Global Health

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Widening Horizons

HMS LGBTQ health elective provides clinical experience 

When Neal Baer was attending Harvard Medical School in the 1990s, he says there were only two out gay students in his class and next to nothing was ever mentioned about LGBTQ health.

Baer received his degree in 1996 and became a pediatrician, an adjunct professor of preventive medicine at UCLA’s Fielding School of Public Health and an award-winning television writer and producer, working on successful TV shows such as China Beach and ER. He eventually became executive producer and showrunner of Law & Order: Special Victims Unit and Under the Dome.  

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More than 20 years after he graduated, however, Baer returned to HMS in 2016 to speak to medical and LGBTQ (lesbian, gay, bisexual, transgender, queer and questioning) students, and when he asked them how much exposure they had had to LGBTQ health issues in medical school, most still said very little. 

Since then, things have changed considerably. HMS has introduced a new LGBTQ health clinical elective course for medical students. Baer himself has also given HMS $250,000 to establish an endowed scholarship to support MD students interested in LGBTQ health.

According to the CDC, members of the LGBTQ community are at increased risk for a greater number of health threats than their heterosexual peers ...

“I’m really excited that HMS is now filling a gap that’s been there for a long time,” Baer said recently during a telephone interview. “Now, more than ever, there is a need for a course like this.”

According to the CDC, members of the LGBTQ community are at increased risk for a greater number of health threats than their heterosexual peers, and some of these risk disparities are associated with “social and structural inequities, such as the stigma and discrimination that LGBTQ populations experience.”

The new elective is a month-long multidisciplinary clinical and scholarly experience that trains HMS students to provide high-quality care to patients who are LGBTQ, gender nonconforming or born with differences of sex development. The course focuses on having the students work with youth, but also provides clinical exposure to and education on working with LGBTQ adults. Different clinical settings include psychiatry, adolescent and young adult medicine, pediatrics, family practice and internal medicine.

“It’s critically important that our students learn to take care of diverse populations of patients, and this elective is designed to help one of our most vulnerable populations,” said Fidencio Saldaña, HMS dean for students. 

Among the learning goals, students taking the course are asked to demonstrate an ability to elicit sensitive information, recognize individual health risks and challenges, communicate ways to reduce high-risk behaviors and develop strategies to prevent health problems and promote wellness. 

“One of the hardest things about becoming a physician is learning to talk about very important and private issues with people who may be very different from yourself,” said Ed Hundert, HMS dean for medical education. “For straight doctors learning to talk with LGBTQ patients, this is a very important competency to develop.”

Clinical Focus

Robert Kitts, an HMS assistant professor of psychiatry at Massachusetts General Hospital, was instrumental in launching the course and is one of its former co-directors. What makes the HMS course unusual, he says, is that unlike LGBTQ courses at most medical schools in the U.S., which are primarily classroom based, the HMS course places emphasis on clinical experience.

Kitts said the HMS course was created in response to faculty and students who identified a growing demand for such a clinical elective. 

“Students don’t want a month of lectures,” Kitts said. “They want actual patients.”

Since its inception, between five and 10 students have taken the class.  Neir Eshel, who graduated in 2016,  was one of them. Now a resident at Stanford University Medical Center, Eshel said he and a few other students began lobbying for broader institutional support for LGBTQ students when they arrived at HMS. In addition, he said, they initiated an extracurricular speaker series with guests who could address LGBTQ health topics, and they began to research LGBTQ health issues and hold presentations themselves, often inviting LGBTQ patients to speak. 

The course, he said, was born of many of those efforts. 

“Ultimately, if we are trying to train practitioners who are cognizant of the difficulties that are faced [by LGBTQ patients] then there is nothing better than spending time with patients,” Eshel said.

“This course gives people the chance to go to clinics that focus on these issues. It gives you the clinical, one-on-one face time during which you can learn a lot. It’s a qualitatively different experience than reading an article. It’s much more memorable,” he said.

Promoting Health

Jennifer Potter is advisory dean for the William Bosworth Castle Society and HMS professor of medicine at Beth Israel Deaconess Medical Center. Potter has been leading an Association of American Medical Colleges advisory committee whose goal is to support the efforts of academic medicine and the biomedical sciences in promoting the health of people within LGBTQ communities. 

When the committee was formed five years ago, she said, it was asked to consider what could be done by medical schools to offer more courses on LGBTQ health and also to support LGBTQ medical students. This initiative followed a nationwide survey revealing that, on average, most medical schools offered only about five hours of LGBTQ study in a four-year curriculum.

One of the committee’s goals has been to explore ways to provide medical students with a broader range of abilities that will help them better respond to diverse patient populations.

“It’s a lot about communication, about establishing a rapport with someone who may not trust you from the get-go,” said Potter. “Really, it’s about teaching students that part of their professional duty is being able to work with all kinds of people. In this profession, you have to figure out how you’re going to take care of all kinds of patients.”

In 2014, Jessica Halem joined HMS as program director managing the School’s first LGBTQ office, which is responsible for enhancing LGBTQ inclusion and fostering a welcoming and affirming community for LGBTQ students, staff, faculty, trainees and fellows at HMS. She said one of the advantages of this course is that it can be tailored to a particular student’s area of interest, whether it be surgery, psychiatry or obstetrics and gynecology. 

“We’re able to craft a very real clinical experience based on what the student is interested in,” she said. “They can touch on all the specialties that LGBTQ care touches on.”

“Overall, it’s just been a really positive experience.  [Students] just really appreciate it,” Kitts said, adding that there has been enthusiasm around expanding the course and including additional HMS affiliates.  

“This elective represents a collaboration for the sake of patients and students,” he said.

