The NIAID Integrated Research Facility at Frederick, Maryland: a unique international resource to facilitate medical countermeasure development for BSL-4 pathogens

Abstract

Scientists at the National Institute of Allergy and Infectious Diseases Integrated Research Facility at Fort Detrick, Frederick, Maryland, coordinate and facilitate preclinical research on infectious diseases to develop medical countermeasures for high-consequence pathogens. This facility is unique in that it is the only maximum containment laboratory in the world where conventional and molecular medical imaging equipments are incorporated into the design of the facility. This capability provides investigators with unique tools to dissect disease pathogenesis, evaluate the ability of animal models to recapitulate human disease, and test candidate countermeasures. Importantly, advanced molecular imaging has the potential to provide alternative endpoints to lethality. Using these alternative endpoints, investigators can reduce the number of animals used in experiments and evaluate countermeasures in sublethal models. With the incorporation of medical imaging modalities, a clinical laboratory modeled after those existing in hospitals, and a highly trained veterinary medicine team, IRF-Frederick is uniquely suited to advance our understanding of emerging infectious diseases and to facilitate the development of medical countermeasures and clinical care paradigms previously considered impossible.

Keywords: BSL-4; countermeasures; medical imaging; viral hemorrhagic fever.

Figure 1

CT 3D volume‐rendered images of lungs of nonhuman primates acquired prior to intratracheal inoculation (baseline) with Middle Eastern respiratory syndrome coronavirus and on days 1, 3, 9, and 13 postinoculation. Images were segmented to highlight pulmonary vasculature (red) and areas of increased consolidation (yellow).

Figure 2

The imaging suite is separated into two sides: a hot side with pathogens present (pink rooms) and a cold side without pathogens (blue rooms). A biocontainment tube of polycarbonate resin thermoplastic extends from the hot side of the imaging suite into the bore of each imaging modality on the cold side.

Figure 3

Representative biocontainment strategy for imaging. (a) The single photon emission computed tomography ‘hot side’ imaging room contains the subject table and the barrier wall that separates the hot side from the cold side (b). With the animal inside the biocontainment tube, the veterinary care team has access to the animal during the procedures to ensure the health and well‐being of the animal. Design of the subject table was simplified to facilitate decontamination and replacement of parts by scientists.