Reemergence of Ebola Virus in Africa

Members of the family Filoviridae, which currently consists of Ebola and Marburg viruses, cause severe and often fatal hemorrhagic fevers in humans and nonhuman primates. The recent isolation and identification of a new Ebola virus from a single nonfatal human case in Côte d’Ivoire (1) and the more recent outbreak of Ebola hemorrhagic fever in and around Kikwit, Zaire (2, 3), have raised concerns about the public health threat of these human pathogens. Filoviruses are classified as biosafety level 4 agents because of the extreme pathogenicity of certain strains and the lack of a protective vaccine or effective antiviral drug. Moreover, filoviruses are among the most mysterious groups of viruses known because their natural history and reservoirs remain undefined and their pathogenesis is poorly understood. Ebola virus infections were first recognized in 1976, when simultaneous but separate outbreaks of human disease caused by two distinct virus subtypes erupted in northern Zaire and southern Sudan (4) and resulted in hundreds of deaths. The Zaire subtype of Ebola virus had a higher case-fatality, nearly 90%, while the Sudan subtype had a case-fatality rate of approximately 50%. Before 1995, the last identified outbreak of Ebola disease in Africa occurred in 1979, when the Sudan subtype of Ebola virus infected 34 persons (5). In late 1989, in Reston, Virginia, a novel Ebola virus infected a colony of cynomolgus macaques that had been imported from the Philippines (6). The new virus, named Reston virus, was shown by researchers at the Centers for disease Control and Prevention (CDC) to be antigenically and genetically distinct from the African Ebola viruses, yet despite its high pathogenicity for nonhuman primates, it did not appear to cause disease in humans. Several persons who handled the infected animals developed antibody to Ebola virus but showed no signs of disease; one of these persons was infected while performing an autopsy on an animal that had died of a Reston virus infection. In 1992, a repeat of the 1989 Reston episode occurred in Siena, Italy when macaques were received from the same Philippine exporter; no evidence of a human infection was found (7). The new Ebola virus recently isolated from a patient in the Côte d’Ivoire has been shown to be genetically distinct from previous Ebola isolates (A. Sanchez, unpublished data) and is the first evidence of Ebola virus in West Africa. Investigations of these outbreaks, as well as of those caused by Marburg viruses, have yet to produce any substantial evidence for the natural reservoir(s) of filoviruses. Filoviruses do not persist in experimentally infected nonhuman primates; therefore, nonhuman primates are likely not the natural reservoir. Like humans, these species probably are infected when direct or indirect contact is made with the natural host. The recent news of a large Ebola outbreak in Kikwit, Zaire, alarmed a worldwide audience already sensitized by an array of books, magazine articles, television programs, and movies dealing with the danger of Ebola virus disease. The public concern is underscored by the potential for the spread of these viruses to far regions of the world as a result of international commerce and jet travel. The Kikwit outbreak was similar to the original 1976 episode in Zaire, which was centered around the small village of Yambuku some 1000 km to the north (8). As in the 1976 outbreak, secondary transmission of the virus in Kikwit occurred through close personal contact with infectious blood and other body fluids and was facilitated by the lack of modern medical facilities and medical supplies that could protect those giving care to the initially affected patients. The chief difference between the Yambuku episode and this year’s outbreak is that Kikwit is a large and densely populated center close to larger cities, such as Kinshasa and Brazzaville, and the potential for communitywide transmission and spread to neighboring areas is greater. Retrospective case surveillance suggests that the index case may have been a charcoal maker that worked in the forest outside Kikwit. Human to human transmission occurred without being recognized until the end of April 1995. Ebola hemorrhagic fever was suspected when nosocomial infections in the surgical teams and the nursing staff followed repeated laparotomies on an infected laboratory technician in Kikwit General Hospital. Specimens were send to CDC through the Tropical Institute of Antwerpen (Belgium). Teams of experts from CDC, the World Health Organization, Belgium, France, South Africa, and Sweden traveled to the region to assist in implementing safe patient care, management, and containment of the Ebola virus outbreak. As of July 1, 1995, 233 deaths had been reported among the 293 cases. Rapid diagnosis and characterization of Ebola virus was performed at CDC in Atlanta on blood specimens from 14 patients received on May 9. Nine hours after the specimens had been delivered to CDC, Ebola virus antigen and/or antibody to this virus was confirmed in specimens from 13 of the patients. Four hours later, reverse transcriptase-polymerase chain reaction (RT-PCR) assays targeting conserved regions of filovirus polymerase or Ebola virus glycoprotein genes each detected Ebola virus RNA in 12 of the patients. Subsequent analysis of the genetic profile of the virus was especially important to understanding the epidemiology of the Kikwit outbreak. Within 48 hours of receiving the specimens, sequence analysis on the PCR DNA (528 bp) amplified from the glycoprotein gene derived from four different patients showed that the Ebola virus Commentary