherwise we will be fighting a much bigger battle in the U.S. and around the globe.”

Previously: How to keep safe while operating on Ebola patients, Experience from the trenches in the first Ebola outbreak, Ebola: A look at what happened and what can be done and Dr. Paul Farmer: We should be saving Ebola patients
Photos courtesy of Colin Bucks

Imaging, Immunology, Infectious Disease, Neuroscience, Research, Stanford News

Some headway on chronic fatigue syndrome: Brain abnormalities pinpointed

Some headway on chronic fatigue syndrome: Brain abnormalities pinpointed

patchbrainHow can you treat a disease when you don’t know what causes it? Such a mystery disease is chronic fatigue syndrome, which not so long ago was written off by many physicians as a psychiatric phenomenon because they just couldn’t figure out what else might be behind it. No one was even able to identify an anatomical or physiological “signature” of the disorder that could distinguish it from any number of medical lookalikes.

“If you don’t understand the disease, you’re throwing darts blindfolded,” Stanford neuroradiologist Mike Zeineh, MD, PhD, told me about a week ago. Zeineh is working to rip that blindfold from CFS researchers’ eyes.

From a release I wrote about some breaking CFS research by Zeineh and his colleagues:

CFS affects between 1 million and 4 million individuals in the United States and millions more worldwide. Coming up with a more precise number of cases is tough because it’s difficult to actually diagnose the disease. While all CFS patients share a common symptom — crushing, unremitting fatigue that persists for six months or longer — the additional symptoms can vary from one patient to the next, and they often overlap with those of other conditions.

A study just published in Radiology may help to resolve those ambiguities. Comparing brain images of 15 CFS patients with those from 14 age- and sex-matched healthy volunteers with no history of fatigue or other conditions causing similar symptoms, Zeineh and his colleagues found distinct differences between the brains of patients with CFS and those of healthy people.

The 15 patients were chosen from a group of 200 people with CFS whom Stanford infectious-disease expert Jose Montoya, MD, has been following for several years in an effort to identify the syndrome’s underlying mechanisms and speed the search for treatments. (Montoya is a co-author of the new study.)

In particular, the CFS patients’ brains had less overall white matter (cable-like brain infrastructure devoted to carrying signals rather than processing information), aberrant structure in a portion of a white-matter tract called the right arcuate fasciculus, and thickened gray matter (that’s the data-crunching apparatus of the brain) in the two places where the right arcuate fasciculus originates and terminates.

Exactly what all this means is not clear yet, but it’s unlikely to be spurious. Montoya is excited about the discovery. “In addition to potentially providing the CFS-specific diagnostic biomarker we’ve been desperately seeking for decades, these findings hold the promise of identifying the area or areas of the brain where the disease has hijacked the central nervous system,” he told me.

No, not a cure yet. But a well-aimed ray of light that can guide long-befuddled CFS dart-throwers in their quest to score a bullseye.

Previously: Unbroken: A chronic-fatigue patient’s long road to recovery, Deciphering the puzzle of chronic-fatigue syndrome and Unraveling the mystery of chronic-fatigue syndrome
Photo by Kai Schreiber

Global Health, In the News, Infectious Disease, Microbiology, Public Health

Exploiting insect microbiomes to curb malaria and dengue

Original Title: Aa_FC2_23a.jpgEvery year, more than 200 million people are affected by malaria and 50 to 100 million new dengue infections occur. Now, a group of scientists from Johns Hopkins University may have found a novel way of curbing both diseases: by “vaccinating” mosquitos against the parasite that causes malaria and the virus that causes dengue. The researchers are using the bacteria Chromobacterium, which prevents the pathogens from effectively invading and colonizing mosquito guts.

As Science magazine reported last week:

Like humans and most other animals, mosquitoes are stuffed with microbes that live on and inside of them—their microbiome. When studying the microbes that make mosquitoes their home, researchers came across one called Chromobacterium sp. (Csp_P). They already knew that Csp_P’s close relatives were capable of producing powerful antibiotics, and they wondered if Csp_P might share the same talent.

In another experiment, done with mosquitoes that weren’t pretreated with antibiotics, Csp_P-fed mosquitoes were given blood containing the dengue virus and Plasmodium falciparum, a single-celled parasite that causes the most deadly type of malaria. Although a large number of the mosquitoes died within a few days of being infected by the Chromobacteriumthe malaria and dengue pathogens were far less successful at infecting the mosquitoes that did survive, the team reports today in PLOS Pathogens. That’s good news: If the mosquito isn’t infected by the disease-causing germs, it is less likely to be able to transmit the pathogens to humans.