According to Potter, one of the next goals of the AAMC committee is to find ways to encourage more medical schools to include LGBTQ health information alongside other health-related materials throughout all four years of the medical school curriculum, in addition to offering an elective course.

“Exposure makes all the difference” in preparing students to be better doctors, she said, adding that she does believe significant progress has been made.

“I think there is much more support than there was, but we still have a long way to go,” said Potter. 

 

 

 

 

 

 

News

Understanding LGBTQ Health

Studies support translational research into health disparities

Sari Reisner, HMS assistant professor of pediatrics and an epidemiologist and researcher at Boston Children’s Hospital, is working to find ways to help school health professionals reduce the bullying of Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ) students.  

Bryn Austin, HMS professor of pediatrics and a behavioral researcher at Boston Children’s Hospital, is investigating how state laws affect the health of gender minorities. 

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Li Zhou, HMS associate professor of medicine and a primary care doctor at Brigham and Women’s Hospital, is investigating ways to identify LGBTQ patients from electronic health records and, in turn, gather more data about their health disparities.

All have recently been awarded pilot funding from the Harvard Catalyst Health Disparities Research Program to embark on research projects that support translational research into LGBTQ health disparities.

The awards will help researchers form a foundation on which to build new programs to reduce health disparities among people who are sexual and/or gender minorities.

“There’s not a lot of data about gender-minority health disparities,” said Ana Progovac, an HMS post-doctoral fellow in health care policy and a member of a team that was awarded one of the $50,000 one-year grants.

“Our work aims to get a better picture of the health needs and concern health outcomes for this community,” Progovac said.

Progovac, who is working with Benjamin Lê Cook, HMS assistant professor of psychiatry at Cambridge Health Alliance, will use the award to work towards building analytic health care tools aimed at helping doctors provide care that meets the needs of gender-minority patients.

“These projects focus on areas for which there hasn’t been as much research, and the researchers have all brought creative thinking to the challenge of investigating LGBTQ health disparities,” said Mark Schuster, the HMS William Berenberg Professor of Pediatrics and chief of the Division of General Pediatrics at Boston Children's Hospital.

Schuster, as director of the Harvard Catalyst Health Disparities Research Program, organized the funding opportunity.

Reach Out

As a key feature of the research, members from each community will participate in the studies.  

For instance, Cook’s and Progovac’s project could lead to analytic tools built into electronic health records, which could then be used by doctors at community hospitals caring for gender-minority patients.

Similarly, Reisner’s project might involve the participation of high school students, faculty and staff who are concerned about LGBTQ bullying. 

To meet the need for community engagement during study design, researchers were asked to present their plans to a panel of individuals from the Boston area, many of whom lead community-based LGBTQ programs.

This new approach, the  Community Engagement Studio, has been encouraged by the National Institutes of Health as a way to gather input from people in the communities that participate in and benefit from research.

The process­, which Harvard Catalyst is planning to continue to use across a spectrum of initiatives, supports the development of evidence-based programs that are more rapidly applicable and effective.

Studios can be used to support a range of initiatives and research efforts, and Harvard Catalyst has encouraged faculty and investigators to consider working with this model.

Community studio panelists dedicated two afternoons of their time to come to HMS to participate in sessions.

“There’s often a disconnect between academia and advocacy outside of academia. The community studio breaks down that lack of communication,” said Mason Dunn, executive director of the Massachusetts Transgender Political Coalition, co-chair of the Freedom Massachusetts campaign, and a member of a CE studio.

“I was very excited to be at the table and taking part in the conversation,” Dunn said.

Join Forces

Academic researchers cannot always see the pitfalls that can occur once their ideas turn into real-life interactions with vulnerable individuals.

“What sounds good or is elegant on paper may not fly in reality,” said Ben Perkins, vice president of multicultural initiatives/health equity for the American Heart Association/American Stroke Association and a member of the CE  studio for this grant proposal process.

“But to engage with folks from the community who have an interest in their community, it just brings a depth and level of understanding to the process that can only make the research better,” he said.

Cook and Progovac, for instance, plan to mine Medicare claims data and Cambridge Health Alliance electronic health records for data that identifies gender-minority patients.

Many medical records include male or female gender identification, but they often do not readily identify patients who do not identify with the gender they were assigned at birth.

Identifying these patients in medical records could help health systems better understand the health and health care needs of their gender-minority patients and may open the door to the development of built-in tools that alert doctors when a gender-minority patient may be at a higher risk for suicide, domestic violence or some other serious concern.

The doctor, in turn, can then offer help.

“They might connect them to a domestic violence shelter that is sensitive to their needs and privacy concerns,” said Progovac.

When Cook and Progovac presented their plan at the CE studio session, community members voiced concerns about flagging LGBTQ individuals.

 “There are ethical considerations,” said Perkins during the studio session. “This diagnostic tool could be used to stigmatize.”

“Shouldn’t I be made aware that I’ve been flagged? It could open up the conversation between doctor and patient, but it could also have serious implications,” said Jodie Elgee, senior director of the Boston Public Schools’ Safe and Welcoming Schools Center.

Progovac and Lê Cook used this kind of feedback to strengthen their proposal. They created a core team of advisors from the gender-minority community to raise and address ethical concerns throughout the evolution of the project.

“We want the findings and future applications that our work produces to be as community grown and transparent as possible,” says Progovac.

To learn more about community engagement studios and their applicability, please contact Victor Shopov, Director,  Harvard Catalyst Community Engagement at Victor_Shopov@hms.harvard.edu


 

News

Inspiring the Next Generation of Global Surgeons

Student-run symposium draws national, global audience

It was a testament to the power of students and their ability to advocate for change. For many of them, surgery had too long been left out of global health and global health had too long been left out of surgery.  

But now, with more students asking for global surgery opportunities at medical schools across the U.S. and around the world, the hope is that surgical programs will expand their framework for academic surgery to include global health.

