Marburg hemorrhagic fever

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2] Aravind Reddy Kothagadi M.B.B.S[3] Aditya Ganti M.B.B.S. [4]

The Marburg virus causes severe viral hemorrhagic fever in humans with case fatality rates ranging from 24% to 88%. ^[1] Rousettus aegypti, fruit bats of the Pteropodidae family, are considered to be natural hosts of Marburg virus. The Marburg virus is transmitted to people from fruit bats and spreads through human-to-human transmission. No specific antiviral treatment or vaccine is available.

Marburg hemorrhagic fever was first detected in 1967 in Marburg after which there has been reports of several sporadic outbreaks all over the world. Subsequently, outbreaks and sporadic cases were reported in Angola, Democratic Republic of the Congo, Kenya, South Africa, and Uganda

There is no established system for the classification of Marburg hemorrhagic fever.

Marburg virus is the causative agent of Marburg haemorrhagic fever (MHF). Initial human infection results from prolonged exposure to mines or caves inhabited by Rousettus bat colonies. After the Marburg virus initially transfers from animal host to human, mode of transmission is usually human-to-human and results from direct contact with bodily fluids of infected persons (blood, secretions) other contact fomites contaminated with infectious blood and tissues. Marburg virus primarily infects macrophages and dendritic cells. A cascade of events leads to Hypotension, metabolic disorders, immunosuppression and coagulopathy, finally resulting in multiorgan failure and shock.

Marburg virus (/ˈmɑːrbərɡ ˈvaɪrəs/ Template:Respell Template:Respell^[2]) is a hemorrhagic fever virus of the Filoviridae family of viruses and a member of the species Marburg marburgvirus, genus Marburgvirus. Marburg virus (MARV) causes Marburg virus disease in humans and nonhuman primates, a form of viral hemorrhagic fever.^[3] The virus is considered to be extremely dangerous. The WHO rates it as a risk group 4 pathogen (requiring biosafety level 4-equivalent containment).^[4] In the United States, the NIH/National Institute of Allergy and Infectious Diseases ranks it as a category A priority pathogen^[5] and the Centers for Disease Control and Prevention lists it as a category A bioterrorism agent.^[6] It is also is listed as a biological agent for export control by the Australia Group.^[7]

In 2009, expanded clinical trials of an Ebola and Marburg vaccine began in Kampala, Uganda.^[8][9]

Marburg hemorrhagic fever must be differentiated from other viral hemorrhagic fevers that may cause fever, abdominal pain,and bleeding such as Ebola, Crimean-Congo hemorrhagic fever (CCHF), Hantavirus Infection, Rift Valley fever, Lujo hemorrhagic fever and Lassa fever. Because many of the signs and symptoms of Marburg hemorrhagic fever are similar to those of other infectious diseases such as malaria or typhoid fever, leptospirosis, Marburg hemorrhagic fever must also be differentiated from those infections.

Recorded cases of Marburg hemorrhagic fever disease are rare. The first documented outbreak of marburg hemorrhagic fever occurred in 1967 in Marburg and Frankfurt, Germany and in Belgrade. Case fatality rates in marburg hemorrhagic fever outbreaks have ranged from 23% to 90%. Marburg hemorrhagic fever commonly affects younger individuals less than 5 years old and adults >50 years old compared to normal age groups.

Common risk factors in the development of Marburg hemorrhagic fever include close contact with African fruit bats, human patients, or non-human primates infected with Marburg virus. Less common risk factors in the development of Marburg hemorrhagic fever include occupations (people who handle non-human primates from Africa) and travellers to endemic areas.

There is insufficient evidence to recommend routine screening for Marburg hemorrhagic fever.

If left untreated symptoms of marburg hemorrhagic fever become increasingly severe and can include jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, massive hemorrhage, and multi-organ dysfunction. Common complications of marburg hemorrhagic fever include orchitis, Transverse myelitis and Parotitis. Prognosis of marburg hemorrhagic fever is generally poor. Case fatality rates in marburg hemorrhagic fever outbreaks have ranged from 23% to 90%.

