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Dr. Nilu Goonetilleke & Team Jumpstart Immune System with Implications for HIV Cure & Vaccine Research
The Explorations in Global Health faculty research grants are designed to foster the development of research partnerships and projects in global health. Grants are made to UNC faculty for international travel or to bring international colleagues to campus to establish or maintain research relationships (with the aim of applying for external funding) or to undertake small-scale, discrete research projects with international collaborators.
This year, the IGHID is supporting six, diverse projects in Nicaragua, West Africa, Indonesia, Sri Lanka, Tanzania and Mexico.
Will you be next? The 2015-16 call for applications will be released in October or November.
Sylvia Becker-Dreps, MD, MPH, Assistant Professor, Department of Family Medicine, UNC School of Medicine, and Ralph Baric, PhD, Professor of Epidemiology, UNC Gillings School of Global Public Health
Gastroenteritis is one of the most common causes of child mortality worldwide. Following the global roll-out of rotavirus vaccines, norovirus is now the most commonly detected enteropathogen in children with gastroenteritis, both in the community and in health facilities in developing countries. In Nicaragua, norovirus was detected in over one in five cases of gastroenteritis. A better understanding of risk factors for norovirus diarrhea and norovirus transmission patterns is crucial to develop effective control strategies. In particular, candidate norovirus vaccines are now entering clinical trials, and our work may inform targeted immunization approaches to avoid spread of norovirus within households.
Ebola in West Africa
“Longitudinal study of Ebola survivor cohort to characterize the clinical sequelae of infection as well as create a biorepository of blood, semen, and vaginal secretions to determine the compartmental dynamics of virus replication and shedding”
William Fischer, MD, Assistant Professor of Medicine, Division of Pulmonary and Critical Care Medicine, UNC School of Medicine, and David Wohl, MD, Associate Professor of Medicine, Division of Infectious Diseases, UNC School of Medicine
The Ebola epidemic currently devastating West Africa has evolved into an unprecedented humanitarian crisis. As of January 14, 2015, 21,296 infections and 8,429 deaths have been reported by the World Health Organization (WHO) – a likely underestimate but already eclipsing the numbers of infections and deaths in all previous Ebola outbreaks combined. While the rate of confirmed cases of Ebola is declining in Liberia and Sierra Leone, it is certain that regardless of the short-term trends in the epidemiology of this outbreak, the social, economic and healthcare dynamics in West Africa will long be altered. The proposed studies will better characterize the viral dynamics in urogenital compartments in a large survivor cohort in order to inform public health policies. In addition to addressing many unknown questions about EVD, the proposed investigations will provide opportunities for Dr. Fischer to develop skills in clinical research design and implementation in outbreak settings that will complement his expertise in emerging viral pathogens.
Malaria in Indonesia
“Malaria Relapses in Indonesia – Detecting genetic signatures of Plasmodium vivax relapse in Indonesian soldiers”
Jessica Lin, MD, Assistant Professor of Medicine, Division of Infectious Diseases, UNC School of Medicine
Plasmodium vivax, the most widespread human malaria parasite, causes over 100 million malaria episodes each year. Those infected can suffer periodic relapses, yet few persons receive adequate antirelapse therapy with primaquine because of the long courses needed and the drug’s side effects. Hence, P. vivax relapses drive ongoing transmission and represent an important obstacle to malaria elimination.
In Southeast Asia, up to two-thirds of P. vivax infections lead to relapse. Relapse potential seems to be intrinsically determined by parasite genetics: historically, those inoculated with different vivax strains exhibited different patterns of relapse. Unfortunately, studies of vivax relapse in endemic settings have been hindered by an inability to distinguish relapses (arising from activation of hypnozoites) from re-infections (due to new mosquito bites). One way to overcome this is to study relapses in persons returning to malaria-free areas where re-infection is impossible. This project aims to achieve a better understanding of the genetic determinants of P. vivax relapse by detecting genetic signatures of relapse among a unique cohort of returning Indonesian soldiers using next generation sequencing methods.
