Animal models of viral hemorrhagic fever

• Viral hemorrhagic fever (VHF) is a syndrome of febrile illness, increased vascular permeability and coagulation defects.
• The causative agents are some 20 different RNA viruses that are transferred to humans from animals.
• Treatments exist for Lassa fever and Argentine HF, but not for other types of VHF.
• Animal models that reproduce the VHF syndrome are critical for the evaluation of medical countermeasures.
• This article reviews currently available animal models for the different types of VHF.

The term “viral hemorrhagic fever” (VHF) designates a syndrome of acute febrile illness, increased vascular permeability and coagulation defects which often progresses to bleeding and shock and may be fatal in a significant percentage of cases. The causative agents are some 20 different RNA viruses in the families Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae, which are maintained in a variety of animal species and are transferred to humans through direct or indirect contact or by an arthropod vector. Except for dengue, which is transmitted among humans by mosquitoes, the geographic distribution of each type of VHF is determined by the range of its animal reservoir. Treatments are available for Argentine HF and Lassa fever, but no approved countermeasures have been developed against other types of VHF. The development of effective interventions is hindered by the sporadic nature of most infections and their occurrence in geographic regions with limited medical resources. Laboratory animal models that faithfully reproduce human disease are therefore essential for the evaluation of potential vaccines and therapeutics. The goal of this review is to highlight the current status of animal models that can be used to study the pathogenesis of VHF and test new countermeasures.