The bacteria also inhibited growth of Plasmodium and dengue in lab cultures, indicating that Csp_P is producing compounds that are toxic to both pests. One possible application of these toxins is to develop treatment drugs for people already infected with malaria or dengue. Real-world applications of this research are many years in the future, but it hints at a whole new way of dealing with otherwise intractable diseases.

Previously: Close encounters: How we’re rubbing up against pathogen-packing pestsClosing the net on malaria and Fighting fire with fire? Using bacteria to inhibit the spread of dengue
Photo by Sanofi Pasteur

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

Paradox: Antibiotics may increase contagion among Salmonella-infected animals

Paradox: Antibiotics may increase contagion among Salmonella-infected animals

cattleMake no mistake: Antibiotics have worked wonders, increasing human life expectancy as have few other public-health measures (let’s hear it for vaccines, folks). But about 80 percent of all antibiotics used in the United States are given to livestock – chiefly chickens, pigs, and cattle – at low doses, which boosts the animals’ growth rates. A long-raging debate in the public square concerns the possibility that this widespread practice fosters the emergence of antibiotic-resistant bugs.

But a new study led by Stanford bacteriologist Denise Monack, PhD, and just published in Proceedings of the National Academy of Sciences, adds a brand new wrinkle to concerns about the broad administration of antibiotics: the possibility that doing so may, at least  sometimes, actually encourage the spread of disease.

Take salmonella, for example. One strain of this bacterial pathogen, S. typhimurium, is responsible for an estimated 1 million cases of food poisoning, 19,000 hospitalizations and nearly 400 deaths annually in the United States. Upon invading the gut, S. typhimurium produces a potent inflammation-inducing endotoxin known as LPS.

Like its sister strain S. typhi (which  causes close to 200,00o typhoid-fever deaths worldwide per year), S. typhimurium doesn’t mete out its menace equally. While most get very sick, it is the symptom-free few who, by virtue of shedding much higher levels of disease-causing bacteria in their feces, account for the great majority of transmission. (One asymptomatic carrier was the infamous Typhoid Mary, a domestic cook who, early in the 20th century, cheerfully if unknowingly spread her typhoid infection to about 50 others before being forcibly, and tragically, quarantined for much of the rest of her life.)

You might think giving antibiotics to livestock, whence many of our S. typhi-induced food-poisoning outbreaks derive, would kill off the bad bug and stop its spread from farm animals to those of us (including me) who eat them. But maybe not.

From our release on the study:

When the scientists gave oral antibiotics to mice infected with Salmonella typhimurium, a bacterial cause of food poisoning, a small minority — so called “superspreaders” that had been shedding high numbers of salmonella in their feces for weeks — remained healthy; they were unaffected by either the disease or the antibiotic. The rest of the mice got sicker instead of better and, oddly, started shedding like superspreaders. The findings … pose ominous questions about the widespread, routine use of sub-therapeutic doses of antibiotics in livestock.

So, the superspreaders kept on spreading without missing a step, and the others became walking-dead pseudosuperspreaders. A lose-lose scenario all the way around.

“If this holds true for livestock as well – and I think it will – it would have obvious public health implications,” Monack told me. “We need to think about the possibility that we’re not only selecting for antibiotic-resistant microbes, but also impairing the health of our livestock and increasing the spread of contagious pathogens among them and us.”

Previously: Did microbes mess with Typhoid Mary’s macrophages?, Joyride: Brief post-antibiotic sugar spike gives pathogens a lift and What if gut-bacteria communities “remember” past antibiotic exposures?
Photo by Jean-Pierre

Chronic Disease, Health Costs, Infectious Disease, Research

Despite steep price tag, use of hepatitis C drug among prisoners could save money overall

Despite steep price tag, use of hepatitis C drug among prisoners could save money overall

pills-384846_640There’s nothing free about the revolution that’s shaking up hepatitis C treatment. A slew of newer drugs, including sofosbuvir, are nearly eliminating the virus with fewer side effects than the old standbys, pegylated interferon and ribavirin, which had limited effectiveness and caused fatigue, nausea and headaches. But at a cost of $7,000 a week, it seems obvious they are more expensive.

Not necessarily, however, says Jeremy Goldhaber-Fiebert, PhD. Working with colleagues including former Stanford graduate student Shan Liu, PhD, Goldhaber-Fiebert developed a model that examines the overall costs and benefits of treating hepatitis C with sofosbuvir rather than the traditional drugs in prisons. Prisoners are more likely than those in the general population to be infected with hepatitis C, a virus that attacks the liver, because it can be transmitted through intravenous drug use and unclean tattoos.

