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Marburg Virus Disease

Marburg Hemorrhagic Fever

Marburg virus disease is characterized by a hemorrhagic fever. There have been past outbreaks of this illness as well as isolated cases that have resulted in high mortality. The clinical presentation typically consists of a progressive disease with fever, hemorrhagic manifestations, multiorgan failure, shock, and other serious complications.


Presentation

Marburg virus disease, also known as Marburg hemorrhagic fever, is a severe illness with a high mortality rate. The responsible pathogen, Marburg virus, is a member of the filoviridae family along with the Ebola virus [1]. The first documented outbreak of this disease was in 1967 in Germany and Yugoslavia (which is currently known as Serbia) [2]. Outbreaks have also occurred between 1998 to 2000 in the Democratic Republic of Congo, Angola in 2004 to 2005 [3] [4] and most recently in Uganda in 2012. Additionally, there have been sporadic cases over the years. The African fruit bat acts as a reservoir for this zoonotic virus affecting human as well as non-human primates. The transmission occurs from human to human contact. The incubation period may range from 2 days to 3 weeks [5].

There are three stages of this illness, which are described as the 1) generalization phase, 2) early organ phase, and 3) late organ or convalescence phase [6]. The first phase lasts about 5 days and is characterized by a high fever, headache, chills, malaise, myalgia, and possibly nausea, emesis, watery diarrhea, abdominal pain, pharyngitis, conjunctivitis, and a rash [2] [7] [8]. As the illness progresses, the patient enters the early organ phase, which involves the liver, kidneys, and pancreas. It features neurological symptoms, impaired mental status, hematemesis, bloody diarrhea, and bleeding from other sites [2] [9]. The final phase is critical and often leads to death secondary to critical manifestations such as multiorgan failure, seizures, coagulopathy, cardiovascular collapse, and shock [1].

Physical exam

Assessment of the vital signs typically reveals fever, hypotension and other abnormalities. Also, the patient appears ill and exhibits mental status changes such as confusion, delirium, and dementia [1]. Other notable findings include conjunctival injection, pharyngitis, petechia, ecchymoses, and palatal exanthem. Bleeding from mucosal sites and orifices is observed in severe cases.