Nathanial Moorman, PhD, Assistant Professor, UNC Department of Microbiology and Immunology
Dengue virus (DENV), transmitted by mosquitos, is the causative agent of dengue fever (DF) and dengue hemorrhagic fever (DHF). Once a public health problem in only a handful of countries in Southeast Asia, today DENV is endemic in over 100 countries worldwide, with over 400 million annual DENV infections resulting in more than 500,000 cases of severe DHF and 20,000 deaths. Dengue pathogenesis is strongly influenced by both host and viral factors. Amongst host factors, the role of pre-existing immunity is a topic of intense study. While it is well established that some dengue virus strains are more pathogenic than others, the viral genetic determinants of severe dengue remain to be defined. In 2009, a new strain of DENV1 emerged that caused more severe disease. This new DENV1 strain is responsible for the majority of current clinical dengue in Sri Lanka.
The project directly advances global public health by beginning to define the DENV genetic determinants underlying viral disease. This project also advances global public health by facilitating a nascent collaboration between Dr. Aruna Dharshan, Director of Genetech Research Institute (GRI) in Sri Lanka and UNC. Future collaborations will analyze samples from patients infected with the same DENV1 genotype that develop mild (DF) versus severe (DHF) disease, in order to determine how DENV1 genetic variation influences clinical outcome.
Christina Shay, PhD, Research Assistant Professor, Department of Nutrition, UNC Gillings School of Global Public Health
The incidence of type 1 diabetes (T1D) is growing around the world and these trends are also evident in Sub-Saharan Africa. Few population-based estimates exist for the prevalence, incidence, or clinical characteristics of T1D in Sub-Saharan Africa and the majority of available reports were published several decades ago. This lack of knowledge has contributed to limited resources for T1D detection and treatment in this region and has led to significantly higher rates of diabetes-related complications and premature mortality in individuals with T1D in Sub-Saharan Africa compared to Western regions. At this critical moment in history, trends in T1D are dynamic yet poorly understood from a global perspective. Understanding the epidemiology and natural history of T1D in Sub-Saharan Africa is essential to improve patient care in this region where T1D is rapidly emerging as an urgent health care need.
Lindsey P. Smith, PhD, Research Assistant Professor, Department of Nutrition, Gillings School of Global Public Health
Currently, the prevalence of obesity in Mexico is over 33 percent for children 1-18 years old and about 70 percent for adults; and in 2006, the prevalence of Type 2 diabetes (T2D) in adults was 14.4 percent. Concurrent with the rise in obesity and diabetes were large increases in a sugar-sweetened beverage (SSB) and nonessential food (often termed ‘junk food’) intake. In an effort to prevent continued increases in obesity and diabetes, in January 2014, the Mexican government implemented a 1 peso per liter excise tax on nonalcoholic beverages with added sugar, and an 8 percent ad valorem tax on nonessential foods with energy density ≥ 275kcal/100g, meant to target foods high in added sugars or solid fats (e.g. chips, snacks, candy, etc.). Together, these taxes cover about 20-25 percent of daily caloric intake in Mexico across age groups. Our team’s preliminary analysis of the SSB tax shows it reduced SSB purchases by 5 percent three months after the tax went into effect. Recently, a short-lived Danish saturated fat tax appeared to change food purchasing behavior. However, it is unclear how these taxes will impact purchases over the long-term, how they will impact the nutritional quality of what people buy, and whether these changes will be greater among low socio-economic subpopulations (SES). The overarching goal of this project is to examine how Mexico’s SSB and “junk food” taxes affect the nutritional profile of food and beverage purchases of the Mexican population.
Bandages, anesthesia and syringes. These are common medical supplies hospitals in the United States always stock. But in Malawi, drug shortages occur frequently, says Innocent Mofolo, MSc, Associate Country Director of UNC Project Malawi. That’s why he decided to look for ways to combat this problem.
Mofolo and physician Jeff Wilkinson applied for and received a donation of supplies worth $1 million from Direct Relief International, a non-profit that “supports existing health providers over the long term, delivering aid without regard to race, ethnicity, political or religious affiliations, or ability to pay.”
“We have seen people suffering in the hospital because there is no medicine,” says Mofolo. “This donation will help those in need get medications for free.”
