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We Are Not All Living The COVID Moment Equally

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We are all living within the Covid moment, but we are not living within the Covid moment equally. The pandemic has exposed a recurrent rift in the United States’ healthcare system: Black Americans and other people of color (POC) are both disproportionately impacted by health issues and disproportionately lack access to care.

In a recent study on North Carolina conditions, Duke researchers found that the “odds of testing positive for [Covid] were higher for both Black and Hispanic individuals as well as within neighborhoods with a higher proportion of Black or Hispanic residents – confirming that Black and Hispanic communities are disproportionately affected.”

In a Coronavirus Conversation sponsored last week by the Science & Society Initiative, Thomas Williams J.D. discussed this and related issues with Duke scholars Keisha L. Bentley-Edwards, Ph.D. of medicine and Jay A. Pearson, M.P.H., Ph.D of public policy.

Williams opened the panel by emphasizing the relevance of this moment: Current Covid impacts are directly informed by historical inequities and intricately span into the future. This is but one system of plaguing racism.

To speak about the intimate intersection of race and healthcare in America, Pearson offered grounding insight to systemic and structural racism. The United States is a country filled with patterns that produce and reproduce systematic advantages for those who are white while simultaneously disadvantaging people of color, most often Black and indigenous populations. Racism in America greatly transcends personal acts of racialized discrimination and harassment, he said. Racism in America is multiplex, foundational, and rooted within our society’s core.

“The U.S. national identity is tied to structural racism. …This is who we are, this is who we’ve been since the beginning of this country,” Pearson said, “The racialized inequities of Covid are simply the latest [manifestations]. We shouldn’t be surprised.”

A recently circulating figure states that 96% of people with severe outcomes or death from Covid had comorbidities, the presence of health conditions in addition to Covid. But Bentley-Edwards cautioned against misuse of this claim: “Many of these people would be alive if not for Covid.”

Though many who have died from the virus had underlying conditions, it is ultimately the virus that killed them. Communities of color often have disproportionate prevalence of underlying conditions, making them more susceptible to complications from Covid. But even when the prevalence of underlying conditions is the same among white and non-white populations, people of color are more likely to be more negatively affected by them.

For example, cardiovascular disease is similarly distributed between white and Black people, yet Black people are more likely to die of it, and at a younger age, compared to white people. Similarly, Black and other POC populations who contract Covid are more likely to die despite similar rates of contracting the virus in certain regions of the country.

Dr. Bentley-Edwards speaking during Friday’s virtual Coronavirus Conversation

Pearson and Bentley-Edwards also offered their insights on who is seen as essential and who is seen as dispensable in the United States.

Those who have been on the front lines with the most exposure and risks have been laborers who are most often under-valued Black and Brown peoples, Bentley-Edwards said. Though Covid terminology has come to dub them essential, it is undeniable that our society continues to see these types of workers as dispensable or replacable, and thus does not protect the people responsible for protecting us. Because many people of color live in multi-generational households as a culturally protective factor, increased chance of contracting Covid has led to uncertainties on the safety of returning home to young and elderly family members, she said. Further, the disproportionate unemployment rate of 13% for Black Americans compared to the 8.4% national rate is a staggering one. Since insurance is tied to employment, Black and Brown communities often avoid treatments due to the financial burden of unaffordable and inaccessible care.

Within the pandemic, we have seen the ever-present epidemiological impacts of police brutality and murder in the U.S with fresh eyes, the panelists said. In many ways, Black peoples’ experiences with healthcare mirrors that of their experiences with police – likely because both systems are anchored by an unjust nucleus.

“[Covid and police brutality] are slightly different manifestations of the same phenomenon,” Pearson said. We are able to easily identify the murders of individuals such as Breonna Taylor, George Floyd, and Ahmaud Arbery as stolen lives due to racist actions, however the slow burn of a racist health care system is less easily conceptualized or reconciled with, he said. Either way, the cause is one and the same.

Racism within systems that are meant to protect have generated a deep mistrust from Black and Brown people. Williams brought up the issue of a potential Covid vaccination amongst communities of color. “You have to know the history and why they would hesitate,” Bentley-Edwards said, bringing up the Tuskegee experiments and the work of J. Marion Sims. These accounts offer grim revelation of a heinous, racist history of exploiting vulnerable people for scientific and medical explorations.

Bentley-Edwards said that governments and healthcare institutions must address the rightful apprehensions of Black and Brown people in order to decrease vaccine hesitancy and serve at-risk communities. “What are they going to do differently?”

Williams also proposed the notion of data collection as a source of bias: In what ways are the data informatics that are collected reflections of an inequitable system? Bentley-Edwards and Pearson both suggest that to understand the current moment, as well as the healthcare system more largely, there needs to be collection and analysis of racial data. Additionally, there simply needs to be measurements for indicators beyond conventional ones which do not properly account for impacts on communities of color.

The push for new and different kind of data is supported by a growing evidence for the manifestations of inequality within biological bodies. For example, Pearson spoke about his own research on telomeres, a protective structure on the ends of chromosomes that protect DNA from degradation. Telomeres are telling both of stress and aging. Pearson’s work found that the average Black American woman is six to seven biological years older than a white American woman of the same age by evaluating telomere lengths, controlling for income, education, and other important socioeconomic factors. This indicates physiological affects linked to the stresses and disproportionalities of race down to the cellular level. Through genetics, mental health, and other physical degradations, the impacts of racism and racist healthcare quite literally last a lifetime and are even intergenerational.