Fever
  • Imported case of Marburg hemorrhagic fever - Colorado, 2008. Morbidity and Mortality Weekly Report. 2009; 58(49):1377-1381. World Health Organization. Case of Marburg Haemorrhagic Fever Imported into the Netherlands from Uganda. 10 July 2008.[cdc.gov]
  • fever virus by real-time reverse transcription-PCR.[doi.org]
  • Marburg virus belongs to the genus Marburgvirus in the family Filoviridae and causes a severe hemorrhagic fever, known as Marburg hemorrhagic fever (MHF), in both humans and nonhuman primates.[ncbi.nlm.nih.gov]
  • Important VHF agents are Ebola and Marburg viruses (MBGV/EBOV), Lassa virus (LASV), Crimean-Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus (RVFV), dengue virus (DENV), and yellow fever virus (YFV).[ncbi.nlm.nih.gov]
  • […] plus at least 3 general symptoms or fever plus unexplained hemorrhage).[doi.org]
Malaise
  • According to the global health body, the illness caused by Marburg virus begins abruptly, with severe headache and malaise.[china.org.cn]
  • A doctor who attempted resuscitation developed symptoms 9 days later but recovered [ 3 ]. 1987 Kenya Kenya 1 1 (100%) A 15-year-old Danish boy was hospitalized with a 3-day history of headache, malaise, fever, and vomiting.[web.archive.org]
  • The first phase lasts about 5 days and is characterized by a high fever, headache, chills, malaise, myalgia, and possibly nausea, emesis, watery diarrhea, abdominal pain, pharyngitis, conjunctivitis, and a rash.[symptoma.com]
  • The symptoms begin suddenly with a high fever, malaise and headaches. Muscle aches and pains are also fairly common in beginning symptoms. Diarrhea, abdominal pain and cramping, nausea and vomiting can begin from the third day of symptoms.[ucsdguardian.org]
  • A doctor who attempted resuscitation developed symptoms 9 days later but recovered. 4 1987 Kenya Kenya 1 1 (100%) A 15-year-old Danish boy was hospitalized with a 3-day history of headache, malaise, fever, and vomiting.[cdc.gov]
Physician
  • On January 9, 2008, an infectious disease physician notified the Colorado Department of Public Health and Environment (CDPHE) of a case of unexplained febrile illness requiring hospitalization in a woman who had returned from travel in Uganda.[ncbi.nlm.nih.gov]
  • The attending physician contracted MVD, but survived.[en.wikipedia.org]
  • She returned to her primary-care physician's clinic on January 8, complaining of persistent diarrhea and abdominal pain, as well as worsening fatigue, generalized weakness, and confusion.[cdc.gov]
  • This patient’s attending physician in Nairobi became the second case. Another human Marburg infection was recognized in 1987 when a young man who had traveled extensively in Kenya, including western Kenya, became ill and later died.[web.archive.org]
  • Unless the physician made another diagnosis, these patients were admitted to a safety room or the Marburg ward for testing.[doi.org]
Veterinarian
  • Veterinarians and laboratory or quarantine facility workers who handle non-human primates from Africa may also be at increased risk of exposure to MVD.[rxwiki.com]
  • Secondary cases involved two physicians, 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.[en.wikipedia.org]
  • 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.[allcountries.org]
Laboratory Technician
  • Summary A number of laboratory technicians and animal-house attendants at the Behringwerke in Marburg and the Paul-Ehrlich Institute in Frankfurt, in contact with monkeys, their blood or tissues, contracted an infection similar to “haemorrhagic fever”[doi.org]
Vomiting
  • Later on, however, the symptoms can become more serious, such as nausea, vomiting, chest pain, sore throat, abdominal pain, and severe diarrhea.[newsweek.com]
  • Features of the illness included high fever, myalgia, vomiting and diarrhoea, hepatitis, a characteristic maculopapular rash, leucopenia, thrombocytopenia, and a bleeding tendency.[ncbi.nlm.nih.gov]
  • A doctor who attempted resuscitation developed symptoms 9 days later but recovered [ 3 ]. 1987 Kenya Kenya 1 1 (100%) A 15-year-old Danish boy was hospitalized with a 3-day history of headache, malaise, fever, and vomiting.[web.archive.org]
