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. [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]

• Anorexia

  Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. [ncbi.nlm.nih.gov]

  Variables eligible for the multivariable models were myalgia or arthralgia, anorexia, asthenia, any hemorrhage, bleeding at an injection site, bloody gingivitis and, for model 2, an epidemiological link. [doi.org]

  The clinical presentation is more or less identical in all three species, showing fever (40–40.5 C), anorexia, weight loss and unresponsiveness. [dmm.biologists.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. [rxlist.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]

• Fatigue

  Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. [ncbi.nlm.nih.gov]

  On physical examination, she appeared pale and fatigued, and had decreased bowel sounds; the remainder of her examination was unremarkable. [cdc.gov]

  Symptoms include the following: Maculopapular rashes that develop in the head, neck and stomach High fever Severe headache Chills Nausea Vomiting Abdomen pain Cramping Muscle pain Sore throat Chest pain Fatigue Watery diarrhea Joint pain Excessive weight [medindia.net]

  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, & malaise. [en.wikipedia.org]

  Appendix Case Definitions for Marburg Hemorrhagic Fever, Uige, Angola, 7 May 2005 Suspected case Unexplained hemorrhage Fever plus 3 of the following symptoms: headache, anorexia, fatigue, myalgia, arthralgia, dyspnea, nausea, vomiting, diarrhea, dysphagia [doi.org]

• Sore Throat

  Symptoms significantly associated with being a MVD case included hiccups, anorexia, fatigue, vomiting, sore throat, and difficulty swallowing. Contact with a case patient and attending a funeral were also significantly associated with being a case. [ncbi.nlm.nih.gov]

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

  Syn: Green - monkey - disease Marburg virus disease, a severe, distinctive, hemorrhagic illness with a high rate of mortality, is heralded early by severe sore throat, a maculopapular rash, and a red exanthem on the hard and soft palate. [histopathology-india.net]

  The illness progresses to a sore throat, abdominal and chest pain, vomiting, diarrhea and a skin rash typically around the body trunk. [iamat.org]

  Other symptoms, such as nausea, vomiting, chest pain, a sore throat, abdominal pain, and diarrhea, may then appear. After 5-7 days, patients may develop severe bleeding from multiple sites. [rxwiki.com]

• Cough

  A severe watery diarrhoea, abdominal pain, nausea and vomiting are early symptoms, as are severe chest and lung pains, sore throat, and cough. [who.int]

  After an incubation period of 2 to 20 days, fever, myalgia, and headache occur, often with abdominal pain, nausea, and upper respiratory symptoms (cough, chest pain, pharyngitis). [merckmanuals.com]

  Besides fever and weakness, early symptoms include severe diarrhea, abdominal pain, nausea and vomiting, severe chest pain, sore throat, and cough, according to the WHO. The incubation period is 3 to 9 days. [cidrap.umn.edu]

  Jaundice and pancreatitis are common, as is an altered mental status or even coma; pharyngitis and a nonproductive cough are less common. [upmc-cbn.org]

  […] travel to certain African countries, the following clinical criteria should be considered in suspected cases: high fever (more than 38 C for less than three weeks), muscle pain and at least two hemorrhagic symptoms (rash, nosebleed, vomiting of blood, coughing [news-medical.net]

• Dyspnea

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

  Appendix Case Definitions for Marburg Hemorrhagic Fever, Uige, Angola, 7 May 2005 Suspected case Unexplained hemorrhage Fever plus 3 of the following symptoms: headache, anorexia, fatigue, myalgia, arthralgia, dyspnea, nausea, vomiting, diarrhea, dysphagia [doi.org]

  […] trauma, another focal disease process, or a response to antibiotics or antimalarial agents; at least three of the following signs and symptoms: fever, generalized body pains, nausea and vomiting, headache, anorexia, malaise, abdominal pain, diarrhea, dyspnea [dx.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]

  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]

  Severe watery diarrhoea, abdominal pain and cramping, nausea and vomiting can begin on the third day. Diarrhoea can persist for a week. [who.int]

• 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]

  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]

  Severe watery diarrhoea, abdominal pain and cramping, nausea and vomiting can begin on the third day. Diarrhoea can persist for a week. [who.int]

• 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]

• Chest Pain

  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 illness progresses to a sore throat, abdominal and chest pain, vomiting, diarrhea and a skin rash typically around the body trunk. [iamat.org]

