Marburg virus disease

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(Redirected from
Marburg fever
)
"MHF" redirects here. For other uses, see MHF (disambiguation).
Marburg virus disease
Other namesMarburg hemorrhagic fever
supportive care[1]
FrequencyRare
Deaths24–88% case fatality rate[2]

Marburg virus disease (MVD; formerly Marburg hemorrhagic fever) is a

Ebola virus disease (EVD).[1]

Egyptian fruit bats are believed to be the normal carrier in nature and Marburg virus RNA has been isolated from them.[4]

Signs and symptoms

The most detailed study on the frequency, onset, and duration of MVD

bruises, and hematomas (especially around needle injection sites) are typical hemorrhagic manifestations. However, contrary to popular belief, hemorrhage does not lead to hypovolemia and is not the cause of death (total blood loss is minimal except during labor). Instead, death occurs due to multiple organ dysfunction syndrome (MODS) due to fluid redistribution, hypotension, disseminated intravascular coagulation, and focal tissue necroses.[5][6][7][8]

Clinical phases of Marburg hemorrhagic fever's presentation are described below. Note that phases overlap due to variability between cases.

  1. Incubation: 2–21 days, averaging 5–9 days.[9]
  2. Generalization Phase: Day 1 up to Day 5 from the onset of clinical symptoms. MHF presents with a high fever 104 °F (~40˚C) and a sudden, severe headache, with accompanying chills, fatigue, nausea, vomiting, diarrhea, pharyngitis, maculopapular rash, abdominal pain, conjunctivitis, and malaise.[9]
  3. Early Organ Phase: Day 5 up to Day 13. Symptoms include prostration,
    ecchymoses, blood leakage from venipuncture sites, mucosal and visceral hemorrhaging, and possibly hematemesis.[9]
  4. Late Organ Phase: Day 13 up to Day 21+. Symptoms bifurcate into two constellations for survivors and fatal cases. Survivors will enter a convalescence phase, experiencing
    convulsions, diffuse coagulopathy, metabolic disturbances, shock and death, with death typically occurring between days 8 and 16.[9]

Causes

Main article: Marburgvirus
Genus Marburgvirus: species and its MVD-causing viruses
Species name Virus name (Abbreviation)
Marburg marburgvirus
* 		Marburg virus (MARV; previously MBGV)
Ravn virus (RAVV; previously MARV-Ravn)
"*" denotes the type species.

MVD is caused by two viruses; Marburg virus (MARV) and Ravn virus (RAVV), family Filoviridae.[10]: 458 

Marburgviruses are endemic in

arid woodlands of equatorial Africa.[11][12][13] Most marburgvirus infections were repeatedly associated with people visiting natural caves or working in mines. In 2009, the successful isolation of infectious MARV and RAVV was reported from healthy Egyptian fruit bat caught in caves.[4][14] This isolation strongly suggests that Old World fruit bats are involved in the natural maintenance of marburgviruses and that visiting bat-infested caves is a risk factor for acquiring marburgvirus infections. 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. Another risk factor is contact with nonhuman primates, although only one outbreak of MVD (in 1967) was due to contact with infected monkeys.[15]

Contrary to

Ebola virus disease (EVD), which has been associated with heavy rains after long periods of dry weather,[12][16]
triggering factors for spillover of marburgviruses into the human population have not yet been described.

Diagnosis

Marburg virus liver injury

MVD is clinically indistinguishable from

electron microscopy due to their unique filamentous shapes, but electron microscopy cannot differentiate the various filoviruses alone despite some overall length differences.[23] Immunofluorescence assays are used to confirm marburgvirus presence in cell cultures. During an outbreak, virus isolation and electron microscopy are most often not feasible options. The most common diagnostic methods are therefore RT-PCR[24][25][26][27][28] in conjunction with antigen-capture ELISA,[29][30][31] which can be performed in field or mobile hospitals and laboratories. Indirect immunofluorescence assays (IFAs) are not used for diagnosis of MVD in the field anymore.[citation needed
]

Classification

Marburg virus disease (MVD) is the official name listed in the

International Statistical Classification of Diseases and Related Health Problems 10 (ICD-10) for the human disease caused by any of the two marburgviruses Marburg virus (MARV) and Ravn virus (RAVV). In the scientific literature, Marburg hemorrhagic fever (MHF) is often used as an unofficial alternative name for the same disease. Both disease names are derived from the German city Marburg, where MARV was first discovered.[15]

