Dr. Veronica Sanchez
The UAB Division of Pediatric Infectious Diseases is internationally known for its studies of congenital and perinatal viral infections as well as its studies of antiviral therapeutics and drug discovery. For 50 years, the division has defined the natural history, pathogenesis, diagnosis, treatment and prevention of congenital cytomegalovirus (CMV) and neonatal herpes simplex virus (HSV) infections and other viral infections in infants. These research programs were started by Dr. Charles Alford in the 1960s, following his return to UAB from training in the laboratory of Nobel Prize winner Dr. Thomas Weller. Applying a critical scientific approach to the emerging field of virology, Dr. Alford established UAB as the national leader in congenital and perinatal viral infections.
Currently, the division consists of 10 physician scientists and three Ph.D. scientists. Collectively, these investigators were responsible for $14.4 million in research grants and contract support in FY2021. Division faculty currently hold seven R awards, eight NIH contracts, three CDC contracts and three U awards, and generate more than 40 major original publications each year. This is in addition to a thriving clinical service and molecular diagnostic laboratory. The legacy of the work initially started in the laboratories of Drs. Weller and Alford continues. Advances in technology promise to take what today is cutting-edge science and make it the foundation upon which tomorrow’s advances stand.
Multiple projects extend the division’s studies of CMV infections. A significant effort, led by Suresh Boppana, M.D., Karen Fowler, Ph.D., and Shannon Ross, M.D., is the completion of the National Institute on Deafness and Other Communication Disorder (NIDCD)-funded CMV and Hearing Multicenter Screening (CHIMES) study. These data have provided new insights into the changing natural history of congenital CMV infection. This study enrolled more than 100,000 infants from seven hospitals in the US and was organized and administered by Drs. Boppana and Fowler. New findings from the study included the development of a highly sensitive and specific PCR-based assay for testing newborn saliva samples to identify babies infected with CMV and lack of sensitivity of newborn blood spots collected for routine screening to detect CMV-infected babies.
Other major findings of the study included a significantly higher prevalence of congenital CMV infection in African American women and teens than previously reported and the failure of newborn hearing screening to identify a significant proportion (~40%) of infants with CMV-associated hearing loss at birth. Most recently, the CHIMES data were utilized to establish the cost savings that would be achieved by a universal screening program for congenital CMV infections. The landmark findings from this pivotal study are being used to develop new guidelines on caring for infants and children locally, nationally and internationally.
Ongoing work continues using the CHIMES study data. Some of the studies include describing the natural history of hearing loss in children with congenital CMV infection, evaluating the increased risk of congenital CMV infection in offspring of adolescent mothers and assessing the role of maternal CMV serostatus in delivering small for gestational age infants.
Swetha Pinninti, M.D., focuses her efforts on defining the prevalence and severity of vestibular and balance disorders in children with asymptomatic congenital CMV infection with hearing loss and those with normal hearing. The goals of this work are to define the burden of vestibular involvement, develop screening methods for early identification of children with vestibular and balance disorders, and develop effective intervention measures to improve outcomes. Dr. Pinninti is also studying the association between sexually transmitted infections and genital tract shedding of CMV.
Some of Dr. Fowler’s current work focuses on behavioral interventions to prevent maternal CMV infections during pregnancy. A past CDC-funded behavioral intervention study recruited young pregnant women into a 12-week cognitive-behavioral intervention to increase knowledge about congenital CMV and decrease self-reported risk behaviors. The results demonstrated that it is possible to raise awareness about congenital CMV and reduce CMV risk behaviors in young CMV seropositive pregnant women. Currently, Dr. Fowler is leading an NIH-funded randomized behavioral intervention study evaluating whether CMV prevention behavior changes result in lowering maternal infection during pregnancy, thereby reducing congenital CMV infection rates in their offspring.