  • The bleeds can be from the gums, nose, venepuncture sites that are used to draw blood from patients for tests and in vomit and feces.[ucsdguardian.org]
Diarrhea
  • It features neurological symptoms, impaired mental status, hematemesis, bloody diarrhea, and bleeding from other sites.[symptoma.com]
  • Later on, however, the symptoms can become more serious, such as nausea, vomiting, chest pain, sore throat, abdominal pain, and severe diarrhea.[newsweek.com]
  • Those include fever, headache, diarrhea and unexplained bleeding. Symptoms Patients infected with Marburg virus typically begin to show symptoms between five and 10 days after exposure.[dailyrx.com]
  • On January 4, she experienced severe headache, chills, nausea, vomiting, and diarrhea ( Figure ). She self-treated for traveler's diarrhea with 2 doses of ciprofloxacin, and developed a diffuse rash.[cdc.gov]
  • The illness progresses to a sore throat, abdominal and chest pain, vomiting, diarrhea and a skin rash typically around the body trunk.[iamat.org]
Nausea
  • Later on, however, the symptoms can become more serious, such as nausea, vomiting, chest pain, sore throat, abdominal pain, and severe diarrhea.[newsweek.com]
  • The first phase lasts about 5 days and is characterized by a high fever, headache, chills, malaise, myalgia, and possibly nausea, emesis, watery diarrhea, abdominal pain, pharyngitis, conjunctivitis, and a rash.[symptoma.com]
  • Diarrhea, abdominal pain and cramping, nausea and vomiting can begin from the third day of symptoms. At this point, patients are described as having a “ghost-like” appearance, with deep set eyes and severe lethargy.[ucsdguardian.org]
  • Severe watery diarrhoea, abdominal pain and cramping, nausea and vomiting can begin on the third day. Diarrhoea can persist for a week.[who.int]
  • About five days into the illness, patients often develop a red, bumpy rash on the stomach or back, diarrhea, nausea, vomiting and stomach pain. Symptoms tend to become more serious as the disease advances.[dailyrx.com]
Hematemesis
  • It features neurological symptoms, impaired mental status, hematemesis, bloody diarrhea, and bleeding from other sites.[symptoma.com]
  • On 21 September he presented to a health center in a suburb of Kyebando, located on the outskirts of Kampala, with fever, headache, arthralgia, anorexia, and hematemesis.[doi.org]
  • […] days, the virus will disseminate via the lymphatics and cause multiorgan failure Prevention vaccines are under development Prognosis high mortality rate Presentation Symptoms flu-like symptoms high fever myalgia headache nausea and vomiting may have hematemesis[medbullets.com]
  • Symptoms include bloody stools, ecchymoses, blood leakage from venipuncture sites, mucosal & visceral hemorrhaging, and possibly hematemesis. Late Organ Phase: Day 13 up to Day 21 .[en.wikipedia.org]
  • Epistaxis and hematemesis were observed in 29 ] but not, typically, in certain diseases for which FHF can be mistaken (eg, typhoid and shigellosis).[doi.org]
Decreased Bowel Sounds
  • On physical examination, she appeared pale and fatigued, and had decreased bowel sounds; the remainder of her examination was unremarkable.[cdc.gov]
Jaundice
  • More severe symptoms can also develop such as jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, and liver failure. Eventually victims may experience massive bleeding from the orifices and finally multi-organ dysfunction.[newsweek.com]
  • Signs and symptoms include fever, headache, myalgias, chest and abdominal pain, jaundice, liver failure, massive hemorrhaging, and multiple organ failure. An rna virus infection of rhesus, vervet, and squirrel monkeys transmissible to man.[icd10data.com]
  • There is functional evidence of liver damage but clinical jaundice has not been reported. Renal damage occurs and is manifested by proteinuria, oliguria and viruria.[europeanmedical.info]
  • Symptoms become increasingly severe and can include jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, and multi-organ dysfunction.[rxwiki.com]