The diagnosis of Marburg hemorrhagic fever relies primarily on the laboratory techniques such as reverse transcriptase PCR and ELISA-based antigen and antibody detection.

Marburg hemorrhagic fever initially appears as a nonspecific febrile illness, which then rapidly progresses and leads to hemorrhagic complications and in severe cases may lead to a septic shock-like syndrome.

Marburg hemorrhagic fever is commonly associated with fever on physical examination at admission. At advanced stages of the disease, physical examination findings are more pertinent and often include unstable vital signs, such as tachycardia or relative bradycardia, orthostatic hypotension, and tachypnea. Physical examination may also be remarkable for abdominal tenderness and distension, evidence of mucosal or visceral bleeding, and neurological impairment.

Marburg virus infection may be confirmed by the laboratory techniques such as antibody-capture enzyme-linked immunosorbent assay, antigen-capture detection tests, serum neutralization test, reverse transcriptase polymerase chain reaction (RT-PCR), antigen detection tests and virus isolation by cell culture.

There are no ECG findings associated with marburg hemorrhagic fever.

There are no x-ray findings associated with Marburg hemorrhagic fever.

There are no echocardiography/ultrasound findings associated with Marburg hemorrhagic fever.

There are no CT scan findings associated with Marburg hemorrhagic fever.

There are no MRI findings associated with Marburg hemorrhagic fever.

There are no other imaging findings associated with Marburg hemorrhagic fever.

There are no other diagnostic studies associated with Marburg hemorrhagic fever.

There has been no approved treatment regimen yet for Marburg virus disease. However, few of the treatment modalities such as blood component therapy, immune therapy, and drug therapy are currently being evaluated. Supportive care such as rehydration with oral or intravenous fluids and maintenance of electrolyte balance, analgesics and symptomatic treatment may be beneficial.

Surgical intervention is not recommended for the management of Marburg hemorrhagic fever.

No specific treatment or vaccine is yet available for Marburg hemorrhagic fever. Several vaccine candidates are being tested but it could be several years before any are available. New drug therapies have shown promising results in laboratory studies and are currently being evaluated. One way to protect against infection is avoiding fruit bats, and sick non-human primates in central Africa. Reducing the risk of infection to people include reducing the risk of bat-to-human transmission as well as human-to-human transmission, health education and, outbreak containment measures.

Effective measures for the secondary prevention of transmission Marburg hemorrhagic fever from person-to-person include barrier nursing techniques (wearing of protective gowns, gloves, and masks, placing the infected individual in strict isolation, sterilization or proper disposal of needles, equipment, and patient excretions).

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Marburg hemorrhagic fever was first detected in 1967 in Marburg after which there has been reports of several sporadic outbreaks all over the world. Subsequently, outbreaks and sporadic cases were reported in Angola, Democratic Republic of the Congo, Kenya, South Africa, and Uganda

• Marburg hemorrhagic fever was initially detected in 1967 after simultaneous outbreaks in Marburg, from which the disease takes its name, Frankfurt, and Belgrade.
• Subsequently, outbreaks and sporadic cases were reported in Angola, Democratic Republic of the Congo, Kenya, South Africa, and Uganda.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief:

There is no established system for the classification of Marburg hemorrhagic fever.

There is no established system for the classification of Marburg hemorrhagic fever.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Marburg virus is the causative agent of Marburg haemorrhagic fever (MHF). Initial human infection results from prolonged exposure to mines or caves inhabited by Rousettus bat colonies. After the Marburg virus initially transfers from animal host to human, mode of transmission is usually human-to-human and results from direct contact with bodily fluids of infected persons (blood, secretions) other contact fomites contaminated with infectious blood and tissues. Marburg virus primarily infects macrophages and dendritic cells. A cascade of events leads to Hypotension, metabolic disorders, immunosuppression and coagulopathy, finally resulting in multiorgan failure and shock.