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To that end, on March 4, a wide-ranging group of medical students held the first ever Boston Global Surgery Symposium at Harvard Medical School, hosted by the Global Surgery Student Alliance (GSSA). 

Drawing medical students not only from Harvard but also from Boston University, Tufts University, the University of Massachusetts, Dartmouth University, Brown University, Yale University and Penn State College of Medicine, the audience also included undergraduate students and surgical residents from the Boston area as well as two population health researchers from the United Nations.

“What you guys have accomplished in a few months is just spectacular. I’ve never seen anything like it. So, don’t underestimate what you’ve done and what you could do in the future. You are just a force of nature and you are the future,” said keynote speaker John Meara, the Steven C. and Carmella R. Kletjian Professor of Global Surgery and Social Medicine at HMS and co-chair of the Lancet Commission on Global Surgery.

More than 19,000 people from around the world joined in via livestreaming to watch the symposium and have viewed subsequent recordings of the different talks on the GSSA website.

Viewers included students from more than 50 medical schools across the U.S. and from 37 different countries. Many more watched via an HMS livestream on video-sharing and social media sites from as far away as South Africa, Morocco, China, Brazil, England and Belgium.

Meara talked about the Lancet Commission’s work and plans for global surgery from the present day through the year 2030, elaborating on the importance of sustainably increasing surgical care worldwide by focusing on infrastructure, workforce, service delivery, finances and information management.

“This symposium made me so much more confident that there will always be a place for me [in global surgery] regardless of what I ultimately want to do.” — Monika Pyarali 

He strongly encouraged students to get involved. Many said they finally saw a future career that captured what they wanted to do by combining global health and surgery.

Others said they realized they could contribute to global surgery no matter what specialty they went into, how often they traveled abroad, what research they did or which patients they saw.

“Each of the presentations was so informative and inspiring. It was incredible to hear from people of such different specialties working together to bring surgery to underserved areas across the world,” said Monika Pyarali, a medical student from Baylor College of Medicine who watched via the livestream.

“This symposium made me so much more confident that there will always be a place for me [in global surgery] regardless of what I ultimately want to do.”

After the keynote speech, students attended panel sessions led by 16 global surgery leaders from 13 specialties, ranging from trauma surgery and neurosurgery to obstetrics and gynecology and anesthesia.

One speaker even joined via video conference call from Benin while another flew in from North Carolina to speak to students.

They spoke on topics ranging from education and capacity building to crisis and humanitarian aid; talks on subspecialties in global surgery, global surgery research and global surgery innovation were also featured.

The symposium concluded with a plenary session on how students can pursue careers in global surgery and how they can tie their interest in surgery to their goals of contributing to the world. 

Some speakers said the symposium ended up inspiring them, too. They each overcame many obstacles to become global surgeons and said they felt energized to see that the next generation was speaking out and advocating for their field.

“Today, I am overwhelmed not merely by the interest of students in global surgery but by the leadership, innovation, foresight and, I believe, the commitment to improve the lot for destitute sick and injured people in the world today,” said Robert Riviello, an HMS assistant professor of surgery and a trauma surgeon at Brigham and Women’s Hospital who is extensively involved in global surgery capacity-building efforts.

GSSA national leadership team with Dr. John Meara. Team members include: Isaac Alty, Nicole Beck, Christena Caminita, Chris Dee, Roya Edalatpour, Parisa Fallah (Chair), Andrew Giles, Austin Herbst, Ray Jhun, Kevin Kiang (not pictured), Sarah Osmulski, Prachi Patel, Adriana Ramirez (not pictured), Marvee Turk, Jason Young. Image:Ahmed Elnaiem and Stacey Giles

Quick Start

The goal of the symposium was to increase awareness of global surgery among medical students and to bring more students into the field. In only four short months, a group of 15 medical students (most of whom were first-years) and residents from HMS/HSDM, Boston University School of Medicine and the Harvard T.H. Chan School of Public Health came together, established a national team, created the globalsurgerystudents.org website, and reached out to 43 schools across 20 states. They also connected with an international global surgery team and contacted speakers and donors in preparation for the symposium.

Since officially launching the group and website in mid-January, students at more than 15 schools have started to work on creating global surgery teams at their institutions by hosting events designed to get them connected to global surgery faculty and engaged in the field.

Next steps for the GSSA include continued systematic national outreach to connect with interested students at more medical schools across the U.S. while partnering with more surgical and global health organizations. Their plan is to create tools to help students create and maintain global surgery working groups at their schools, as well as encouraging student action for global surgery around the country.

The group is also creating a database of global surgery contacts so students can know who to contact to get involved.

Moving forward, the GSSA hopes to be a unifying force that encourages collaboration among students across the country so that efforts can be coordinated and can more effectively impact the field of global surgery in a meaningful way.

The Global Surgery Student Alliance is the national student global surgery working group for the U.S.

To watch the talks from the Boston Global Surgery Symposium, visit: globalsurgerystudents.org/live-streaming-recording.

To learn more, visit:

Website: globalsurgerystudents.org
Twitter: @gsurgstudents
Email: globalsurgerystudents@gmail.com

The GSSA would like to thank the Audio Visual Communications Division of the HMS Education Computing Department for their hard work in making the livestreaming and recording of the conference possible so that people around the world could watch. They would also like to thank the Program in Global Surgery and Social Change at HMS, the Center for Surgery and Public Health at Brigham and Women’s, the HMS Department of Global Health and Social Medicine, the Department of Plastic and Oral Surgery at Boston Children’s Hospital, and the Harvard Chan Student Surgery Society at the Harvard Chan School for their donations that made the symposium a reality.

News

The Ebola Suspect’s Dilemma

What to do when seeking treatment is more likely to harm than to help?

