Current Landscape and Future Directions of Pediatric Transplant Infectious Diseases Free

Abstract

Over the past two decades, the field of pediatric transplant infectious diseases (TID) has changed dramatically. The indications for pediatric hematopoietic cell transplantation (HCT) and solid organ transplantation (SOT) have expanded, pushing the boundaries of our understanding and bringing ever more immunosuppressed individuals to transplant [1–3]. Concurrently, there has been a proliferation in immunosuppressive medications to treat rejection, graft-versus-host-disease, and other post-transplant immunological phenomena [4, 5] potentially modifying clinical presentation, frequency, and severity of infectious sequelae in these children. The number of infections due to uncommon pathogens or atypical manifestations of common infections is increasing. Newly available diagnostic assays to identify and predict risk for infectious diseases lack data about their optimal use limiting our ability to use them in a cost-effective fashion [6]. Many of these assays are immunological in nature, and extrapolating adult data to children with a developing immune system is an additional challenge for pediatric infectious disease practitioners. At the same time, new medications and other treatment modalities have been added to our armamentarium to prevent and cure infections. However, children are frequently excluded from clinical trials of new agents, forcing pediatricians to deduce dosing regimens and expected efficacy from adult data. Understanding the optimal use, dosing strategies, and clinical impact of these novel therapies provides an additional challenge to pediatric infectious diseases specialists. Furthermore, not all interventions are available universally, and experience and comfort with newer diagnostic tests and treatment modalities vary widely. This lack of standardization complicates our ability to move the field forward. Lastly, as the field of pediatric TID has grown, the number of available positions has outpaced educational and training opportunities in our field.

With the growing patient population and increasing opportunities for evaluation and management, education and training the pediatric infectious diseases workforce to be prepared to manage the infectious and noninfectious complications of transplantation is imperative [7, 8]. Similarly, sharing of and adding context to emerging data are critical to continue to advancing care for pediatric transplant recipients. The annual Pediatric Infectious Diseases Society (PIDS)/St. Jude Pediatric Infectious Diseases Research Conference does include a Pediatric TID symposium as part of its overall agenda. The conference has grown significantly in recent years, but its scope is limited as a sub-section of the overall conference. To that end, this supplemental issue of the Journal of the Pediatric Infectious Diseases Society was developed to explore challenging topics in the field of pediatric TID and highlight recent changes in clinical practice so that they can be more evenly applied across programs. The articles in this supplement will provide exposure to novel strategies for the management of infections in pediatric transplantation, including cytomegalovirus prophylaxis and treatment, use of virus-specific T-cells, and novel antifungal agents. Other articles will highlight recent consensus guidelines for the management of EBV-associated post-transplant lymphoproliferative disorder in children undergoing SOT and HCT, and present new data and insights relating to respiratory viruses in transplant recipients, the management of non-tuberculous mycobacterial infections, and the impact of the microbiome in transplantation. These articles are designed to augment the clinical training and practical experience that many pediatric infectious diseases specialists have acquired through the management of pediatric transplant recipients.

However, it must be recognized that the role of the pediatric TID specialist extends beyond clinical care. The articles in this supplement will also highlight unmet needs and areas requiring investigation. Therefore, the pursuit of knowledge to fill these substantive gaps should be prioritized to inform future clinical care of pediatric transplant recipients. Given the relatively small numbers of pediatric organ transplants performed at most individual centers, multicenter collaborations for clinical research should be pursued whenever possible [7]. Prospective studies or clinical trials may be the preferred forms of study design, but there is value to be gleaned from retrospective clinical epidemiology studies as well. The PIDS promotes pediatric TID research through the Research Subcommittee of the Transplant Infectious Diseases Committee, which partners with the St. Jude Children’s Research Hospital on the Pediatric Infectious Diseases Transplant Network (https://www.stjude.org/research/departments/infectious-diseases/pidtran-coordinating-center.html) to support well-designed research studies focused on infectious complications of transplantation. This and other collaborative efforts across institutions provide a model to advance the field of pediatric TID more efficiently.

Ultimately, this supplemental issue of the Journal of the Pediatric Infectious Diseases Society only represents a snapshot in time, covering a limited number of topics. As the field progresses there will undoubtedly be new clinical issues that will require the intellectual energy of pediatric TID specialists. However, we hope that this supplement will be a resource for all pediatric infectious diseases specialists, regardless of their involvement in pediatric TID, and will provide a roadmap of priorities for future clinical and translational research.

Notes

Financial support. None declared.

Supplement sponsorship. This article appears as part of the supplement “Advances in Pediatric Transplant Infectious Diseases,” sponsored by Eurofins Viracor.

Potential conflicts of interest. All authors: No reported conflicts.

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