Diagram of telomere from a study conducted by Dr. Pearson

Pearson closed the panel by urging attendees to take action where they find themselves. Though the need for animated policy which reflects recent discussions and protests is dire, the local spaces we find ourselves in need to be reshaped as well – including our universities.

In this moment, our responsibilities to one another have become more obvious than ever before. We must become more adept in thinking about and taking action for the communities in which we live and are connected to, whether they are comprised of people who look like us or not.

Post by Cydney Livingston

“Do No Harm to Whom?” Challenge Trials & COVID-19

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DAVIDE BONAZZI / SALZMANART

Imagine: you wake on a chilly November morning, alarm blaring, for your 8:30 am class. You toss aside the blankets and grab your phone. Shutting the alarm off reveals a Washington Post notification. But this isn’t your standard election headline. You almost drop your phone in shock. It can’t be, you think. This is too good to be true. It’s not — a second later, you get a text from the SymMon app, notifying you of your upcoming appointment in the Bryan Center.

A vaccine for COVID-19 is finally available, and you’re getting one.

This scenario could be less far-fetched than one might think: the Centers for Disease Control and Prevention has told officials to prepare for a vaccine as soon as November 1st. To a country foundering due to the economic and social effects of COVID-19, this comes as incredible news — a bright spot on a bleak horizon. But to make a vaccine a reality, traditional phase 3 clinical trials may not be enough. What are challenge trials? Should they be used? What’s at stake, and what are the ethical implications of the path we choose?

At Duke Science and Society’s “Coronavirus Conversations: The Science and Ethics of Human Challenge Trials for COVID-19” on Aug. 24, Kim Krawiec of the Duke School of Law posed these and other questions to three experts in health.

Dr. Marc Lipsitch, Director of the Center for Communicable Disease Dynamics at the Harvard School of Public Health, began by comparing traditional phase 3 trials and challenge trials. 

In both kinds of trials, vaccines are tested for their “safety and ability to provoke an immune response” in phases 1 and 2. In phase 3 trials, large numbers (typically thousands or tens of thousands) of individuals are randomly assigned either the vaccine being tested or a placebo. Scientists observe how many vaccinated individuals become infected compared to participants who received a placebo. This information enables scientists to assess the efficacy — as well as rarer side effects — of the vaccine. 

Marc Lipsitch

In challenge trials, instead of random assignment, small numbers of low-risk individuals are deliberately infected in order to more directly study the efficacy of vaccine and treatment candidates. Though none are underway yet, the advocacy group 1Day Sooner has built a list of more than 35,000 volunteers willing to participate.

Dr. Cameron Wolfe, an Infectious Disease Specialist, Associate Professor of Medicine, and Clinical Expert In Respiratory and Infectious Disease at the Duke Medical School, provided an overview of the current vaccine landscape.

Cameron Wolfe

There are currently at least 150 potential vaccine candidates, from preclinical to approved stages of development. Two vaccines, developed by Russia’s Gamelaya Research Institute and China’s CanSinoBIO, have skipped phase 3, but are little more than an idiosyncrasy to Dr. Wolfe, as there is “minimal clarity about their safety and efficacy.” Three more vaccines of interest — Moderna’s mRNA vaccine, Pfizer’s mRNA vaccine, and Oxford and AstraZeneca’s adenovirus vaccine — are all in phase 3 trials with around 30,000 enrollees. Scientists will be watching for a “meaningful infection and a durable immune response.”

Dr. Nir Eyal, the Henry Rutgers Professor of Bioethics and Director of The Center for Population-Level Bioethics at Rutgers University, explained how challenge trials could fit into the vaccine roadmap.

According to Dr. Eyal, challenge trials would most likely be combined with phase 3 trials. One way this could look is the use of challenge trials to weed out vaccine candidates before undergoing more expensive phase 3 trials. Additionally, if phase 3 trials fail to produce meaningful results about efficacy, a challenge trial could be used to obtain information while still collecting safety data from the more comprehensive phase 3 trial.

Nir Eyal

Dr. Eyal emphasized the importance of challenge trials for expediting the arrival of the vaccine. According to his own calculations, getting a vaccine — and making it widely available — just one month sooner would avert the loss of 720,000 years of life and 40 million years of poverty, mostly concentrated in the developing world. (Dr. Eyal stressed that his estimate is extremely conservative as it neglects many factors, including loss of life from avoidance of child vaccines, cancer care, malaria treatment, etc.) Therefore, speed is of “great humanitarian value.”

Dr. Wolfe added that because phase 3 trials rely on a lot of transmission, if the US gets better at mitigating the virus, “the distinction between protective efficacy and simple placebo will take longer to see.” A challenge study, however, is “always a well defined time period… you can anticipate when you’ll get results.” 

The panelists then discussed the ethics of challenge trials in the absence of effective treatment — as Krawiec put it, “making people sick without knowing if we can make them better.”

Dr. Wolfe pointed to the flu, citing challenge trials that have been conducted even though current treatments are not uniformly effective (“tamiflu is no panacea”). He then conceded that the biggest challenge is not a lack of effective therapies, but the current inability to “say to a patient, ‘you will not have a severe outcome.’ It varies so much from person to person, I guess.” (See one troubling example of that variance.)

