As I've noted before, filoviruses are some of my favorite pathogens. I don't work on them myself--though in the pre-children era I certainly thought about it--but I find them absolutely fascinating to read about and follow the literature. Mostly, I think, this is because after knowing about them for so many years (Marburg was discovered in 1967), and so much research (over 1500 papers in Pubmed, or roughly a paper for every person these viruses have killed), we still know relatively little about the most basic questions--such as where there viruses are maintained in nature, and how they enter the human (or non-human primate) population, and why they're so deadly.

Anyway, after a long time in Ebola's shadow, Marburg virus has been in the news recently. As such, this is part one in a mini-series on Marburg virus, with an introduction to the virus and its history after the jump.

[See also Marburg in bats: has the elusive reservoir species been found?]

The year was 1967. Several laboratory workers, all from the same lab in Marburg, Germany, were hospitalized with a severe and strange disease. The physicians on staff realized the workers were all suffering from the same ailment, with symptoms that included fever, diarrhea, vomiting, massive bleeding from many different organs, shock, and eventually circulatory system collapse. An investigation began in an attempt to uncover the source of the outbreak. This led to the identification of the source of the virus in Germany: a species of African green monkeys, imported from Uganda, which were being used by the scientists for polio vaccine research. The virus was isolated, and found to exhibit a unique morphology, leading to the designation of a new group: the Filoviridae In that outbreak, a total of 31 human cases were observed, and the disease presented with a 23% mortality rate (7 deaths occurred out of 31 total infections).

After this episode, the virus went back into hiding for almost a decade, not surfacing again until 1975 in South Africa. The origin of this outbreak is unknown, although based on epidemiological studies it is assumed that the index case (the first person known to have been infected), a young man hitchhiking through Africa, acquired the disease in Zimbabwe, and then infected 2 others in South Africa when he arrived there. Only the index case died from the disease; the secondary cases (those infected due to contact with the index case) survived.

Marburg again disappeared until one case was reported in Kenya in 1980, and again in 1987 in the same area. In the first outbreak, again only the index case died, while a second patient survived. Only one infection was noted in the 1987 outbreak, resulting in death of the patient. Both of these Kenyan outbreaks occurred in the vicinity of a volcano named Mount Elgon, and there is evidence both index cases had spent time in a cave inside the mountain. This has led to (unconfirmed) speculation that bats may be a reservoir for filoviruses; a hypothesis which will be discussed in more detail in later posts.

Between 1987 and 1998, the only cases of Marburg were due to laboratory accidents, both in the former Soviet Union. One of these cases was fatal. However, in 1998, the largest natural outbreak of Marburg virus disease to date began in northeastern Democratic Republic of the Congo (DRC). This time, the focus of the outbreak was a town called Durba (population 16,000). A large number of men in this region work for the Kilo Moto Mining Company, which runs a number of illegal gold mines in the area. Working in this area is precarious; civil war broke out in 1996, and the socio-economic situation has deteriorated since then. Infectious diseases of all types are common, as vaccinations and medication are in short supply. The Marburg outbreak is thought to have started in November of 1998, although it was not reported to any international agencies until late April of 1999, following the death of the chief medical officer in the area from the disease.

At this time, local officials contacted the Medecins sans Frontieres (Doctors without Borders) in Belgium regarding the ongoing hemorrhagic fever epidemic. Both this group and their sister group in Holland sent officers to investigate and to stem the spread of the epidemic. Patient samples were immediately sent to the National Institute of Virology in Johannesburg, South Africa; a diagnosis of Marburg virus as the cause of the illness was made on May 6th. Barrier nursing procedures were instituted, and isolation wards were fashioned at the hospital. Over the course of the epidemic, 149 cases with 123 deaths were recorded (83% fatality rate). Miners were found to be at a significantly higher risk of contracting Marburg than the general population of this area, suggesting they may be more frequently exposed to the natural reservoir of Marburg virus.

This outbreak was eclipsed beginning in 2004, when Marburg hit Angola in the fall. Due to civil war in the country and a non-existent public health infrastructure, the outbreak wasn't identified until almost 6 months later, in March of 2005. 252 people were infected, with 227 deaths (90% fatality rate). The outbreak was declared over in November of 2005, after no additional cases had been reported since summer.

This brings us to present-day Uganda, where another Marburg outbreak is ongoing, again associated with miners. So far, this one has been minor, and seems to be contained; meanwhile, back in the DRC, there comes a report of another outbreak of hemorrhagic fever. It's not known at the time what the causative agent is, but a hundred deaths have already been reported:

The deaths began following the funeral of 2 village chiefs. "Everyone that attended those funerals is now dead," said the medical inspector. According to Kanow, haemorrhagic fever is transmitted by contact with an infected person. In all, 4 villages are affected and 217 people have come down with the illness.

Is this the next Marburg or Ebola outbreak? A number of other pathogens can cause hemorrhagic fever, but the geography and epidemiology do point to either Marburg or Ebola as likely agents. It appears that Marburg infection is endemic in this area of the DRC; thus, sporadic cases are expected. The instability and conflict in this region makes it difficult to supply regular international aid; thus, it is likely that we will see future outbreaks in this region. More information on the reservoir and transmission of this virus would go a long way toward controlling both Marburg and Ebola virus infections in this region.

Images from http://www.who.int/features/marburg/02.jpg

Additional references and resources:

Bausch DG, et al. 2003. Risk factors for Marburg hemorrhagic fever, Democratic Republic of the Congo. Emerg. Infect. Dis. 9:1531-1537.

Beer B, Kurth R. 1999. Characteristics of Filoviridae: Marburg and Ebola Viruses. Naturwissenschaften, 86:8-17.

Burton, A. Marburg Miner Mystery. The Lancet Infections Diseases, Vol. 4, 2004

Preston, R. 1994. The Hot Zone. New York: Random House.