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Infectious Disease

Global Health, HIV/AIDS, Infectious Disease, Public Health, Research, Rural Health

Drought causes spike in HIV infections in Africa

Drought causes spike in HIV infections in Africa

75148497_50e081cd5b_zHere in California, the drought is plenty serious. Shortages mean short showers, brown lawns, empty reservoirs and fallow fields.

But in sub-Saharan Africa, drought spreads disease, including the still-rampant HIV virus. The phenomenon is more sociological than ecological: Slim harvests slash farmers’ incomes, forcing them to find new ways to earn money. Some turn to sex, according to a new study in The Economic Journal.

As described in a recent article from Stanford’s Center on Food Security and the Environment (FSE):

Analyzing data on more than 200,000 individuals across 19 African countries, the research team finds that by changing sexual behavior, a year of very low rainfall can increase local infection rates by more than 10 percent.

That means condoms and sex education aren’t all that’s needed to thwart the epidemic’s spread, the study’s authors say. Affected farmers also need economic support and alternatives to help them weather the dry period, without sacrificing their health.

“These are the people who really suffer when the rains fail, and who are forced to turn to more desperate measures to make ends meet,” co-author Marshall Burke, PhD, a fellow at the FSE, said in the piece.

Previously: Spread of drug-resistant HIV in Africa and Asia is limited, Stanford research finds, Stanford study: South Africa could save millions of lives through HIV prevention and Changing the prevailing attitude about AIDS, gender and reproductive health in southern Africa 
Photo by Jon Rawlinson

Cancer, Dermatology, Infectious Disease, Stanford News, Transplants

This summer’s Stanford Medicine magazine shows some skin

This summer's Stanford Medicine magazine shows some skin

below surface banner and 1 blogSkin is superficial, literally. But it’s also really deep, as I realized while editing the just-published issue of Stanford Medicine magazine. The summer issue features the special report “Skin deep: The science of the body’s surface.”

I learned from the chair of Stanford’s Department of Dermatology, Paul Khavari, MD, PhD, that thousands of diseases affect the skin. And I learned it’s surprisingly abundant: An average-sized adult is covered with about 20 square feet of skin.

Research on skin is thriving, in part, because skin is so easy to get hold of, Khavari told me. “The accessibility of skin tissue to the application of new technologies, including genomics, proteomics, and metabolomics, make this a watershed moment for progress in alleviating the tremendous suffering caused by the global burden of skin disease,” he said.

The magazine, produced with support from the dermatology department, includes articles not only about new treatments, but also insights into how skin works when it’s healthy and how to keep it that way. In a Q&A and audio interview, actress and playwright Anna Deavere Smith, who is African-American, addresses skin’s social meaning, discussing her relationship to her own skin and how, as a writer and actor, she gets under the skin of her characters. The online version of the magazine includes audio of an interview with Smith.

Also in the issue:

  • The butterfly effect“: A story about two young men coping with one of the world’s most painful diseases — the skin-blistering condition epidermolysis bullosa — including news about an experimental treatment to replace their broken genes. The online version includes a video with a patient at home and interviews with experts on the condition.
  • Surviving melanoma“: A report on progress being made after years of stagnation in treating the most deadly skin cancer: melanoma.
  • The rarest of rashes“:  A look at one of Stanford Medicine’s great accomplishments in dermatology: successful treatment of a rare but dangerous rash — cutaneous lymphoma, a form of blood cancer that spreads to the skin.
  • Take cover“: Tips on keeping skin safe from the sun.
  • Wither youth“: A feature on research seeking to answer the question: Why does skin age?
  • New lungs, new life“: The story of a young woman who lost her smile and had it restored through surgery.

The issue also includes a story considering the rise in number of castoff donor hearts, despite a shortage of the organs for transplants, and an excerpt from Jonas Salk: A Life, a new biography of the polio-vaccine pioneer, written by retired Stanford professor Charlotte Jacobs, MD.

