The first outbreak of human VHF caused by a filovirus, Marburg virus, occurred in 1967 in Germany and Yugoslavia. In 1976, simultaneous outbreaks of two distinct Ebola virus subtypes erupted near the Ebola River Valley in Zaire and southern Sudan, resulting in hundreds of deaths. Since then, additional reports of human VHFs secondary to filoviruses have appeared sporadically, mainly in Africa, with mortality rates ranging from 50 to 90 percent. Outbreaks involving the Ebola virus subtypes, however, have remained the most deadly .
There are currently four recognized subtypes of Ebola virus: Zaire (the most aggressive), Sudan, Reston, and Côte d'Ivoire. The Reston subtype is pathogenic in monkeys but does not cause lethal infection in humans. Epidemiological evidence suggests that transmission of Ebola virus to humans usually occurs after direct contact with blood, secretions, or tissues of affected patients or nonhuman primates. Following infection, patients initially present with an unremarkable symptom complex that includes fever, headache, muscle pain, nausea, vomiting, abdominal pain, and diarrhea. As the infection progresses, patients exhibit marked thrombocytopenia with abnormal platelet aggregation, and coagulation abnormalities, which together cause severe bleeding often involving the gastrointestinal tract and conjunctiva. Exaggerated inflammatory responses and hematological irregularities, including lymphopenia with subsequent neutrophilia, are also often observed. Although the viral infection can run its course in 14 to 21 days, damage to the liver, combined with massive viremia, can lead to disseminated intravascular coagulopathy (DIC). Death is usually associated with shock characterized by fluid distribution abnormalities (secondary to increased vascular permeability), hypotension, variable degrees of hemorrhages, and widespread focal tissue destruction, especially affecting the liver, lymphoid organs, and kidneys.
Unfortunately, current treatment options for filovirus infection consist primarily of contact isolation and supportive care. The identification of suitable therapeutic targets for effective antiviral therapies or vaccines requires a strong understanding of the pathogenesis of these enigmatic viruses . In this regard, there are many questions that remain unanswered about the filoviruses. Among them are explanations for their extreme virulence, the differences in aggressiveness among the different subtypes, and the specific mechanisms that facilitate their pathogenicity. Although many of these questions remain unanswered, emerging evidence suggests that the vascular endothelium is a principle target in Ebola pathogenesis.
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