The researchers found that the high upfront cost saves money in later years by reducing the number of liver transplants and other more invasive treatments needed. In accordance with standard practices, this  study examined the overall societal cost without accounting for the source of the money. For example, the prison system’s are more likely to spend more money upfront, although savings might be recouped by Medicaid or other private insurers several decades later. From our release:

“Overall, sofosbuvir is cost-effective in this population, though its budgetary impact and affordability present appreciable challenges,” said Goldhaber-Fiebert,who is also a faculty member at Stanford’s Center for Health Policy/Center for Primary Care and Outcomes Research, which is part of the university’s Freeman Spogli Institute for International Studies.

Goldhaber-Fiebert called hepatitis C a “public health opportunity.”

“Though often not the focus of health-policy research, HCV-infected inmates are a population that may benefit particularly from a highly effective, short-duration treatment,” he said.

The research appears in this week’s Annals of Internal Medicine.

Previously: Fortune teller: Mice with ‘humanized’ livers predict HCV drug candidate’s behavior in humans, A primer on hepatitis C and For patients with advanced hepatitis C, benefits of new drugs outweigh costs
Photo by stevepb

Ebola, Global Health, Infectious Disease, Patient Care, Stanford News, Surgery

How to keep safe while operating on Ebola patients

How to keep safe while operating on Ebola patients

surgical instrumentsAmid the Ebola crisis, two U.S. surgeons with a combined 30 years of working in developing countries have stepped forward to help disseminate well-defined protocols for operating on any patient with the virus or at-risk of having contracting the virus.

In an op-ed piece published today in the San Jose Mercury News, the two surgeons first ask, then answer, their own question: “Why should anyone care about surgery and Ebola? Ebola is a virus.” Their answer is that patients still have accidents. They still need things like appendectomies and C-sections and treatment for gunshot wounds.

The piece points to shocking news reports like those of 16-year-old Shacki Kamara, a patient in Sierra Leone who died of gunshot wounds to his leg during the Ebola quarantine of West Point, Liberia because people were afraid to operate on him. The growing fear of operating on anyone suspected of having contracted the Ebola virus, which is transmitted by bodily fluids, is a flashback to the early days of the AIDS crisis when operating room personnel and physicians often declined to treat patients, said Stanford surgeon Sherry Wren, MD, who co-authored the op-ed with Johns Hopkins surgeon Adam L. Kushner, MD, founder and director of Surgeons OverSeas. The two wrote:

With supportive medical care, patients may survive an Ebola infection. Without surgery for severe trauma, obstructed labor, a strangulated hernia, or a perforated ulcer, some patients may die. The moral dilemma is overwhelming. How does one operate on a patient infected with Ebola, yet at the same time protect the surgical staff?

Last week, the two came together to write an Ebola surgery protocol and send it to a number of surgical organizations, and the largest one – the American College of Surgeons – immediately accepted and posted it on their website. The response to the new guidelines was immediate and overwhelming, Wren said. In Africa, 10 countries have since adopted the protocol. Press articles on the guidelines have also appeared around the world, including in the New York Times and Washington Post and on Al Jazeera. Wren told me in a phone interview that she was both a bit surprised and overwhelmed by the reaction:

I’ll tell you, it was amazing. I’ve seen very few things in surgery go that fast. There was a need to start the discussion. It was never my intent to be the definitive Ebola expert. I’ve never seen a case of Ebola in my life. We expanded existing  CDC guidelines for prevention of transmission of other infections such as HIV and hepatitis and then added common sense from years of  experience operating.

Both Wren and Kushner acknowledged the “unsung heroes” who bravely choose to treat Ebola patients and stress the importance of working to keep them as safe as possible by increasing the availability of supplies of protective gear especially in West Africa and working toward increased training for health care workers. As they state in their op-ed:

 The management of Ebola is new to many clinicians in the United States and elsewhere. We hope to see more training, protocols and personal protective supplies to lower risks to surgical staff and patients. Just as surgery is a necessary part of a functioning health system, surgery must be part of the discussion during this time of Ebola; otherwise, the death toll will not only include those unfortunate to have died from the virus but also those unlucky to have developed a treatable surgical condition in this time of Ebola.

Previously: Experience from the trenches in the first Ebola outbreak, Ebola: A look at what happened and what can be done, Paul Farmer: We should be saving Ebola patients, Ebola panel says 1.3 million cases possible, building trust key to containment and Should we worry? Stanford’s global health chief weighs in on Ebola
Photo by Badly Drawn Dad

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