West Africa. 2014. The height of the Ebola outbreak sweeping the region. A person experiences sudden onset of fever, vomiting, diarrhea—textbook early symptoms of Ebola.

But there’s a catch. A person with those symptoms is just as likely to have malaria as Ebola, creating a potentially deadly dilemma, said the authors of a newly published essay in Lancet Global Health. Someone with malaria has a 1 in 500 risk of dying if they choose to avoid treatment, while someone without Ebola seeking care at an Ebola treatment unit at the time would have a 1 in 5 chance of getting infected and perishing from the virus.

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The 64 percent mortality rate in treatment units, the authors said, stemmed from the fact that many Ebola units were ill-equipped to provide even the most rudimentary resuscitative care like intravenous fluids. What this meant, the authors add, is that even a person already sick with Ebola would be only marginally more likely to survive by seeking what then passed for treatment in such a poorly staffed and stocked facility.

Impossible Choices

In the absence of effective therapy, the authors argue, the choice between going to a clinic and staying home represents a higher-stakes version of the so-called prisoner’s dilemma, a game theory model of collaboration and betrayal that tries to tease out the rational basis for cooperation and altruism.

“You hear this notion that Ebola was driven by selfish ‘superspreaders’ who were unwilling to seek care,” said lead author Eugene Richardson, HMS instructor in medicine at Brigham and Women’s Hospital. “But the reality is that there was very little effective care available for most people, because of the region’s catastrophically underdeveloped health systems.”

“What’s more,” added Paul Farmer, the Kolokotrones University Professor of Global Health and Social Medicine at HMS, “many of the ‘superspreaders’ were caregivers, most of them traditional healers working in precisely those settings bereft of nurses and doctors.”

They nursed the sick and were involved in last rights and burial of the dead, he said.

“These are the main acts of caregiving—including its final act,” Farmer said.

Beyond a deconstruction of the impossible clinical and moral choices facing people with symptoms of Ebola, the essay is a call to action for policy makers, global health organizations and international development institutions to reframe and rethink the persistent misconceptions that the authors say have hamstrung an effective response to the suffering caused by Ebola.  

Diverse Perspectives

The authors of the essay represent a diverse group that includes frontline clinicians who treated Ebola during the outbreak and researchers who conducted extensive studies of the clinical, biological and social aspects of the disease.

Farmer, who is also co-founder of Partners In Health, is senior author on the commentary. Other authors include faculty and leaders at HMS, Brigham and Women’s, Partners In Health, governmental and nongovernmental agencies in Liberia and Sierra Leone, and other institutions.

Some of the survivors who shared their stories with the authors talked about the heart-rending struggle to care for their loved ones in a place where the already strained health infrastructure was so overwhelmed by Ebola that clinics and hospitals were amplifying the outbreak instead of healing the afflicted, Richardson said.

"The essay is a call to action for policy makers, global health organizations and international development institutions to reframe and rethink the persistent misconceptions that the authors say have hamstrung an effective response to the suffering caused by Ebola."  

In most cases, the afflicted sought help from caregivers—professional caregivers if they were available and lay caregivers if they were not. It bears noting, the authors added, that the three most affected countries were also the world’s most medically impoverished. There were, in other words, few professional caregivers. And so, the disease was transmitted from patient to caregiver, spreading not just from patient to family members but to nurses and doctors, as well. The story of Ebola in West Africa, Farmer has said, is the story of a “caregiver’s disease in a clinical desert.”

In other cases, people sought help but had to wait days for an ambulance to come.  At that point, Richardson said, their choice was to stand back and watch their sick family members suffer or to try their best to care for them and keep them clean.

“They knew about Ebola, knew how it spread, and they knew their mothers, their brothers, their children were probably infected,” Richardson said. “They weren’t going to sit there and watch their loved ones suffer. It’s a basic human response.”

Discerning Solutions

Ebola doesn’t have to be just about making impossible choices between watching your loved ones suffer without helping or choosing to help and risking a horrible death yourself, Richardson said, adding that the 70 percent mortality rate seen at some points during the epidemic would be more like 5 percent if all patients had access to the kind of intensive resuscitative treatment available with modern health care.

It doesn’t even need to be all that modern. The authors point out that since 1832 intravenous fluids have been known to prevent death from hypovolemic shock, but Richardson said there are still some in the global health community who debate whether IV fluids should be considered part of the standard of care for Ebola, a disease that kills by sending some people into shock due to loss of blood and fluids.

“Not all people who die of Ebola die of hypovolemia,” Farmer said. “With this virus, sepsis kills people without volume loss, too. But the fact that some of those who die do so of shock is good news because there’s a straightforward, easy to implement way of providing effective care. The Ebola suspect’s dilemma arose because that almost never happened in West Africa, alas.”

Any solution that leaves out fundamental clinical aspects of treatment while ignoring the social context where it must function is unlikely to work, the authors said. Blaming patients—who choose to avoid dangerous medical facilities or who choose to take care of their sick loved ones—for the spread of the disease while focusing on attempts to contain Ebola through isolation without providing effective treatment in quarantine is like watching the shadows on the wall of Plato’s cave, the authors argued.

“It is an illusion to believe that any one discipline can deliver a simple solution to a problem as complex as Ebola,” Farmer said. “Understanding the daily lives of the people who have lived with the disease and its aftermath, as well as acknowledging the political, historical and economic forces that shaped those lives and the contours of the Ebola outbreak in West Africa, is every bit as important as understanding the pathophysiology of the disease or identifying new ways to deliver care.”

News

Zika’s Entry Points

Fast-spreading virus can take multiple routes into the growing brain

Around the world, hundreds of women infected with the Zika virus have given birth to children suffering from microcephaly or other brain defects, as the virus attacks key cells responsible for generating neurons and building the brain as the embryo develops.