Dr. Eyal acknowledged the trouble of informed consent when the implications are scarcely known, but argued that “in extraordinary times, business as usual is no longer the standard.” He asserted that if people volunteer with full understanding of what they are committing to, there is no reason to assume they are less informed than when making other decisions where the outcome is as yet unknown. 

Dr. Lipsitch compared this to the military: “we are not cheating if we cannot provide a roadmap of future wars because they are not yet known to us.” Rather, we commend brave soldiers (and hope they come home safe). 

Furthermore, Dr. Eyal asserted that “informed consent is not a comprehensive understanding of the disease,” lest much of the epidemiological research from the 1970s be called into question too. Instead, volunteers should be considered informed as long as they comprehend questions like, “‘we can’t give you an exact figure yet; do you understand?’”

Agreeing, Dr. Wolfe stated that when critics of challenge trials ask, isn’t your mission to do no harm?, he asks, “Do no harm in regards to whom?” “Who is in front of you matters,” Dr. Wolfe confirmed, “that’s why we put up safeguards. But as clinicians it can be problematic [to stop there]. It’s not just about the patient, but to do no harm in regards to the broader community.”

The experts then discussed what they’d like to see in challenge trials.

Dr. Wolfe said he’d like to see challenge trials carried out with a focus on immunology components, side effect profiles, and a “barrage” of biological safety and health standards for hospitals and facilities. 

Dr. Eyal stated the need for exclusion criteria (young adults, perhaps age 20-25, with no risk factors), a “high high high” quality of informed consent ideally involving a third party, and access to therapies and critical care for all volunteers, even those without insurance. 

Dr. Lipsitch stressed the scientific importance of assessing participants from a “virological, not symptom bent.” He mused that the issue of viral inoculum was a thorny one — should scientists “titrate down” to where many participants won’t get infected and more volunteers will be needed overall? Or should scientists keep it concentrated, and contend with the increased risk? 

Like many questions pondered during the hour — from the ideal viral strain to use to the safest way to collect information about high risk patients — this one remained unanswered. 

So don’t mark November 1st on your calendar just yet. But if you do get that life-changing notification, there’s a chance you’ll have human challenge trials to thank.

Post By Zella Hanson

COVID-19, and the Costs of Big Data

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TikTok’s illicit collection of user data recently drew fire from US officials. But TikTok’s base—largely young adults under 25—was unfazed. In viral videos posted in July and August, users expressed little concern about their digital privacy. 

“If china wants to know how obsessed i am with hockey,” wrote one user, “then just let them its not a secret.” “#Takemydata,” captioned another, in a video racking up 6,000 likes and over 42,000 views. 

As digital technologies become ever more pervasive – or even invasive – concerns for privacy should be a concern, a pair of experts said in a Duke Science & Society webinar earlier this month. 

TikTok and digital marketing aside, data collection can have real, tangible benefits. Case in point: COVID-19. Researchers at Duke and elsewhere are using peoples’ fitness trackers and smart watches to try to understand and predict the pandemic’s spread by monitoring a variety of health metrics, producing real-time snapshots of heart rate, blood pressure, sleep quality, and more. Webinar speaker Jessilyn Dunn of Duke biomedical engineering and her team have tapped into this data for CovIdentify, a Duke-funded effort to predict COVID infections using data collected by smartphones and wearable devices. 

Health data from smartphones and fitness trackers may help predict and identify disease.

For several years, Dunn’s lab has researched digital biomarkers of disease—that is, how health data collected by tech we carry every day can predict anything from heart disease to cognitive decline. 

It’s a potential goldmine: One recent poll suggests that 40 million Americans own some kind of smartwatch or fitness tracker. And the wearables market is rapidly expanding—by 2022, it may be worth upwards of 25 billion dollars.

As coronavirus cases began to rise in the US, Dunn’s lab quickly pivoted to develop COVID-specific biomarkers. “We have these devices … that perform physiologic monitoring,” Dunn said, “This is a method of taking vitals continuously to try to monitor what’s going on with people.” 

Say you’re a participant in Dr. Dunn’s study. You download the CovIdentify app, which analyzes health data collected by your phone or smartwatch. Short daily surveys then assess your exposure to COVID-19 and whether you’ve developed any symptoms. Dunn and her team hope to find a link, some specific change in vitals that corresponds to COVID-19 infection.   

There are some challenges. CovIdentify must account for variability between devices—data collected from a Fitbit, for example, might differ dramatically from an Apple Watch. And because COVID-19 manifests in unique ways across populations, a truly universal biomarker may not exist. 

However, panelist Marielle Gross—a bioethicist at the University of Pittsburgh—said projects like Dunn’s raise questions of digital privacy. Gross emphasized how easily our health data can be abused. 

Left: Jessilyn Dunn, PhD, a professor at Duke University and CovIdentify Researcher
Right: Marielle Gross, MD, MBE, a bioethicist and professor at the University of Pittsburgh

“Digital specimen is the digital representation of the human body,” she said. “Disrespecting it disrespects the body it represents.”

