There is limited knowledge of the pathogenesis of human
ebolavirus infections and no reported human cases acquired by the
aerosol route. There is a threat of ebolavirus as an aerosolized
biological weapon, and this study evaluated the pathogenesis of
aerosol infection in 18 rhesus macaques. Important and unique findings include early
infection of the respiratory lymphoid tissues, early
fibrin deposition in the splenic white pulp, and perivasculitis and
vasculitis in superficial dermal blood vessels of haired skin with
rash. Initial
infection occurred in the respiratory lymphoid tissues, fibroblastic reticular cells, dendritic cells, alveolar macrophages, and blood monocytes. Virus spread to regional lymph nodes, where significant viral replication occurred. Virus secondarily infected many additional blood monocytes and spread from the respiratory tissues to multiple organs, including the liver and spleen.
Viremia, increased temperature,
lymphocytopenia, neutrophilia,
thrombocytopenia, and increased
alanine aminotransferase,
aspartate aminotransferase, γ-
glutamyl transpeptidase, total
bilirubin, serum
urea nitrogen,
creatinine, and
hypoalbuminemia were measurable mid to late
infection.
Infection progressed rapidly with whole-body destruction of lymphoid tissues, hepatic
necrosis,
vasculitis,
hemorrhage, and extravascular
fibrin accumulation.
Hypothermia and
thrombocytopenia were noted in late stages with the development of
disseminated intravascular coagulation and
shock. This study provides unprecedented insight into pathogenesis of human
aerosol Zaire
ebolavirus infection and suggests development of a medical countermeasure to
aerosol infection will be a great challenge due to massive early
infection of respiratory lymphoid tissues. Rhesus macaques may be used as a model of
aerosol infection that will allow the development of lifesaving medical countermeasures under the Food and Drug Administration's animal rule.