Ebola haemorrhagic fever

Abstract

Ebola viruses are the causative agents of a severe form of viral haemorrhagic fever in man, designated Ebola haemorrhagic fever, and are endemic in regions of central Africa. The exception is the species Reston Ebola virus, which has not been associated with human disease and is found in the Philippines. Ebola virus constitutes an important local public health threat in Africa, with a worldwide effect through imported infections and through the fear of misuse for biological terrorism. Ebola virus is thought to also have a detrimental effect on the great ape population in Africa. Case-fatality rates of the African species in man are as high as 90%, with no prophylaxis or treatment available. Ebola virus infections are characterised by immune suppression and a systemic inflammatory response that causes impairment of the vascular, coagulation, and immune systems, leading to multiorgan failure and shock, and thus, in some ways, resembling septic shock.

Figure 1. Locations of Ebolavirus infections and outbreaks

(A) Regions in Africa (approximate distribution 10° north and south of the equator) with reported outbreaks of Ebola haemorrhagic fever caused by the three central African species of Ebola virus, Zaire Ebola virus (ZEBOV), Sudan Ebola virus (SEBOV), and Bundibugyo Ebola virus (BEBOV). The Tai Forest region in Côte d’Ivoire reported the only case so far of Ebola virus in western Africa caused by the species Côte d’Ivoire Ebola virus (CIEBOV). (B) Reston ebolavirus REBOV has been introduced several times through imported macaques into USA from 1989 to 1996 (Philadelphia, PA; Reston, VA; San Antonio, TX) and into Italy (Siena) in 1992 (C). The source of the introduction in all cases of REBOV has been a primate export facility in the Philippines (Ferlite farm) (D). Animals of this farm have been diagnosed with REBOV infection several times in the 1990s. REBOV has been detected in pigs on two farms in the Philippines (Pangasinan, Bulacan). DRC=Democratic Republic of the Congo.

Figure 2. Model of Ebola virus pathogenesis

Virus spreads from the initial infection site (small lesions) to regional lymph nodes, liver, and spleen. Although Ebola virus does not infect lymphocytes, their rapid loss by apoptosis is a prominent feature of disease. The direct interaction of lymphocytes with viral proteins cannot be discounted as having a role in their destruction, but the substantial loss of lymphocytes probably results from a combination of factors including infection-mediated impairment of dendritic cells and release of soluble factors from monocytes and macrophages. Soluble factors released from target cells also contribute to the impairment of the vascular system leading to vascular leakage as demonstrated here in cultures of endothelial cells (white arrowheads). The systemic virus spread and replication, the general dysregulation of the host immune response, the coagulation abnormalities, the impairment of the vascular system, and hypotension all together finally result in shock and multiorgan failure. IL=interleukin. MCP-1=monocyte chemoattractant protein-1. MIPs=macrophage inflammatory proteins. NO=nitric oxide. TNFα=tumour necrosis factor α.

Figure 3. Haemorrhagic manisfestations noted in non-human primates infected with Ebola virus

Petechiae on the arm and axillary region of a Cynomolgus monkey infected with Sudan Ebola virus (A). Also shown are haemorrhages in the ileum (B) and a gastroduodenal lesion (C) from a Cynomolgus monkey infected with Sudan Ebola virus and fibrin thrombi (arrows) in sinusoids of a rhesus monkey infected with Zaire Ebola virus (D).