Dr. Gross cited South Korea’s efforts to curb COVID-19 as a cautionary tale. As part of the government’s  response, which quickly minimized cases early in the pandemic, exposed or infected South Koreans were expected to stay home and isolate, tracked using GPS-enabled devices.

But many South Koreans chose to leave their devices at home, rather than be tracked by their government. In response, the government required its citizens to carry their devices, 24/7. In a pandemic, desperate measures may be called for. But, Gross suggests, it isn’t hard to imagine a grimmer future—where the government requires all citizens to share their location, all the time.

Gross argues that we must fundamentally shift how we think about our personal data. “There’s this broad assumption that we have to give up privacy to reap the benefits of collective data.” Gross noted. “And that’s false.”

Most ‘digital natives’ aren’t naive. They’re well aware that internet companies collect, analyze, and sell their data, sometimes to malicious effect.  But many view data collection as a necessary tradeoff for an intuitive and tailored web experience.

So where do we go from here? Dr. Gross points to new developments like zero knowledge proofs, which use complex algorithms to verify data without actually seeing it. This technique promises anonymity without compromising the value of collective data. And as computing power increases, it may also be possible to perform real-time analysis without ever transmitting or storing collected health data.

And for future tech? In Dr. Gross’s opinion, ethical implications must be considered from day one. “Those sorts of considerations are not the kind of thing that you can tack on later. They have to be built into devices…at the ground floor.”

Post by Jeremy Jacobs

Duke’s Fundamental Research Can Turn Viruses Into Marvels

The COVID-19 epidemic has impacted the Duke research enterprise in profound ways. Nearly all laboratory-based research has been temporarily halted, except for research directly connected to the fight against COVID-19. It will take much time to return to normal, and that process of renewal will be gradual and will be implemented carefully.

Trying to put this situation into a broader perspective, I thought of the 1939 essay by Abraham Flexner published in Harper’s magazine, entitled “The Usefulness of Useless Knowledge.” Flexner was the founding Director of the Institute for Advanced Study at Princeton, and in that essay, he ruminated on much of the type of knowledge acquired at research universities —  knowledge motivated by no objective other than the basic human desire to understand. As Flexner said, the pursuit of this type of knowledge sometimes leads to surprises that transform the way we see that which was previously taken for granted, or for which we had previously given up hope. Such knowledge is sometimes very useful, in highly unintended ways.

Gregory Gray, MD MPH
Gregory Gray, MD MPH

The 1918 influenza pandemic led to 500 million confirmed cases, and 50 million deaths. In the Century since, consider how far we have come in our understanding of epidemics, and how that knowledge has impacted our ability to respond. People like Greg Gray, a professor of medicine and member of the Duke Global Health Institute (DGHI), have been quietly studying viruses for many years, including how viruses at domestic animal farms and food markets can leap from animals to humans. Many believe the COVID-19 virus started from a bat and was transferred to a human. Dr. Gray has been a global leader in studying this mechanism of a potential viral pandemic, doing much of his work in Asia, and that experience makes him uniquely positioned to provide understanding of our current predicament.

From the health-policy perspective, Mark McClellan, Director of the Duke Margolis Center for Health Policy, has been a leading voice in understanding viruses and the best policy responses to an epidemic. As a former FDA director, he has experience bringing policy to life, and his voice carries weight in the halls of Washington. Drawing on faculty from across Duke and its extensive applied policy research capacity, the Margolis Center has been at the forefront in guiding policymakers in responding to COVID-19.

Through knowledge accrued by academic leaders like Drs. Gray and McClellan, one notes with awe the difference in how the world has responded to a viral threat today, relative to 100 years ago. While there has been significant turmoil in many people’s lives today, as well as significant hardship, the number of global deaths caused by COVID-19 has been reduced substantially relative to 1918.

One of the seemingly unusual aspects of COVID-19 is that a substantial fraction of the population infected by the virus has no symptoms. However, those asymptomatic individuals shed the virus and infect others. While most people have no or mild symptoms, other people have very adverse effects to COVID-19, some dying quickly.

This heterogeneous response to COVID-19 is a characteristic of viruses studied by Chris Woods, a professor medicine in infectious diseases. Dr. Woods, and his colleagues in the Schools of Medicine and Engineering, have investigated this phenomenon for years, long before the current crisis, focusing their studies on the genomic response of the human host to a virus. This knowledge of viruses has made Dr. Woods and his colleagues leading voices in understanding COVID-19, and guiding the clinical response.

A team led by Greg Sempowski, a professor of pathology in the Human Vaccine Institute is working to isolate protective antibodies from SARS-CoV-2-infected individuals to see if they may be used as drugs to prevent or treat COVID-19. They’re seeking antibodies that can neutralize or kill the virus, which are called neutralizing antibodies.

Barton Haynes,MD
Barton Haynes, MD

Many believe that only a vaccine for COVID-19 can truly return life to normal. Human Vaccine Institute Director Barton Haynes, and his colleagues are at the forefront of developing that vaccine to provide human resistance to COVID-19. Dr. Haynes has been focusing on vaccine research for numerous years, and now that work is at the forefront in the fight against COVID-19.

Engineering and materials science have also advanced significantly since 1918. Ken Gall, a professor of mechanical engineering and materials science has led Duke’s novel application of 3D printing to develop methods for creatively designing personal protective equipment (PPE). These PPE are being used in the Duke hospital, and throughout the world to protect healthcare providers in the fight against COVID-19.

