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| {{Taxobox_begin | color = violet | name = Marburg virus}}
| | #redirect:[[Marburg hemorrhagic fever]] |
| {{Taxobox_image | image = [[Image:Marburg virus.jpg|250px|Marburg virus]] | caption = Marburg virus particles, approx. 100,000x magnification}}
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| {{Taxobox_begin_placement_virus}}
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| {{Taxobox_group_v_entry}}
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| {{Taxobox_ordo_entry | taxon = ''[[Mononegavirales]]''}}
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| {{Taxobox_familia_entry | taxon = ''[[Filoviridae]]''}}
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| {{Taxobox_genus_entry | taxon = '''''Marburgvirus'''''}}
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| {{Taxobox_species_entry | taxon = '''''Lake Victoria Marburgvirus'''''}}
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| {{Taxobox_end_placement}}
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| {{Taxobox_end}}
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| {{Infobox_Disease |
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| Name = Marburg Virus Disease |
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| Image = |
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| Caption = |
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| ICD10 = {{ICD10|A|98|3|a|90}} |
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| ICD9 = {{ICD9|078.89}} |
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| DiseasesDB = 7835 |
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| ICDO = |
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| OMIM = |
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| eMedicineSubj = ped |
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| eMedicineTopic = 2406 |
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| MeshName = Marburg |
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| MeshNumber = C02.782.417.560 |
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| }}
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| The '''Marburg virus''' is the causative [[Biological agent|agent]] of ''' Marburg [[Viral hemorrhagic fever|hemorrhagic fever]]'''. Both the [[disease]] and [[virus]] are related to [[Ebola]] and originate in [[Uganda]] and Eastern [[Democratic Republic of the Congo|Congo]]. The [[zoonosis]] is of unknown origin, but [[fruit bat]]s are suspected.<ref>
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| {{cite web
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| | url = http://www.msnbc.msn.com/id/20382188/
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| | title = Deadly Marburg virus discovered in fruit bats
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| | language = English
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| | accessdate = 2007-08-21
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| }}</ref> <!-- Green monkeys can be infected with Marburg but are not believed to be the host -->
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| In the spring of [[2005]], the virus attracted widespread press attention for an outbreak in [[Angola]].
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| In September 2007 ''[[New Scientist]]'' magazine reported <ref>{{Citation | last= Mackenzie | first= Debora | publication-date= 2007-09-01 | title= Marburg virus found in fruit bats. | periodical= [[New Scientist]] | issue= 2619 | pages= p14 | url= http://www.newscientist.com/channel/health/mg19526193.200-fruit-bats-carry-deadly-marburg-virus.html | accessdate= 2007-09-26}}</ref> 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 bat 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 <ref>{{cite book | last = Towner | first = Jonathan S. | coauthors = Xavier Pourrut, César G. Albariño1, Chimène Nze Nkogue, Brian H. Bird, Gilda Girard, Thomas G. Ksiazek1, Jean-Paul Gonzalez, Stuart T. Nichol1, Eric M. Leroy | title = Marburg Virus Infection Detected in a Common African Bat | origdate = 2007-08-22 | doi = 10.1371/journal.pone.0000764}}</ref> suggesting that the bats had been previously infected. Although no-one has yet found complete live virii from a bat the team suggest that "[I] think we can be sure that these fruit bats are the reservoir of Marburg virus".
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| ==The Marburg virus==
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| The viral structure is typical of [[filovirus]]es, with long threadlike particles which have a consistent diameter but vary greatly in length from an average of 800 [[nanometer]]s up to 14,000 nm, with peak infectious activity at about 790 nm. ''[[Virion]]s'' (viral particles) contain seven known structural [[protein]]s. While nearly identical to [[Ebola]] virus in structure, Marburg virus is [[antigen]]ically distinct from Ebola virus — in other words, it triggers different [[antibodies]] in infected organisms. It was the first [[filovirus]] to be identified. The Marburg virus was briefly described in the book written by [[Richard Preston]] entitled [[The Hot Zone]].
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| ==Infection==
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| 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.
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| The disease is spread through [[bodily fluid]]s, including [[blood]], [[excrement]], [[saliva]], and [[vomit]]. Early symptoms are often non-specific, and usually include fever, headache and [[myalgia]] after an incubation period of 3-9 days. After five days, a macropapular rash is often present on the trunk. Later-stage Marburg infection is acute and can include jaundice, pancreatitis, weight loss, delirium and neuropsychiatric symptoms, hemorrhaging, [[Hypovolemia|hypovolemic shock]] and multi-organ dysfunction with liver failure most common. Accounts of external [[hemorrhage|hemorrhaging]] from [[Body orifice|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 between 23-90% and more. <ref>
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| {{cite web
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| | url = http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marburg.htm
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| | title = CDC special pathogins branch- Marburg page
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| | language =
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| | accessdate = 2007-05-03
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| }}</ref>
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| <ref>
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| {{cite web
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| | url = http://www.who.int/csr/don/2005_08_24/en/index.html
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| | title = World Health Orginization - Report after final death 2004-2005 outbreak
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| | language =
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| | accessdate = 2007-05-03
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| }}</ref>
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|
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| If a patient survives, recovery is usually prompt and complete, though it may be prolonged in some cases. These symptoms may include inflammation or secondary infection of various organs, including: [[orchitis]] ([[testicle]]s), [[hepatitis]] ([[liver]]), [[transverse myelitis]] ([[spinal cord]]), [[uveitis]] ([[eye]]s), or [[parotitis]] ([[parotid gland|salivary glands]]).