Transmission

The details of the initial transmission of MVD to humans remain incompletely understood. Transmission most likely occurs from

non-human primates or through the consumption of bushmeat, but the specific routes and body fluids involved are unknown. Human-to-human transmission of MVD occurs through direct contact with infected bodily fluids such as blood.[4] Transmission events are relatively rare – there have been only 11 recorded outbreaks of MARV between 1975 and 2011, with one event involving both MARV and RAVV.[32]

Prevention

Main article: Prevention of viral hemorrhagic fever

There are currently no

disinfection.[citation needed
]

Endemic zones

The natural maintenance hosts of marburgviruses remain to be identified unequivocally. However, the isolation of both MARV and RAVV from bats and the association of several MVD outbreaks with bat-infested mines or caves strongly suggests that bats are involved in Marburg virus transmission to humans. Avoidance of contact with bats and abstaining from visits to caves is highly recommended, but may not be possible for those working in mines or people dependent on bats as a food source.[citation needed]

During outbreaks

Since marburgviruses are not spread via aerosol, the most straightforward prevention method during MVD outbreaks is to avoid direct (skin-to-skin) contact with patients, their

traditional healers.[40]

In the laboratory

Marburgviruses are World Health Organization Risk Group 4 Pathogens, requiring Biosafety Level 4-equivalent containment,[41] laboratory researchers have to be properly trained in BSL-4 practices and wear proper personal protective equipment.

Treatment

There is currently no effective marburgvirus-specific

antifungals to treat secondary infections.[42][43]

Prognosis

Although supportive care can improve survival chances, marburg virus disease is fatal in the majority of cases. As of 2023[update] the case fatality rate was assessed to be 61.9%.[44]

Epidemiology

Pandemic potential

The WHO identifies marburg virus disease as having pandemic potential.[44]

Historical outbreaks

Below is a table of outbreaks concerning MVD from 1967 to 2023:

Marburg virus disease outbreaks [45]
Year Country Virus Human cases Human deaths Case fatality rate Notes
1967
  West Germany
 Yugoslavia 		MARV 31 7 23%
1975  Rhodesia
 South Africa 		MARV 3 1 33%
1980  Kenya MARV 2 1 50%
1987  Kenya RAVV 1 1 100%
1988  Soviet Union MARV 1 1 100%
1990  Soviet Union MARV 1 0 0%
1998–2000  Democratic Republic of the Congo MARV & RAVV 154 128 83%
2004–2005  Angola MARV 252 227 90%
2007  Uganda MARV & RAVV 4 1 25% [46]
2008  Uganda
 Netherlands
 United States 		MARV 2 1 50% [47]
2012  Uganda MARV 18 9 50% [48][49]
2014  Uganda MARV 1 1 100% [50][51]
2017  Uganda MARV 3 3 100% [52]
2021  Guinea MARV 1 1 100% [53][54][55]
2022  Ghana MARV 3 2 66.66% [56]
2023  Equatorial Guinea MARV 40 35 88% [57][58][59]
2023  Tanzania MARV 9 6 66% [60][61]

1967 outbreak

Main article:
1967 Marburg virus outbreak in West Germany

MVD was first documented in 1967, when 31 people became ill in the

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 physicians became infected through accidental skin pricks when drawing blood from patients.[62][63][64][65]

1975 cases

In 1975, an Australian tourist became infected with MARV in Rhodesia (today Zimbabwe). He died in a hospital in Johannesburg, South Africa. His girlfriend and an attending nurse were subsequently infected with MVD, but survived.[66][67][68]

1980 cases

A case of MARV infection occurred in 1980 in Kenya. A French man, who worked as an electrical engineer in a sugar factory in Nzoia (close to Bungoma) at the base of Mount Elgon (which contains Kitum Cave), became infected by unknown means and died on 15 January shortly after admission to Nairobi Hospital.[69] The attending physician contracted MVD, but survived.[70] A popular science account of these cases can be found in Richard Preston's book The Hot Zone (the French man is referred to under the pseudonym "Charles Monet", whereas the physician is identified under his real name, Shem Musoke).[71]

1987 case

In 1987, a single lethal case of RAVV infection occurred in a 15-year-old Danish boy, who spent his vacation in Kisumu, Kenya. He had visited Kitum Cave on Mount Elgon prior to travelling to Mombasa, where he developed clinical signs of infection. The boy died after transfer to Nairobi Hospital.[72] A popular science account of this case can be found in Richard Preston's book The Hot Zone (the boy is referred to under the pseudonym "Peter Cardinal").[71]

1988 laboratory infection

In 1988, researcher Nikolai Ustinov infected himself lethally with MARV after accidentally pricking himself with a syringe used for inoculation of

USSR (today Russia).[73] Very little information is publicly available about this MVD case because Ustinov's experiments were classified. A popular science account of this case can be found in Ken Alibek's book Biohazard.[74]