Much of the work discussed above, in addition to being motivated by the desire to understand and adapt to viruses, is motivated from the perspective that viruses must be fought to extend human life.

In contrast, several years ago Jennifer Doudna and Emmanuelle Charpentier, academics at Berkeley and the Max Planck Institute, respectively, asked a seemingly useless question. They wanted to understand how bacteria defended themselves against a virus. What may have made this work seem even more useless is that the specific class of viruses (called phage) that infect bacteria do not cause human disease. Useless stuff! The kind of work that can only take place at a university. That basic research led to the discovery of clustered regularly interspaced short palindromic repeats (CRISPR), a bacterial defense system against viruses, as a tool for manipulating genome sequences. Unexpectedly, CRISPR manifested an almost unbelievable ability to edit the genome, with the potential to cure previously incurable genetic diseases.

Charles Gersbach, a professor of Biomedical Engineering, and his colleagues at Duke are at the forefront of CRISPR research for gene and cell therapy. In fact, he is working with Duke surgery professor and gene therapy expert Aravind Asokan to engineer another class of viruses, recently approved by the FDA for other gene therapies, to deliver CRISPR to diseased tissues. Far from a killer, the modified virus is essential to getting CRISPR to the right tissues to perform gene editing in a manner that was previously thought impossible. There is hope that CRISPR technology can lead to cures for sickle cell and other genetic blood disorders. It is also being used to fight cancer and muscular dystrophy, among many other diseases and it is being used at Duke by Dr. Gersbach in the fight against COVID-19. 

David Ashley, Ph.D.
David Ashley, Ph.D.

In another seemingly bizarre use of a virus, a modified form of the polio virus is being used at Duke to fight glioblastoma, a brain tumor. That work is being pursued within the Preston Robert Tisch Brain Tumor Center, for which David Ashley is the Director. The use of modified polio virus excites the innate human immune system to fight glioblastoma, and extends life in ways that were previously unimaginable. But there are still many basic-science questions that must be overcome. The remarkable extension of life with polio-based immunotherapy occurs for only 20% of glioblastoma patients. Why? Recall from the work of Dr. Woods discussed above, and from our own observation of COVID-19, not all people respond to viruses in the same way. Could this explain the mixed effectiveness of immunotherapy for glioblastoma? It is not known at this time, although Dr. Ashley feels it is likely to be a key factor. Much research is required, to better understand the diversity in the host response to viruses, and to further improve immunotherapy.

The COVID-19 pandemic is a challenge that is disrupting all aspects of life. Through fundamental research being done at Duke, our understanding of such a pandemic has advanced markedly, speeding and improving our capacity to respond. By innovative partnerships between Duke engineers and clinicians, novel methods are being developed to protect frontline medical professionals. Further, via innovative technologies like CRISPR and immunotherapy — that could only seem like science fiction in 1918 (and as recently as 2010!) — viruses are being used to save lives for previously intractable diseases.

Viruses can be killers, but they are also scientific marvels. This is the promise of fundamental research; this is the impact of Duke research.

“We shall not cease from exploration
And the end of all our exploring
Will be to arrive where we started
And know the place for the first time.”

T.S. Eliot, Four Quartets

Post by Lawrence Carin, Vice President for Research

Paleo Fact and Fiction: the Key to Being Healthy

Humans have conquered smallpox and drastically reduced child mortality rates, yet we now face problems never seen before. Conditions like heart disease, obesity, cancer, and diabetes pose serious threats to our health. How can we overcome them? The answer may lie in our past.

Herman Pontzer, an associate professor of evolutionary anthropology at Duke, thinks we have something to learn by looking at hunter gatherers.

For most of human evolution, we had to work for our food. Recent developments like supermarkets and cities are strange and have flipped the script on daily life. Pontzer believes if we could live more like our ancestors, maybe we wouldn’t get sick.

Pontzer started off by studying a hunter gatherer group in Tanzania known as the Hadza. The Hadza cling tight to cultural traditions and live off the land in the African savannah. There are no domesticated animals, no guns, and no vehicles. Women spend their days digging for fibrous tubers and gathering berries and baobab fruits. When men aren’t hunting game, they collect honey. Honey plays a major role in the Hadza diet — around 15-20% of their caloric intake.

The Hadza live a very active lifestyle. They walk between 13,000 and 20,000 steps a day, compared to the generic Fitbit goal of 10,000 steps (which most of us don’t even meet, if we’re being honest).

Curious to see if the Hadza’s vigorous activity levels had something to do with their superior health, Pontzer used the doubly labeled water technique to measure total energy expenditure. Shockingly, he found that Hadza and Americans burn the same amount of calories on average.

All our lives we’ve been told exercise converts to burned calories. But evidence from the Hadza tells us this is not the case. What really happens is natural systems in our body adjust to suppress other activity, keeping total expenditure constant. This means that exercise alone is an ineffective tool for weight loss. But don’t quit the gym quite yet — while the Hadza spend most of their total energy being active, an inactive body will spend it on unhealthy things such as inflammation and stress reactivity. This constrained energy mechanism makes exercise essential for overall health. But in the words of Pontzer, “in order to end obesity, we need to fix our diet.”

