Marburg virus

Marburg virus
Marburg virus particles, approx 100,000x magnification
Virus classification
Group:	Group V ((-)ssRNA)
Order:	Mononegavirales
Family:	Filoviridae
Genus:	Marburgvirus
Species
Lake Victoria Marburgvirus

Marburg virus or simply Marburg is the common name for the the genus of viruses Marburgvirus, which contains one species, Lake Victoria marburgvirus. The virus causes the disease Marburg Hemorrhagic Fever (MHF), also referred to as Marburg Virus Disease, and previously also known as green monkey disease due to its primate origin. Marburg originated in Central and East Africa, and infects both human and nonhuman primates. The Marburg Virus is in the same taxonomic family as Ebola, and both are identical structurally although they elicit different antibodies.

Etymology

The genera Marburgvirus and Ebolavirus were originally classified as the species of the now nonexistent Filovirus genus. In March 1998, the Vertebrate Virus Subcommittee proposed to the International Committee on Taxonomy of Viruses (ICTV) to change the Filovirus genus to Filovirus family with two specific genera: Ebola-like viruses and Marburg-like viruses. This proposal was implemented in Washington DC as of April 2001 and in Paris as of July 2002. In 2000, another proposal was made in Washington DC to change the "-like viruses" to "-virus" (e.g. Ebolavirus, Marburgvirus) in addition to renaming the only species in the Marburgvirus genus from Marburg virus to Lake Victoria Marburgvirus.^[1]

The item "Marburg" was named after the location of the first outbreak in 1967 in Marburg, Germany.

Virology

Structure

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.

Genome

Marburg contains a single molecule of linear negative-sense, 19.1 kb single-stranded RNA.^[2]

Natural reservoir(s)

The epidemical Marburg virus was found in 2007 in specimens of the Egyptian fruit bat, confirming the suspicion that this species may be a reservoir for this dangerous virus¹¹¹. See Megabats.

Epidemiology

Prevalence

Outbreaks of Marburg are centered in Africa, where the natural reservoir is believed to be located.

Transmission

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 torso. 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%.^[3][4]

Medical aspects

Prevention

Caregivers require barrier infection control measures including double gloves, impermeable gowns, face shields, eye protection, leg and shoe coverings.

Marburg is a biosafety level-four agent (BSL-4), and thus requiring the highest level of precautions.^[5]

A few research groups are working on antiviral 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^[6] 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.

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 virus - which is thought to be of no threat to humans.^[7] In the rhesus macaque monkey model of the disease, the vaccine is effective even post-infection with the virus.^[8]

Symptoms

Many of the symptoms of Marburg haemorrhagic fever are similar to those of other infectious diseases, such as malaria or typhoid, but are most similar to those of Ebola strains.

Diagnosis

Diagnosis of Marburg is similar to Ebola using the Enzyme-Linked ImmunoSorbent Assay (ELISA) test.^[9] Polymerase Chain Reaction (PCR) technique has been successfully used for detection of Marburg virus. PCR detection for Marburg virus by Hänninen 2001

Prognosis

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)^[10] Recovered patients often have little or no memory of being sick, though only 10-40% survive.

Treatment

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.

History

Early outbreaks

This virus was first documented in 1967, when 31 people became ill in the German town of Marburg ( after which it is named) 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.^[11] This outbreak originated with miners in Durba and Watsa in Orientale, Congo.

2004-2005 Outbreak in Angola

In early 2005, the World Health Organization (WHO) 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.

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.

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 approximately 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 protective equipment (PPE) 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 4 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, suited in full protective gear, were gruesomely attacked in the countryside.^[12]

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.

* This represents the difference between WHO reports of April 1 and April 29.

† This represents the difference between WHO reports of April 29 and May 27.

* No WHO report was issued between the 15th and the 21st. This appears associated with the administrative reclassification of cases.

† Not an entire week. No WHO report for the 13th.

‡ Over a week.

§ No explanation provided for the decrease in cumulative deaths.

