Fueled by movies and books such as Outbreak, The Hot Zone, and The Coming Plague and spurred by sporadic media attention, reports of Ebola and Marburg hemorrhagic fevers have generated fear and curiosity among the American public. While such accounts are often presented in a highly dramatic, graphic, and sensational manner, they have succeeded in periodically bringing public attention to the threat of emerging viral infections. Coverage of emerging infections, however, waxes and wanes in accordance with the general populace’s attention span, while the threat of emerging diseases continues unabated. The Ebola outbreak of 1995 received a great deal of media coverage, but subsequent large outbreaks in Gabon and Uganda went largely unnoticed by most of the world’s press, as were the preliminary stages of the AIDS pandemic in Africa. In addition to the threat of future outbreaks, which may continue to kill hundreds of humans in sub-Saharan Africa, thousands of members of endangered nonhuman primate species, including gorillas, have already died in their sanctuaries in West Africa, further challenging the survival of these animal populations.

The first known instance of Marburg hemorrhagic fever (MHF) occurred in 1967 in vaccine production facilities in Marburg and Frankfurt, Germany, and Belgrade, Serbia (at the time, part of Yugoslavia). The outbreak began among 25 persons working with African green (vervet) monkeys from Uganda (primary cases) and later spread to six of their family members or health care workers (secondary cases). Seven of the primary cases died (mortality rate of 28% among primary cases).

Another small outbreak occurred in 1975, originating with a tourist who had a history of recent travel in Zimbabwe and South Africa. Two cases of secondary infection resulted: a traveling companion and a nurse, both of whom survived. In 1980, two persons were infected in western Kenya. These people had visited the Kitum cave, which was believed to be the source of the infection. Later, researchers placed sentinel animals in the cave, but none of them became infected. A large number of different animal species were trapped in the vicinity of the cave (including rodents, bats, insects, grazing animals, and large African cats). These also had no sign of the causative virus. Laboratory tests did find, however, that the virus is able to replicate in experimentally infected bats. Lake Victoria marburgvirus (Marburg virus), the causative agent, has subsequently led to disease in several areas of Africa, including Uganda, western Kenya, South Africa, and Zimbabwe. Far more deadly epidemics of MHF occurred among gold miners near Durba in the Democratic Republic of Congo (DRC; formerly Zaire) in 1998–2000, with 154 cases and 128 deaths (mortality rate of 83%) and in the Uige province of Angola in 2004–2005 (374 cases, 88% mortality). An outbreak of MHF also occurred in 2008 in a bat-infested mine in Uganda. Disease spread in many of these outbreaks was amplified by unsanitary injections given in health care centers or private clinics or by self-administration in homes.

A similar disease, Ebola hemorrhagic fever (EHF), emerged in 1976 in two simultaneous outbreaks involving over 550 persons in the DRC and Sudan. The mortality rate was very high—88% in Zaire and 53% in Sudan. The outbreak in the DRC began in a missionary hospital in Yambuku, in the vicinity of the Ebola River, and spread rapidly among patients, health care providers, and patients’ relatives. The patients were taken to a regional center in Kinshasa. Most of the primary cases (72 of 103, or 70%) were spread by the local hospital via improperly sterilized needles used for multiple patients. Of the persons infected by secondary contact with an infected person, 43% survived, compared to only 7.5% of those infected by a contaminated needle. In that outbreak, the Ebola strain was passed for four generations in humans and then disappeared for no apparent reason.

At approximately the same time, a separate epidemic of this hemorrhagic fever began in Maridi and N’zara in Sudan and rapidly spread to members of the medical staff. This outbreak had a lower mortality rate than that occurring concurrently in the DRC. An investigator in Porton Down, England, was subsequently infected with virus from this outbreak following an accidental injection into his thumb. He was given antifungal medication, interferon, and immune serum and survived the infection. The major risk factors in this outbreak were determined to be the performance of local rituals of preparing relatives’ bodies for funerals and association with the regional hospitals (nosocomial spread). Up to 30% of the health care workers became infected in this outbreak. N’zara had a population of approximately 20,000 and was the economic center of the area due to its cotton factory. This factory was infested with bats, rats, boll weevils, and spiders, and all of the early cases were among factory workers. This outbreak passed through at least eight generations in humans. Over 400 miles separated these epidemics in the DRC and Sudan. Due to the extremely poor road conditions at the time, the differences in mortality rates, and differential ability to survive multiple passages in humans, it is unlikely that the disease was spread to Sudan by a person traveling between the two areas; it is more likely that these were separate outbreaks involving different strains of the causative agent, which were later designated as Zaire ebolavirus (Ebola Zaire) and Sudan ebolavirus (Ebola Sudan).

Both the Marburg and Ebola viruses cause serious and often fatal hemorrhagic fever in humans and some nonhuman primates. Pathological responses entail an intense, systemic inflammatory response similar to septic shock, resulting from an overwhelming activation of infected monocytes, macrophages, and dendritic cells, which produce large amounts of proinflammatory cytokines. This hyperactivation of the innate immune system is responsible for much of the subsequent pathology induced by filoviruses. The severity of the symptoms and the high mortality rates associated with these diseases have made them popular topics for the media and for several best-selling movies and books.

Marburg Hemorrhagic Fever (MHF)

Marburg hemorrhagic fever (MHF) has an abrupt onset with severe headache, high fever, chills, and back pain. This is followed by severe watery or bloody diarrhea, abdominal cramping, vomiting, and a rash on the trunk. Severe bleeding (hemorrhaging) occurs from multiple sites, particularly the gastrointestinal tract, gums, eyes, and lungs, within five to seven days of onset. Disease manifestations include jaundice, inflammation of the pancreas, severe weight loss, delirium, central nervous system involvement, terminal shock, liver failure, pulmonary edema, and multiorgan dysfunction. Major lesions may be present in the liver (focal hepatic necrosis), spleen, lymph nodes (follicular necrosis), and kidneys and are accompanied by hemorrhaging in the gastrointestinal tract; the pleural, pericardial, and peritoneal spaces; and the renal (kidney) tubules. Laboratory findings include severe thrombocytopenia, leading to the hemorrhagic manifestations; hemoconcentration; and amylase, blood urea nitrogen, creatinine, and transaminase elevation, with aspartate aminotransferase (AST) greater than alanine aminotransferase (ALT). A profound leucopenia may result from apoptosis of lymphocytes; the resultant drop in immunity may lead to secondary bacteremia. Death may occur after 7 to 16 days due to shock resulting from severe decreases in blood pressure following hemorrhaging. The mortality rate ranges from 23% to 88%. MHF occurs in humans, Old World primates, and guinea pigs but not in mice or New World primates.

Ebola Hemorrhagic Fever (EHF)

Infection with the Ebola Zaire or Ebola Sudan virus results in a disease similar to MHF. Following an incubation period of 2 to 21 days (most commonly, 7 to 14 days), Ebola hemorrhagic fever (EHF)