Global health research is a collaborative process, and each researcher at the Institute for Global Health & Infectious Diseases contributes a piece to solving the puzzle of disease and morbidity. With a new academic year underway, read what some of our investigators are working on to improve the health of global populations. Their multi-disciplinary findings will be used to tackle key global health problems. Happy new (academic) year!
“During the upcoming year our group, which includes researchers in the Schools of Medicine, Pharmacy, and Public Health, plans to continue our work with the Multicenter AIDS Cohort Study (MACS)/Women’s Interagency HIV Study (WIHS) Combined Cohort Study (MWCCS). Our research will include evaluations of disparities in care, the effects of HIV on comorbid conditions, such as cardiovascular and neurologic disease, and novel epidemiologic methods. In a separate study this year we plan to begin evaluating a new long-acting investigational drug for preventing HIV infection among women.”
“Our research is entirely patient-centered: integrating novel sequencing methodologies in our investigation of gut microbial-host interactions that impact infectious and immunologic complications in patients with cancer. We perform deep metagenomic sequencing using short-read and long-read sequencing modalities to approximate microbial dynamics such as antimicrobial horizontal gene transfer events in the gut under antibiotic and chemo/immunotherapy pressure. Our research efforts are threefold:
To investigate how the dynamics of antimicrobial resistance within the gut impact infectious risk in patients undergoing hematopoietic stem cell transplantation (HCT).
- To understand host immune-microbial interactions that underlie immunotherapy efficacy and toxicity in patients with hematologic malignancies.
- To develop the Lineberger Cancer Center biorepository to integrate microbiome research across the various disciplines within the Cancer Center.
Within the next year, we will start enrolling patients in a new study funded by the CGIBD at UNC, investigating gut microbial species associated with multiple myeloma progression and treatment response.”
“The establishment of long-lived reservoirs of latent HIV that persist despite effective antiretroviral therapy (ART) remains a formidable barrier to an HIV cure. Most of what we know about HIV persistence is from studies performed using cells obtained mostly from men and from work done on cells isolated from blood. However, most of the HIV reservoir is sequestered in tissues. Furthermore, given that HIV latency is controlled by many factors, combinations of drugs targeting multiple pathways may be necessary to robustly disrupt latency, while clearance of cells containing reactivated virus will likely require an enhanced immune function.
“In the coming fiscal year, one of the primary focuses of our laboratory will be to use state-of-the-art methods such as single cell and spatial transcriptomics to better define the sources of persistent and latent HIV infection in gut tissues of both men and women, assess whether sex differences contribute to HIV persistence in tissues, determine whether combination latency reversal agents can target this reservoir better than single drugs, and test whether novel approaches to enhance the immune effector function capacity of natural killer (NK) cells and CD8 T lymphocytes can eliminate cells containing virus emerging from latency.”
“Our group has just received an R01 to study congenital Chagas disease with collaborators in Bolivia, Peru, and Johns Hopkins. We will be starting a cohort of 2000 Chagas-infected women and their newborns in Santa Cruz, Bolivia to study epidemiological, immunological, and parasitological factors that affect risk of congenital infection and to develop a new point of care diagnostic test to identify infect infants at birth. We will also be continuing work in Bolivia and Peru studying neurological infections in people living with HIV and developing new diagnostic tests, especially focusing on Chagas disease, toxoplasmosis, and tuberculosis. Based in North Carolina, we are continuing as part of a multi-site study of household transmission of flu and COVID-19.”
Evelyn Cook is associate director of the Statewide Program for Infection Control & Epidemiology (SPICE), which promotes prevention and control of health care associated infections in North Carolina and beyond by providing evidence-based education and consultation across the healthcare spectrum. Following are two grants she is working on this fiscal year.