¶ Report states that a review of data has led to a downward estimation in total deaths.

2007-2008 Uganda cases

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 the Python 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.^[13] The Ugandan Ministry of Health closed the cave after this case.^[14]

2008 United States case

On February 9, 2009, it was reported that in January 2008, a US Citizen from Colorado was the 1st patient treated in the United States for Marburg. The patient had contracted the virus while overseas in Uganda and traveled back to the USA, where she was later treated successfully for the infection. [4],[5]

Weaponization

The former Soviet Union reportedly had a large biological weapons program involving Marburg.^[15] 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. This new strain, called "Variant U," was successfully weaponized and approved by Soviet Ministry of Defense in 1990.^[16] Bioterrorism grants in the United States are funding research to develop a vaccine for Marburg virus.^[17]

Popular culture

• In the TV series Millennium, at the End of Season 2 a prion version of the Marburg virus breaks out in Seattle, killing (amongst others) Frank Black's wife, Catherine. In the Season 3 Episode Collateral Damage Peter Watt's daughter is infected with the virus by a Gulf War Veteran who claims that the Millennium Group did the same to American soldiers in the First Gulf War.
• In the crossover event of the TV series Medical Investigation, episode 17, and Third Watch, season 6 episode 16, the Marburg virus breaks out in New York City, killing 5 from a total of 6 infected persons.
• In the TV series ReGenesis, episode 11, the source of an earlier Marburg outbreak is investigated.
• In the Sarah Jane Smith series of audios (Series Two) the virus is used as a weapon by a doomsday cult.
• In the novel Cain by James Byron Huggins, the being known as Cain, a genetically engineered monster, is infected with a modified form of the Marburg virus which, if released, could potentially wipe out humanity.
• In the short story Hell Hath Enlarged Herself by Michael Marshall Smith, one of the original scientists is infected with Marburg in an attempt to test ImmunityWorks ver. 1.0.
• In the novel Gravity by Tess Gerritsen, an outbreak of Marburg virus is suspected on the International Space Station. The infectious agent turns out to be not Marburg, but rather a chimera virus.
• In the non-fiction thriller, The Hot Zone, Richard Preston investigates the origins of incidents involving hemorrhagic fevers and both the Ebola and Marburg viruses.
• In the novel Microserfs by Douglas Coupland, the Marburg virus is mentioned several times as a metaphor for the spread of information through the internet.
• In the film WW3: Winds of Terror (2001), directed by Robert Mandel, a variant of Marburg becomes a deadly bioweapon that can be used by terrorists.
• In the Tamil (India) film Dasavatharam the protogonist Kamal Hassan tests this virus in combination with Ebola in a renowned American lab, places it in a vial, and escapes with it to India in order to avoid it being sold to terrorists.
• In the novel Resident Evil: Caliban Cove an insane scientist and former professor named Nicolas Griffith is referred to by Rebecca Chambers as having infected three men with the Marburg virus after they had been led to believe it was a harmless cold virus which the professor, using his mother's maiden name of Dunne, would then attempt to cure.
• In the novel Pandora's Legion by Harold Coyle and Barrett Tillman, an Al-Qaeda cell in Pakistan injects volunteers with Marburg virus, who then board flights to major international airports in the Western world where the large flow of people would facilitate the spreading of the virus into a pandemic.
• In the play Berlin Blues (2007), by Drew Hayden Taylor, Birgit Heinze says: "Actually I was born in Marburg. It's a lovely town. They named a strain of the Ebola virus after it, after it was identified in a lab there."^[18]
• In the USA network series Psych, a virus with similar symptoms and presentation called the "Thornburg" virus was the subject of an episode titled "Death is in the Air" in February 2010.

References

¹¹¹ = ^ Hevey, M.; Negley, D.; Pushko, P.; Smith, J.; Schmaljohn, A. (Nov 1998). "Marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates". Virology 251 (1): 28–37. doi:10.1006/viro.1998.9367. ISSN 0042-6822. PMID 9813200

Bibliography

Further reading

External links