Image result for paleo diet

The idea that the “paleo diet” is necessarily low-carb is a myth, Pontzer says. Hadza rely heavily on starches and fructose for sustenance. Furthermore, what you eat as a hunter gatherer is entirely dependent on geographical location. Hunter gatherer diets do things in common, though: they eat no processed foods, and energy dense foods are hard to come by. 

Never before have we had so much food high in energy available at such a low effort. In supermarkets, the cheapest food is the most rich in energy. In the wild, it’s the complete opposite. Pontzer says, “traditional diets are diverse, modern diets are perverse.”

Image result for supermarket cereal aisle

He calculated that an American can get twenty times as much food energy in an hour’s work as a Hadza could with the same effort. Plus, the Hadza don’t have irresistible Doritos they can’t stop eating. When the Hadza are full, they’re full.

The Hadza are naturally protected from the same “diseases of civilization” that we are likely to die from. A beautiful combination of diet and how they expend energy provides a shield that modernization seems to have taken from us. Energy has become too available. But staying healthy is still in our control. It’s about finding the right balance of exercise and eating right.  

There is still a lot to be learned from hunter gatherer societies. For now, let the Hadza inspire you to get outside, get active, and cut out processed foods!

Teens Have the Feels About Their Family’s Standing

A study of British twins appearing this week in the Proceedings of the National Academy of Sciences shows that an adolescent’s sense of their own family’s social and economic standing is closely linked to that child’s physical and cognitive health.

In fact, the adolescent’s perception of status was a more powerful predictor of their well-being and readiness for further education than their family’s actual status. The study sample represented the full range of socioeconomic conditions in the U.K.

“Testing how young people’s perceptions related to well-being among twins provided a rare opportunity to control for poverty status as well as environmental and genetic factors shared by children within the same family,” said lead author Joshua Rivenbark, an MD/PhD student in Duke’s Medical School and Sanford School of Public Policy.

Joshua Rivenbark is an MD/PhD student in medicine and policy

“Siblings grew up with equal access to objective resources, but many differed in where they placed their family on the social ladder – which then signaled how well each twin was doing,” Rivenbark said.

Researchers followed 2,232 same-sex twins born in England and Wales in 1994-95 who were part of the Environmental Risk (E-Risk) Longitudinal Twin Study based at King’s College London. Adolescents assessed their family’s social ranking at ages 12 and 18. By late adolescence, these beliefs signaled how well the teen was doing, independent of the family’s access to financial resources, healthcare, adequate nutrition and educational opportunities. This pattern was not seen at age 12.

“The amount of financial resources children have access to is one of the most reliable predictors of their health and life chances,” said Candice Odgers, a professor of psychological science at the University of California, Irvine, who is the senior author of the report. “But these findings show that how young people see their family’s place in a hierarchical system also matters. Their perceptions of social status were an equally good, and often stronger, indicator of how well they were going to do with respect to mental health and social outcomes.”

Study findings also showed that despite growing up in the same family, the twins’ views were not always identical. By age 18, the twin who rated the family’s standing as higher was less likely to be convicted of a crime; was more often educated, employed or in training; and had fewer mental health problems than his or her sibling.

“Studies that experimentally manipulate how young people see their social position would be needed to sort out cause from effect,” Rivenbark said.

The E-Risk study was founded and is co-directed by Duke professors Avshalom Caspi and Terrie Moffitt at King’s College London.

Guest Post by Pat Harriman, UC-Irvine News @UCIPat

Flu No More: The Search for a Universal Vaccine

Chances are, you’ve had the flu. 

Body aches, chills, congestion, and cough—for millions across the globe, these symptoms are all too familiar.

For some, though, the flu leads to serious complications. Last year, as many as 647,000 Americans were hospitalized due to flu-related illness, with an additional 61,000 deaths.

Countless hours of lost productivity also accompany the illness. Including hospitalization costs, estimates for the flu’s total economic burden range from 10 to 25 billion dollars each year.

Flu prevention efforts have yielded mixed results. For many viruses, vaccines provide protection that lasts a lifetime, building up a network of antibodies primed to neutralize future infections. Influenza viruses, however, mutate quickly, rendering vaccines from years past ineffective. As a result, new vaccines are constantly in development. 

Every year, researchers predict which flu viruses are likely to dominate the upcoming flu season. Based on these predictions, new vaccines target these specific strains. Consequentially, the effectiveness of these vaccines vary with the prediction. When a vaccine is a good match for the dominant flu strain, it can lower rates of infection by 40-50%. When it isn’t, its preventative power is far lower; in 2014, for example, the yearly influenza vaccine was only 19% effective

Peter Palese, Ph. D, might have a better solution. Working at the Icahn School of Medicine, Palese and his team are developing a vaccine that takes a new approach to flu prevention. 

Just before classes ended last month, Palese spoke at the Duke Influenza Symposium, a showcase of Duke’s current research on influenza. The symposium is part of Duke’s larger push to improve the efficacy of flu vaccination.

Palese’s vaccines work by redirecting the immune response to the influenza virus. Traditional vaccines create antibodies that target hemagglutinins, proteins found on the outermost part of influenza viruses. Hemagglutinins are divided into two regions: a head domain and a stalk domain (Fig. 1).