1) ELC Enhanced Detection Expansion (August 1, 2022- July 31, 2023) The purpose of this contract is to expand North Carolina’s existing HAI and communicable disease prevention capacity by addressing gaps in practices within infection prevention programs, and training, specifically in congregate care facilities. In partnership with the NC Department of Health and Human Services (NCDHHS) SPICE shall conduct 440 infection control and response assessments (ICAR) in long term care settings and provide six (6) infection prevention educational webinars to healthcare personnel across the healthcare spectrum, including public health, long-term, acute, and outpatient care (including dialysis).
2) Strengthening Healthcare Associated Infection and Antimicrobial Resistance Capacity (HAI/AR) (October 1, 2022-July 31, 2023) The purpose of this contract is to expand and improve North Carolina’s infection prevention, preparedness, and response capacity by implementing prevention strategies for novel and targeted multi-drug resistant organisms (MDROs). SPICE shall provide workforce development through educational activities and program strengthening, to conduct infection control and response assessments (ICAR) in healthcare facilities including local health departments (LHDs), dialysis, post-acute and high-acuity post-acute care, facilities. Focus will include activities in four (4) project areas: HAI/AR Program Network for Prevention and Response; Antibiotic Stewardship; Enhancing Use of NHSN and CDC’s Project Firstline.
“My research focuses on vector-borne diseases – that is infections transmitted by insects like mosquitoes and ticks – both domestically and internationally. I work with partners from the Mbarara University of Science and Technology (MUST) at a number of clinical sites in rural western Uganda, where malaria is major driver of pediatric morbidity and mortality. Currently, we have an ongoing, NIH-funded study exploring ways to more efficiently identify mosquito breeding sites so that they can be targeted for control. We are also conducting a randomized controlled trial of insecticide-treated baby wraps that women use to carry infants and young children on their backs. The goal is provide an additional layer of protection, especially when children are outside the house.
“In North Carolina, I work with a talented, multi-disciplinary team of researchers from local universities and public health agencies to address endemic tick-borne diseases like Rocky Mountain Spotted Fever and Ehrlichiosis. We are currently pursuing a number of projects intended to improve our understanding of the epidemiology of these diseases, especially as we are seeing the emergence of pathogens that have not been as common in the state, including Lyme disease and tick-borne viral diseases. We are also launching a new project in western North Carolina in partnership with Western Carolina University and Mission Hospital to better understand the burden of LaCrosse Virus, which is the leading cause of pediatric encephalitis.”
“I have a new project funded by the NIH to evaluate HIV transmission networks in North and South Carolina, and to develop and implement a partner services intervention to use a social network strategy to increase testing and linkage to HIV care or prevention. This project involves the Ending the HIV Epidemic team in Mecklenburg County as well as public health and academic partners in North and South Carolina. I also lead the HIV PROMPT (Phylodynamics for Response, Monitoring, and Prevention of HIV Transmission) study which involves collaborators in public health, epidemiology, bioethics, phylodynamic modeling, bioinformatics, and next-generation sequencing. My team is also partnering with UCSD to investigate the social and sexual networks of racial and gender minority groups living in the Raleigh-Durham region to determine how network data can improve linkage to HIV care and prevention services.”
Our research group has a long-standing interest in the innate and adaptive immune responses that influence the natural history and host protection from N. gonorrhoeae infection. N. gonorrhoeae is long known to evade immunologic clearance by its human host, our group has ongoing studies to understand the mechanisms that support this immune evasion by N. gonorrhoeae. Our studies of N. gonorrhoeae pathogenesis and immunity have been bolstered by the use of a unique human challenge model for N. gonorrhoeae infection through a longstanding collaboration with Dr. Marcia Hobbs. Recent studies have demonstrated that vaccines against Group B Neisseria meningitidis generate cross-species immunologic responses to the related pathogen N. gonorrhoeae that appear to protect against N. gonorrhoeae infection in both animal models of infection and in observational studies of humans. We currently are focused on understanding the immunologic mechanisms of protection generated by these Group B N. meningitidis vaccines against N. gonorrhoeaewith preclinical studies supported by a funded project within a multi-institution Gonococcal Vaccine Cooperative Research Center (NIH/NIAID U19AI144180). We also co-lead an NIH-funded clinical trial (NIH/NIAID U01AI162457) to test whether an already FDA-approved vaccine against Group B N. meningitidis provides protection from N. gonorrhoeae infection in the unique experimental human gonococcal challenge model. These projects will begin to define the immunologic correlates of protection against N. gonorrhoeae positioning, a key knowledge gap to the development of effective N. gonorrhoeae vaccines.