Previously: Stanford Medicine magazine reports on time’s intersection with health, Stanford Medicine magazine traverses the immune system and Stanford Medicine magazine opens up the world of surgery
Photo, from the Summer 2015 issue of Stanford Medicine, by Max Aguilera-Hellweg

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

Study shows toothed whales have persisted millions of years without two common antiviral proteins

Study shows toothed whales have persisted millions of years without two common antiviral proteins


Our ability to fend off the flu, HIV and other viruses is enhanced when proteins are produced by two “immune genes,” called MX1 and MX2. Other mammals also have these genes, but little is known about the role they play in the immune responses of these animals.

Now a study comparing the genomes and Mx genes of 60 mammal species has revealed a surprising finding: Every species in the study has functioning Mx1 and Mx2 genes except for dolphins, whales and orcas — species from a lineage of toothed whales that’s persisted for roughly 33 million years.

Gill Bejerano, PhD, a geneticist and developmental biologist, graduate student Benjamin Braun and their team wanted to know more about the status and function of Mx genes in non-human mammals. To do this, they examined and compared the part of the genome that contains the Mx genes in 60 different species including humans, cows, whales, dolphins and orcas.

I think this will open up very exciting research avenues, either to better protect the compromised whales, or to study their different viral defenses, and someday add them to our own arsenal.

The study, published this week in the Proceedings of National Sciences, showed that the Mx1 and Mx2 genes in the toothed whales (bottlenose dolphin, orca, Yangtze river dolphin and sperm whale) they tested were non-functional, and couldn’t produce the proteins that help fight viral infections. Bejerano explained the significance of this finding in our press release:

Given how important the Mx genes seem to be in fighting off disease in humans and other mammals, it’s striking to see a species lose them both and go about its business for millions of years.

To find out when in evolutionary history these genes became inactive the researchers compared the genomes of toothed whales to that of their closest ancestors, the baleen whales and hoofed mammals (ungulates). They found that the Mx genes function in baleen whales and hoofed mammals, but not in toothed whales. This means that some — perhaps all — toothed whales likely lost use of their Mx genes when this lineage split off from these ancestors about 33 million years ago (see Fig. 1).

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Biomed Bites, Genetics, Infectious Disease, Research, Videos

Why are viruses so wily? One researcher thinks she knows — and is working to thwart them

Why are viruses so wily? One researcher thinks she knows — and is working to thwart them

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers. 

Some of the world’s best known viruses use RNA, rather than DNA, to code for proteins, including polio, measles and hepatitis C. There are a few differences:  RNA uses a component not used in DNA, and RNA is usually single-stranded, rather than the familiar double helix of DNA.

RNA viruses change rapidly, evading efforts to develop vaccines and therapies. But the change is uneven — some genes evolve with nearly every replication, others stay the same for generations. Molecular biologist Karla Kirkegaard, PhD, wondered why. The chair of Stanford’s Department of Microbiology and Immunology explains her discovery in the video above:

The answer was unusual. It turns out that there are different kinds of selective pressures on these regions, and it is very hard for new variants to arise in certain regions because their family members around them poison their advantage.

Alone, for example, a mutated gene might perform better than one that is unaltered. But when it is mixed with other genes, it might make the resultant virus less competitive.

That offers valuable insight for drug development, she said. Consider the interaction of genes and viruses together, rather than aiming to disable a single player, Kirkegaard advises:

My quest right now is to convince people who target antivirals for the common cold, West Nile virus and SARS to think about those processes the viruses have to cooperate on so we won’t have such a big problem with drug resistance.

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

Previously: Ending enablers: Stanford researcher examines genes to find virus helpers, A conversation on West Nile virus and its recent California surge and Exploring the role of extracellular RNA communication in human disease

Evolution, Genetics, HIV/AIDS, Immunology, Infectious Disease, Research, Stanford News

Study: Chimps teach people a thing or two about HIV resistance

Study: Chimps teach people a thing or two about HIV resistance

I, personally, have never had trouble distinguishing a human being from a chimp. I look, and I know.

