Ebola hemorrhagic fever and septic shock.

Ebola virus is the cause of sporadic outbreaks of lethal Ebola hemorrhagic fever (EHF) in central Africa. Despite the difficulties of studying this virus, much has been learned over the past decade about the pathogenesis of Ebola virus infection in humans and nonhuman primates. Two articles in this issue of the Journal of Infectious Diseases report further progress. The article by Bosio et al. [1] confirms findings that the virus is able to infect den-dritic cells (DCs), impairing their innate antiviral activity and limiting their ability to initiate adaptive immune responses [2]. The article by Geisbert et al. [3] identifies a molecular trigger for disseminated in-travascular coagulation (DIC) through the expression of tissue factor (TF) on the surface of virus-infected monocytes and mac-rophages. Together, these findings shed light on early events that both permit rapid viral dissemination and cause some of the major features of EHF. Geisbert et al. [3] note that TF expression by monocytes and macrophages has also been identified as the basis of the DIC that is seen in septic shock and point out that 2 other features of EHF, high levels of circulating proinflammatory cytokines and lymphocyte apoptosis, also occur in severe bacterial infections. Other investigators have also noticed these similarities and have suggested that the comparison of EHF with septic shock could lead to insights into pathogenesis and to improvements in therapy [4]. Although viral and bacterial infections obviously differ in fundamental respects, it is now recognized that the interactions of pathogens or their components with pattern-recognition receptors on macrophages and related cells tend to evoke fairly similar sets of innate responses. It is therefore worth comparing EHF with septic shock to see to what extent they share basic mechanisms of pathogenesis. To do this, it is first necessary to describe the basic features of each syndrome. The limited published information on human Ebola virus infection has almost all been obtained during recent outbreaks caused by the Zaire subtype, in which reported case-fatality rates have ranged from ∼60% to 90% [5–7]. High fever, prostra-tion, and a variety of nonspecific signs and symptoms begin about a week after exposure to the virus, often leading to steadily worsening coagulopathy, shock, and death during the second week of illness. A maculopapular rash may be noted early in the course of disease, but the clinical picture otherwise lacks specific diagnostic features. For this reason, the first individuals to become …