“Our research team works in Sub-Saharan Africa and the U.S. to improve diagnosis and care for patients with lymphoma, particularly lymphoma arising in the setting of HIV infection. During the upcoming year, we will continue to enroll newly diagnosed lymphoma patients in Malawi and South Africa into an observational cohort study, and work to characterize the tumor-microenvironment in the most common aggressive B-cell lymphoma worldwide. We have identified differences in the tumor microenvironment that associate with HIV and antiretroviral status. As lymphomas in HIV-infected patients arise in a different immunologic context than lymphoma in the immunocompentent population, these microenvrionmental differences may be of critical importance to therapeutic selection and outcome. We also plan to expand our efforts to other common lymphoma subtypes, including Classic Hodgkin Lymphoma.”
“I am the PI of studies that address mental health needs in low- and middle-income countries. VITAL is an NIDA-funded R34 in Hanoi, Vietnam. In this pilot randomized trial, we are testing whether a problem-solving psychotherapy called Friendship Bench, which we have adapted to meet the needs of an HIV positive, methadone-maintenance clinic population with common mental disorders in Vietnam, which can be delivered with fidelity by both professional counsellors and peer counselors. We are currently nearing the end of the recruitment phase. Guided by these findings, we plan to write and submit an R-01 grant application using this adapted form of Friendship Bench in a fully powered randomized controlled trial to test whether it can improve HIV, methadone maintenance treatment, and mental health outcomes compared to usual care. This one is not run through IGHID, but it’s a part of our collection of funded projects addressing mental health needs in low- and middle-income countries.
My primary collaborator, Dr. Brian Pence, and I are developing a critical mass of both research and training in low- and middle-income countries to build the Department of Psychiatry’s Division of Global Health, which is a joint collaboration with the Department of Epidemiology in the School of Public Health. This one is called HEADS-UP. It’s also an R34, and we are adapting and testing another version of Friendship Bench in a group of adolescent Malawians with HIV and depression.
“I am also PI for WARMHEART (Malawian Program for Mental Health Research Training), along with Kazione Kulisewa, MBBS, MMed, the Head of Department of Mental Health at Kamuzu University of Health Sciences. This is an NIH-Fogarty-funded training program in Malawi. Here, we are training Malawian post-doctoral fellows and psychiatrists to become the next generation of Malawian mental health services researchers. We have selected four psychiatrists and three PhDs for the program so far. Last summer, we had a virtual workshop to identify critical mental health research needs in Malawi. This summer, we will have a three-month training on how to write grant applications for these trainees and will hold an annual Malawi Mental Health Research conference in September 2022.”
“Following is a summary of some of my projects. Bloodsafe Malawi: Malawi struggles to meet the blood supply required to meet the demands of the country plagued by malaria induced anemia, post-partum hemorrhage, trauma, and other conditions. The primary goal of this project is to evaluate strategies to increase blood donation in Malawi. Secondary students in Malawi are the group with the highest rates of donation and account for the vast majority of the blood supply in the country. But after completion of school, they often stop donating. We will conduct a cluster randomized clinical trial evaluating the use of school based and post-school donor clubs (entitled “Club 25”) as a model to increase regular blood donation.