But I’m not a molecular biologist. Today’s sophisticated DNA-sequencing technologies show that the genetic materials of the two species, which diverged only 5 million or so years ago (an eye-blink in evolutionary time), are about 98 percent identical. Think about that next time you eat a banana.

One major exception to that parallelism: a set of three genes collectively called the major histocompatibility complex, or MHC. These genes code for proteins that sit on the surfaces of each cell in your body, where they serve as jewel cases that display bits of proteins that were once inside that cell but have since been chopped into pieces by molecular garbage disposals, transported to the cell surface and encased in one or another of the MHC proteins. That makes the protein bits highly visible to roving immune cells patrolling our tissues to see if any of the cells within are harboring any funny-looking proteins. If those roving sentry cells spot a foreign-looking protein bit, they flag the cell on whose surface it’s displayed as possibly having been infected by a virus or begun to become cancerous.

Viruses replicate frequently and furiously, so they evolve super-rapidly. If they can evade immune detection, that’s groovy from their perspective. So our MHC has to evolve rapidly, too, and as a result, different species’ MHC genes  diverge relatively quickly.  To the extent they don’t, there’s probably a good reason.

Stanford immunologist and evolutionary theorist Peter Parham, PhD, pays a lot of attention to the MHC genes. In a new study in PLOS Biology, he and his colleagues have made a discovery that may prove relevant to AIDS research, by analyzing genetic material found in chimp feces. Not zoo chimps. Wild Tanzanian chimps. As I noted in a news release about the study:

The wild chimps inhabit Gombe Stream National Park, a 13.5-square-mile preserve where they have been continuously observed from afar since famed primatologist Jane Goodall, PhD, began monitoring them more than 50 years ago.

One thing that sets the Gombe chimps apart from captive chimps, unfortunately, is a high rate of infection by the simian equivalent of HIV, the virus responsible for AIDS.

The study’s lead author, postdoc Emily Wroblewski, PhD, set up shop in a corner of Parham’s lab and extracted DNA from fecal samples legally obtained by other researchers (close contact with the animals is prohibited). Each sample could be tied to a particular Gombe-resident chimp. RNA extracted from the same sample indicated that chimp’s infection status.

Parham, Wroblewski and their colleagues found that one particular MHC gene came in 11 different varieties – astounding diversity for such a small collection of chimps (fewer than 125 of them in the entire Gombe). Surprisingly, one small part of one of those 11 gene variants was nearly identical to a piece of a protective version of its human counterpart gene, a version that seems to protect HIV- infected people slowing HIV progression to full-blown AIDS.

Why is that important? Because any piece of an MHC gene that has maintained its sequence in the face of 5 million years of intense evolutionary pressure must be worth something.

Sure enough, fecal samples from chimps with that MHC gene variant, so strikingly analogous to the protective human variant, had lower counts of virus that those from infected chimps carrying other versions of the gene.

You can believe that scientists will be closely examining the DNA sequence contained in both the human and chimp gene variant, as well as the part of the MHC protein that DNA sequence codes for. Because it must be doing something right.

Previously: Revealed: Epic evolutionary struggle between reproduction and immunity to infectious disease, Our species’ twisted family tree and Humans share history – and a fair amount of genetic material – with Neanderthals
Photo by Emily Wroblewski

Big data, Emergency Medicine, Genetics, Infectious Disease, Research, Stanford News

Study means an early, accurate, life-saving sepsis diagnosis could be coming soon

Study means an early, accurate, life-saving sepsis diagnosis could be coming soon

image.img.320.highA blood test for quickly and accurately detecting sepsis, a deadly immune-system panic attack set off when our body wildly overreacts to the presence of infectious pathogens, may soon be at hand.