Fig. 1: Left: General influenza structure. Right: Hemagglutinins are divided into two regions: a head domain and a stalk. The head domain is prone to mutation and undergoes rapid change while the stalk domain is more resistant to mutation.
Source: Frontiers in Immunology

In a traditional vaccination, the head domain is immunodominant—that is, the antibodies produced by vaccines preferentially target and neutralize the head domains. However, the head domain is highly prone to mutation and varies between different strains of influenza. As a result, antibodies for one strain of the virus provide no protection against other strains.

The new vaccines pioneered by Palese and his team instead target the stalk domain, a part of hemagglutinin that mutates far slower than the head domain. The stalk is also conserved across different subtypes of the influenza virus. As a result, these vaccines should theoretically provide long-lasting protection against most strains of influenza.

Testing in ferret, mice, and guinea pigs have produced promising results. And early human trials suggest that this new kind of vaccination grants broad immunity against influenza. But long-term results remain unclear—and more trials are underway. “We would love to say it works,” Palese says. “But give us 10 years.”

In the meantime, the seasonal flu vaccine is our best option.“The recommendation to vaccinate everyone is the right policy,” Palese tells us.

Post by Jeremy Jacobs

Infants, Immunity, Infections and Immunization

This is the fourth of several posts written by students at the North Carolina School of Science and Math as part of an elective about science communication with Dean Amy Sheck.

Dr. Giny Fouda’s research focuses on infant immune responses to infection and vaccination.

Her curiosity about immunology arose during her fourth year of medical school in Cameroon, when she randomly picked up a book on cancer immunotherapy and was captivated. Until then, she conducted research on malaria and connected it to her interest in pediatrics by studying the effects of the parasitic disease on the placentas of mothers.

Genevieve Giny Fouda M.D., Ph.D.

As a postdoctoral fellow at Duke, she then linked pediatrics and immunology to begin examining mother to child transmission of disease and immunity.

Today she is an M.D. and a Ph.D. and a member of the Duke Human Vaccine Institute. She’s an assistant professor in pediatrics and an assistant research professor in the Department of Molecular Genetics and Microbiology at Duke University School of Medicine.

Based on the recent finding that children of HIV-positive mothers are more susceptible to inheriting the disease, Fouda believes that it is important to understand how to intervene in passive immunity transmissions in order to limit them. Children and adults recover from diseases differently and uncovering these differences is important for vaccine development.

This area of research is personally important to her, because she learned from her service in health campaigns in Central Africa that it is much easier to prevent disease than to treat.

Babies!

However, she believes that it is important to recognize that research is a collaborative experience with a team of scientists. Each discovery is not that of an individual, but can be accredited to everyone’s contribution, especially those whose roles may seem small but are vital to the everyday operations of the lab.

At the Duke Human Vaccine Institute, Fouda enjoys collaborating as a team and contributing her time as a mentor and trainer of young scientists in the next generation.

Outside of the lab, Fouda likes to spend time reading books with her daughter, traveling, decorating and gardening. If there was one factor that improve how science in immunology is conducted, she would stress that preventing disease is significantly cheaper than treating those that become infected by it.

Dr. Fouda has made some remarkable progress in the field of disease treatment with her hard working and optimistic personality, and I know that she will continue to excel in her objectives for years to come.

Post by Vandanaa Jayaprakash NCSSM 2020

Understanding and Addressing Vaccine Hesitancy

In the midst of increasing outbreaks of vaccine-preventable disease, Duke global health researcher Lavanya Vasudevan (PhD, MPH, LPH) is investigating the reasons for vaccine hesitancy with focus on America and Tanzania.

Vaccine hesitancy refers to the refusal of or delay in accepting vaccinations, despite their availability. Vasudevan hopes to figure out what interventions will change the minds of target populations on such a heated topic.

She presented at Duke’s Global Health Institute on November 15th about her “big 5 research areas:” identification of sub-optimal vaccine uptake, contextualization of barriers to uptake, measuring parental concern, debunking misinformation, and developing and testing strategies aimed at addressing vaccine hesitancy.

Lavanya Vasudevan presenting at Duke’s Global Health Institute.

Globally, Vasudevan says that there are too many kids playing catch-up with their vaccines, meaning that even when children are getting vaccinated, the vaccinations they receive are not on time with the scheduled progression of immunizations, putting them at risk for contracting disease. Different countries measure vaccination coverage in different ways and on different timelines, which makes it harder to understand where sub-optimal vaccine uptake is happening. A better standard for assessing timeliness of vaccines is crucial. Vasudevan is working to confront this issue to gain better understanding of who and where hesitancy is coming from.

Identification of specific regions of vaccine hesitancy is crucial to navigating interventions, she added. Vasudevan wants to be able to pinpoint areas and understand the context-specific issues that vary across time, place, and vaccine type in order to be most effective.

She said that her work in Tanzania has provided insight to the problem of geographic accessibility and lack of proper supplies in the country, prompting delayed and missed vaccinations among 72% of children, according to self-reporting by their mothers. Tanzanian mothers expressed their frustrations during interviews. They frequently arrange to go to a clinic where vaccinations are offered on specific dates and travel long distances to get there. However, if there are not enough kids who come to be vaccinated, the facilities just won’t vaccinate those who did manage to show up for immunizations.  