The 20 pallets of medications and supplies included antibiotics, catheters and post childbirth maternity pads. The donation will serve the patients of Kamuzu Central Hospital, Bwaila Hospital, Kasunga District Hospital and Child Legacy International. Mofolo enjoys knowing his fellow countrymen and women will now have access to these medications and supplies when they visit any of hospitals.
“I’m happy to help my fellow Malawians,” he says.
A team of researchers has discovered HIV can begin replicating in the brain as early as four months after initial infection. The study followed 72 treatment naïve participants during the first two years of HIV infection. Through analysis of cerebral spinal fluid (CSF) and blood samples, 20 percent of subjects showed replication in the central nervous system (CNS) at four months. Additionally, 30 percent of participants showed evidence of a marked CSF inflammatory response in at least one time point and 16 percent of study volunteers showed a marked CSF inflammatory response at multiple time points, suggesting an ongoing infection in the CNS. The findings will be published in the scientific journal PLoS Pathogens.
“This shows that viral replication and inflammation can occur early in infection with the concern being that the damage caused could be irreversible,” says study virologist Ronald Swanstrom, PhD, Director of the University of North Carolina’s Center for AIDS Research (CFAR) and Professor of Biochemistry and Biophysics at UNC’s School of Medicine. “HIV and inflammation have the potential to accelerate the aging process and cause neurocognitive impairment, in the extreme case resulting in HIV-associated dementia.”
One-third of people not taking antiretroviral therapy (ART) to control their HIV will eventually develop HIV-associated dementia, Swanstrom says. For him, the study’s results in these newly infected people stress the importance of routine HIV testing to catch the infection as early as possible to allow the prompt initiation antiretroviral therapy.
“This is yet another reason we want people on ART right away to limit the possibility of replication and inflammation in the brain,” Swanstrom says.
Future studies could focus on whether or not damage to the brain caused by this early replication and inflammation is reversible. Swanstrom collaborated on the study with senior author and neurologist Serena Spudich, MD, Division Chief of Neurological Infections & Global Neurology and Associate Professor of Neurology at Yale School of Medicine, and neurologist Richard Price, MD, Professor of Neurology at the University of California San Francisco School of Medicine. The first author on the study was a UNC graduate student in the Department of Microbiology and Immunology, Christa Sturdevant, who is now a postdoctoral fellow at Duke University. The study was funded by the National Institute of Mental Health.
UNC pharmacy student Michael Chargualaf learned firsthand why Malawi is known as the “Warm Heart of Africa.” In June 2014, he traveled there along with fellow pharmacy student Jordan McNair, and instructors Amanda Corbett, PharmD, and Daniel Forrister, PharmD. The trip exposed Chargualaf to pharmacy practices in a developing country.
“The overall experience in Malawi was extremely humbling and enlightening,” Chargualaf says. “The Malawian people that we met along the way were very kind-hearted and welcoming.”
This inaugural trip was a pilot to prepare for an ambitious program being launched by the UNC Eshelman School of Pharmacy, called the Global Pharmacy Scholars (GPS) Program, in an effort to expand global experiential training for pharmacy students. The School of Pharmacy’s Global Engagement Fellow David Steeb, Pharm D, spearheaded development of the program. Corbett says six students will travel to Malawi this summer, two each month from June to August.
“The goal is to give UNC pharmacy students a global, experiential education,” Corbett says. “We also identified four sites in Malawi where we could offer our assistance long-term and we will continue our work with these partners.”
Relationships established with UNC Project Malawi leaders over many years include Mike Cohen, MD; Irving Hoffman, PA, MPH; Mina Hosseinipour, MD, MPH; and Francis Martinson, MD, PhD, as well as relationships developed this past year including Innocent Mofolo, MSc; Dorothy Sichali, Wilberforce Mhango, and many, many others. In addition, UNC works with many partners in Lilongwe, Malawi, including Kamuzu Central Hospital, Lighthouse Trust, Bwaila Hospital and the District Health Center. Many individuals from these programs were instrumental in making the pilot project a success, including Tadala Hamisi, Sam Phiri, MSc, PhD; Colin Speight, MBChB; and Rose Chikumbe.
During last summer’s pilot of the program, the team visited the District Health Center’s medication dispensary in Lilongwe. Corbett says the office faces challenges including a broken printer and no cooling system to control the temperature of medications.