Internationally, William Britt, M.D., and Drs. Boppana and Fowler have ongoing projects in Brazil and South Africa (supported by the NIH). In Brazil, more than 30,000 women and their newborn infants are being enrolled in studies to define the natural history of congenital CMV infection in a population of women with universal immunity to CMV, a critical question in the design of prophylactic vaccines for this infection. Studies in Brazilian women and their offspring were initiated by Dr. Britt nearly 20 years ago and have provided significant information on the role of maternal immunity and congenital CMV infections that are designed to identify sources of virus infection in these women. The Brazilian study will also address the potential impact of behavioral interventions in the prevention of reinfections in pregnant women. These studies are supported by the NIH and Merck Co.
Veronica Sanchez, Ph.D., and Drs. Britt, Boppana, Ross and Pinninti all lead robust laboratory research programs as well, with studies in basic molecular virology, virus-host interactions and correlates of protection. A significant effort led by Dr. Britt has been focused on understanding the role of virus-induced inflammation and brain development in a small animal model of CMV infection of the developing central nervous system. This system was developed in collaboration with investigators in Erlangen, Germany, and this collaboration continues today. This system has pointed to the role of inflammation in altered cell positioning in the developing brain, a finding that recapitulates aspects of the pathology of brain disease in infants with congenital CMV infection. A second major focus of this project is defining mechanisms of hearing loss in infants with congenital CMV infections. This small animal model closely recapitulates the findings of hearing loss in infants with congenital CMV infection, and findings generated from studies in this system have identified mechanisms of hearing loss, which include virus-induced inflammation. Dr. Britt has established an active collaboration with investigators in Croatia who have considerable expertise in innate immunity. This active collaboration in this area of study has been ongoing for more than 25 years.
Dr. Sanchez has several ongoing projects that directly address key steps in the assembly in infectious CMV. Together with Dr. Britt, Dr. Sanchez’s research will improve the understanding of fundamental aspects of virus replication and virus-host interactions, including several projects directed at dissecting the role of the functional components of the infected cell in the efficient production of infectious virus from an infected cell—a project that can be translated into the identification of novel targets for antiviral agents. In addition, these studies have developed a new and previously unknown function of novel modes of regulation of cellular function, viral micro RNA molecules.
Dr. Ross research is centered on identifying markers of hearing outcome in congenital CMV. She is investigating the role of neuroimaging and other markers to identify infants with congenital CMV that are at risk for hearing loss.
Major clinical trials of the treatment of life-threatening viral infections have been performed by David Kimberlin, M.D., and Richard Whitley, M.D. Over the past two decades, their NIH-funded work has established the standard of care for the management of neonatal herpes simplex virus (HSV) disease and congenital cytomegalovirus (CMV) infection. Studies being completed now include assessment of whether there is benefit in starting antiviral therapy later in childhood for children with hearing loss caused by congenital CMV. They also are determining the appropriate dose of these medications to use in babies born extremely premature. A study of the treatment of babies with asymptomatic congenital CMV infection recently has been halted due to toxicity and has been converted to a large natural history study to assess for biomarkers of clinical outcome (hearing loss) that may improve the risk-benefit ratio of future clinical studies in this population. Studies of potential biomarkers for neonatal HSV infections also are being completed at this time.
New studies being conducted include leading the NIH’s assessment of Acute Flaccid Myelitis (AFM), which includes steering a group of up to 35 study sites in the United States, Canada and Peru. Through the Congenital and Perinatal Infections Consortium (CPIC), a member of the Rare Diseases Clinical Research Network, large multi-center natural history studies of neonatal enteroviral and parechoviral sepsis are being conducted. Clinical Phase 1 trials of valacyclovir and letermovir in neonates are in development, as is a longitudinal follow-up study to determine the durability of treatment benefit on hearing in children previously enrolled in studies in the 2000s. The Congenital and Perinatal Infections Consortium brings together 28 study sites, led by researchers at UAB, to investigate the natural history and treatment of herpes simplex virus, cytomegalovirus and enterovirus in the neonatal population.
Scott H. James, M.D., utilizes conventional and next-generation DNA sequencing techniques to identify and characterize treatment-emergent antiviral resistance and viral subpopulations with diminished susceptibility to antiviral drugs from treated babies.