Though the qualitative data gained through extensive interviewing and group discussions has been extremely useful and rich, Vasudevan says there is a need for quantitative tools that can rapidly screen for parent’s concerns when it comes to the vaccination of their children. Qualitative data is simply not informative on a large scale.

A review of pre-existing measures evaluated 159 studies, but the quantitative scales found were often complex and context-specific, as well as designed and validated for high-income settings. On this basis, Vasudevan and her larger research team decided to design a scale for use in Tanzania because of its specificity in addressing the contexts of the region. Tailored counseling is also being used to address the local concerns and issues.

Another parallel research project that Vasudevan is involved with aims to identify common vaccine myths, creating a taxonomy to tag these myths and developing and testing an intervention that will highlight and debunk misinformation found on the internet. The current end-goal for the work being done is a “vaccine fact-checker” that could be used on web browsers to identify the myths in vaccine-related information found online.

A common example of needles and vials containing immunization products (Creative Commons).

In closing, Vasudevan identified three main areas for developing and testing intervention strategies. She says these are behavioral nudges, educational strategies, and vaccination policy and legislation.

There is a need for parent-focused strategies that recognize parental concern for their child’s safety on all sides of the vaccination issue, she said. Stringent policies are likely to alienate hesitant parents rather than increasing vaccine uptake. This is why Vasudevan is so focused on understanding and contextualizing issues specific to hesitancy among parents. It seems that increase of vaccinations and improvement of immunization timeliness lies in hearing and reconciling with parental apprehensions and underlying root causes of these hesitations.

One area of focus that Vasudevan feels is underutilized is pre-natal care. Reduction of the divide between obstetrician/gynecologists (OBGYNs) and pediatric care may be a crucial component to educate parents and enrich their understanding about vaccinations following the birth of the child.

Beyond everything else, she said, building trust is essential; simply providing information to parents is not enough. It takes time and empathy to be enable parents to make healthy vaccination choices. Providing credible resources in a safe environment while tuning in to the causes of hesitancy may be the next step to the reduction of vaccine-preventable disease, a current top ten threat to global health.

Post by Cydney Livingston

Malaria Hides In People Without Symptoms

It seems like the never-ending battle against Malaria just keeps getting tougher. In regions where Malaria is hyper-prevalent, anti-mosquito measures can only work so well due to the reservoir that has built up of infected humans who do not even know they carry the infection.

In high-transmission areas, asymptomatic malaria is more prevalent than symptomatic malaria. Twenty-four percent of the people in sub-Saharan Africa are estimated to harbor an asymptomatic infection, including 38 to 50 percent of the school-aged children in western Kenya. Out of the 219 million malaria cases in 2017 worldwide, over 90%  were in sub-Saharan Africa.  

Using a special vacuum-like tool, Kelsey Sumner, a former Duke undergraduate now completing her Ph.D. at UNC-Chapel Hill, collected mosquitoes in households located in rural western Kenya. These weekly mosquito collections were a part of her pre-dissertation study on asymptomatic, or invisible, malaria. She visited Duke in September to catch us up on her work in Data Dialogue event sponsored by the mathematics department.

Sumner and colleague Verona Liao, in front of a sticky trap for mosquitoes

People with asymptomatic malaria carry the infection but have no idea they do because they do not have any indicators. This is incredibly dangerous because without symptoms, they will not get treated and can then infect countless others with the disease. As a result, people with an asymptomatic infection or infections have become a reservoir for malaria — a place for it to hide. Reservoirs are a group that is contributing to transmission at a higher rate or proportion than others.

Sumner’s study focused on examining the effect of asymptomatic malaria on malaria transmission as well as whether asymptomatic malaria infections would protect a person against future symptomatic infections from the same or different malaria infections. They were particularly looking into Plasmodium falciparum malaria. In Kenya, more than 70% of the population lives in an area with a high transmission of this potentially lethal parasite.

“P. falciparum malaria is very diverse in the region,” she said. “It’s constantly mutating, which is why it’s so hard to treat. But because of that, we’re able to actually measure how many infections people have at once.” 

The researchers discovered that many study participants were infected with multiple, genetically-distinct malaria infections. Some carried up to fourteen strains of the parasite.

Participants in the study began by filling out an enrollment questionnaire followed by monthly questionnaires and dried blood spot collections. The project has collected over nearly 3,000 dried blood spots from participants. These blood spots were then sent to a lab where DNA was extracted and tested for P. falciparum malaria using qPCR

“We used the fact that we have this really diverse falciparum species in the area and sequenced the DNA from falciparum to actually determine how many infections people have,” Sumner said. “And then, if there’s a shared infection between humans and mosquitoes.”

Sumner and her team also visited symptomatic participants who would fill out a behavioral questionnaire and undergo a rapid diagnostic test. Infected participants were able to receive treatment. 

While people in the region have tried to prevent infection through means like sleeping under insecticide-treated nets, malaria has persisted. 

One of the Kenyan staff members hanging a CDC light trap for mosquitoes

Sumner is continuing to analyze the collected DNA to better understand asymptomatic malaria, malarial reservoirs and how to best intervene to help stop this epidemic. 

“We’re basically looking at how the number of shared infections differ between those that have asymptomatic malaria versus those that have symptomatic malaria.”

She and her team hypothesize that there are more asymptomatic infections that would result in and explain the rapid transmission of malaria in the region.

Post by Anna Gotskind

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