Pediatric Transplant Infectious Diseases Research

Duke is the coordinating center of the $11M NIH-funded International Pediatric Fungal Network (IPFN), which is a 55-site multi-national consortium designed to investigate the epidemiology, diagnosis, and treatment of invasive fungal infections in children, largely in those following transplantation.  William Steinbach, MD, director of the Duke Pediatric Transplant Program, is the director of the IPFN and is currently enrolling patients in three cutting-edge clinical trials. This includes the PEACE study examining the comparative effectiveness of antifungal therapy for the treatment of invasive candidiasis. This is the largest pediatric antifungal study to date and has now completed enrollment of 750 children with candidiasis, and we are currently analyzing the data for publication. The second ongoing study is the BIOPIC study, which is investigating the novel molecular diagnosis of invasive candidiasis using newer biomarkers that have not been previously tested in children. This is the largest fungal biomarker study in any age group with a planned enrollment is 500 patients--the study is approximately half-completed. The third study is the DOMINIC study that will begin in 2019. This study will focus on the diagnosis and treatment of pulmonary invasive mold infection in patients following chemotherapy for malignancy or hematopoietic stem cell transplant, using novel host signatures to define infection as well as next-generation sequencing to detect mold pathogens. This is a novel scientific approach for both adult and pediatric patients.

Debra Lugo, MD, is the site lead investigator on a clinical trial investigating a new antiviral, letermovir, that is highly effective against Cytomegalorivus (CMV). Duke is the coordinating research site and is only the second institution in the country to use letermovir in pediatric patients. We are leveraging that experience to help design and lead this pivotal clinical trial that could potentially lead to FDA-approval for children.

Dan Chang, MD, is the site lead investigator on a clinical trial to investigate the efficacy of a new antifungal, isavuconazole, in children. Duke was a leading enroller for patients in the initial pediatric pharmacokinetic study, and now Dr. Chang will be enrolling patients in a study that evaluates isavuconazole for the treatment of invasive mold infections such as aspergillosis and mucormycosis.  This agent, which was approved for adults in 2015, appears to have less toxicity than currently approved agents. Notably, this is the first efficacy study in children, and we are happy to be able to offer participation in this clinical trial to our Duke pediatric transplant recipients.

The Duke Transplant Center is currently leading the effort to compile a comprehensive adult and pediatric organ transplant database. The database will include detailed clinical information on each transplant performed at Duke, as well as links to a biorepository that houses a large variety of clinical specimens for analysis. This is another example where close alignment with one of the largest adult transplant centers in the country allows the Duke Pediatric Transplant Program to have greater access to cutting-edge research.

William Steinbach, MD, is the lead editor of the upcoming Pediatric Transplant and Oncology Infectious Diseases textbook (Elsevier, planned release 2020). This textbook is the first of its kind and is distinguished as the only collection of the work of leading authorities in the pediatric transplant infectious diseases field. Duke is leading this effort, and multiple Duke faculty are authors of leading chapters.

The Duke pediatric transplant infectious diseases team has developed multiple detailed evidence-based protocols to deliver optimal and standardized care for common transplant infectious diseases concerns, such as CMV, EBV, HHV6, PJP, vaccinations, among many others. These protocols are aligned with the larger adult transplant center. Protocol development is complex but ultimately leads to improved, integrated clinical care for our patients, as well as the opportunity to lead new research efforts to identify gaps in knowledge and contribute to new understandings.