  • Symptoms become increasingly severe and may include jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, massive hemorrhaging, and multi-organ dysfunction.[web.archive.org]
Bone Pain
  • Approximately 5 days after disease onset, a nonpruritic rash may appear, followed by nausea, vomiting, diarrhea, bone pain, and abdominal pain.[doi.org]
Red Eye
  • Symptoms usually include Fever Headache Joint and muscle aches Weakness Diarrhea Vomiting Stomach pain Lack of appetite Other symptoms including rash, red eyes, and internal and external bleeding, may also occur.[medlineplus.gov]
  • . • Diarrhea (may be bloody) • Red eyes. • Raised rash. • Chest pain and cough. • Stomach pain. • Severe weight loss. • Bleeding, usually from the eyes, and bruising (people near death may bleed from other orifices, such as ears, nose and rectum) 11 12[slideshare.net]
Exanthema
  • Symptoms include prostration, dyspnea, edema, conjunctival injection, viral exanthema, and CNS symptoms, including encephalitis, confusion, delirium, apathy, and aggression.[en.wikipedia.org]
Epistaxis
  • Epistaxis and hematemesis were observed in 29 ] but not, typically, in certain diseases for which FHF can be mistaken (eg, typhoid and shigellosis).[doi.org]
Headache
  • According to the global health body, the illness caused by Marburg virus begins abruptly, with severe headache and malaise.[china.org.cn]
  • A doctor who attempted resuscitation developed symptoms 9 days later but recovered [ 3 ]. 1987 Kenya Kenya 1 1 (100%) A 15-year-old Danish boy was hospitalized with a 3-day history of headache, malaise, fever, and vomiting.[web.archive.org]
  • The first phase lasts about 5 days and is characterized by a high fever, headache, chills, malaise, myalgia, and possibly nausea, emesis, watery diarrhea, abdominal pain, pharyngitis, conjunctivitis, and a rash.[symptoma.com]
  • Early symptoms come on quickly and can include fever, chills, headache and muscle pain. A few days after symptoms begin to show, those symptoms usually become more serious.[dailyrx.com]
  • On 21 September he presented to a health center in a suburb of Kyebando, located on the outskirts of Kampala, with fever, headache, arthralgia, anorexia, and hematemesis.[doi.org]
Confusion
  • Also, the patient appears ill and exhibits mental status changes such as confusion, delirium, and dementia. Other notable findings include conjunctival injection, pharyngitis, petechia, ecchymoses, and palatal exanthem.[symptoma.com]
  • During the last and most severe phase of Marburg, patients have a constant high fever and an affected central nervous system that results in confusion, irritability and aggression.[ucsdguardian.org]
  • Symptoms include prostration, dyspnea, edema, conjunctival injection, viral exanthema, and CNS symptoms, including encephalitis, confusion, delirium, apathy, and aggression.[en.wikipedia.org]
  • Involvement of the central nervous system can result in confusion, irritability, and aggression. Orchitis (inflammation of one or both testicles) has been reported occasionally in the late phase of disease (15 days).[who.int]
  • Later symptoms include inflammation of the pancreas, pronounced weight loss, confusion, shock, liver failure and unexplained bleeding. Diagnosis Marburg virus disease can be difficult to diagnose.[dailyrx.com]
Seizure
  • The final phase is critical and often leads to death secondary to critical manifestations such as multiorgan failure, seizures, coagulopathy, cardiovascular collapse, and shock.[symptoma.com]
  • On 13 July, he developed confusion, seizures, hematemesis, and hematochezia, and died later that day. A blood sample collected on 13 July was sent on 23 July to CDC for testing.[doi.org]
Apathy
  • Symptoms include prostration, dyspnea, edema, conjunctival injection, viral exanthema, and CNS symptoms, including encephalitis, confusion, delirium, apathy, and aggression.[en.wikipedia.org]
Aura
  • Aura Timen, Marion P.G. Koopmans, Ann C.T.M. Vossen, Gerard J.J. van Doornum, Stephan Günther, Franchette van den Berkmortel, Kees M. Verduin, Sabine Dittrich, Petra Emmerich, Albert D.M.E. Osterhaus, Jaap T. van Dissel, and Roel A.[doi.org]