Studies have suggested that Zika enters these cells, called neural progenitor cells or NPCs, by grabbing onto a specific protein called AXL on the cell surface. Now scientists at the Harvard Stem Cell Institute (HSCI) and Novartis have shown that this is not the only route of infection for NPCs.

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The scientists demonstrated that the Zika virus infected NPCs even when the cells did not produce the AXL surface receptor protein that is widely thought to be the main vehicle of entry for the virus.

“Our finding really recalibrates this field of research, because it tells us we still have to go and find out how Zika is getting into these cells,” said Kevin Eggan, principal faculty member at HSCI, professor of stem cell and regenerative biology at Harvard University’s Faculty of Arts and Sciences and Harvard Medical School, and co-corresponding author on a paper reporting the research in Cell Stem Cell.

“It’s very important for the research community to learn that targeting the AXL protein alone will not defend against Zika,” agreed Ajamete Kaykas, co-corresponding author and a senior investigator in neuroscience at the Novartis Institutes for Biomedical Research (NIBR).

Previous studies have shown that blocking expression of the AXL receptor protein does defend against the virus in a number of human cell types. Given that the protein is highly expressed on the surface of NPCs, many labs have been working on the hypothesis that AXL is the entry point for Zika in the developing brain.

“We were thinking that the knocked-out NPCs devoid of AXL wouldn’t get infected,” said Max Salick, a NIBR postdoctoral researcher and co-first author on the paper. “But we saw these cells getting infected just as much as normal cells.”

Working in a facility dedicated to infectious disease research, the scientists exposed two-dimensional cell cultures of AXL-knockout human NPCs to the Zika virus. They followed up by exposing three-dimensional mini-brain “organoids” containing such NPCs to the virus. In both cases, cells clearly displayed Zika infection. This finding was supported by an earlier study that knocked out AXL in the brains of mice.

“We knew that organoids are great models for microcephaly and other conditions that show up very early in development and have a very pronounced effect,” said Kaykas. “For the first few months, the organoids do a really good job in recapitulating normal brain development.”

Historically, human NPCs have been difficult to study in the lab because it would be impossible to obtain samples without damaging brain tissue. With the advancements in induced pluripotent stem cell (iPS cell) technology, a cell reprogramming process that allows researchers to coax any cell in the body back into a stem cell-like state, researchers can now generate these previously inaccessible human tissues in a petri dish.

The team was able to produce human iPS cells and then, using gene-editing technology, modify the cells to knock out AXL expression, said Michael Wells, a Harvard postdoctoral researcher in the Eggan Lab and co-first author. The scientists pushed the iPS cells to become NPCs, building the two-dimensional and three-dimensional models that were infected with Zika.

The Harvard and NIBR collaborators started working with the virus in mid-April 2016, only six months before they published their findings. This unusual speed of research reflects the urgency of Zika’s global challenge, as the virus has spread to more than 70 countries and territories.

“At the genesis of the project, my wife was pregnant,” Eggan remarked. “One can’t read the newspapers without being concerned.”

The collaboration grew out of interactions at the Broad Institute of Harvard and MIT’s Stanley Center for Psychiatric Research, where Eggan directs the stem cell program. His lab already had developed cell culture systems for studying NPCs in motor neuron and psychiatric diseases. The team at Novartis had created brain organoids for research on tuberous sclerosis complex and other genetic neural disorders.

“Zika seemed to be a big issue where we could have an impact, and we all shared that interest,” Eggan said. “It’s been great to have this public/private collaboration.”

The researchers are studying other receptor proteins that may be open to Zika infection in hopes that their basic research eventually will help in the quest to develop vaccines or other drugs that defend against the virus.

Adapted from a Harvard Stem Cell Institute news release.

News

Intensive Training

International leaders come together to learn how to deliver on the promise of global health

Delivering effective interventions to patients who need them remains one of the greatest hurdles facing medicine and public health, despite significant global health resources and many known solutions. The Global Health Delivery Project at Harvard (GHD) brings together and trains ministry leaders, care providers, educators, researchers, and students to bridge that gap.

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Participants in the project’s Global Health Delivery Summer Intensive (GHDI) program spend three weeks at Harvard in July, enrolling in three courses that take place at the Harvard Chan School of Public Health, where they learn how to understand epidemiology and manage programs to strengthen health systems and delivery structures.

These three courses are also part of a separate Master of Medical Sciences in Global Health Delivery (MMSc-GHD) degree-program offered through Harvard Medical School.

GHD is a joint initiative of Harvard Medical School, Harvard Business School, and Brigham and Women’s Hospital launched eight years ago by current World Bank President Jim Kim, Partners In Health co-founder and Kolokotrones University Professor Paul Farmer, and Michael Porter, the Bishop William Lawrence University Professor at the Harvard Business School. GHD welcomed 52 mid-career global health professionals from 27 countries to this summer’s intensive training session.

The goal of the program is to improve how care is delivered and health organizations are managed around the world.  

“We’ve recognized for years that transnational inequities in health are explained not by a lack of solutions to prevent and treat disease, but by the failure to deliver them to those in greatest need,” said Farmer, who is also and head of the HMS Department of Global Health and Social Medicine.

“Improving health care delivery requires training new leaders in the complex work of implementation. GHDI is doing just that, and will continue to do so for professionals around the world.”

"At the World Bank, we realize that one of the most pressing issues to solve is global health delivery,” Kim said. “It's a fundamental problem in development, and GHDI seeks to address the delivery issue from different angles. I'm moved and inspired by how the program has taken off. It was just a dream when it started, and it's incredible to have expanded to three courses and a cohort of more than 50 students.”