  Other symptoms, such as nausea, vomiting, chest pain, a sore throat, abdominal pain, and diarrhea, may then appear. After 5-7 days, patients may develop severe bleeding from multiple sites. [rxwiki.com]

  Nausea, vomiting, chest pain, a sore throat, abdominal pain, and diarrhea then may appear. [web.archive.org]

  Symptoms include the following: Maculopapular rashes that develop in the head, neck and stomach High fever Severe headache Chills Nausea Vomiting Abdomen pain Cramping Muscle pain Sore throat Chest pain Fatigue Watery diarrhea Joint pain Excessive weight [medindia.net]

• Conjunctival Injection

  Other notable findings include conjunctival injection, pharyngitis, petechia, ecchymoses, and palatal exanthem. Bleeding from mucosal sites and orifices is observed in severe cases. [symptoma.com]

  Photophobia, conjunctival injection, jaundice, and lymphadenopathy also occur. Vomiting and diarrhea may soon follow. Delirium, stupor, and coma may occur, indicating CNS involvement. [merckmanuals.com]

  injection Studies Labs thrombocytopenia hepatic transaminitis detection of viral RNA on reverse-transcriptase polymerase chain reaction (RT-PCR) Making the diagnosis diagnosis based on clinical presentation and detection of viral RNA on RT-PCR Differential [medbullets.com]

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

  injection, postural hypotension, edema) and neurologic (headache, confusion, seizure, coma) manifestations. [dmm.biologists.org]

• Petechiae

  Other notable findings include conjunctival injection, pharyngitis, petechia, ecchymoses, and palatal exanthem. Bleeding from mucosal sites and orifices is observed in severe cases. [symptoma.com]

  Hemorrhagic symptoms begin within the first few days and include petechiae, ecchymoses, and frank bleeding around puncture sites and mucous membranes. A maculopapular rash, primarily on the trunk, begins around day 5. [merckmanuals.com]

  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]

  A maculopapular rash, petechiae, purpura, ecchymoses, and hematomas (especially around needle injection sites) are typical hemorrhagic manifestations. [en.wikipedia.org]

  Hemorrhagic signs (including petechiae) were found to occur in 42% of hospitalized patients in Uige, Angola (P.R., unpublished data), and in 69% of all patients in Durba and Watsa, Democratic Republic of the Congo [ 1 ]. [doi.org]

• Skin Rash

  The illness progresses to a sore throat, abdominal and chest pain, vomiting, diarrhea and a skin rash typically around the body trunk. [iamat.org]

  Rhesus macaques in particular develop petechial skin rashes, resembling human cases where rashes have been described on the arms and thighs, and to a lesser extend on the thorax, face and neck. [dmm.biologists.org]

  In humans, marburgviruses are responsible for Marburg virus disease (MVD), a zoonotic disease that is characterized by high fever, malaise, nausea, vomiting, diarrhea, skin rash, and hemorrhage (bleeding). [britannica.com]

• 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]

• Myalgia

  RESULTS: A MHF case definition comprising (1) an epidemiological link or (2) the combination of myalgia or arthralgia and any hemorrhage could potentially serve as an alternative to current case definitions. [ncbi.nlm.nih.gov]

  Of the generalized symptoms, myalgia or arthralgia was the strongest predictor of MHF but had intermediate sensitivity and specificity. [doi.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]

• Arthralgia

  RESULTS: A MHF case definition comprising (1) an epidemiological link or (2) the combination of myalgia or arthralgia and any hemorrhage could potentially serve as an alternative to current case definitions. [ncbi.nlm.nih.gov]

  Of the generalized symptoms, myalgia or arthralgia was the strongest predictor of MHF but had intermediate sensitivity and specificity. [doi.org]

  Survivors of Marburg hemorrhagic fever experience a prolonged convalescence characterized by myalgia, muscle weakness, arthralgia, myelitis, hepatitis, ocular disease, hearing loss, and in some instances even psychosis. [news-medical.net]

• 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]

• Vaginal Bleeding

  She had no signs of gross hemorrhage other than vaginal bleeding attributed to menses. During her hospitalization, she underwent cholecystectomy for acalculous cholecystitis. [cdc.gov]

• 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]

  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]

  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]

• 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].

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