“The people working at the district office were incredibly warm and helpful,” Corbett says. “They wanted to do the right thing, but they lack the resources.”
The pharmacy team also had the opportunity to visit the University of Malawi College of Medicine Pharmacy Department in Blantyre and establish connections with Department Chair Nettie Dzabala and Professor Lutz Heide among other faculty members. The team learned a lot about each of the respective pharmacy programs and agreed to continue collaborations in the future.
“I had an amazing experience in Malawi. I learned so many new things about the country, the people, and their health care system. It reaffirmed my career interests in public health, but really elucidated the opportunities in infectious disease as well,” says McNair. “A powerful and sustainable pharmacy influence is greatly needed in Malawi. Medication experts who can provide guidance on research and drug regimens and who can be accessible to the thousands of people who get lost in the system would be of great public health benefit as well as financial benefit to the country.”
Also while in Malawi last year, the UNC pharmacists and pharmacy students gave two lectures on conditions commonly treated in Malawi – HIV and cancer. Corbett presented on antiretroviral therapy, discussing side effects and proper dosing. Chargualaf focused on cancer treatment. He and Corbett also joined physicians on rounds at the Kamuzu Central Hospital (KCH). Unlike hospitals in the United States where a variety of medications for each condition are readily available, Corbett says KCH clinicians need to check each day what drugs are available in the hospital pharmacy before ordering medications for their patients.
Still, Chargualaf was able to roll up his sleeves and help. He mixed chemotherapy drugs with KCH pharmacists.
“I strongly believe that it is important to all future pharmacists to be culturally competent and have the ability to connect and assist people from diverse backgrounds, even if they chose not to become involved with global health in their ultimate career,” Chargualaf says. “I believe pharmacists can impact and influence patient lives in more ways than medication safety and management. To do this, we all need to be culturally competent.”
Alex Duncan, MD, PhD, knew he wanted to pursue a career as a physician scientist, but infectious diseases wasn’t always on his radar. A clinical rotation under the guidance of an infectious diseases attending physician during his third year of medical school changed all of that.
“I went down the infectious diseases rabbit hole,” Duncan says with a laugh. “Infectious diseases captured a way for me to do research and stay in medicine at the same time.”
Duncan wears many hats at UNC: He sees patients at UNC’s Infectious Diseases Clinic at NC Memorial Hospital; He conducts research in his lab with a focus on innate immune signaling or how the body recognizes and responds to pathogens; He is an Associate Professor of Medicine and Pharmacology at UNC’s School of Medicine; and Duncan recently accepted the role as Director of UNC’s Infectious Diseases Fellowship program.
As a clinician, he says he applies the same conceptual process he uses to conduct research in his lab to treating a patient in the clinic. For example, if Duncan sees a patient suffering from a fever of unknown origin, a common reason that he and other infectious diseases physicians are consulted, he gathers preliminary information by examining the patient’s medical records as well as taking detailed note of their travel and exposure history. This information guides formulation of his hypothesis on the origin of the patient’s illness. He then orders tests and based on these results, he either verifies the diagnosis or revises his hypothesis.
“You can take a scientific experimental approach to each patient,” Duncan says. “In this way, practicing infectious diseases is intellectually compatible with performing translational research.”
Research has always been his passion. Duncan is especially interested in the body’s inflammatory response to pathogens like bacteria.
“In my heart of hearts, I am a hardcore bench translational researcher,” Duncan says. “I love going into my lab and seeing new data. That new answer to a question no one has seen before. That discovery that drives patient care down the line. UNC provides a great environment for our trainees to develop careers as physician scientists.”
And it’s the career development component that Duncan really wants the ID Fellowship experience at UNC to stress. The three-year program provides fellows with a mix of clinical and research training. But Duncan says under his direction, he wants the program to also provide mentoring, networking and cultivation of other necessary skills for this career path, such as grant writing.
“I recognized early on in my career as an MD-PhD that to be successful in research took a lot more than me just knowing how to do research or being a decent clinician,” Duncan says. “I really relied on the help of a lot of people, networking and developing skills outside of things that we normally think of physicians receiving traditional training in. Career development is very important. We can help with all of these. We limit the number of fellows we take. We give them a lot of personal attention. That’s been the hallmark of our program.”