Since 2009 the program has trained more than 250 practitioners who make real world impact. This year’s cohort includes:

  • Maxi Raymonville, executive director of the University Hospital in Mirebalais, Haiti
  • Ntombifuthi Dennis, prevention manager for Swaziland’s National AIDS Council
  • Vera Mussah, program manager for performance-based financing for the Liberian Ministry of Health   

David Golan, HMS dean for basic science and graduate education, notes, “The students who enroll in GHDI are an impressive group of leaders. They come to Harvard to learn, but they also bring a wealth of experience and knowledge and invariably teach one another, building enduring collaborative relationships. Their passion and dedication to improving health throughout the world is palpable.”

Alumni include:

  • Nicholas Muraguri (2011), head of Kenya’s national AIDS commission at the time, later director of an international effort to eliminate HIV among children, and now the director of medical services for Kenya
  • Lorenzo Dorr (2012), senior program manager at Last Mile Health, a key leader in Liberia’s Ebola outbreak
  • Benjamin Grant (2014), another senior program manager at Last Mile Health, who oversaw Ebola preparedness trainings across one of the country’s 15 counties

Dorr and Grant acknowledge GHDI as a “great opportunity for senior level management training” that helped them with the outbreak response.

“We know so much that could help so many, but making sure the right people have that knowledge and can implement it is critical to improving care,” said Rebecca Weintraub, Faculty Director of the GHD and HMS assistant professor of global health and social medicine. Weintraub is also co-director of the GHDI along with Joseph Rhatigan, HMS associate professor of global health and social medicine.

This story is adapted from a GHD news release.

 

News

HMS Receives $20 Million from Ronda Stryker and William Johnston

Investment will support global health research and education

Philanthropists Ronda Stryker and her husband, William Johnston, have pledged $20 million to the Harvard Medical School Department of Global Health and Social Medicine over the next five years.

This generous gift will support senior and junior faculty, research fellows and students in their work to provide equitable health care around the world, HMS leaders said.

“I believe that, in my lifetime, we can create a movement and effect real change in billions of people’s lives around the world, particularly women and children who often bear the brunt of the lack of access to health care,” said Ronda Stryker, director of the Stryker Corporation and a member of the Harvard Medical School Board of Fellows and Advisory Council on Global Health and Service.

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“A significant investment in HMS to support current and future leaders in global health, under Paul Farmer’s leadership, will change things for the better. It comes down to kindness to humanity, and if Harvard Medical School can teach and train others to replicate the work Paul and his team do every day, the world will be better for it,”  she said.

HMS Dean Jeffrey S. Flier, said he is deeply grateful to Stryker and Johnston for their generosity and for their meaningful commitment to global health and to advancing the vision of Paul Farmer.

“This remarkable gift will enable our faculty within the Department of Global Health and Social Medicine to continue to improve the lives of people throughout the world while also supporting the next generation of global health leaders,” Flier said.

The gift, which is the largest in the department’s history, will

  • establish the Ronda Stryker and William Johnston Professorship in Global Health;
  • bolster the careers of junior faculty and fellows by supporting research in fields such as HIV and Ebola and by creating an annual forum in which researchers can receive mentorship and build community;
  • enable students from around the world to enroll in the HMS Master of Medical Sciences in Global Health Delivery program;
  • support the development and execution of projects in the HMS Global Health Research Core that inform patient care; and
  • enhance HMS research and advocacy efforts in global surgery.

“This gift gives us the ability to solidify our foundation of collaborative research, care delivery and education for global health equity, while also providing crucial flexibility to respond to the needs of the communities we serve, as defined by the people within them,” said Paul Farmer, chair of the HMS Department of Global Health and Social Medicine and Kolokotrones University Professor at Harvard.

Farmer said the gift will also allow the department to continue offering need-blind admission to students in the MMSc program in global health delivery.

One recent student provides a tangible example of the importance of the kind of flexibility the gift will allow, department leadership said. When Mohamed Bailor Barrie applied to the program, he intended to pursue a research project focused on tuberculosis. Between the time of his acceptance and the beginning of the program, Ebola erupted in his native Sierra Leone.

Barrie shifted the focus of his work to delivering clinical care to those affected and to furthering the understanding of Ebola, not just as an isolated biomedical phenomenon but in the context of history, economics and culture.

The HMS Research Core in Global Health was also able to direct its efforts toward West Africa when cases of Ebola were on the rise. Working with partners in Sierra Leone, the Research Core drew on established relationships with caregivers in rural Ebola treatment units to field test a new rapid Ebola diagnostic that could become a crucial tool in the battle against the virus. 

Farmer emphasizes the importance of looking at the many facets of global health not as competitors for scarce resources, but as crucial, interlocking parts of a whole that reinforce one another.

“Research and training don’t take away from care delivery, they make it better,” Farmer said. “The connective tissue that allows all of these different elements to work together is philanthropy, and this gift will be truly transformational.”

 

News

Doubling Down on Dengue

HMS researchers have discovered 2 ways a compound blocks dengue virus 

Harvard Medical School scientists have found a compound that in laboratory dishes blocks the dengue virus in two ways, raising hopes for a future drug whose dual activity could suppress the otherwise likely emergence of drug resistance.

The HMS team, led by Priscilla Yang, an HMS associate professor of microbiology and immunobiology, reported its findings April 21 in Cell Chemical Biology.

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Spread by mosquitoes, dengue belongs to the same family of viruses as Zika, whose emerging strain has just been linked by the U.S. Centers for Disease Control and Prevention to severe birth defects. Like Zika, dengue virus has no antiviral drugs to prevent illness or stop its spread.

Dengue virus infects more than 300 million people a year worldwide, causing no symptoms in some people but flu-like misery or dangerous hemorrhagic fevers in others.