Workup

Patients presenting with the above symptoms warrant a thorough evaluation consisting of a detailed personal and travel/exposure history, physical exam, and the appropriate studies.

Laboratory tests

A complete blood count (CBC) and complete metabolic panel (CMP) including liver function tests (LFTs) will feature typical findings such as leukopenia, thrombocytopenia, and elevated liver transaminases. Furthermore, a coagulation panel and disseminated intravascular coagulation profile will reveal abnormalities about the patient's critical state.

Diagnostic tests

Viral detection studies such as reverse transcription polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay (ELISA) are the first-line tests [10]. In addition to conventional RT-PCR, quantitative real-time RT-PCR is also used [1] [11].

Other studies such as immunoglobulin (Ig) M and IgG ELISA are used to identify antibodies against the virus [1]. Moreover, IgM–capture ELISAs are commonly performed for the diagnosis of acute disease while IgG antibodies are used retrospectively post-disease [12]. Additionally, there is a promising future for the reverse transcription–loop–mediated isothermal amplification method in diagnosing Marburg virus [13].

There are two other techniques, virus isolation, and electron microscopy, but these are limited to specialized sites [1].

Treatment

  • Guided tours of the Marburg treatment units in Kapchorwa and Kween were organized in order to dispel fear of the treatment center and rumours of wrong practices by healthcare workers that cause death of admitted patients.[who.int]
  • Treatment is essentially supportive. Patients and contacts must be isolated and monitored, and extreme precautions must be taken by hospital and laboratory staff to prevent their own infection.[ncbi.nlm.nih.gov]
  • This article will review the clinical aspects of MHF and discuss the pathogenesis and possible options for diagnosis, treatment and prevention.[ncbi.nlm.nih.gov]
  • The other two patients were given vigorous supportive treatment and prophylactic heparin and recovered after an acute phase lasting about seven days.[ncbi.nlm.nih.gov]
  • Supportive care – rehydration with oral or intravenous fluids – and treatment of specific symptoms, improves survival. There is as yet no proven treatment available for Marburg virus disease.[who.int]

Prognosis

  • Marburg Virus Disease Prognosis The case-fatality rate for Marburg virus disease (MVD) is between 23-90%.[rxwiki.com]
  • Pathogenesis the virus targets endothelial cells, hepatocytes, phagocytes, and dendritic cells after an incubation period up to 21 days, the virus will disseminate via the lymphatics and cause multiorgan failure Prevention vaccines are under development Prognosis[medbullets.com]
  • Prognosis is generally poor. If a patient survives, recovery may be prompt and complete, or protracted with sequelae, such as orchitis, hepatitis, uveitis, parotitis, desquamation or alopecia.[en.wikipedia.org]
  • Clinical course and prognosis of Marburg virus (‘green-monkey’) disease. In: Marburg Virus Disease. Martini GA, Siegert R (Eds). Springer-Verlag, NY, USA, 10–18 ( 1971 ). Google Scholar 27 Bente D, Gren J, Strong JE, Feldmann H.[dx.doi.org]

Etiology

  • Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology.[icd10coded.com]
  • It was soon apparent that the infectious agent was neither bacterial nor rickettsial in origin but that a viral etiology was probable.[link.springer.com]
  • The admission diagnosis was acute hepatitis, nausea, and vomiting of unknown etiology. On admission, the patient was afebrile (temperature 96.2 F [35.7 C]).[cdc.gov]
  • On the etiology of an unknown human infection originating from monkeys, Dtsch Med Wochenschr, 1967 , vol. 92 51 (pg. 2341 - 2343 ) 2., In: Virus taxonomy, VIIIth report of the International Committee on Taxonomy of Viruses, 2009 London, UK Elsevier/Academic[doi.org]
  • Only six secondary infections (five nosocomial and one sexually transmitted) were noted of the 32 cases reported during the original MHF outbreak in 1967 in Europe, despite the fact that the etiologic agent was unknown at the time of the outbreak and[doi.org]

Epidemiology

  • The analysis was severely hampered by a lack of completeness in epidemiologic data.[ncbi.nlm.nih.gov]
  • This underlines the importance of a community surveillance system that provides epidemiological data on prior patient contacts and of integrating epidemiological data into the clinical assessment when deciding on isolation or PCR testing.[doi.org]
  • The response was supported by WHO, UNICEF, USAID, World Vision, Uganda Red Cross, Médecins Sans Frontières (MSF), the African Field Epidemiology Network (AFENET) and the US Centers for Disease Control and Prevention (CDC).[who.int]
  • The WHO and international partners, including the CDC, the Uganda Red Cross, African Field Epidemiology Network and Médecins-Sans-Frontières, are supporting the national authorities in outbreak investigation and response.[healio.com]
  • Abstract Marburg virus disease is an African disease of unknown epidemiology. The infection is pantropic and highly contagious. Haemorrhage and other features cause serious morbidity and high mortality, and early diagnosis is essential.[ncbi.nlm.nih.gov]
Sex distribution
Age distribution

Pathophysiology

  • Pathophysiology Once the virus enters the body though breaks in the skin or mucous membranes, it infects dendritic cells and macrophages which then carry it to lymph nodes.[upmc-cbn.org]
  • Novel viruses have recently been identified. [6, 7] Pathophysiology Although common themes occur, the different viruses display variable pathophysiology.[emedicine.com]