HPTN 084: New infections due to HIV have been decreasing over time but young women in Africa remain extremely vulnerable to acquire HIV. The HPTN 084 study is a randomized trial comparing daily oral TDF/FTC to 2 monthly injection of Cabotegravir. The study has found that Injectable Cabotegravir is superior to TDF/FTC, largely due to the adherence advantage of the injections. Cabotegravir has now been FDA approved for use as prevention. The study is now unblinded and all participants are transitioning to their preferred prevention product through the Open Label Extension (OLE). Through the OLE, we will evaluate the continued effectiveness of CAB LA, participant choice, safety of Cabotegravir in pregnancy and breastfeeding, and strategies for HIV testing while using Cabotegravir. The composite of this work will assist the transition to access for these participants, inform prevention guidelines and programs, and ensure the groundbreaking research findings are translated in practice.
UNC Global CTU: The Global CTU is led by me, Dr. Joe Eron and Dr. David Wohl. The CTU supervises Clinical research sites in North Carolina (Chapel Hill and Greensboro), Malawi, and Vietnam. These Clinical research sites conduct clinical trials for the four major NIH DAIDS networks (HVTN, HPTN, IMPAACT, ACTG) for HIV treatment and Prevention. At the Malawi site, we conduct research protocols for all four networks. At any given time, approximately 10-12 protocols, may be actively enrolling and following participants.”
“I am PI of the NC HIV Training & Education Center (NCHTEC). In the coming year, NCHTEC will continue supporting the capacity-building and training needs of HIV professionals in the state. With NCHTEC Manager Cassandra Durham and Coordinator Ben Clack, we are part of the Southeast regional network of AIDS Education and Training Centers funded through the Ryan White HIV/AIDS Program (HRSA U1OHA30535). Since the current grant cycle began in 2019, I have directed the expansion of the Center’s training opportunities to better engage medical case managers, social workers, and other non-prescribers. These committed professionals are essential to HIV service delivery but are often overlooked for training opportunities. NCHTEC has also coordinated a series of trainings on how structural and institutional racism impact HIV service delivery. In recognition of its recent successes, the NCHTEC team was awarded supplemental discretionary funding for the 2022-23 fiscal year. These funds will be used to help HIV professionals learn more about the federal Ending the HIV Epidemic (EHE) initiative and how it impacts their work – now and in the future. The team also plans on offering additional, more clinician-focused trainings and expanding its support of local health department implementation of PrEP services, statewide.”
Anne Lachiewicz, MD, MPH, is director of the UNC ID Inpatient Studies Team which is currently participating in the following studies.
NECTAR “Novel Experimental COVID Therapies Affecting Host Response (clinical trial) Master Protocol for Clinical Trials targeting macro-, micro-immuno-thrombosis, vascular hyperinflammation, and hypercoagulability and renin-angiotensin-aldosterone system (RAAS) in hospitalized patients with COVID-19” (ACTIV-4 Host Tissue). Site PI: Subha Sellers
DISRUPT (clinical trial) “Direct lysis of Staphylococcus aureus resistant pathogen trial of exebacase.” Site PI: Anne Lachiewicz
PROVE (retrospective chart review) “Drug Use-Associated Infective Endocarditis: Patient Perspectives and Treatment Preferences” (prospective, observational cohort study) PI: Asher Schranz
“Study of cefiderocol real world outcomes and safety in the treatment of patients with Gram-negative bacterial infections.” Site PI: Anne Lachiewicz
“In the new year, I’ll be busy analyzing data from my malaria TranSMIT study in Tanzania, with the help of MPH students Kano Amagai, Brian Swinehart, Allison Newman, and Guozheng Yang, to understand how malaria transmission is sustained by asymptomatic carriers. We will also ramp up implementation of our Zanzibar Imported Malaria study, collecting >20,000 dried blood spots from Zanzibar and mainland Tanzania to map hotspots of malaria important on Unguja, Zanzibar’s main island.
“Our IDEEL malaria group (which also includes Dr. Jonathan Parr and Dr. Jon Juliano) will continue pioneering studies in the epidemiology and genomics of the relapsing malaria species, Plasmodium ovale, in Africa. This work is led by PhD students Kelly Carey-Ewend, Wenqiao He (visiting scholar from China), and Rachel Sendor; postdoc Zachary Popkin-Hall; and undergraduate Varun Potlapalli.”
