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UJMT Fogarty Global Health Fellow Camille Morgan is an MD-PhD candidate working on her PhD in epidemiology. Currently in Kinshasa, in the Democratic Republic of the Congo (DRC), her project applies epidemiological, spatial, and genomic approaches to the largest-known household study of hepatitis B virus (HBV) in Kinshasa, to understand HBV transmission dynamics and drivers of transmission. This will inform expanded prevention programs to meet the World Health Organization goal to reach HBV elimination by 2030. Her work builds on the research of Drs. Jonathan Parr, Peyton Thompson and the late Steve Meshnick, as well as many others.

Camille Morgan (4th from left) with mentors Drs. Peyton Thompson (far left) and Jonathan Parr (3rd from right), and fellow PhD student (now graduate) Alix Boisson (2nd from left) at HBV research collaborating site, Binza Maternity Center, Kinshsasa, DRC. June 2021.

What is the national prevalence of Hepatitis B virus (HBV) in the DRC?

“Hepatitis B virus (HBV) is highly endemic in sub-Saharan Africa. UNC-led research has found the national prevalence is around 3%, with prevalence in certain subgroups (pregnant women, people living with HIV, healthcare workers) found to be even higher. A national prevalence of ~3% translates to around 3.5 million infections in a setting where advanced hepatology care is essentially inaccessible. The only HBV prevention currently implemented is the pentavalent vaccine (which protects a child from five life-threatening diseases: Diphtheria, Pertussis, Tetanus, Hepatitis B and Hib) given at 6, 10 and 14 weeks in infancy. This three-dose pentavalent series was introduced in 2007, but there was no catchup vaccination for those who were born before 2007. HBV birth-dose vaccination has not been implemented; prenatal screening for HBV is not done despite a prenatal HIV screening program; healthcare workers are not tested routinely nor vaccinated against HBV; and while blood banks have plans to screen donor samples for HBV, many patients especially in rural areas or in urgent situations will still receive blood products that have not been adequately screened. For us, in the U.S. and other parts of the world, many of these policies and prevention measures have been going on for 30+ years without much thought at this point.

“There is, however, an infrastructure for testing and treating HIV, as well as an incredible history around HIV research and care.  When I first arrived, I thought implementation of HBV prevention alongside HIV systems was a no-brainer and should be straightforward. I’ve learned a lot about the health system and the health priorities. I still advocate for implementation of HBV prevention, but am a bit more understanding about the nuances and challenges.”

Camille Morgan and director of laboratory operations, Martine Tabala (R), at Kintambo Hospital, giving training on venous blood collection for her project (September 2022, Kinshasa, DRC).

If there is an effective vaccine for HBV, why is it important to understand HBV transmission?

“Understanding pathogen transmission is important for thinking about approaches to prevention. Perinatal transmission from mother-to-child (“vertical”) has been the prevailing theory for HBV endemicity globally. But most HBV research comes from Asia, where there is more frequent perinatal transmission seen compared with sub-Saharan Africa, where circulating genotypes appear to behave differently epidemiologically and clinically. The evidence from sub-Saharan Africa suggests that transmission at the household- and community-levels (“horizontal” modes) are important drivers of HBV transmission.

“When we think about why this might be, it likely relates to HBV genotype and varying expression of HBV “e” antigen. HBV “e” antigen is a marker we use to reflect infectivity: individuals with HBV infection who express “e” antigen are considered more infectious to others. Comparing HBV serological profiles in Asia and Africa broadly, HBV surface antigen prevalence, which is how we diagnose HBV infection, appears similar across the two regions. The risk of a vertical transmission event given surface antigen and “e” antigen status are similar, but “e” antigen positivity is more frequently expressed in East Asia (~40%) relative to sub-Saharan Africa (~10%). So the higher frequency of perinatal transmission in Asia is likely related to more frequent expression of “e” antigen, which is related to HBV genotype. There is so much we don’t fully understand, especially about HBV genotypes in Africa (e.g. why HBV genotypes in Africa are associated with horizontal transmission at older ages). We hope to describe some of these epidemiological, molecular, and eventually clinical features of HBV infections.

“There are many interesting scientific questions, but at the end of the day, the goal is to improve health by preventing HBV infection. Additional prevention measures are needed for HBV control, which first require a better understanding of HBV transmission in sub-Saharan Africa.”

Camille Morgan with collaborators Dr. Patrick Ngimbi (L), supervisor of HBV research studies, and Martine Tabala (R), director of laboratory and sample collection, at Binza Maternity Center for the launch of antenatal HBV screening within the HOVER study. (Kinshasa, DRC, February 2022).

How did this project come about?

“UNC has been collaborating with researchers in the DRC since the 1980s, starting with HIV clinical research with Projet SIDA. After civil unrest in DRC in the 1990s, collaborations resumed in the early 2000s that led Professor Steve Meshnick, who was one of my mentors, to begin several malaria research projects in Kinshasa. Many UNC and Congolese faculty and students before me have been trained through these collaborations – to collect and analyze data and samples, to administer studies, and to investigate additional pathogens.

