The rapid emergence of SARS-CoV-2 has created a global health emergency. While most human SARS-CoV-2 disease is mild, some people develop severe, life-threatening disease.
Effective therapeutics have been developed against acute Ebola virus disease (EVD) in both humans and experimentally infected nonhuman primates. However, the risk of viral persistence and associated disease recrudescence in survivors receiving these therapeutics remains unclear. In contrast to rhesus macaques that survived Ebola virus (EBOV) exposure in the absence of treatment, we discovered that EBOV, despite being cleared from all other organs, persisted in the brain ventricular system of rhesus macaque survivors that had received monoclonal antibody (mAb) treatment. In mAb-treated macaque survivors, EBOV persisted in macrophages infiltrating the brain ventricular system, including the choroid plexuses. This macrophage infiltration was accompanied by severe tissue damage, including ventriculitis, choroid plexitis, and meningoencephalitis. Specifically, choroid plexus endothelium-derived EBOV infection led to viral persistence in the macaque brain ventricular system. This resulted in apoptosis of ependymal cells, which constitute the blood–cerebrospinal fluid barrier of the choroid plexuses. Fatal brain-confined recrudescence of EBOV infection manifested as severe inflammation, local pathology, and widespread infection of the ventricular system and adjacent neuropil in some of the mAb-treated macaque survivors. This study highlights organ-specific EBOV persistence and fatal recrudescent disease in rhesus macaque survivors after therapeutic treatment and has implications for the long-term follow-up of human survivors of EVD.
One of the most critical aspects of safe operations in biosafety level 3 and 4 and animal biosafety level 3 and 4 biocontainment laboratories is the effective inactivation of biological select agents and toxins in the waste generated in these environments. Steam sterilization has been used for decades to effectively kill microbial contaminants in a variety of medical and commercial settings. In biocontainment research settings, steam sterilization is often used to inactivate biological select agents and toxins in various types of waste prior to removal from the containment laboratory. This method is especially important for types of waste for which other decontamination methods are not as effective or practical, such as chemical decontamination (quaternary ammonium, sodium hypochlorite, formalin fixation, paraformaldehyde), ultraviolet light, or incineration. Bulk trash, animal waste, and animal carcasses in particular do not easily lend themselves to decontamination via chemical or radiation methods. Decontamination of these types of waste remains most effectively achieved with steam sterilization. Here we review the method used in our institute to validate the steam sterilizers (autoclaves) and associated procedures to ensure destruction of microbial contaminants from these challenging types of waste.
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