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| ==Treatment and prevention==
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| 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 hemorrhagic fever]] (VHF) patients tend to respond poorly to fluid infusions and may develop [[pulmonary edema]].
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| Caregivers require barrier infection control measures including double gloves, impermeable gowns, face shields, eye protection, leg and shoe coverings.
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| A few [[research]] groups are working on [[medication|drug]]s 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<ref>
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| {{cite web
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| | url = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9813200&query_hl=1&itool=pubmed_docsum
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| | title = USAMRID report on immunizations on guinea pigs that prevented infection
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| | language =
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| | accessdate = 2007-05-03
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| }}</ref>
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| 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. {{Fact|date=May 2007}} 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". {{Fact|date=May 2007}}
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| 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|vesicular stomatitis]] - which is thought to be of no threat to humans.<ref name="Jones2006">{{cite journal | author=Jones SM, Feldmann H, Stroher U ''et al.'' | title=Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses | journal=Nature Med | year=2005 | volume=11 | issue=7 | pages=786–90 | id=PMID 15937495 | doi=10.1038/nm1258 }}</ref> In the rhesus macaque monkey model of the disease, the vaccine is effective even when given after infection with the virus.<ref name="Daddario-DiCaprio2006">{{cite journal | author=Daddario-DiCaprio KM, Geisbert TW, Ströher U, ''et al.'' | title=Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates: an efficacy assessment | journal=Lancet | volume=367 | issue=9520 | pages=1399–1404 | url=http://www.thelancet.com/journals/lancet/article/PIIS0140673606685462/abstract | doi=10.1016/S0140-6736(06)68546-2 }}</ref>
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| ==Early outbreaks==
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| This virus was first documented in [[1967]], when 31 people became ill in the [[Germany|German]] town of [[Marburg]], after which it is named, as well as in [[Frankfurt am Main]] and the then [[Yugoslavia]]n 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 [[monkey]]s or their tissues. The secondary cases involved two [[Physician|doctor]]s, 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.
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| The outbreak was traced to infected African [[grivet]]s of the [[species]] ''[[Cercopithecus aethiops]]'' taken from [[Uganda]] and used in developing [[polio]] [[vaccines]]. The monkeys were imported by [[Behringwerke]], a Marburg [[company (law)|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 [[blood plasma|sera]] against [[tetanus]] and [[diphtheria]].
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| In [[1975]], three people in the [[South African]] city 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]].
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| ==2004-2005 outbreak in Angola==
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| 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.
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| 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. {{Fact|date=May 2007}} The virus has also taken a toll on health care workers, including 14 nurses and two doctors.
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| 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.
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| ===Deaths by month===
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| {| class="wikitable"
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| |+ [http://www.reliefweb.int/rw/RWB.NSF/db900SID/DDAD-6B6KXM?OpenDocument Monthly Reported Deaths]
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| |-
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| ! Month year !! Deaths reported during month
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| |October 2004 || 3
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| |-
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| |November 2004 || 4
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| |-
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| |December 2004 || 7
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| |-
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| |January 2005 || 20
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| |-
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| |February 2005 || 30
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| |-
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| |March 2005 || 47
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| |-
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| |April* 2005 || 123
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| |-
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| |May** 2005 || 80
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| |}
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| * *This represents the difference between WHO reports of April 1 and April 29..
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| * **This represents the difference between WHO reports of April 29 and May 27.
