Both Marburg virus and Ebola virus cause an acute febrile illness associated with a high mortality rate. This illness is characterized by multisystem involvement that begins with the abrupt onset of headache, myalgias, and fever and proceeds to prostration, rash, and shock and often to bleeding manifestations. Epidemics usually begin with a single case acquired from an unknown reservoir in nature (bats are suspected; see “Epidemiology,” below) and spread mainly through close contact with sick persons or their body fluids, either at home or in the hospital.
The family Filoviridae (Fig. 197-1) comprises two antigenically and genetically distinct genera: Marburgvirus and Ebolavirus. Ebolavirus has five readily distinguishable species named for their original sites of recognition: Zaire, Sudan, Côte d′Ivoire, Bundibugyo, and Reston. Except for the Reston virus, all the Filoviridae are African viruses that cause severe and often fatal disease in humans (Figs. 197-2 and 197-3). The Reston virus, which has been exported from the Philippines on several occasions, has caused fatal infections in monkeys but only subclinical infections in humans. Different strains of the five Ebola species, isolated over time and space, exhibit remarkable sequence conservation, indicating marked genetic stability in their selective niche.
Phylogenetic tree of filoviruses. Marburgvirus and Ebolavirus are seen to be two different genera. The genus Ebolavirus includes five distinct species. Note that the Yambuku and Kikwit Zaire viruses are virtually identical even though the epidemics for which they were responsible are separated by two decades and hundreds of kilometers. Virtually every virus sequenced from each of those two epidemics is identical over the part of the genome examined. This pattern is typical of that seen with single introductions followed by human-to-human passage via needle or close contact in an African hospital. In the Marburgvirus branch of the tree, there is one major clade with a slightly divergent group characterized by the Ravn 1987 Kenya isolate. All the viruses from the major Angola 2005 outbreak are represented by a single virus because the sequences in this human-to-human epidemic are virtually identical. However, in the outbreak occurring in the Democratic Republic of the Congo (DRC) in 1999 and resulting from multiple independent infections after cave entry, two viruses with slightly different phylogenies are represented within the major group, and there is even another virus within the Ravn subgroup. These sequences were selected from hundreds determined at the U.S. Centers for Disease Control and Prevention and elsewhere. (Adapted from Peters, 2010.)
Left: Geographic sites of Ebolavirus species identification, as represented by dots (yellow, Zaire; green, Sudan; red, Côte d'Ivoire; black, Bundibugyo), in or adjacent to the Central African primary or secondary forest. Even Ebolavirus Côte d'Ivoire was isolated in the Tai forest reserve. Right: Amplified map of Uganda shows the zone along the border of the Democratic Republic of the Congo (DRC, formerly Zaire) where the newest Ebolavirus species, Bundibugyo, was identified. Bundibugyo and the nearby town of Kikyo, which was also affected by this epidemic, are tourist destinations close to the Ugandan capital of Kampala. (Adapted from Peters, 2010.)
Maps of the African continent and the country of Gabon (with adjacent Republic of the Congo) show the geographic distribution of Marburgvirus identification. Red dots indicate a case or an epidemic. Uige, Angola, is the site of the largest Marburg epidemic (252 cases, 90% mortality rate). The Angolan strains differ by only 0–0.07% at the nucleotide level (Fig. 197-1). The Durba outbreak lasted 3 years and was characterized by multiple introductions of virus into men entering a subterranean mine. Nine distinct lineages were detected, of which one was in the rather distant (21%) Ravn lineage. Red dots on the Gabon map indicate detection of virus in bats by PCR. (Adapted from Peters, 2010.)
Typical filovirus particles contain a single linear, negative-sense, single-stranded RNA arranged in a helical nucleocapsid. The virions are 790–970 nm in length; they may also appear in elongated, contorted forms (Fig. 197-4). The lipid envelope confers sensitivity to lipid solvents and common detergents. The viruses are largely destroyed by heat (60°C, 30 min) and by acidity but may persist for weeks in blood at room temperature. The glycoprotein self-associates to form the virion surface spikes, which presumably mediate attachment to cells and fusion. The glycoprotein's high sugar content may contribute to its low capacity to elicit effective neutralizing antibodies. A smaller form of the glycoprotein, bearing many of its antigenic determinants, is produced by in vitro–infected cells and is found in the circulation in human disease; it has been speculated that this circulating soluble protein may suppress the immune response to the virion surface protein or block antiviral effector mechanisms. Both Marburg virus and Ebola virus are biosafety level 4 pathogens because of their high associated mortality rate and aerosol infectivity.
Ebola virions: diagnostic specimen from the first passage in Vero cells of a blood sample from a patient. Some of the filamentous (negatively stained) virions were fused together, end-to-end, giving the appearance of a "bowl of spaghetti." This image was from the first isolation and visualization of Ebola virus in 1970. (Courtesy of Fredrick A. Murphy, MD, University of Texas Medical Branch, Galveston, Texas; with permission.)
Marburg virus was first identified in Germany in 1967, when infected African green monkeys (Cercopithecus aethiops) imported from Uganda transmitted the agent to workers in a vaccine laboratory. Of the 25 human cases acquired from monkeys, seven ended in death. ...