At least once a week, Christopher Hurt, MD, Clinical Assistant Professor at the University of North Carolina’s School of Medicine, receives an email from a physician or other health care professional seeking advice about treating a patient living with HIV infection. “Clearly, there are providers out there who are caring for people living with HIV infection and are looking for more education,” says Hurt.
In response, UNC’s School of Medicine, Eshelman School of Pharmacy, and Center for AIDS Research (CFAR), along with the Greensboro Area Health Education Center (AHEC) and the NC AIDS Training and Education Center (NCATEC) have organized an annual training each May. It is the largest statewide HIV conference offered in North Carolina. The two-day training will feature tracks dedicated to arming clinicians, allied health professionals, dentists and pharmacists with the latest HIV, hepatitis C virus (HCV) and other sexual transmitted infection news.
“Even if you only have one patient with HIV or HCV, you should attend,” adds Hurt. “PrEP (pre-exposure prophylaxis) is one of the recent developments in HIV care that I get a lot of calls about – there’s just been a lot of new treatment information for HIV and HCV in just the last couple of years. We have experts in the field who will get you up to speed so that you can provide your patients with better care.”
In its 20th year, the conference is called Clinical Care in 2015: HIV, Hepatitis C and Vulnerable Populations. It will be held Monday and Tuesday, May 4 and 5.
“The conference includes a track for non-prescribers who are still very important team members in taking care of these patients,” says Heidi Swygard, MD, MPH, who has been organizing the event for the past six years. “The vulnerable populations track for non-prescribers is intended to highlight a specific population and heighten cultural competency.”
For the second year in a row, day two of the conference will feature presentations specifically tailored to dentists and pharmacists. The conference planning committee creates the agenda with participant feedback in mind, says David Wohl, MD, Associate Professor of Medicine at UNC and Director of the NC AIDS Training and Education Center, a conference sponsor.
“We listen to the evaluations we solicit at the end of each year’s conference,” Wohl says. “We are guided by participant input. We want this conference to be worth people’s time and to get even better every year.”
More than 28,000 people in North Carolina were living with HIV at the beginning of 2014, according to the NC Department of Health and Human Services. Hurt opens the conference with a presentation called HIV in America, which he says will give participants an overview of the epidemiology of HIV with an eye toward new information.
“Young, African American men who have sex with men continue to have the highest incidence of new infection and that’s not because they are engaging in any riskier behavior,” Hurt says. “So a portion of my talk will discuss why this is happening.”
One of the phone calls Hurt received recently was from a physician who had started a patient on pre-exposure prophylaxis or PrEP to prevent HIV. Although the Food and Drug Administration (FDA) approved PrEP in 2012, it has not been widely prescribed.
“I’ve noticed in the past six months a growing interest for PrEP in the community and that is driving physician interest,” says Hurt.
The conference will feature a PrEP panel. Local people taking PrEP daily to prevent HIV infection will share their experiences. Adam Ward, a graduate student at NC State University is one of the panelists. He started taking PrEP daily this fall after learning his partner had been unfaithful.
“It gives me peace of mind and reduces my risk of getting HIV,” Ward says.
HCV is another popular topic that will be discussed as it relates to treating patients who are mono-infected or co-infected with HCV and HIV.
“We are light years ahead of where we were five to 10 years ago, when people took twice-daily pills along with a weekly shot for 48 weeks. They experienced horrible side effects,” Hurt says. “Now we have oral treatment for a maximum of 24 weeks that is much better tolerated. This is a rapidly evolving field and there is a big wave of patients coming to us seeking treatment.”
The second day will focus on the latest HIV news as it relates to pharmacists and dentists. Amanda Corbett, PharmD, Clinical Associate Professor at UNC’s Eshelman School of Pharmacy, is one of the day’s presenters.
“It is always rewarding to meet with colleagues and share ideas and experiences in caring for HIV patients,” Corbett says. “The complexities of medication management with antiretrovirals are ever changing and critical for pharmacists to play a significant role. Last year was the inaugural pharmacy focused session on day two of the conference. It was a great success for which we hope to build upon for 2015!”
To register for the conference, visit http://www.aheconnect.com/ncahec/findevents.aspx?a=5