• Marburg virus is the causative agent of Marburg haemorrhagic fever (MHF). Marburg and Ebola viruses are the two members of the Filoviridae family (filovirus). Though caused by different viruses, the two diseases are clinically similar.
• 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. Peak infectious activity is at approximately 790 nm.
• Virions contain seven known structural proteins. Four proteins form the nucelocapsid of the Marburg virus: NP, VP35, VP30, and L.^[2] While nearly identical to Ebola virus in structure, Marburg virus is antigenically distinct from Ebola virus.
• Marburg virus was the first filovirus to be identified.

• Initial human infection results from prolonged exposure to mines or caves inhabited by Rousettus bat colonies. The reservoir host of Marburg virus is the African fruit bat, Rousettus aegyptiacus. Marburg virus can infect primates (including humans) and may cause serious disease with high mortality.^[3][4]
• After the Marburg virus initially transfers from animal host to human, mode of transmission is usually human-to-human and results from direct contact with bodily fluids of infected persons (blood, secretions) other contact fomites contaminated with infectious blood and tissues.^[5]
• Transmission to health-care workers has been reported while treating Marburg patients, mainly due to incorrect or inadequate use of personal protective equipment.

• The incubation period (interval from infection to onset of symptoms) varies from 5 to 10 days.

Pathogenesis of hemorrhagic fever by Marburg virus is as follows:

• Marburg virus primarily infects macrophages and dendritic cells.^[6]
• Infection of dendritic cells leads to paralysis of cellular antiviral response and dysregulation of costimulation of lymphocytes.
• Infection of macrophage leads to the production of proinflammatory mediators including TNF-α, IL-6 and tissue factor.
  • TNF-α induce apoptosis in lymphocyte and results in lymphopenia and immunosuppression.
  • IL-6 and TNF-α also induces increase in vascular permeability.
  • Tissue factor produced by infected macrophages leads to dysregulation of coagulation (e.g., DIC).
• Hepatocyte infection further reinforces coagulation dysregulation due to ineffective production of clotting factors.
• Adrenal cortical cells infection results in hypotension and metabolic disorders.
• Hypotension, metabolic disorders, immunosuppression and coagulopathy results in multiorgan failure and shock.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief:

Marburg virus (/ˈmɑːrbərɡ ˈvaɪrəs/ Template:Respell Template:Respell^[1]) is a hemorrhagic fever virus of the Filoviridae family of viruses and a member of the species Marburg marburgvirus, genus Marburgvirus. Marburg virus (MARV) causes Marburg virus disease in humans and nonhuman primates, a form of viral hemorrhagic fever.^[2] The virus is considered to be extremely dangerous. The WHO rates it as a Risk Group 4 Pathogen (requiring biosafety level 4-equivalent containment).^[3] In the United States, the NIH/National Institute of Allergy and Infectious Diseases ranks it as a Category A Priority Pathogen^[4] and the Centers for Disease Control and Prevention lists it as a Category A Bioterrorism Agent.^[5] It is also is listed as a biological agent for export control by the Australia Group.^[6]

In 2009, expanded clinical trials of an Ebola and Marburg vaccine began in Kampala, Uganda.^[7][8]

Marburg virus was first described in 1967.^[9] It was noticed during small outbreaks in the German cities Marburg and Frankfurt and the Yugoslav capital Belgrade in the 1960s. German workers were accidentally exposed to tissues of infected grivet monkeys (Chlorocebus aethiops) at the city’s former main industrial plant, the Behringwerke, then part of Hoechst, and today of CSL Behring. During these outbreaks, 31 people became infected and seven of them died. MARV is a Select Agent,^[10]

The virus is one of two members of the species Marburg marburgvirus, which is included in the genus Marburgvirus, family Filoviridae, order Mononegavirales. The name Marburg virus is derived from Marburg (the city in Hesse, Germany, where the virus was first discovered) and the taxonomic suffix virus.^[1]

According to the rules for taxon naming established by the International Committee on Taxonomy of Viruses (ICTV), the name Marburg virus is always to be capitalized, but is never italicized, and may be abbreviated (with MARV being the official abbreviation).

