The Marburg virus is the causative agent of Marburg haemorrhagic fever (also known as green monkey disease). Both the disease and virus are related to Ebola and originate in Uganda and Eastern Congo. The zoonosis is of unknown origin, but Egyptian fruit bats are suspected. In the spring of 2005, the virus attracted widespread press attention for an outbreak in Angola.
In September 2007, New Scientist magazine reported that the virus has been found in cave-dwelling African fruit bats in Gabon, the first time the virus has been found outside humans and primates. A team in Uganda is also testing bats in a mine after two miners contracted Marburg in August 2007. Ebola genes (a close relative to Marburg) were found in three species of fruit bats in 2005. The same techniques used to identify those genes were also used to identify Marburg genes found in Egyptian fruit bats, Rousettus aegyptiacus. Marburg antibodies have now been found in healthy bats, suggesting that the bats had been previously infected. Although no-one has yet found complete live viruses from a bat, the team suggest that "[I] think we can be sure that these fruit bats are the reservoir of Marburg virus".
The viral structure is typical of filoviruses, with long threadlike particles which have a consistent diameter but vary greatly in length from an average of 800 to 14,000 nanometers (nm), with peak infectious activity at about 790 nm. Virions (viral particles) contain seven known structural proteins. While nearly identical to Ebola virus in structure, Marburg virus is antigenically distinct from Ebola virus; in other words, it triggers different antibodies in infected organisms. It was the first filovirus to be identified.
Because many of the signs and symptoms of Marburg haemorrhagic fever are similar to those of other infectious diseases, such as malaria or typhoid, diagnosis of the disease can be difficult, especially if only a single case is involved.
The disease is spread through bodily fluids, including blood, excrement, saliva, and vomit. Early symptoms are often non-specific, and usually include fever, headache and myalgia after an incubation period of three to nine days. After five days, a maculopapular rash is often present on the trunk. Later-stage Marburg infection is acute and can include jaundice, pancreatitis, weight loss, delirium and neuropsychiatric symptoms, haemorrhaging, hypovolemic shock and multi-organ dysfunction, with liver failure most common. Accounts of external haemorrhaging from bodily orifices are pervasive in popular references to the disease but are in fact rare. Time course varies but symptoms usually last for one to three weeks until the disease either resolves or kills the infected host. The fatality rate is from 23% to over 90%.
If a patient survives, recovery is usually prompt and complete, though it may be prolonged in some cases, with inflammation or secondary infection of various organs, including: orchitis (testicles), hepatitis (liver), transverse myelitis (spinal cord), uveitis (eyes), and parotitis (salivary glands).
There is no specific antiviral therapy indicated for treating Marburg, and hospital care is usually supportive in nature. Hypotension and shock may require early administration of vasopressors and haemodynamic monitoring with attention to fluid and electrolyte balance, circulatory volume, and blood pressure. Viral haemorrhagic fever (VHF) patients tend to respond poorly to fluid infusions and may develop pulmonary edema.
Caregivers require barrier infection control measures including double gloves, impermeable gowns, face shields, eye protection, leg and shoe coverings.
A few research groups are working on drugs and vaccines to fight the virus. In 1998, a group at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) published the first peer reviewed article detailing the development of the first experimental Marburg virus vaccine demonstrated to completely protect animals from lethal Marburg virus infection Following, in 2002, Genphar, a company doing research for the United States Army's biodefense program, announced that an experimental vaccine protected animals from a high dose of Marburg virus. The tests were conducted by the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). According to the company, all animals in the control group died within days whereas all animals that received the regular dosage of the vaccine were fully protected. The company has moved on to non-human primate trials. Late in 2003, the US government awarded the company a contract worth $8.4 million for what was described as "a multivalent Ebola, Marburg filovirus vaccine program".
In June 2005 scientists at Canada's National Microbiology Laboratory announced that they had also developed vaccines for both Marburg and Ebola that showed significant promise in primate testing. Studies on mice also suggested that the vaccine might be an effective treatment for the disease if it is administered shortly after a patient is infected. To make the vaccines the scientists fused a surface protein from the viruses they hope to protect against onto an animal virus - vesicular stomatitis - which is thought to be of no threat to humans. In the rhesus macaque monkey model of the disease, the vaccine is effective even when given after infection with the virus.
This virus was first documented in 1967, when 31 people became ill in the German town of Marburg, after which it is named, as well as in Frankfurt am Main and the then Yugoslavian city of Belgrade. The outbreak involved 25 primary infections, with 7 deaths, and 6 secondary cases, with no deaths. The primary infections were in laboratory staff exposed to the Marburg virus while working with monkeys or their tissues. The secondary cases involved two doctors, a nurse, a post-mortem attendant, and the wife of a veterinarian. All secondary cases had direct contact, usually involving blood, with a primary case. Both doctors became infected through accidental skin pricks when drawing blood from patients.
The outbreak was traced to infected African grivets of the species Cercopithecus aethiops taken from Uganda and used in developing polio vaccines. The monkeys were imported by Behringwerke, a Marburg company founded by the first winner of the Nobel Prize in Medicine, Emil von Behring. The company, which at the time was owned by Hoechst, was originally set up to develop sera against tetanus and diphtheria.