“My research is in collaboration with Dr. Lisa Hightow-Weidman as we co-Direct our IGHID Batlab. One of the cross-cutting initiatives in our lab is the expansion of the HealthMpowerment platform – originally developed by Lisa and now in use across numerous research studies and countries.
“Our most recently funded project using the HealthMpowerment platform is a study that will be led by new ID faculty member, Dr. Sarah Rutstein and me. This is an NIH-funded study focused on a collaboration with NC DHHS to promote innovative models of HIV Pre-Exposure Prophylaxis care provision in North Carolina, with a particular focus on rural North Carolina.”
“Our team studies drug use-associated infective endocarditis (DUA-IE). DUA-IE, a life-threatening infection of the heart and bloodstream, is a severe complication of injection drug use. People who acquire DUA-IE are generally young and physically healthy and therefore typically survive and recover in the short term. Yet, in the medium and long term they face the challenges of completing long courses of antibiotics needed to treat DUA-IE, getting care for addiction (should they desire treatment), and continuing to receive outpatient care despite frequently not having insurance and residing in areas remote from specialist providers.
“In the coming year, we will be examining these medium and long-term outcomes for patients after DUA-IE, understanding long-term mortality and readmissions, among other outcomes, in North Carolina and how those may be modulated by sociodemographic and clinical factors. We are also working with inpatients during the time they are hospitalized with DUA-IE to understand their knowledge of and treatment preferences towards DUA-IE care and post-discharge needs.”
“I work closely with Dr. Lameck Chinula and Dr. Friday Saidi. This year, the UNC Project-Malawi OB-GYN team will be focusing on completing study LCCC 1905, which has been co-funded by USAID/National Academy of Sciences, R21-CA236770, U54-CA254562, and a Lineberger Comprehensive Cancer Center Tier 2 Stimulus Award. LCCC 1905 has enrolled 1,250 Malawian women, half of whom are living with HIV. Participants were all offered cervical cancer screening by self-collection of cervicovaginal samples for HPV testing. Participants who were positive for HPV, and 10% of those who were HPV-negative, were offered same-day colposcopy, cervical biopsy, and thermocoagulation treatment for the HPV, if they were eligible. Participants found to have high-grade cervical dysplasia (CIN2/3) on biopsy are followed up 6 months after treatment for repeat colposcopy and cervical biopsy, to ensure that they have been adequately treated.
“Only two participants still need to return for their 6-month follow-up visit, after which we can perform analyses for all of the study’s aims: 1) To assess completion and performance of our same-day screen-and-treat strategy for cervical cancer prevention; 2) To determine the 24-week efficacy of thermocoagulation among women with CIN2/3; and 3) To explore women’s experiences with the proposed screen-and-treat strategy through qualitative interviews. We have also received additional funding to continue follow-up visits until 24 months after treatment to evaluate the long-term success of the treatment and are waiting for Malawi IRB approval to start this study extension.”
David J. Weber, MD, PhD, is focused on two new research projects.
- UNC will lead a study on reducing sink contamination of multidrug-resistant pathogens. “Healthcare-associated infections” is supported by the CDC – Duke/UNC Epicenter (year 11/14 of funding).”
- “COVID-19 mitigation in K-12 schools,” a Duke/UNC collaborative study, is supported by the NIH.
About the Institute for Global Health & Infectious Diseases
Established in 2007, the Institute for Global Health & Infectious Diseases (IGHID) brings transformative solutions to the most important global health issues of our time, through research, training and service. The IGHID has saved millions of lives and shaped policy worldwide through cutting-edge research, especially in the areas of HIV, Malaria and now COVID, where UNC is the most cited university in the nation for coronavirus research. Working in over 50 countries around the globe, the IGHID provides a unique pan-university framework for collaboration and facilitating global health science and practice. It is this framework that continues to catalyze a global health community committed to improving health worldwide while building the capacity of thousands of scientists and health professionals globally.