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| ===Deaths by week===
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| {| class="wikitable"
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| |+ Weekly Reported Deaths
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| |-
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| ! WHO report date !! Cumulative deaths !! Deaths during prior week
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| |[http://www.who.int/csr/don/2005_04_01/en/index.html April 1,2005] || 132|| ''n/a''
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| |-
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| |[http://www.who.int/csr/don/2005_04_08a/en/index.html April 8, 2005] || 180 || 48
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| |-
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| |[http://www.who.int/csr/don/2005_04_15/en/index.html April 15, 2005]* || 207|| 27
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| |-
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| |[http://www.who.int/csr/don/2005_04_22/en/index.html April 22, 2005] || 244|| 37
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| |[http://www.who.int/csr/don/2005_04_29/en/index.html April 29, 2005] || 255|| 11
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| |[http://www.who.int/csr/don/2005_05_06/en/index.html May 6, 2005] || 277|| 22
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| |-
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| |[http://www.who.int/csr/don/2005_05_11/en/index.html May 11, 2005]** || 276|| -1****
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| |[http://www.who.int/csr/don/2005_05_18/en/index.html May 18, 2005] || 311|| 35
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| |[http://www.who.int/csr/don/2005_05_27a/en/index.html May 27, 2005]*** || 335|| 24
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| |[http://www.who.int/csr/don/2005_06_07/en/index.html June 7, 2005]*** || 357|| 22
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| |[http://www.who.int/csr/don/2005_06_17/en/index.html June 17, 2005]*** || 356|| -1****
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| |[http://www.who.int/csr/don/2005_07_13/en/index.html July 13, 2005] || 312 || *****
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| |}
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| * *No WHO report was issued [http://www.who.int/csr/don/archive/disease/marburg_virus_disease/en/ between the 15th and the 21st]. This appears associated with the [http://www.who.int/csr/don/2005_04_15/en/index.html administrative reclassification of cases].
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| * **Not an entire week. No WHO report for the 13th.
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| * ***Over a week.
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| * **** No explanation provided for the decrease in cumulative deaths.
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| * ***** Report states that a review of data has led to a downward estimation in total deaths.
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| ===2007 Uganda cases===
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| Marburg haemorrhagic fever (MHF) has been 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.
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| 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.
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| ===Control efforts===
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| 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 [[Angolan War of Independence|civil war]] and the countryside remains littered with [[land mine]]s.
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| 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.
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| 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.<ref>
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| {{cite web
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| | url = http://www.iol.co.za/index.php?set_id=1&click_id=84&art_id=qw1113046741868B243
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| | title = World Health Orginization workers attacked in angola
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| | language =
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| | accessdate = 2007-05-03
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| }}</ref>
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| 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. {{Fact|date=May 2007}}
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| ==As a weapon==
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| The former [[Soviet Union]] reportedly had a large [[biological weapon]]s program involving Marburg. The development was conducted in [[Vector State Research Center of Virology and Biotechnology|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]]. <ref name="Alibek"> 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 </ref> United States bioterrorism grants are funding the research to develop vaccine for Marburg virus.<ref>
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| {{cite web
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| | url = http://www.npr.org/templates/story/story.php?storyId=4681932
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| | title = Scientists Race to Find Vaccine for Ebola, Marbug -richard knox - NPR
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| | language =
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| | accessdate = 2007-05-03
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| }}</ref>
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| ==Fiction==
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| In the TV series [[Millennium (TV series)|''Millennium'']], a [[prion]] version of the Marburg virus breaks out in Seattle, killing (amongst others) Frank Black's wife, Catherine.
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| 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.
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| In the TV series ''[[ReGenesis]]'', episode 11, the source of an earlier Marburg outbreak is investigated.
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| In the Sarah Jane Smith series of audios (Series Two) the virus is used as a weapon by a [[doomsday event|Doomsday cult]]. [http://doctorwho.co.uk/drwho_sarahjane/SJS203_fatal.shtml here]
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| 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.
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| 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.
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| 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)|chimera virus]].
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| 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.
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| 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.
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| 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 led to believe it was a harmless cold virus.
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| ==Further reading (Nonfiction)==
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| {{commons|Marburg virus}}
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| * [[Ebola]]
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| * ''[[Biohazard (book)|Biohazard]]'', a book by [[Ken Alibek]]
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| * ''[[The Hot Zone]]'', a book by [[Richard Preston]] ISBN 0-517-17158-9
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| * ''The Coming Plague'', a book by [[Laurie Garrett]] ISBN 0-374-12646-1
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| * ''Plagues and Peoples'', a book by [[William McNeill]] ISBN 0-8446-6492-8
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| * [[Lassa fever]]
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| ==References==
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| <div class="references-2column">{{reflist|2}}</div>
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| ==External links==
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| * [[Center for Disease Control]], ''[http://www.cdc.gov/ncidod/dvrd/spb/mnpages/vhfmanual.htm Infection Control for Viral Haemorrhagic Fevers In the African Health Care Setting]''.
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| * Center for Disease Control, ''[http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marburg.htm Marburg Haemorrhagic Fever]''.
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| * Center for Disease Control, ''[http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marburg/marburgtable.htm Known Cases and Outbreaks of Marburg Hemorrhagic Fever]''
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| * [[World Health Organization]], ''[http://www.who.int/csr/disease/marburg/en/ Marburg Haemorrhagic Fever]''.
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| *[http://www.ifrc.org/cgi/pdf_appeals.pl?/05/05me021.pdf#xml=http://www.ifrc.org/cgi/webinator/texis.exe/webinator/search/xml.txt?query=marburg&pr=english&order=r&cq=&id=4259e31f18 Red Cross PDF]
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