1990 laboratory infection

Another laboratory accident occurred at the Scientific-Production Association "Vektor" (today the

USSR, when a scientist contracted MARV by unknown means.[75]

1998–2000 outbreak

A major MVD outbreak occurred among illegal

Democratic Republic of Congo from 1998 to 2000, when co-circulating MARV and RAVV caused 154 cases of MVD and 128 deaths. The outbreak ended with the flooding of the mine.[5][76][77]

2004–2005 outbreak

In early 2005, the

capital Luanda set up a special isolation ward to treat infected people from the countryside. Unfortunately, because MVD often results in death, some people came to view hospitals and medical workers with suspicion and treated helpers with hostility. For instance, a specially-equipped isolation ward at the provincial hospital in Uíge 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 it described as a "harm reduction strategy", which entailed distributing disinfectants to affected families who refused hospital care. Of the 252 people who contracted MVD during outbreak, 227 died.[78][79][80][81][82][83][84]

2007 cases

In 2007, four miners became infected with marburgviruses in Kamwenge District, Uganda. The first case, a 29-year-old man, became symptomatic on July 4, 2007, was admitted to a hospital on July 7, and died on July 13. Contact tracing revealed that the man had had prolonged close contact with two colleagues (a 22-year-old man and a 23-year-old man), who experienced clinical signs of infection before his disease onset. Both men had been admitted to hospitals in June and survived their infections, which were proven to be due to MARV. A fourth, 25-year-old man, developed MVD clinical signs in September and was shown to be infected with RAVV. He also survived the infection.[14][85]

2008 cases

On July 10, 2008, the

antibodies and RNA.[87]

2017 Uganda outbreak

Kween District in Uganda
Main article: 2017 Uganda Marburg virus outbreak

In October 2017 an outbreak of Marburg virus disease was detected in Kween District, Eastern Uganda. All three initial cases (belonging to one family – two brothers and one sister) had died by 3 November. The fourth case – a health care worker – developed symptoms on 4 November and was admitted to a hospital. The first confirmed case traveled to Kenya before the death. A close contact of the second confirmed case traveled to Kampala. It is reported that several hundred people may have been exposed to infection.[88][89]

2021 Guinean cases

Main article: 2021 Marburg virus disease outbreak in Guinea

In August 2021, two months after the re-emergent Ebola epidemic in the Guéckédou prefecture was declared over, a case of the Marburg disease was confirmed by health authorities through laboratory analysis.[54] Other potential case of the disease in a contact awaits official results. This was the first case of the Marburg hemorrhagic fever confirmed to happen in West Africa. The case of Marburg also has been identified in Guéckédou.[53] During the outbreak, a total of one confirmed case, who died (CFR=100%), and 173 contacts were identified, including 14 high-risk contacts based on exposure.[90] Among them, 172 were followed for a period of 21 days, of which none developed symptoms. One high-risk contact was lost to follow up.[90] Sequencing of an isolate from the Guinean patient showed that this outbreak was caused by the Angola-like Marburg virus.[91] A colony of Egyptian rousettus bats (reservoir host of Marburg virus) was found in close proximity (4.5 km) to the village, where the Marburg virus disease outbreak emerged in 2021.[92] Two of sampled fruit bats from this colony were PCR-positive on the Marburg virus.[92]

2022 Ghanaian cases

Main article: 2022 Marburg virus disease outbreak in Ghana

In July 2022, preliminary analysis of samples taken from two patients – both deceased – in Ghana indicated the cases were positive for Marburg. However, per standard procedure, the samples were sent to the Pasteur Institute of Dakar for confirmation.[93] On 17 July 2022 the two cases were confirmed by Ghana,[94] which caused the country to declare a Marburg virus disease outbreak.[95] An additional case was identified, bringing the total to three.[96]

2023 Equatorial Guinea outbreak

Main article: 2023 Marburg virus disease outbreak in Equatorial Guinea

In February 2023, Equatorial Guinea reported an outbreak of Marburg virus disease.[97] Neighbouring Cameroon detected two suspected cases of Marburg virus disease on 13 February 2023.[98]

Research

Experimentally, recombinant

vesicular stomatitis Indiana virus (VSIV) expressing the glycoprotein of MARV has been used successfully in nonhuman primate models as post-exposure prophylaxis.[99] A vaccine candidate has been effective in nonhuman primates.[100] Experimental therapeutic regimens relying on antisense technology have shown promise, with phosphorodiamidate morpholino oligomers (PMOs) targeting the MARV genome [101] New therapies from Sarepta[102] and Tekmira [103]
have also been successfully used in humans as well as primates.

