Marburg virus
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| Marburg virus | ||||||||||
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 Marburg virus particles, approx. 100,000x magnification |
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| Virus classification | ||||||||||
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| ICD-10 | A98.3 | |
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| ICD-9 | 078.89 | |
| DiseasesDB | 7835 | |
| eMedicine | ped/2406 | |
| MeSH | C02.782.417.560 | |
The Marburg virus is the causative agent of Marburg hemorrhagic fever. Both the disease and virus are related to Ebola and originate in the same part of Africa (Uganda and Eastern Congo). The zoonosis is of unknown origin, but some scientists believe it may be hosted by bats.
The disease is spread through bodily fluids, including blood, excrement, saliva, and vomit. There is no cure or vaccine for this deadly and infectious virus. Victims suffer a high fever, diarrhea, vomiting, and severe bleeding from bodily orifices and usually die within a week. Fatality rates range from 25 to 100%.
In the spring of 2005, the virus attracted widespread press attention for an outbreak in Angola. Beginning in October 2004 and continuing into 2005, the outbreak was the world's worst epidemic of any kind of hemorrhagic fever.
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[edit] The 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 nanometers up to 14,000 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. Briefly described in the book written by Richard Preston entitled The Hot Zone.
[edit] Infection details
Because many of the signs and symptoms of Marburg hemorrhagic 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 characterised by the sudden onset of fever, headache, and muscle pain after an incubation period of 3-9 days. Within a week, a maculopapular rash develops, followed by vomiting, chest and abdominal pain, and diarrhea. The symptoms soon increase in severity leading to jaundice, delirium, organ failure, and extensive hemorrhage. Patients generally die from hypovolemic shock as fluid leaks out of the blood vessels, causing blood pressure to drop. Depending upon health care and hospitalization support, the disease can have very high fatality rates, with estimates ranging from 25% up to 100%. [3] [4] If a patient survives, recovery from the disease is prolonged and can be marked by inflammation or infection of various organs, including: orchitis (testicles), hepatitis (liver), transverse myelitis (spinal cord), uveitis (eyes), or parotitis (salivary glands).
According to a report in The New York Times, the virus moves very quickly. "On Day 3 of the infection, fewer than 200 viruses are in a drop of blood. By Day 8, there are five million."
[edit] Treatment and prevention
As with other hemorrhagic fever viruses, the treatment options for Marburg are limited. 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 hemorrhagic fever (VHF) patients tend to respond poorly to fluid infusions and rapidly develop pulmonary edema. This is especially true of patients infected with Hantaan and Seoul viruses.
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 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. [5] 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.[1] In the rhesus macaque monkey model of the disease, the vaccine is effective even when given after infection with the virus.[2]
[edit] 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, as well as in Frankfurt am Main and the then Yugoslavian city of Belgrade. The outbreak involved 13 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 the South African town of Johannesburg 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 123 of 149 cases were fatal. This outbreak originated with miners in Durba and Watsa in Orientale, Congo.
[edit] 2004-2005 outbreak in Angola
In early 2005, the World Health Organization began investigating an outbreak of a then-undiagnosed hemorrhagic fever in Angola, which was centered around 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 hemorrhagic 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. [6] 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.
[edit] Deaths by month
| Month year | Deaths reported during month |
|---|---|
| October 2004 | 3 |
| November 2004 | 4 |
| December 2004 | 7 |
| January 2005 | 20 |
| February 2005 | 30 |
| March 2005 | 47 |
| April* 2005 | 123 |
| May** 2005 | 80 |
- *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.
[edit] Deaths by week
| WHO report date | Cumulative deaths | Deaths during prior week |
|---|---|---|
| April 1,2005 | 132 | n/a |
| 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 | ***** |
- *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.
[edit] Control efforts
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. [7] 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. [8] 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.
[edit] As a weapon
The former Soviet Union reportedly had a large biological weapons program involving Marburg. The development was conducted in Vector Institute under leadership of Dr. Ustinov who accidentally died from the virus. The samples of Marburg taken from Ustinov's organs were more powerful than the original strain. New strain called "Variant U" had been successfully weaponized and approved by Soviet Ministry of Defense in 1990. [3] United States bioterrorism grants are funding the research to develop vaccine for Marburg virus.[4]
[edit] Fiction
In the TV series Millennium, a prion version of the Marburg virus breaks out in Seattle, killing (amongst others) Frank Black's wife, Catherine.
In the TV series Medical Investigation, episode 17, 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. here
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 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 novel Resident Evil: Caliban Cove a mad Scientist named Nicolas Griffith is referred to by Rebecca Chambers as having infected two men with the Marburg virus after they had been lead to believe it was a harmless cold virus.
[edit] Further reading (Nonfiction)
- Ebola
- Biohazard, a book by Ken Alibek
- The Hot Zone, a book by Richard Preston ISBN 0-517-17158-9
- The Coming Plague, a book by Laurie Garrett ISBN 0-374-12646-1
- Plagues and Peoples, a book by William McNeill ISBN 0-8446-6492-8
- Lassa fever
[edit] References
- ^ Jones SM, Feldmann H, Stroher U et al. (2005). "Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses". Nature Med 11 (7): 786–90. DOI:10.1038/nm1258. PMID 15937495.
- ^ Daddario-DiCaprio KM, Geisbert TW, Ströher U, et al.. "Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates: an efficacy assessment". Lancet 367 (9520): 1399–1404. DOI:10.1016/S0140-6736(06)68546-2.
- ^ Alibek,K. and S. Handelman. Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World - Told from Inside by the Man Who Ran it. 1999. Delta (2000) ISBN 0-385-33496-6 [1]
- ^ "Scientists Race to Find Vaccine for Ebola, Marburg." Richard Knox, National Public Radio. Morning Edition, June 6, 2005. [2]
[edit] External links
- Center for Disease Control, Infection Control for Viral Haemorrhagic Fevers In the African Health Care Setting.
- Center for Disease Control, Marburg Haemorrhagic Fever.
- Center for Disease Control, Known Cases and Outbreaks of Marburg Hemorrhagic Fever
- World Health Organization, Marburg Haemorrhagic Fever.
- Red Cross PDF