Marburg virus was first introduced under this name in 1967.^[9] In 2005, the virus name was changed to Lake Victoria marburgvirus, which unfortunately was the same spelling as its species Lake Victoria marburgvirus.^[11][12] However, most scientific articles continued to refer to Marburg virus. Consequently, in 2010, the name Marburg virus was reinstated and the species name changed.^[1] A previous abbreviation for the virus was MBGV.

MARV is one of two marburgviruses that causes Marburg virus disease (MVD) in humans (in the literature also often referred to as Marburg hemorrhagic fever, MHF). Both viruses fulfill the criteria for being a member of the species Marburg marburgvirus because their genomes diverge from the prototype Marburg marburgvirus or the Marburg virus variant Musoke (MARV/Mus) by <10% at the nucleotide level.^[1]

Like all mononegaviruses, marburgvirions contain non-infectious, linear nonsegmented, single-stranded RNA genomes of negative polarity that possesses inverse-complementary 3′ and 5′ termini, do not possess a 5′ cap, are not polyadenylated, and are not covalently linked to a protein.^[44] Marburgvirus genomes are approximately 19 kb long and contain seven genes in the order 3′-UTR–NP–VP35–VP40–GP–VP30–VP24–L–5′-UTR.^[45] The genomes of the two different marburgviruses (MARV and RAVV) differ in sequence.

Like all filoviruses, marburgvirions are filamentous particles that may appear in the shape of a shepherd’s crook or in the shape of a “U” or a “6”, and they may be coiled, toroid, or branched.^[45] Marburgvirions are generally 80 nm in width, but vary somewhat in length. In general, the median particle length of marburgviruses ranges from 795 to 828 nm (in contrast to ebolavirions, whose median particle length was measured to be 974–1,086 nm ), but particles as long as 14,000 nm have been detected in tissue culture.^[47] Marburgvirions consist of seven structural proteins. At the center is the helical ribonucleocapsid, which consists of the genomic RNA wrapped around a polymer of nucleoproteins (NP). Associated with the ribonucleoprotein is the RNA-dependent RNA polymerase (L) with the polymerase cofactor (VP35) and a transcription activator (VP30). The ribonucleoprotein is embedded in a matrix, formed by the major (VP40) and minor (VP24) matrix proteins. These particles are surrounded by a lipid membrane derived from the host cell membrane. The membrane anchors a glycoprotein (GP_1,2) that projects 7 to 10 nm spikes away from its surface. While nearly identical to ebolavirions in structure, marburgvirions are antigenically distinct.

Niemann–Pick C1 (NPC1) cholesterol transporter protein appears to be essential for infection with both Ebola and Marburg virus. Two independent studies reported in the same issue of Nature showed that Ebola virus cell entry and replication requires NPC1.^[48][49] When cells from patients lacking NPC1 were exposed to Ebola virus in the laboratory, the cells survived and appeared immune to the virus, further indicating that Ebola relies on NPC1 to enter cells. This might imply that genetic mutations in the NPC1 gene in humans could make some people resistant to one of the deadliest known viruses affecting humans. The same studies described similar results with Marburg virus, showing that it also needs NPC1 to enter cells.^[48][49] Furthermore, NPC1 was shown to be critical to filovirus entry because it mediates infection by binding directly to the viral envelope glycoprotein^[49] and that the second lysosomal domain of NPC1 mediates this binding.^[50]

In one of the original studies, a small molecule was shown to inhibit Ebola virus infection by preventing the virus glycoprotein from binding to NPC1.^[49][51] In the other study, mice that were heterozygous for NPC1 were shown to be protected from lethal challenge with mouse-adapted Ebola virus.^[48] Together, these studies suggest NPC1 may be potential therapeutic target for an Ebola antiviral drug.