See also

References

  1. ^ a b c d e f g h "Ebola Virus Disease & Marburg Virus Disease - Chapter 3 - 2018 Yellow Book | Travelers' Health | CDC". wwwnc.cdc.gov. Retrieved 19 July 2019.
  2. ^ "Marburg virus disease". www.who.int. Retrieved 8 February 2020.
  3. ^ Spickler A. "Ebolavirus and Marburgvirus Infections" (PDF).
  4. ^
    PMID 32758690
    .
  5. ^
    PMID 16943403
    .
  6. S2CID 260056835
    .
  7. S2CID 260058558
    .
  8. ISBN 978-0-387-05199-4
    .
  9. ^
    PMID 22046196
    .
  10. ISBN 978-1-4398-8431-7
    . Retrieved 28 October 2017.
  11. PMID 15078595
    .
  12. ^
    PMID 16267968
    .
  13. PMID 16837700
    .
  14. ^
    PMID 19649327
    .
  15. ^
    S2CID 116556454
    .
  16. ^ Tucker CJ, Wilson JM, Mahoney R, Anyamba A, Linthicum K, Myers MF (2002). "Climatic and Ecological Context of the 1994–1996 Ebola Outbreaks". Photogrammetric Engineering and Remote Sensing. 68 (2): 144–52.
  17. PMID 2665013
    .
  18. PMID 565951
    .
  19. PMID 16267962
    .
  20. PMID 9612907
    .
  21. PMID 4988544
    .
  22. ^ Ksiazek TG (1991). "Laboratory diagnosis of filovirus infections in nonhuman primates". Lab Animal. 20 (7): 34–6.
  23. PMID 8837880
    .
  24. PMID 11735297
    .
  25. PMID 12089242
    .
  26. PMID 15072761
    .
  27. PMID 17079496
    .
  28. PMID 17360231
    .
  29. S2CID 24207187
    .
  30. PMID 16603611
    .
  31. PMID 17060700
    .
  32. ISBN 978-0-323-95389-4
    , retrieved 2023-03-05
  33. PMID 15113924
    .
  34. ^
    PMID 16973570
    .
  35. ^
    S2CID 23200723
    .
  36. PMID 12922144
    .
  37. PMID 9813200
    .
  38. S2CID 5450135
    .
  39. ^ "Ebola/Marburg Vaccine Development" (Press release). National Institute of Allergy and Infectious Diseases. 2008-09-15. Archived from the original on 2010-03-06.
  40. ^ Centers for Disease Control and Prevention and World Health Organization (1998). Infection Control for Viral Haemorrhagic Fevers in the African Health Care Setting (PDF). Atlanta, Georgia, USA: Centers for Disease Control and Prevention. Archived from the original (PDF) on 2009-05-07. Retrieved 2009-05-31.
  41. ^ US Department of Health and Human Services. "Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition". Retrieved 2011-10-16.
  42. PMID 17940941
    .
  43. S2CID 101015
    .
  44. ^
    PMID 38040006
    .
  45. ^ "Outbreak Table | Marburg Hemorrhagic Fever | CDC". www.cdc.gov. Centers for Disease Control and Prevention. Retrieved 4 August 2018.
  46. ^ "WHO | Marburg haemorrhagic fever in Uganda". www.who.int. Archived from the original on October 8, 2014. Retrieved 23 October 2017.
  47. ^ "Imported Case of Marburg Hemorrhagic Fever --- Colorado, 2008". cdc.gov. Retrieved 23 October 2017.
  48. ^ "Marburg hemorrhagic fever outbreak continues in Uganda". October 2012.
  49. ^ "WHO | Marburg haemorrhagic fever in Uganda – update". www.who.int. Archived from the original on August 10, 2014. Retrieved 29 October 2017.
  50. ^ "1st LD-Writethru: Deadly Marburg hemorrhagic fever breaks out in Uganda". October 5, 2014.
  51. ^ "WHO | Marburg virus disease – Uganda". www.who.int. Archived from the original on November 17, 2014. Retrieved 29 October 2017.
  52. ^ "Uganda controls deadly Marburg fever outbreak, WHO says". ABC News. Archived from the original on 8 December 2017. Retrieved 8 December 2017.
  53. ^ a b "Guinea records probable case of Ebola-like Marburg virus". Reuters. 7 August 2021. Retrieved 7 August 2021.
  54. ^ a b "West Africa's first-ever case of Marburg virus disease confirmed in Guinea". who.int. 9 August 2021.
  55. ^ "Guinea records West Africa's first Marburg virus death, WHO says". Reuters. August 10, 2021. Retrieved August 10, 2021.