“Dengue’s been an understudied virus.”—Priscilla Yang

The compound found by Yang’s team, GNF-2, keeps the dengue virus from infiltrating and overwhelming cells in the body. It does this by blocking its known kinase target inside the cell and by also inhibiting a viral target found on the surface of the virus. Yang considers the discovery of GNF-2 to be serendipitous.

“We had screened a library of known kinase inhibitors and had a ‘problem compound’ where we could not explain all the antiviral activity that we were seeing based on just the effect it had on the host kinase it normally targets,” Yang said.

That instance of serendipity was followed by years of experiments in collaboration with scientists across HMS, in particular, Stephen Harrison and Nathanael Gray, both professors in the Department of Biological Chemistry and Molecular Pharmacology. The dengue work was carried out through one of three Centers for Excellence in Translational Research at HMS, a National Institutes of Health effort designed to move discoveries about emerging infections closer to clinical applications in diagnosis, treatment and prevention.

“The compound was inhibiting the virus by targeting the host kinase, but then somehow it also was binding to the surface of the virion, and then preventing entry of the virus,” Yang said. “That’s not at all what we thought we would find when we did the original kinase inhibitor screen.”Protective membrane and membrane proteins of the dengue virus visualized with cryo-electron microscopy. Image: Hong Zhou, UCLA/NIH

GNF-2 had surfaced in a chemical screen Yang’s lab performed in 2007, one compound among many showing some activity against dengue virus. Viruses invade host cells and replicate there, so jamming one or both processes could mean relieving the symptoms of infection and preventing transmission of the virus.

Yang said they zeroed in on host factors as antiviral targets because it seemed likely that related viruses would rely on the same or similar host factors to replicate. If they found a compound that worked against one virus, they surmised, it might work against others in the same family. Cellular kinases seemed likely to be required by the virus because they regulate most cellular processes.

Yang also hoped that finding a way to help the host cell repel the virus would overcome the virus’ ability to thwart antiviral drugs. Viruses evolve so frequently that their elements are moving targets for antiviral drugs. Tamiflu, for example, has lost much of its efficacy in the years since it was aimed against influenza, Yang said. By comparison, combination therapies, such as those used against HIV, can be successful because they fight the virus on more than one front.

In the case of dengue and other understudied and emerging viruses, resources to develop the kinds of drug combinations that have proven effective against HIV and hepatitis C virus may not be available. In these cases, a single drug that acts by targeting multiple viral processes simultaneously may provide an alternate way to suppress resistance.

“Dengue’s been an understudied virus,” Yang said. “Everything changed when the NIH made it a priority pathogen because the number of severe infections where people get very sick has been increasing. Like Zika right now or Ebola a few years back, it’s hard to predict when that will happen and where that will happen and the scale of how many people will be affected.”

This work was supported by a Harvard Medical School Faculty Development Grant, an Armenise-Harvard Junior Faculty Grant and NIH Grants R01 CA130876, R01 AI076442, R01 AI095499, R56 AI095499, U19 AI109740, U54 AI057159 and a Catalyst grant from the Harvard Clinical and Translational Science Center (NIH UL1TR001102).

News

Growing Surgery Globally

Plan outlines coordinated effort to bring safe surgery to billions

More than 5 billion people worldwide lack access to essential surgical care, but an international group of surgeons, anesthesiologists, journalists, advocates and business and biotechnology leaders have outlined a plan to bring safe, affordable surgical care to the men, women and children who need it most.

“Building surgical systems that work for everyone is affordable and achievable,” said co- first author Josh Ng-Kamstra, a Paul Farmer Global Surgery Research Fellow at Harvard Medical School and a general surgery resident at the University of Toronto.  “It’s also essential if we are to meet the global goals of ending poverty, improving health, ensuring gender equality and creating economic growth.”

The paper, which appears in the inaugural issue of the BMJ Global Health, outlines a series of actions that universities, hospitals, surgeons, biotech companies and the media in wealthy countries can pursue to improve access to surgery worldwide.

The effort builds on a landmark 2015 report by the Lancet Commission on Global Surgery. The commission found that nearly a third of the global disease burden can be attributed to surgically treatable conditions. For billions of people in low- and middle-income countries, a lack of infrastructure, insufficient numbers of trained surgeons and anesthesiologists, and the prohibitive costs of receiving care prevent people from receiving the care they need. The commission estimated that 143 million additional surgical procedures are needed each year to save lives and prevent disability. But the case for action isn’t just humanitarian: Investing in surgery would save developing countries approximately $12.3 trillion in lost GDP by 2030.

As Jim Yong Kim, president of the World Bank Group, said in his address to the Lancet Commission in May 2015, “The stakes are high, because failing to fix this problem will have a substantial impact on people’s lives, well-being and even their economic health going forward.”

The current publication highlights a series of actionable recommendations that those in high-income countries can take to enhance the world’s capacity to deliver surgical and anesthesia care. Specifically, the paper calls for:

  • Colleges and academic medical centers to develop global partnerships for training and ongoing professional development and to support research efforts in quality, safety and outcomes measurement
  • High-income country surgery and anesthesia trainees to develop long-term clinical and research relationships with colleagues in low- and middle-income countries
  • Academic surgeons and journals to support research by surgeons in low- and middle-income countries and eliminate barriers to publishing and disseminating research in the communities where it was conducted
  • Global health funders to aggressively invest in strengthening health systems with a specific focus on surgery as a critical component of universal health care coverage
  • The biomedical devices industry to design and manufacture user-centered equipment appropriate for resource-limited environments and train health professionals and biomedical equipment technicians in low- and middle-income countries
  • Press and advocacy groups to develop public support by telling the stories of those affected by surgical disease, and to independently investigate the state of surgery around the world

HMS and its affiliate hospitals are currently engaged in a number of research efforts, capacity building and training programs that embrace these recommendations.