In 1975, three people in Johannesburg, South Africa were infected by the Marburg virus by a man returning from Zimbabwe, resulting in one death. Two similar cases in 1980 and 1987 occurred in Kenya after European visitors went to Kitum Cave. Both later died. The next major outbreak occurred in the Democratic Republic of Congo from 1998 to 2000, where 128 of 154 cases were fatal. This outbreak originated with miners in Durba and Watsa in Orientale, Congo.
In early 2005, the World Health Organization began investigating an outbreak of a then-undiagnosed haemorrhagic fever in Angola, which was centered in the northeastern Uige Province. The disease may have surfaced as early as March 2004 in a crowded children's ward. A doctor noted that a child, who subsequently died, was displaying signs of haemorrhagic fever. By October, the death rate on the ward went from three to five children a week to three to five a day. On March 22, 2005, as the death toll neared 100, the cause of the illness was identified as the Marburg virus. By July 2005, Angola's health department reported more than 300 cases were fatal. There were cases in 7 of 18 provinces but the outbreak was mostly confined to Uige province.
According to the World Health Organization, 80% of the deaths in the early stages of the Angola outbreak were children under the age of 15, but that dropped to 30 to 40% in later stages. The virus has also taken a toll on health care workers, including 14 nurses and two doctors.
There has been speculation that the high death rate among children in the early stages of this outbreak may simply be due to the initial appearance of the disease in the children's ward at the Uige hospital. Early death rates (prior to effective monitoring) are meaningless as only the dead are adequately counted.
|Month year||Deaths reported during month|
|April 2005||123 *|
|May 2005||80 †|
|WHO report date||Cumulative deaths||Deaths during prior week|
|April 8, 2005||180||48|
|April 15, 2005 *||207||27|
|April 22, 2005||244||37|
|April 29, 2005||255||11|
|May 6, 2005||277||22|
|May 11, 2005 †||276||-1§|
|May 18, 2005||311||35|
|May 27, 2005 ‡||335||24|
|June 7, 2005 ‡||357||22|
|June 17, 2005 ‡||356||-1§|
|July 13, 2005||312||n/a¶|
Countries with direct airline links, such as Portugal, screened passengers arriving from Angola. The Angolan government asked for international assistance, pointing out that there are only about 1,200 doctors in the entire country, with some provinces having as few as two. Health care workers also complained about a shortage of personal protection equipment such as gloves, gowns and masks. Médecins Sans Frontières (MSF) reported that when their team arrived at the provincial hospital at the center of the outbreak, they found it operating without water and electricity. Contact tracing is complicated by the fact that the country's roads and other infrastructure have been devastated after nearly three decades of civil war and the countryside remains littered with land mines.
One innovation in the Angola outbreak has been the use of a portable laboratory operated by a team of Canadian doctors and technicians. The lab, which can operate on a car battery, has eliminated the need to send blood samples outside the country for testing. This has reduced the turnaround time from days or weeks to about four hours.
Meanwhile, at Americo Boa Vida Hospital in the capital, Luanda, an international team prepared a special isolation ward to handle cases from the countryside. The ward was able to accommodate up to 40 patients, but there was some resistance to medical treatment. Because the disease almost invariably resulted in death, some people came to view hospitals and medical workers with suspicion and there was a brief period when medical teams were attacked in the countryside.
A specially-equipped isolation ward at the provincial hospital in Uige was reported to be empty during much of the epidemic, even though the facility was at the center of the outbreak. WHO was forced to implement what they described as a "harm reduction strategy" which entailed distributing disinfectants to affected families who refused hospital care. An education effort and an increase in the number of Angolan health practitioners in the outbreak area, resulted in improved relations with the community.
Marburg haemorrhagic fever was confirmed in a 29-year-old man in Uganda. The man became symptomatic on 4 July 2007, was admitted to hospital on 7 July and died on 14 July. The disease was confirmed by laboratory diagnosis on 30 July.
The man had had prolonged close contact with a 21-year-old co-worker with a similar illness to whom he had been providing care. The 21-year-old had developed symptoms on 27 June and was hospitalized with a haemorrhagic illness. He then recovered and was discharged on 9 July. Both men were working in a mine in western Uganda.
On July 10, 2008, the Netherlands National Institute for Public Health and the Environment, declared that a Dutch woman, who had visited a bat cave during her holiday in Uganda, had been infected with the Marburg virus, and had been admitted to a hospital in the Netherlands. The woman died when under treatment in the Leiden University Medical Centre in Leiden on 11 July.
The former Soviet Union reportedly had a large biological weapons program involving Marburg. The development was conducted in Vector Institute under the leadership of Dr. Nikolai Ustinov, who died after accidentally injecting himself with the virus. The post-mortem samples of Marburg taken from Dr. Ustinov's organs were more powerful than the original strain that he had infected himself with. This new strain, called "Variant U," was successfully weaponized and approved by Soviet Ministry of Defense in 1990. Bioterrorism grants in the United States are funding research to develop a vaccine for Marburg virus.