The marburg virus life cycle begins with virion attachment to specific cell-surface receptors, followed by fusion of the virion envelope with cellular membranes and the concomitant release of the virus nucleocapsid into the cytosol. The virus RdRp partially uncoats the nucleocapsid and transcribes the genes into positive-stranded mRNAs, which are then translated into structural and nonstructural proteins. Marburgvirus L binds to a single promoter located at the 3′ end of the genome. Transcription either terminates after a gene or continues to the next gene downstream. This means that genes close to the 3′ end of the genome are transcribed in the greatest abundance, whereas those toward the 5′ end are least likely to be transcribed. The gene order is therefore a simple but effective form of transcriptional regulation. The most abundant protein produced is the nucleoprotein, whose concentration in the cell determines when L switches from gene transcription to genome replication. Replication results in full-length, positive-stranded antigenomes that are in turn transcribed into negative-stranded virus progeny genome copies. Newly synthesized structural proteins and genomes self-assemble and accumulate near the inside of the cell membrane. Virions bud off from the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny particles then infect other cells to repeat the cycle.^[11]

In 2009, the successful isolation of infectious MARV was reported from caught healthy Egyptian rousettes (Rousettus aegyptiacus).^[38] This isolation, together with the isolation of infectious RAVV,^[38] strongly suggests that Old World fruit bats are involved in the natural maintenance of marburgviruses. Further studies are necessary to establish whether Egyptian rousettes are the actual hosts of MARV and RAVV or whether they get infected via contact with another animal and therefore serve only as intermediate hosts. Recently the first experimental infection study of Rousettus aegyptiacus with MARV provided further insight into the possible involvement of these bats in MARV ecology.^[52] Experimentally infected bats developed relatively low viremia lasting at least 5 days, but remained healthy and didn’t develop any notable gross pathology. The virus also replicated to high titers in major organs (liver and spleen), and organs that might possibly be involved in virus transmission (lung, intestine, reproductive organ, salivary gland, kidney, bladder and mammary gland). The relatively long period of viremia noted in this experiment could possibly also facilitate mechanical transmission by blood sucking arthropods or infection of susceptible vertebrate hosts by direct contact with infected blood.

The Soviet Union had an extensive offensive and defensive biological weapons program that included MARV.^[53] At least three Soviet research institutes had MARV research programs during offensive times: the Virology Center of the Scientific-Research Institute for Microbiology in Zagorsk (today Sergiev Posad), the Scientific-Production Association “Vektor” (today the State Research Center of Virology and Biotechnology “Vektor”) in Koltsovo, and the Irkutsk Scientific-Research Anti-Plague Institute of Siberia and the Far East in Irkutsk. As most performed research was highly classified, it remains unclear how successful the MARV program was. However, Soviet defector Ken Alibek claimed that a weapon filled with MARV was tested at the Stepnogorsk Scientific Experimental and Production Base in Stepnogorsk, Kazakh Soviet Socialist Republic (today Kazakhstan),^[53] suggesting that the development of a MARV biological weapon had reached advanced stages. Independent confirmation for this claim is lacking. At least one laboratory accident with MARV, resulting in the death of Koltsovo researcher Nikolai Ustinov, occurred during offensive times in the Soviet Union and was first described in detail by Alibek.^[53] After the dissolution of the Soviet Union, MARV research continued in all three institutes.