Sepsis is the leading cause of hospital deaths in the United States and is tied to the early deaths of at least 750,000 Americans each year. Usually caused by bacterial rather than viral infections, this intense, dangerous and rapidly progressing whole-body inflammatory syndrome is best treated with antibiotics.

The trouble is, sepsis is exceedingly difficult to distinguish from its non-infectious doppelganger: an outwardly similar but pathogen-free systemic syndrome called sterile inflammation, which can arise in response to traumatic injuries, surgery, blood clots or other noninfectious causes.

In a recent news release, I wrote:

[H]ospital clinicians are pressured to treat anybody showing signs of systemic inflammation with antibiotics. That can encourage bacterial drug resistance and, by killing off harmless bacteria in the gut, lead to colonization by pathogenic bacteria, such as Clostridium difficile.

Not ideal. When a patient has a sterile inflammation, antibiotics not only don’t help but are counterproductive. However, the occasion for my news release was the identification, by Stanford biomedical informatics wizard Purvesh Khatri, PhD, and his colleagues, of a tiny set of genes that act differently under the onslaught of sepsis from they way they behave when a patient is undergoing sterile inflammation instead.

In a study published in Science Translational Medicine, Khatri’s team pulled a needle out of a haystack – activity levels of more than 80 percent of all of a person’s genes change markedly, and in a chaotically fluctuating manner over time, in response to both sepsis and sterile inflammation. To cut through the chaos, the investigators applied some clever analytical logic to a “big data” search of gene-activity results on more than 2,900 blood samples from nearly 1,600 patients in 27 different data sets containing medical information on diverse patient groups: men and women, young and old, some suffering from sterile inflammation and other experiencing sepsis,  and (as a control) healthy people.

The needle that emerged from that 20,000-gene-strong haystack of haywire fluctuations in gene activity consisted of an 11-gene “signature” that, Khatri thinks, could serve up a speedy, sensitive, and specific diagnosis of sepsis in the form of a simple blood test.

The 11-gene blood test still has to be validated by independent researchers, licensed to manufacturers, and approved by the FDA. Let’s hope for smooth sailing. Every hour saved in figuring out a possible sepsis sufferer’s actual condition represents, potentially, thousands of lives saved annually in the United States alone, not to mention billions of dollars in savings to the U.S. health-care system.

Previously: Extracting signal from noise to combat organ rejection and Can battling sepsis in a game improve the odds for material world wins?
Photo by Lightspring/Shutterstock

Autoimmune Disease, Cancer, Infectious Disease, Microbiology, Nutrition, Stanford News

Getting to the good gut: how to go about it

Getting to the good gut: how to go about it

In a blog post a few years ago I wrote, The Good Gutwith misplaced parenthetical self-assuredness:

Anybody who’s ever picked up an M&M off the sidewalk and popped it into his or her mouth (and, really, who among us hasn’t?) will be gratified to learn that the more germs you’re exposed to, the less likely you are to get asthma … hay fever and eczema.

I soon learned to my surprise, if not necessarily to my embarrassment, that virtually nobody – at least nobody over 6 – cops to having stooped-and-scooped as I routinely did as a kid on what I called my “lucky-sidewalk” days.

But those M&Ms may have been the best pills I ever took.

Stanford microbiologists Justin Sonnenburg, PhD, and Erica Sonnenburg, PhD, (they’re married) have written a new book, The Good Gut, about the importance of restocking our germ-depleted lower intestines.

Massive improvements in public sanitation and personal hygiene, the discovery of antibiotics and the advent of sedentary lifestyles have taken a toll on the number and diversity of microbes that wind up inhabiting our gut. According to The Good Gut, we need more, and more varieties, of them. And we need to treat them better. The dearth of friendly microorganisms in the contemporary colon is due not just to a lack of bug intake but to a lack of fiber in the modern Western diet. Indigestible to us, roughage is the food microbes feast on.