Prevention

  • Training of health workers on infection prevention and control, surveillance and clinical case management is ongoing, and the first shipment of personal protective equipment arrived recently.[healio.com]
  • How is Marburg hemorrhagic fever prevented? Due to our limited knowledge of the disease, preventive measures against transmission from the original animal host have not yet been established.[web.archive.org]
  • Patients and contacts must be isolated and monitored, and extreme precautions must be taken by hospital and laboratory staff to prevent their own infection.[ncbi.nlm.nih.gov]
  • This article will review the clinical aspects of MHF and discuss the pathogenesis and possible options for diagnosis, treatment and prevention.[ncbi.nlm.nih.gov]
  • Author information 1 Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, Georgia. 2 Uganda Ministry of Health. 3 Uganda Virus Research Institute. 4 World Health Organization. 5 Viral Special Pathogens Branch, Centers for[ncbi.nlm.nih.gov]

References

Article

  1. Mehedi M, Groseth A, Feldmann H, Ebihara H. Clinical aspects of Marburg hemorrhagic fever. Future virology. 2011;6(9):1091-1106.
  2. Martini GA, Knauff HG, Schmidt HA, Mayer G, Baltzer G. [On the hitherto unknown, in monkeys originating infectious disease: Marburg virus disease] Dtsch Med. Wochenschr. 1968;93(12):559–571.
  3. World Health Organization. Viral haemorrhagic fever/Marburg, Democratic Republic of the Congo. Wkly Epidemiol Rec. 1999;74(20):157–8.
  4. Ndayimirije N, Kindhauser MK. Marburg hemorrhagic fever in Angola--fighting fear and a lethal pathogen. N Engl J Med. 2005;352(21):2155-7.
  5. Slenczka WG. The Marburg virus outbreak of 1967 and subsequent episodes. Curr Top Microbiol Immunol. 1999;235:49–75.
  6. Stille W, Boehle E. Clinical course and prognosis of Marburg virus (‘green–monkey’) disease. In: Martini GA, Siegert R, eds. Marburg Virus Disease. New York, NY: Springer-Verlag;1971:10–18.
  7. Sanchez A, Geisbert T, Feldmann H. Filoviridae – Marburg and ebola viruses. In: Knipe D, ed. Fields Virology. Philadelphia, PA: Williams and Wilkins; 2007:1410–1448.
  8. Colebunders R, Tshomba A, Van Kerkhove MD, et al. Marburg hemorrhagic fever in Durba and Watsa, Democratic Republic of the Congo: clinical documentation, features of illness, and treatment. J Infect Dis. 2007; 196(Suppl. 2): S148–S153.
  9. Gear JS, Cassel GA, Gear AJ, et al. Outbreak of Marburg virus disease in Johannesburg. BMJ. 1975;4(5995):489–493.
  10. Grolla A, Lucht A, Dick D, Strong JE, Feldmann H. Laboratory diagnosis of ebola and Marburg hemorrhagic fever. Bull Soc Path Exot. 2005;98(3):205–209.
  11. Drosten C, Gottig S, Schilling S, et al. Rapid detection and quantification of RNA of ebola and Marburg viruses, Lassa virus, Crimean–Congo hemorrhagic fever virus, rift valley fever virus, dengue virus, and yellow fever virus by real–time reverse transcription–PCR. J Clin Microbiol. 2002;40(7):2323–2330.
  12. Bray M. Filoviruses. In: Richman DD, Whitley RJ, Hayden FG, eds. Clinical Virology. 3rd ed. Washington, DC: American Society of Microbiology; 2009: 923–941.
  13. Kurosaki Y, Grolla A, Fukuma A, Feldmann H, Yasuda J. Development and evaluation of a simple assay for Marburg virus detection using a reverse transcription–loop–mediated isothermal amplification method. J Clin Microbiol. 2010; 48(7):2330–2336.

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Last updated: 2019-06-28 10:46