Abstract
An inhalation exposure system was characterized to deliver aerosolized monkeypox virus (MPXV), and a non-human primate (NHP) inhalation monkeypox model was developed in cynomolgus macaques. A head-only aerosol exposure system was characterized, and two sampling methods were evaluated: liquid impingement via an impinger and impaction via a gelatin filter. The aerosol concentrations obtained with the gelatin filter and impinger were virtually identical, indicating that either method is acceptable for sampling aerosols containing MPXV. The mass median aerodynamic diameter (MMAD) for individual aerosol tests in the aerosol system characterization and the NHP study ranged from 1.08 to 1.15 μm, indicating that the aerosol particles were of a sufficient size to reach the alveoli. Six cynomolgus macaques (four male and two female) were used on study. The animals were aerosol exposed with MPXV and received doses between 2.51 × 104 to 9.28 × 105 plaque forming units (PFUs) inhaled. Four of the six animals died or were euthanized due to their moribund conditions. Both animals that received the lowest exposure doses survived to the end of the observation period. The inhalation LD50 was determined to be approximately 7.8 × 104 pfu inhaled. These data demonstrate that an inhalation MPXV infection model has been developed in the cynomolgus macaque with disease course and lethal dose similar to previously published data.
Highlights
Smallpox, caused by the variola virus, a member of the Poxviridae family, is a highly contagious and debilitating systemic disease that is lethal to approximately 25% of its victims (Fenner et al, 1988, 1989)
The aerosol concentrations obtained with the filter compared to the impinger were virtually identical, indicating that either method is acceptable for sampling aerosols containing monkeypox virus (MPXV) (Figure 1)
The aerosol contained particles with mass median aerodynamic diameter (MMAD) of 1.10 μm and ranged from 1.08–1.15 μm for each individual test, and the geometric standard deviation (GSD) was 1.61 μm with a range of 1.58–1.64 μm for each individual test. These results indicated that the aerosol distribution was relatively monodispersed and contained particles capable of reaching the deep lung in animal testing (Schlesinger, 1985)
Summary
Smallpox, caused by the variola virus, a member of the Poxviridae family, is a highly contagious and debilitating systemic disease that is lethal to approximately 25% of its victims (Fenner et al, 1988, 1989). The World health Organization (WHO) initiated in 1959 a global operation to eradicate smallpox through vaccination, with the last case reported in 1977. Control of a smallpox outbreak poses significant challenges to first responders and local and national health care systems. The current international strategy for control of a smallpox outbreak calls for mass immunization of the general population with the vaccinia virus vaccine (CDC Smallpox Response Plan; Executive Summary, 2003). In preparation for this contingency, health care workers and many in the US military are currently being vaccinated. Vaccinia vaccination was the cornerstone of the smallpox eradication campaign, and much of the world was vaccinated during that effort. To control an outbreak today, vaccination of at risk individuals would be enacted
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