“One of Steve’s projects used >23,000 leftover dried blood samples from the nationally representative Demographic and Health Surveys (DHS) in DRC, first to evaluate malaria epidemiology, but later to look at a variety of pathogens at the request of the Ministry of Health, including Hepatitis B. Drs. Jonathan Parr and Peyton Thompson, who are my current mentors, led a seroprevalence study to understand the epidemiology of infection. The moderately high HBV prevalence observed in this study (~3%) has led to many spin-off HBV studies, with Dr. Peyton Thompson at the helm on the UNC end. She led a study assessing feasibility of implementing prevention of mother-to-child transmission of HBV using HIV infrastructure, published in Lancet Global Health, as well as studies on the immunogenicity of HBV birth-dose vaccination (with Samantha Tulenko, fellow MD/PhD trainee), implementation of HBV birth-dose (with fellow PhD trainee Alix Boisson), and the “Horizontal and Vertical Transmission of HBV” (HOVER-HBV) household study, forming the basis of my dissertation and Fogarty year. These studies have been in collaboration with Dr. Marcel Yotebieng from Albert Einstein College of Medicine, a former graduate from the UNC Department of Epidemiology.”

Are there household practices or community exposures that could be related to transmission?

Camille Morgan with Dr. Patrick Ngimbi, supervisor of HBV studies outside the Kintambo Hospital Office (Kinshasa, DRC, 2021)

“HBV is very infectious. It can last on surfaces and remain infectious for up to seven days. The goal of the HOVER study is to describe possible modes of horizontal HBV transmission – the use of shared objects, anything that nicks your skin, for instance, like a razor that could then be shared by someone else as a possible source of transmission. With the high malaria burden, blood transfusions are also frequent, and in rural areas or urgent cases, a family member may donate blood that’s not tested. And so that could be a source of transmission. Other considerations might be incomplete sanitization of instruments used in traditional practices, such as piercings or tattoos or in medical procedures. These are the kinds of things we’re looking at. We had hoped to analyze HBV molecularly from dried blood spots to connect with this epidemiological analysis, but serological analysis and sequencing of HBV from a small amount of blood has proven quite challenging. So my Fogarty project was designed to return to households of interest, such as those with clusters of infections, to collect venous blood samples and more in-depth medical histories in order to do this analysis.

“Through my Fogarty project, we’ve returned to 25 households and are currently working on the molecular analysis. We have many more ideas for future research questions, and hope this work will lead to informing relevant and effective prevention measures in this setting.”

Describe your typical day in Kinshasa?

“I walk to our field office based at the Kintambo Hospital around 7-7:30 am. Most days I work at the office, where I’m going over data that we’ve collected, such as medical histories from enrollments in my Fogarty project; some days we’re going out to a household for an enrollment visit; or some days we’re going over samples in the lab, which is based at Université Protestante au Congo (UPC). UPC could be a 15-minute drive or a 2.5-hour drive from our office, depending on very unpredictable traffic patterns. All day is in French, with plenty of Lingala as well; some days I don’t hear or speak any English, which is interesting to reflect on. I’m not a native French speaker but enjoy learning languages; most of all, the mixture of many languages has given me a new appreciation for the effort (and accompanying exhaustion) of non-native English speakers working the U.S. where many residents only speak English. Between work and language and culture, I’m learning something new every day, which is fun and humbling.

Camille Morgan (second from right) after a soccer game organized with colleagues from the HBV team (Kinshasa 2021).

“Kinshasa is, by some estimates, the largest city in Africa, even larger than Lagos, and there are a lot of logistics to coordinate, with households located across the city, lots of traffic, and the samples having a limited time window for processing. Plus, many of these households we are trying to follow often have moved or have a new phone number, and so returning can present a challenge. But I am fortunate to have incredible partners here that have relationships with these communities, and we’ve been able to work through these challenges.

“After work, I coach middle and high school girls’ soccer three days a week, which has been a rewarding experience to promote girls’ sports and leadership development.”

What do you like about this opportunity? Tell us about working with your mentors?

“I love being just on the edge of my comfort zone in terms of learning something new every day and having to adapt to ever-changing circumstances. Additionally, DRC has an incredibly rich but fraught history, which I’ve appreciated learning more about from Congolese themselves. This experience has taught me that science and medicine are never separated from history, geography, politics, or other disciplines; the more these contextual factors are understood, the more relevant and impactful the research questions and research partnership. The history of HIV and HIV research in DRC encapsulate this well.

Left to right: Camille Morgan’s mentors include the late Steve Meshnick, MD, PhD, Peyton Thompson, MD, MSCR, and Jonathan Parr, MD, MPH

“I am thankful for great mentors. Dr. Parr is an incredible scientist and mentor; he balances in-depth, detailed knowledge while also taking a step back and allowing me as a student to have some autonomy and develop as an independent researcher. He has also exhibited how to develop a bilateral research program, taking time to support researchers from collaborating sites to spend time in our lab or for graduate training at UNC, just as much as we may be traveling. Dr. Thompson is a knowledgeable clinician and decisive researcher; she balances doing what is right during a study or for a collaboration, while being efficient and effective. Together, Drs. Parr and Thompson have highlighted how one can be a knowledgeable and productive researcher, while also being a kind and supportive collaborator. Through them, I have learned about what is important to me in a career, which is an important but overlooked element of training.”

Camille Morgan is in the Global Health Scholarly Concentration Program through the Office of Global Health Education (OGHE), now structured within the Institute for Global Health & Infectious Diseases at the UNC School of Medicine. Last year, she received funding from OGHE and the Infectious Disease Society of America’s GERM Award, to go to Kinshasa, and this experience provided the basis for the questions she is exploring through her Fogarty fellowship, granted through the Institute.