The Good Gut packages that message for non-scientists. “We wanted to convey the exciting findings in our field to the general public,” Justin Sonnenberg recently told me. “We’d noticed we were living our life differently due to our new understanding. We were eating differently and had modified both our own lifestyle and the way we were raising our children.”

In simple language, the Sonnenburgs explain how the pieces of our intestinal ecosystem fit together, what can go wrong (obesity, cancer, autoimmunity, allergy, depression and more), and how we may be able to improve our health by modifying our inner microbial profiles. Their book includes everything from theories to recipes, along with some frank discussion of digestive processes and a slew of anecdotes capturing their family’s knowledge-altered lifestyle.

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Infectious Disease, Patient Care, Pediatrics, Research, Stanford News

Antibiotic use in California neonatal intensive care units varies widely, study finds

Antibiotic use in California neonatal intensive care units varies widely, study finds

baby in NICUCalifornia neonatal intensive care units have huge differences in their rates of antibiotic use, a new study has found. And when it comes to antibiotics for hospitalized babies, more is not better: The study found no connection between a NICU’s rate of antibiotic use and several measures of how its young patients fared.

The research, spearheaded by the California Perinatal Quality Care Collaborative and published last last week in Pediatrics, analyzed data from 52,061 infants in 127 California NICUs. Rates of antibiotic use varied 40-fold across the NICUs studied, as news reports about the research have explained. The study looked for correlations between antibiotic use and each NICU’s rate of proven infection, rate of a serious complication of prematurity called necrotizing enterocolitis, average length of hospital stay, surgical volume and rate of patient deaths. No links were found.

“Variation in antibiotic prescribing practice appears to hinge on variation in how practitioners frame, interpret and respond to clinical situations ultimately considered unproven infection,” said lead author Joseph Schulman, MD, of the California Department of Health Care Services, in an email about the research. “There are tradeoffs between benefits and harms when treating suspected but unproven infection.”

Overuse of antibiotics presents real risks for babies, according to an accompanying editorial (.pdf) in Pediatrics. In addition to the potential for development of antibiotic-resistant pathogens, new research on the human microbiome raises the possibility that antibiotics may alter colonization of the body with healthy bacteria, the editorial says, possibly increasing the risk of necrotizing enterocolitis and of childhood obesity.

Yet there’s also no question that, for many babies, antibiotics are lifesaving. Researchers and clinicians now face the tricky task of figuring out when antibiotics can safely be reduced.

“More research is needed, but there are important things we can do right now,” senior author and Stanford neonatologist Jeffrey Gould, MD, told me. For instance, preterm babies whose mothers have signs of chorioamnionitis (an infection of the membranes around the baby) “are solid candidates for antibiotic prescriptions, but should be promptly taken off of antibiotics when cultures are negative and they have no symptoms,” he said.

As the editorial concludes, “there is great potential to substantially reduce both risk and cost for this vulnerable population through more judicious use of antibiotics.”

Previously: Study finds gap in referring California’s tiniest babies to follow-up care, Stanford-led study suggests changes to brain-scanning guidelines for preemies and Helping families navigate the NICU
Photo, which originally appeared in Stanford Medicine News, courtesy of Lucile Packard Children’s Hospital Stanford

Ebola, Global Health, Infectious Disease, Microbiology, Research

Can a single drug outsmart many kinds of viral invaders?

Can a single drug outsmart many kinds of viral invaders?

blue virus

We’ve got plenty of effective antibiotics – maybe even too many– to knock off bacteria we don’t like. But when it comes to viruses, it’s a different story, Stanford infectious-disease specialist Shirit Einav, MD, and postdoc Elena Bekerman, PhD, write in a recently published perspective piece in Science.

“Although hundreds of viruses are known to cause human disease, antiviral therapies are approved for fewer than 10,” the authors write, before going on:

[Antiviral drugs that interfere with crucial viral enzymes] have shown considerable success in the treatment of HIV and hepatitis C virus… infections. However, this approach does not scale easily and is limited particularly with respect to emerging viruses against which no vaccines or antiviral therapies are approved.