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• In the non-fiction thriller, The Hot Zone, Richard Preston describes several MARV infections.
• In the 2008 Indian science fiction movie Dasavathaaram by Kamal Haasan, the plot features an intended bio weapon of “Ebola Marburg” virus.
• In the TV series Millennium, at the end of Season 2, a “prion version” of MARV causes a disease outbreak in Seattle, killing (amongst others) Frank Black’s wife, Catherine. In the Season 3 episode “Collateral Damage”, Peter Watt’s daughter is infected with MARV by a Gulf War veteran who claims that the Millennium Group did the same to American soldiers during the first Gulf War.
• In the crossover event of the TV series Medical Investigation, episode 17, and Third Watch, season 6 episode 16, Marburg virus disease breaks out in New York City, killing five of six infected people.
• In the Sarah Jane Smith series (Series Two), MARV is used as a weapon by a doomsday cult.
• In the short story Hell Hath Enlarged Herself by Michael Marshall Smith, one of the original scientists is infected with MARV in an attempt to test ImmunityWorks ver. 1.0.
• In the novel Microserfs by Douglas Coupland, MARV is mentioned several times as a metaphor for the spread of information through the internet
• 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 MARV after they had been led to believe it was a harmless common cold virus.
• In the novel Pandora’s Legion by Harold Coyle and Barrett Tillman, an Al-Qaeda cell in Pakistan injects volunteers with MARV, 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 TV series Body of Proof, Season 2, episodes 18 and 19 include a MARV outbreak.
• In Mira Grant‘s novel Feed, a modified Marburg virus that cures cancer combines with a virally transmitted cure for the common cold, resulting in a virulent viral plague that turns infected humans and animals into zombies.
• Motaba, the fictional deadly viral hemorrhagic fever, in the movie Outbreak, is based on MARV.
• In the video game Trauma Team, the seventh chapter of the game, named “Patient Zero”, has a storyline of a mass outbreak of the fictional Rosalia Virus, which has similar symptoms to the Ebola Virus and Marburg Virus.
• In the episode “The Order 23 Job” of the TV show Leverage, the team’s mark is led to believe that he is caught in an outbreak of weaponized Marburg virus made by the Soviets.
• In the episode “Death Is in the Air” of the TV show Psych, the fictional Thornburg virus is based on the Marburg virus.
• In the episode “Small Sacrifices” of the TV show “House MD“, the team explores Marburg as a diagnosis for a patient
• In the episode “The Promise” of the Canadian TV show ReGenesis Marburg was the subject of a war games exercise and a weaponized strain out of a lab in South Africa poses a potential threat.
• In the episode “Honor Among Thieves” of the TV show Person of Interest, the Marburg virus is shown to be used as a potential bioterrorism agent to cause a pandemic starting in New York.
• In the episode “I Am the Apocalypse” of the TV show Chicago Fire, a man with Marburg virus attempts to start an outbreak in a Chicago hospital.
• In the TV series Bergerac, a potential Marburg outbreak is the subject of the episode “The Deadly Virus”.

Wikimedia Commons has media related to Marburg virus.

• International Committee on Taxonomy of Viruses (ICTV)
• FILOVIR – scientific resources for research on filoviruses

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Marburg hemorrhagic fever must be differentiated from other viral hemorrhagic fevers that may cause fever, abdominal pain,and bleeding such as Ebola, Crimean-Congo hemorrhagic fever (CCHF), Hantavirus Infection, Rift Valley fever, Lujo hemorrhagic fever and Lassa fever. SInce many of the signs and symptoms of marburg hemorrhagic fever are similar to those of other infectious diseases such as malaria or typhoid fever, leptospirosis, marburg hemorrhagic fever must also be differentiated from those infections.

Marburg hemorrhagic fever must be differentiated from other viral hemorrhagic fevers that may cause fever, abdominal pain,and bleeding such as Ebola, Crimean-Congo hemorrhagic fever (CCHF), Hantavirus Infection, Rift Valley fever, Lujo hemorrhagic fever and Lassa fever. SInce many of the signs and symptoms of marburg hemorrhagic fever are similar to those of other infectious diseases such as malaria or typhoid fever, leptospirosis, marburg hemorrhagic fever must also be differentiated from those infections.^{[1][2][3][4][5][6][7][8][9][10][11][12][13][14]}

Shown below is a table summarizing the typical findings of the differential diagnoses of MHF.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Recorded cases of Marburg hemorrhagic fever disease are rare. The first documented outbreak of marburg hemorrhagic fever occurred in 1967 in Marburg and Frankfurt, Germany and in Belgrade. Case fatality rates in marburg hemorrhagic fever outbreaks have ranged from 23% to 90%. Marburg hemorrhagic fever commonly affects younger individuals less than 5 years old and adults >50 years old compared to normal age groups.

• Recorded cases of Marburg hemorrhagic fever disease are rare. Hence it is difficult to obtain accurate data of incidence and prevalence of Marburg hemorrhagic fever.

