Ebola Virus Dose Response Model for Aerosolized Exposures: Insights from Primate Data

Abstract

This study develops dose-response models for Ebolavirus using previously published data sets from the open literature. Two such articles were identified in which three different species of nonhuman primates were challenged by aerosolized Ebolavirus in order to study pathology and clinical disease progression. Dose groups were combined and pooled across each study in order to facilitate modeling. The endpoint of each experiment was death. The exponential and exact beta-Poisson models were fit to the data using maximum likelihood estimation. The exact beta-Poisson was deemed the recommended model because it more closely approximated the probability of response at low doses though both models provided a good fit. Although transmission is generally considered to be dominated by person-to-person contact, aerosolization is a possible route of exposure. If possible, this route of exposure could be particularly concerning for persons in occupational roles managing contaminated liquid wastes from patients being treated for Ebola infection and the wastewater community responsible for disinfection. Therefore, this study produces a necessary mathematical relationship between exposure dose and risk of death for the inhalation route of exposure that can support quantitative microbial risk assessment aimed at informing risk mitigation strategies including personal protection policies against occupational exposures.

Characterization of Ebola Virus Mucosal Challenge Routes in Cynomolgus Macaques

“…In the case of the first study, despite the mode of administration making it difficult to discern the actual challenge dose received, it is likely the high dose contributed to the 75% observed CFR. Alternatively, there may be a random aspect to generating aerosols during the oral inoculation and aerosol doses between 1 and 10 PFU of EBOV have a dose dependent lethal outcome (with doses greater than 10 PFU being uniformly lethal) ( 34 – 36 ). This could also potentially explain the reduced prodrome in the oral challenge NHP model of EBOV infection.…”

Critical Capability Needs for Reduction of Transmission of SARS-CoV-2 Indoors

“…Such models account for the distribution of pathogens within the matrix and the probability that a pathogen can survive to initiate infection reaching a target receptor. While models have been developed for highly infectious viruses through the inhalation route previously ( Watanabe et al, 2010 ; Mitchell et al, 2020 ), a SARS-CoV-2 specific model has not yet been developed. In the absence of a dose-response model, the Wells-Riley equation has been used for simple and quick assessments for airborne pathogens including SARS-CoV-2 ( Sze To and Chao, 2010 ).…”