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

  Marburg Hemorrhagic Fever View PDF (132KB) What is Marburg hemorrhagic fever? Marburg hemorrhagic fever is a rare, severe type of hemorrhagic fever which affects both humans and non-human primates. [web.archive.org]

  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]

  […] in past outbreaks of Marburg hemorrhagic fever. [dx.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]

  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]

  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]

• 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]

  Veterinarians may also be at higher risk if they are exposed to African monkeys. [medicinenet.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]

• Abdominal Pain

  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]

  Later on, however, the symptoms can become more serious, such as nausea, vomiting, chest pain, sore throat, abdominal pain, and severe diarrhea. [newsweek.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]

  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]

• 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]

  Bleeding from the nose, gums, and eyes is common, and extensive gastrointestinal hemorrhage will often manifest as frank blood in the stool or hematemesis. [infectionlandscapes.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]

• 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]

• 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]

• Eczema

  Forest disease A98.3 Marburg virus disease A98.4 Ebola virus disease A98.5 Hemorrhagic fever with renal syndrome A98.8 Other specified viral hemorrhagic fevers A99 Unspecified viral hemorrhagic fever B00 Herpesviral [herpes simplex] infections B00.0 Eczema [icd10data.com]

• Epistaxis

  Hemorrhagic manifestations may develop during the peak of the illness and include petechiae, ecchymoses, uncontrolled bleeding from venipuncture sites, epistaxis and other mucosal hemorrhages, and postmortem evidence of visceral hemorrhagic effusions. [dmm.biologists.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]

• Headache

  According to the global health body, the illness caused by Marburg virus begins abruptly, with severe headache and malaise. [china.org.cn]

  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]

  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]

  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]

  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]

• 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]

  Symptoms include prostration, dyspnea, edema, conjunctival injection, viral exanthema, and CNS symptoms, including encephalitis, confusion, delirium, apathy, and aggression. [en.wikipedia.org]

  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]

  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]

  […] prostration, lethargy), gastrointestinal (anorexia, nausea, vomiting, abdominal pain, diarrhea), respiratory (chest pain, shortness of breath, cough), vascular (conjunctival injection, postural hypotension, edema) and neurologic (headache, confusion, seizure [dmm.biologists.org]

• Stupor

  Delirium, stupor, and coma may occur, indicating CNS involvement. Hemorrhagic symptoms begin within the first few days and include petechiae, ecchymoses, and frank bleeding around puncture sites and mucous membranes. [merckmanuals.com]

• Apathy

  Symptoms include prostration, dyspnea, edema, conjunctival injection, viral exanthema, and CNS symptoms, including encephalitis, confusion, delirium, apathy, and aggression. [en.wikipedia.org]

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].

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.