• The first documented outbreak of marburg hemorrhagic fever occurred in 1967 in Marburg and Frankfurt, Germany and in Belgrade (in the former Yugoslavia) among laboratory workers exposed to blood and tissue products of African green monkeys imported from Uganda.
• Secondary transmission to medical staff and family members was also documented.^[1][2]
• In total, 31 patients became infected, and 7 of these patients died.^[3]
• During the next 2 decades, Marburg hemorrhagic fever was associated with sporadic, isolated, usually fatal cases among residents and travelers in southeast Africa.
• In 1998 to 2000, there was a prolonged outbreak involving 154 cases of Marburg hemorrhagic fever in Durba, Democratic Republic of the Congo (DRC) that was associated with individuals working in an underground gold mine.
• The largest and most lethal Marburg virus outbreak to date occurred in 2004 to 2005 in northern Angola.^[4]
  • This outbreak involved 252 cases, with a case-fatality rate of 90%.
• Between 2007 and 2012, several small episodes of Marburg hemorrhagic fever were reported in Uganda, with one case being exported to the United States and one to the Netherlands.
• In October 2014, a single case of Marburg hemorrhagic fever was reported in Uganda.

• Case fatality rates in marburg hemorrhagic fever outbreaks have ranged from 23% to 90%.

• Patients of all age groups may develop marburg hemorrhagic fever.
• Marburg hemorrhagic fever commonly affects younger individuals less than 5 years old and adults >50 years old compared to normal age groups.

There is no racial predilection to marburg hemorrhagic fever.

Marburg hemorrhagic fever affects men and women equally.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Common risk factors in the development of Marburg hemorrhagic fever include close contact with African fruit bats, human patients, or non-human primates infected with Marburg virus. Less common risk factors in the development of Marburg hemorrhagic fever include occupations (people who handle non-human primates from Africa) and travellers to endemic areas.

Common risk factors in the development of Marburg hemorrhagic fever include close contact with African fruit bats, human patients, or non-human primates infected with Marburg virus.^[1][2]

• Common risk factors in the development of Marburg hemorrhagic fever include close contact with infected:^[1][2]
  • African fruit bats
  • Human patients
  • Non-human primates

Less common risk factors in the development of Marburg hemorrhagic fever include:^[2]

• Occupations (people who handle non-human primates from Africa)
  • Veterinarians
  • Laboratory workers
  • Quarantine facility workers
• Travellers to endemic area

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

If left untreated symptoms of marburg hemorrhagic fever become increasingly severe and can include jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, massive hemorrhage, and multi-organ dysfunction. Common complications of marburg hemorrhagic fever include orchitis, Transverse myelitis and Parotitis. Prognosis of marburg hemorrhagic fever is generally poor. Case fatality rates in marburg hemorrhagic fever outbreaks have ranged from 23% to 90%.

• Humans and nonhuman primates are susceptible to filovirus infection and are considered to be end hosts.^[1]
• Surveys to identify animal reservoirs and arthropod vectors have been aggressively undertaken in endemic areas, particularly after most large filovirus outbreaks.
• If left untreated symptoms of marburg hemorrhagic fever become increasingly severe and can include jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, massive hemorrhage, and multi-organ dysfunction.
• Because many of the signs and symptoms of Marburg hemorrhagic fever are similar to those of other infectious diseases such as malaria or typhoid fever, clinical diagnosis of the disease can be difficult, especially if only a single case is involved.

Common complications of marburg hemorrhagic fever include:^[2][3]

• Orchitis
• Transverse myelitis
• Parotitis
• Pancreatic hemorrhage
• Chronic hepatitis

• Prognosis of marburg hemorrhagic fever is generally poor.^[4][5]
• Case fatality rates in marburg hemorrhagic fever outbreaks have ranged from 23% to 90%.
• Both acute kidney injury and higher viral load are associated with adverse outcome and increased mortality.
• Younger children (<5 years) and adults (> 40 years) have a higher mortality rate compared with adolescents and younger adults.
• Patients who live through the second week of infection have a >75% chance of surviving.
• Viral shedding in seminal fluid may continue for more than a year and a half after recovery.
• Patients who survive commonly exhibit a protracted recovery characterized by arthralgias, fatigue, ocular symptoms, headache, abdominal pain, anemia, and deafness.