Scott H. James, M.D., leads an interdisciplinary team of investigators to help select molecules with optimal antiviral activity against a broad array of DNA viruses. In partnership with the NIH’s in vitro antiviral screening program, an NIH R01 grant, as well as through independent research collaborations, Dr. James’ group provides preclinical data to support drug development and human clinical trials. The expertise of his laboratory has been expanded from herpesviruses and poxviruses to all the DNA viruses, including the adenoviruses, polyomaviruses and papillomaviruses. Collaborative research endeavors designed to serve the wider research community in the development of novel antiviral agents have led to national and international partnerships among universities, biotech companies and non-profit organizations. Under the guidance of the late Mark N. Prichard, Ph.D., and continuing under the current leadership of Dr. James, preclinical work performed in this laboratory has helped to support the advance of five drugs for the treatment of viral infections into clinical trials: maribavir (for CMV), brincidofovir (for CMV), tecovirimat (for smallpox), and most recently, filociclovir (for CMV), N- Methanocarbathymidine (for VZV) and ABI-1968 (for HPV).
Dr. James’ antiviral program employs the study of antiviral drug resistance to help understand the molecular mechanisms of action of novel compounds and to help manage their clinical use. Molecular biology and reverse genetic techniques are used to identify the molecular targets of antiviral drugs in DNA viruses and to describe the essential functions of these enzymes in viral replication.
Dr. James led preclinical studies of the novel compounds filociclovir and brincidofovir, including mechanism of action studies, in vitro efficacy and toxicity assays, and genomic studies of laboratory-generated resistant strains of CMV. In partnership with the Collaborative Antiviral Study Group, our team also investigates the emergence of resistance to antiviral therapies during clinical trials in infants and children with viral infections and has characterized the rates of resistance in pediatric patients. Corollary to his area of research expertise, Dr. James has also been recruited to serve on an international multidisciplinary workgroup to develop clinical practice guidelines on the use of antiviral agents in children with COVID-19.
Under the leadership of William Britt, M.D., the Molecular Diagnostic Virology Laboratory provides an essential service for the University of Alabama Hospital and Clinics and Children’s of Alabama.
Stephanie Moore, Ph.D., and Richard Whitley, M.D., and have built a team of experienced scientists in virology, viral immunology, pathogenesis and medicinal chemistry from eight partnering academic institutions, plus Southern Research, to develop small molecule therapeutics for the treatment of emerging viral infections under the umbrella of the Antiviral Drug Discovery and Development Center (AD3C). Members of several genera of RNA viruses that are major causes of human disease, bioterrorist threats or emerging infectious diseases are being studied. Projects focus on coronaviruses that cause SARS and MERS, alphaviruses that cause Venezuelan equine encephalitis virus and chikungunya, flaviviruses (dengue, West Nile virus, and Zika) and influenza A virus.
The team utilizes the existing data and compounds to perform proof of principle studies in animal models, thereby delivering potential small molecule therapeutics to the government. Work performed by this team has been influential within the field as an effective model for drug discovery and development.
The group has also evaluated a limited number of additional, novel compounds provided by collaborators at the Emory Institute for Drug Discovery (EIDD), Gilead Sciences and Pardes Biosciences. Expertise exists in the AD3C for IND preparation and filing as well as Phase I studies with adequate resources. The projects are supported by three Cores: Administrative, the Assay and the Medicinal Chemistry and Lead Development. The organization and interaction between all projects and Cores are monitored by the Administrative Core. This collaboration has already contributed significant data to two INDs filed for SARS/MERS and two patents and proof of principle data for chikungunya, one for West Nile and additional patents being filed for coronavirus compounds.
In October of 2021, Dr. Whitley and a collaborative group of national and international institutions replied to an Emergency Award Funding Opportunity from the NIH with money provided by the American Rescue Plan Act of 2021 and submitted a grant proposal aimed at creating additional avenues for drug candidates for clinical use against future pandemics.
