Informing CONOPS and medical countermeasure deployment strategies after an improvised nuclear device detonation: the importance of delayed treatment efficacy data

Abstract

Purpose: In the wake of a nuclear detonation, individuals with acute radiation syndrome will be a significant source of morbidity and mortality. Mathematical modeling can compare response strategies developed for real-world chaotic conditions after a nuclear blast in order to identify optimal strategies for administering effective treatment to these individuals. To maximize responders’ abilities to save lives it is critical to understand how treatment efficacy is impacted by real-world conditions and levels of supportive care. To illustrate the importance of these factors, we developed a mathematical model of cytokine administration 24 h after the blast with varying levels of supportive care described in the primary literature.

Conclusion: The results highlight the proportionally higher life-saving benefit of administering cytokines to individuals with a moderate to high dose of radiation exposure, compared to those with a lower dose. However, the fidelity of mathematical models is dependent on the primary data informing them. We describe the data needed to fully explore the impact of timing, dosage, and fractional benefit of cytokines and supportive care treatment in non-optimal situations that could be seen after a nuclear detonation. Studies addressing these types of knowledge gaps are essential to evaluating the relative efficacy of countermeasures to refine existing plans and help develop new strategies and priorities.

Keywords:

• Acute radiation syndrome (ARS)
• cytokines
• atomic bomb effects
• modeling
• models of radiation response

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This project has been funded in whole or in part with Federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under Contract No. HHSO100201600017I.

Notes on contributors

N. Yeddanapudi

Neelima Yeddanapudi, MS, is a Quantitative Analyst with Leidos. She is currently supporting the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services in Washington, DC.

M. A. Clay

Matthew Clay, PhD, is a Senior Quantitative Analyst with Leidos. He is currently supporting the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services in Washington, DC.

D. P. Durham

David Durham, PhD, is a Senior Quantitative Analyst with Leidos. He is currently supporting the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services in Washington, DC.

C. M. Hoffman

Corey Hoffman received his Ph.D. in Pharmacology at the University of Rochester in 2017. His work there focused on regulation of hematopoietic stem cells by their niches in the context of aging or radiation injury. Corey was also a summer fellow at the US Food and Drug Administration, where he looked at the activity of ADAMTS13 and Von Willebrand Factor in neonates with congenital heart defects. Corey is currently an ORISE fellow at the Biomedical Advanced Research and Development Authority.

M. J. Homer

Dr. Mary Homer is the Chief of Radiological and Nuclear Medical Countermeasures at the Biomedical Advanced Research and Development Authority in the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services in Washington, DC. Her team manages the medical countermeasure portfolio for injuries resulting from nuclear or radiological national security threats, covering advanced research and development through to Project Bioshield procurement for inclusion as a part of the Strategic National Stockpile.

J. M. Appler

Dr. Jessica Appler is the Chief of Modeling and Simulation in the Office of the Assistant Secretary for Preparedness and Response (ASPR) within the U.S. Department of Health and Human Services in Washington, DC. Her team provides analytic support across ASPR to assess medical and public health consequences; reduce operational gaps in medical countermeasure development, deployment, and administration; and inform the federal government's response to national security threats including chemical, biological, radiological, nuclear, and pandemic influenza public health emergencies.