Which is too bad, because viruses can be nasty. Not to mention creepy: They’re master puppeteers when it comes to manipulating us into submission. They can’t even replicate on their own. The little body-snatchers need our own cells, which they break into, bamboozle, and bully into producing copies of themselves and then squirting them out so they can infect other cells and, with luck, other people.

A partial list of merging and re-emerging viruses for which there are no decent treatments includes dengue, estimated to infect 400 million people each year; SARS and MERS, responsible for outbreaks of severe acute respiratory syndromes; and Ebola, which, as everybody now knows, caused an ongoing epidemic in Africa.

Developing antiviral drugs is a huge challenge. It takes, on average, more than $2 billion and about a decade, plus or minus a couple of years, to develop a new drug targeting just one single type of virus, Bekerman and Einav write. To make things worse, these nano-villains evolve even faster than bacteria do.

Einav’s research has been taking a different tack. She’s working on drugs that, instead of gumming up this or that viral enzyme (at least until it mutates into a form the drug can’t gum up), interfere with the activity of components in our cells that the viruses absolutely depend on for their own survival and replication. There are already drugs, many of them already approved for far different indications such as cancer, that can do just that – without, however, disabling our own cells so much that the cure becomes worse than the disease.

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Global Health, Immunology, Infectious Disease, Pediatrics, Stanford News

Researchers tackle unusual challenge in polio eradication

Researchers tackle unusual challenge in polio eradication

poliovaccinationPolio is a tricky foe. One of the biggest hurdles in the World Health Organization’s polio eradication campaign is that the virus causes no symptoms in 90 percent of people who contract it. But these silently infected individuals can still spread the virus to others by coughing, sneezing or shedding it in their feces. And those they infect may become permanently paralyzed by or die.

Polio’s evasiveness has also led to a big speed bump on the road to eliminate the disease. As I report in the current issue of Inside Stanford Medicine, scientists are trying to figure out how to stop a form of poliovirus that is derived from one type of  polio vaccine. Oral vaccines, which consist of live poliovirus that has been inactivated, can occasionally mutate in someone’s intestines to regain infectiousness. And, in rare instances, these viruses escape to the environment in feces, spreading to other people via sewage-contaminated water.

These “circulating vaccine-derived viruses” are threatening to overtake naturally occurring, “wild” poliovirus as the main source of paralysis in the communities where polio persists. The CDC’s most recent report on polio infections in Nigeria says that during the first nine months of 2014, the vaccine-derived viruses caused 22 cases of paralyzing poliomyletis, whereas wild virus caused six cases, for instance.

To tackle the problem, researchers are investigating how the injected polio vaccine, which is made with killed virus, might be substituted for the oral vaccine. The injected vaccine has some potential disadvantages for use in developing countries, so it’s not necessarily an easy substitution. In my story, Stanford’s Yvonne Maldonado, MD, who is studying the problem with a grant from the Bill & Melinda Gates Foundation, explains:

“We don’t really understand how well the killed vaccine is going to work in kids in developing countries, where there is lots of exposure to sewage, and malnutrition leaves children with weakened immune systems,” Maldonado said.

Her Gates Foundation grant examines semi-rural communities in Mexico where children now receive routine doses of the killed vaccine, followed by twice-a-year doses of the live vaccine.

“It’s an opportunity for us to study a natural experiment,” Maldonado said. Her team wants to know if the primary immune response to the killed vaccine will reduce shedding and transmission of later doses of live vaccine. They hope that starting with one or more doses of the injected vaccine will give kids the best of both worlds: from the shot, protection against circulating vaccine-derived viruses; from the oral vaccine, intestinal immunity.

Previously: TED talk discusses the movement to eradicate polio and New dollar-a-dose vaccine cuts life-threatening rotavirus complications by half
Photo of children in South Sudan receiving oral polio vaccine by United Nations Photo

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