At the beginning of the SARS-CoV-2 pandemic, leveraging their virology expertise, Drs. Boppana, Britt and Pinninti have implemented a natural history to determine virologic and immunologic characteristics of COVID-19 infections in children and established a biorepository of specimens (nasopharyngeal, nasal, saliva, rectal swabs and peripheral blood) from infected adults and children. Drs. Boppana, Britt and Pinninti have sought extramural funding for a number of studies of SARS-CoV-2 infection and were successful in obtaining funding from the National Cancer Institute to understand the relationship between adaptive immunity and SARS-CoV-2 replication in children undergoing cancer chemotherapy or other immunomodulatory treatments (1U01CA260462-01). Drs. Boppana and Pinninti have been conducting both Pfizer and Moderna COVID-19 vaccine trials in children between six months and 11 years of age. Thus far, more than 210 children have been enrolled in these trials since May, 2021. Lastly, through a subcontract from the Rockefeller Foundation, Drs. Britt, Boppana and Pinninti will derive SARS-Cov-2 sequence surveillance data from medically underserved children in central Alabama as part of an overall project to provide surveillance in underserved populations.
With funding from two Center for Disease Control and Prevention (CDC) contracts and one CDC cooperative agreement, Claudette Poole, M.D., has established the UAB Sanitation Health Program. There are currently three separate projects funded by the CDC to screen residents of Black Belt counties for intestinal parasites and related infections that community residents may be at risk for due to failing sanitation systems throughout the region. The first two projects are focusing on children who live in Wilcox, Lowndes and Perry counties. These are primarily screening programs for children in the three counties to test for soil transmitted helminth infection, provide necessary treatment and identify risk factors. The third project is a public health promotion project to expand surveillance for sanitation related infections across West Central Alabama, educate both healthcare workers and the public regarding sanitation-related health concerns and link residents to resources. This project will be a collaborative effort between UAB, the West Central Alabama Area Health Education Center (AHEC), the Rural Health Medical Program, Inc. (RHMP), the Alabama Department of Public Health (ADPH), the Consortium for Rural Alabama Water and Wastewater Management (CFRAWAWM) and the CDC. Dr. Poole and her team are working closely with the CDC, the state and local ADPH, and healthcare providers providing health services for at-risk communities.
Antimicrobial Stewardship Program (ASP)
The Infection Control and Prevention team, which includes the medical director, the nurse manager and three infection prevention nurses, work together to identify, investigate and develop processes to prevent infections acquired in the hospital.
J Infect Dis. 2021 Dec 1;224(11):180701809. Coronavirus Disease 2019 and Children. Boppana SB, Pinninti SG, Britt WJ.
Nature Cancer. pg.1018-1038. RNF2 ablation reprograms the tumor-immune microenvironment and stimulates durable NK and CD4+ T-cell-dependent antitumor immunity. Zhang Z, Luo L, Xing C, Chen Y, Xu P, Li M, Zeng L. Li C, Ghosh DD, Townes T, Britt WJ, Wajapeyee N. Slcekman BP, Chong Z, Leavenworth JW, Yang ES.
Scott James, M.D.
David Kimberlin, M.D.
Shannon Ross, M.D.
Richard Whitley, M.D.
Nour Hasan, M.D.
The mission of the Pediatric Infectious Disease Fellowship Program is to train, educate and mentor fellows to become exceptional clinicians and researchers in the field of pediatric infectious diseases. We strive to prepare our trainees to be future leaders in healthcare who will advance the field of pediatric infectious diseases as innovative physician-scientists. Our trainees are immersed in a learning environment that values excellence in clinical care, scholarly activity and professionalism. We have special expertise in combined fellowship programs that include not only pediatric infectious diseases training but also neonatology, critical care medicine and adult infectious diseases training. All of our former fellows over the past decade have easily passed their pediatric infectious diseases boards. During their training, our fellows gain experience in a wide variety of clinical conditions and settings, participate in quality improvement and patient safety initiatives, and are provided with close mentorship and guidance for the development of successful research careers.
Markus Buchfellner, M.D.
Residency: University of South Florida
Ayesha Ahmed, M.D.
Residency: University of Alabama at Birmingham
Joshua Cooper, M.D.
Combined Infectious Diseases/Critical Care Fellow
Residency: University of Alabama at Birmingham
Audrey Lloyd, M.D.
Combined Adult and Pediatric Infectious Diseases Fellow
Residency: Ohio State University
Scott James, M.D.
Claudette Poole, M.D.
Associate Program Director