ABSTRACT
Viral hemorrhagic fevers (VHFs) are acute clinical syndromes caused by diverse viruses that have a distinct vasotropism. Capillaropathy, coagulation abnormalities, fever, hemorrhages, and high lethality are hallmarks of the clinical presentation of VHFs (1,2). Hemorrhages typically occur because of increased endothelial permeability or potentially endothelial destruction due to viral replication. Contrary to widespread belief, however, hemorrhages are almost never severe enough to cause life-threatening hypovolemia (3). Instead, lethal disease outcomes are usually a direct consequence of aberrant innate immune responses (4). Dendritic cells, which are probably an initial target of most VHF-causing viruses, become rapidly impaired. Lymphocytes undergo mass apoptosis, and infected macrophages and other cells release an abundance of diverse cytokines (5). Together, these events lead to decreased directed immune responses to infected cells, altered vascular function, coagulopathy frequently resulting in focal organ necroses due to clogged microvasculature, and, eventually, death due to multiorgan failure (6).