"The goal is universal access to safe, affordable surgical and anesthesia care when needed," said co-author John Meara, the Steven C. and Carmella R. Kletjian Professor of Global Health and Social Medicine in the field of Global Surgery and director of the Program in Global Surgery and Social Change at HMS, Plastic Surgeon-in-Chief at Boston Children's Hospital, and co-chair of the Lancet Commission on Global Surgery. "This reports demonstrates a common policy agenda between major actors and provides a road map for maximizing benefit to surgical patients worldwide."

While the authors highlight the role of individuals and institutions in wealthy nations in the current paper, they also emphasize the important role of health professionals and policymakers who live and work in low- and middle income countries, noting that unilateral action by high-income country groups without an ethos of partnership is unlikely to bring about sustainable change. Instead, the authors wrote, high-income country resources can be brought into the service of local interests, building sustainable health systems and providing a durable solution for the world’s poor.

“We’re thrilled to be launching this paper at such a crucial time for global surgery,” said Paul Farmer, Kolokotrones University Professor at HMS, co-founder of Partners In Health and a Lancet Commissioner. “We have an opportunity to turn surgery from the ‘neglected stepchild of global health’ to a centerpiece in national health systems, averting death and disability for millions.”

 

Five billion people worldwide do not have access to safe and affordable surgery and anesthesia when they need it, and millions of people are dying from common, easily treatable conditions like appendicitis, fractures, or obstructed labor. Video: TheLancetTV

This story is adapted from a multi-institution news release.

News

TB’s Ticking Time Bomb?

An unprecedented outbreak in Papua New Guinea

An outbreak of multidrug resistant tuberculosis (MDR-TB) in Papua New Guinea may well become a replay of the disastrously delayed response to the West African Ebola pandemic, says Jennifer Furin, Harvard Medical School lecturer on global health and social medicine, in a commentary she co-authored with Helen Cox, senior lecturer in the Division of Medical Microbiology at the University of Cape Town, South Africa. The commentary was published in Lancet Respiratory Medicine on March 23 to coincide with World TB Day, which is today, March 24.

Harvard Medicine News spoke to Furin to learn more about the situation in the island province of Daru, just north of Australia in the southwestern Pacific.

HMN: What’s happening on Daru?

JF: Currently, on Daru Island in Papua New Guinea, there is a significant and ongoing outbreak of MDR-TB. It is spreading throughout the country and could possibly move to Australia. 

HMN: How does it compare to other outbreaks globally?

JF: Conservative estimates show that 1 percent of the population of Daru is sick with MDR-TB. This translates to about 150 cases per year in a population of 15,000. As a point of comparison, an outbreak on nearby Chuuk Island, one that the CDC was able to get under control, had 26 cases in a population of 108,000.

In one community in South Africa, Khayelitsha, there are about 200 MDR-TB cases a year, with a population of about 400,000 and an HIV prevalence above 20 percent. 

Since Daru has almost no HIV—which greatly increases the risk of contracting MDR-TB—the number of cases there is even more staggering.

HMN: How did things get so bad?

JF: A number of factors. For example, some MDR-TB patients from Papua New Guinea who had been getting treatment in Australia were sent back home—many of them to Daru—in order to give them care closer to their families.

This was well-intended, but available care was limited on Daru. Once the infection started spreading on the island, it became difficult to stop.

Because the islanders are poor, people share accommodations—often crowding 20 people into a single room. In addition, there were few diagnostic and treatment services available on the island.

Although services have improved over the years, they have not improved fast enough to keep up with the current outbreak of the disease. 

Finally, international health and policy advisors to Papua New Guinea have not given the health program leaders advice that will help them to stop this outbreak.

HMN: You’ve called the outbreak a “time bomb.” Why do you use that term?

JF: Because one does not notice the full devastation of the event right away. 

With TB, people can become infected with the bacterium and not become sick until months or years later.

Someone with TB can cough in a room and expel the bacterium, where it will remain infectious for hours. Hundreds of people could breathe in those infectious organisms and not know for some time that they have been infected. 

Because infection is not readily apparent, TB is much more frightening than diseases we tend to hear a lot about, such as Ebola, where infection tends to lead rapidly to disease development. 

But when I describe the situation as being like a time bomb, I also mean that if we act to do something now, we might be able to defuse the situation.

HMN: What would it take to stem this disease in Papua New Guinea?

JF: There needs to be a massive influx of resources—human and financial—into the country. Although the government has put together an excellent plan to stop the outbreak, it does not have the funding or the staff to put the plan into action. And it is likely that the situation on Daru Island is also happening elsewhere in the country. 

Urgent action on a large scale is needed now to support the planning done by the government. These plans include active case finding, rapid diagnosis and treatment with optimal therapy and preventive measures for those who have been exposed to pathogens. 

HMN: TB is a treatable disease, but it still kills more than a million people every year. What does the reaction to this outbreak say about efforts to get to zero deaths?

JF: According to the new WHO “End TB Strategy,” we are supposed to eliminate TB by 2030, which is only 14 years away. But we don’t know how to actually eliminate TB; we have tried to control only the impact the disease has on the world’s populations.

This control strategy has been highly ineffective: TB is once again the infectious disease that causes the highest mortality among adults around the world, even though it is curable.  

But if we are serious about ending TB in just a decade and a half, we have to start actually eliminating it. Daru would be the ideal place to make this happen, since the number of cases is manageable and the geographic location where the cases are occurring is small.  

However, so far there has been no real attempt to try to eliminate the disease on Daru. Since the global health organizations cannot even commit to eliminating MDR-TB on Daru, it is hard to believe that we will be successful in getting to zero anytime soon.

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