  56. ^ "Ghana confirms first cases of deadly Marburg virus". BBC News. 18 July 2022. Retrieved 18 July 2022.
  57. ^ "Equatorial Guinea declares outbreak of Ebola-like Marburg virus". BNO News. 13 February 2023. Retrieved 14 February 2023.
  58. ^ Schnirring L (4 April 2023). "Equatorial Guinea confirms another Marburg virus case". University of Minnesota. CIDRAP. Retrieved 4 April 2023.
  59. ^ Schnirring L (24 April 2023). "New fatal Marburg case reported in Equatorial Guinea". University of Minnesota. CIDRAP. Retrieved 25 April 2023.
  60. ^ Schnirring L (22 March 2023). "Tanzania declares Marburg virus outbreak". University of Minnesota. CIDRAP. Retrieved 22 March 2023.
  61. ^ "Tanzania reports additional Marburg virus disease case". Outbreak News Today. 24 April 2023. Retrieved 25 April 2023.
  62. S2CID 30252321
    .
  63. PMID 5005859
    .
  64. S2CID 12791113
    .
  65. ISBN 978-0-387-05199-4
    .
  66. PMID 811315
    .
  67. PMID 406394
    .
  68. PMID 569445
    .
  69. ^ Dellatola L (May 1980). "Victory for Virology". South African Panorama. 25 (5): 2–6 – via Internet Archive.
  70. S2CID 42832324
    .
  71. ^
    ISBN 978-0-385-47956-1
    .
  72. PMID 8800792
    .
  73. S2CID 25789824
    .
  74. ISBN 978-0-385-33496-9
    .
  75. PMID 7941853
    .
  76. PMID 10546197
    .
  77. PMID 14720391
    .
  78. PMID 20441515
    .
  79. PMID 16038348
    .
  80. PMID 15917379
    .
  81. PMID 16775337
    .
  82. PMID 17940944
    .
  83. PMID 17940945
    .
  84. PMID 18838150. Archived from the original
    (PDF) on 2017-08-09. Retrieved 2018-04-29.
  85. PMID 21987753
    .
  86. PMID 19751577
    .
  87. PMID 20019654
    .
  88. ^ "Marburg virus disease – Uganda and Kenya". WHO. 7 November 2017. Archived from the original on November 9, 2017. Retrieved 2017-12-04.
  89. ^ Dana Dovey (18 November 2017). "WHAT IS MARBURG? THIS VIRUS CAUSES VICTIMS TO BLEED FROM EVERY ORIFICE AND DIE". Newsweek. Retrieved 2017-12-04.
  90. ^ a b "Marburg virus disease - Guinea". www.who.int. Retrieved 2022-11-29.
  91. S2CID 250114159
    .
  92. ^
    bioRxiv 10.1101/2022.11.03.514981v1
    .
  93. ^ "Ghana reports first-ever suspected cases of Marburg virus disease". World Health Organization. 7 July 2022. Retrieved 7 July 2022.
  94. ^ "Ghana confirms its first outbreak of highly infectious Marburg virus". Reuters. 2022-07-18. Retrieved 2022-07-18.
  95. ^ "Ghana Declares First Marburg Virus Disease Outbreak". Bloomberg.com. 2022-07-18. Retrieved 2022-07-18.
  96. ^ @Ghana Health Service Official (July 28, 2022). Health Service Official/status/1552716814974689280 "Update on Marburg Virus Disease Outbreak in Ghana" (Tweet) – via Twitter. {{cite web}}: Check |url= value (help)
  97. ^ "Equatorial Guinea confirms first-ever Marburg virus disease outbreak". World Health Organization. 13 February 2023. Retrieved 13 February 2023.
  98. ^ "Cameroon detects two suspected cases of Marburg virus near Eq. Guinea". Reuters. Retrieved 14 February 2023.
  99. S2CID 14039727. Archived
    from the original on 2017-09-27. Retrieved 2018-04-29.
  100. PMID 35622847
    .
  101. S2CID 205387144
    .
  102. ^ "Sarepta Therapeutics Announces Positive Safety Results from Phase I Clinical Study of Marburg Drug Candidate - Business Wire" (Press release). 2014-02-10. Retrieved 12 October 2014.
  103. ^ "Successful Marburg Virus Treatment Offers Hope for Ebola Patients". National Geographic. 2014-08-20. Archived from the original on August 22, 2014. Retrieved 12 October 2014.

Further reading

External links

Wikimedia Commons has media related to Marburg virus.
Scholia has a topic profile for Marburg virus disease.
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