Epidemiology and pathogenesis of filovirus infections

Filoviruses, including Ebola and Marburg, are among the deadliest viruses known and are capable of causing severe hemorrhagic fever outbreaks with case fatality rates as high as 90%, depending on the virus. Almost all filovirus outbreaks have so far originated and occurred in Africa, with a frequency that has been increasing since the first outbreak was recorded in 1967. Mounting ecological and epidemiological evidence now implicates several species of bats as at least one reservoir for filoviruses. Studies suggest that contact with these animals, as well as certain other susceptible hosts, including primates, plays a significant role in transmitting virus to humans. Indeed, it is thought that human filovirus outbreaks originate from multiple spillover events from a widely distributed reservoir or host, an assertion that is supported by serological evidence indicating a potentially large geographic distribution of these viruses. In humans, most filoviruses cause severe hemorrhagic fever that often results in death precipitated by multi-organ failure and shock. Early infection of phagocytic cells permits rapid and systemic virus replication that elicits the formation of a cytokine storm and a critically dysfunctional immune system. The defective immune response, in conjunction with massive virus replication, results in the coagulation and vascular abnormalities that are hallmarks of filovirus hemorrhagic fevers, as well as the extreme organ and tissue damage that, in many cases, overwhelms the patient. Despite the increasing frequency of filovirus outbreaks, and the risk of importation or bioterrorism, there are still no licensed vaccines or therapeutics to treat filovirus infections.