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Copyright 2004 Tara K. Harper.  All rights reserved.

TKH Virology Notes:
Marburg Hemorrhagic Fever

•  Description      •  Mechanism      •  Outbreaks
•  Location      •  Incubation Period      •  Vaccine
•  Vector      •  Symptoms      •  Odds 'n' Ends
     •  Diagnosis      •  Links
     •  Mortality Rates
     •  Treatment

Science and Literary  Links for Writers
Science and Technical  References for Writers


NOTE:  This file is for information only.  It is not intended for diagnosis.


Marburg Virus Disease
     •  Marburg Hemorrhagic Fever

Description.   A rare, acute, infectious, hemorrhagic viral fever which affects both human and nonhuman primates.  Marburg is the first member of the family, Filoviridae (or "thread" viruses), which also includes the Ebola virus.  Like Ebola, Marburg is an enveloped, single-stranded, unsegmented, negative-sense RNA virus.  It has the same characteristic filamentous structure, can appear shaped like a U, a 6, or spiraled like a snail; and can sometimes be branched.  (Refer to Links, at the bottom of this page, for electron micrographs.)   They tend to include long noncoding regions at their 3' and/or 5' ends, which probably contributes to the stability of the viral transcript.

Marburg virions are 80 nm in diameter and average approximately 800 nm in length, although length can vary up to 14,000 nm.  The virion length associated with peak infectivity is 790 nm.  

The virions contain seven major structural proteins (such as membrane proteins);  no other virion-specific proteins have been identified in infected cells.  Virion lipids reflect the composition of lipids in the host-cell membranes.

The Marburg virus is identical to Ebola in form and structure; however, it is antigenically distinct from Ebola (meaning that it stimulates the production of different antibodies).  The virus is classified as a biosafety level 4 agent because of its extreme pathogenicity and the lack of a vaccine or antiviral drug.

Marburg is named after the German town in which some of the first cases were described.

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Location.  Endemic areas appear to be Central and East Africa.  One particularly "fertile" area is on the border of Kenya and Uganda, in the Mt. Elgon region.  In particular, visitors to the Kitum cave on top of Mt. Elgon have contracted Marburg.  Marburg may also have a natural reservoir in Zimbabwe.

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Vector.     The natural reservoir for the virus is unknown.  Epidemiologists have tested bats, monkeys, spiders and ticks for the virus, but were not able to acquire definitive data.  Common factors indicate that the natural reservoir is part of rural Africa. 

Secondary spread of the disease is via contact with infected persons or contact with blood, secretions, or excretions of infected persons.  The virus may continue to be shed in the patient's semen for up to 3-4 months after illness.  Sexual transmission of the disease did occur in one instance in Germany.

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Mechanism.  As with Ebola, the exact mechanism of Marburg is unknown.  However, virion surface spikes are made soley of large glycoprotein.  It is presumed that, as with other negative-strand RNA viruses, these surface spikes bind to receptors on the host cell and mediate entry into susceptible cells.  The Marburg virus has 22 potential N-linked glycosylation sites on its surface.  Viral replication takes place in the cytoplasm, and envelopment is the result of budding preformed nucleocapsids.  Systemically, the virus involves the liver, lymphoid organs, and kidneys.

Refer to the detailed description of the proposed mechanism for Ebola.

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Incubation Period:  Usually 5-7 days, but can range from 3-10 days.

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Symptoms.   Sudden onset of fever, chills, and malaise, with extreme prostration and weight loss.  The fever typically lasts 7 days.  On the fifth day of fever, a maculopapular petechial (tiny--pinpoint or pinhead size papula) rash appears, and hemorrhaging begins.  In survivors, the skin will eventually begin to shed or peel.  

Other symptoms are headache, myalgia, and inflammation of the eyelid and eye membrane, intestine, and liver.  Excessive effusions from internal organs occurs, followed by pulmonary interstitial edema and renal dysfunction.  Renal failure is common.  Some patients become jaundiced.  Within 7 to 10 days, patients who will survive begin to recover.  

Recovery can take 5 weeks or more, and is marked by prostration, weight loss, and amnesia for the period of acute illness.  Complications during convalescence can include recurrent hepatitis, as well as inflammation of the spinal cord, bone marrow, eyes, testes, and parotid gland.

Patients who are at greatest risk of dying experience diffuse or extensive hemorrhage into the skin, mucous membranes, internal organs, stomach, and intestines.  Swelling of the spleen, lymph nodes, kidneys, sometimes pancrease, and especially brain occurs.  Patients finally experience coma and convulsions, followed by death.  Death from shock usually occurs 6-9 days after clinical onset of symptoms.

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Diagnosis.   For patients presenting with Marburg symptoms, initial possible diagnoses can include malaria and tyhpoid fever.  As with Ebola, diagnosis of Marburg virus is confirmed by IgG ELISA, although IgM ELISA can be used to distinguish acute infections from old infections.  IFA results can be misleading.  Electron microscopy is useful in diagnosing filovirus infection, but does not help distinguish Marburg from Ebola.  

Laboratory findings include:
     •  Maculopapular rash, which is distinctive of Marburg, Ebola, dengue, and lassa.
     •  Reduction in the number of lymphocytes (lymphopenia) and increased number of neutrophilic leukocytes (neutrophilia).
     •  Thrombocytopenia and abnormal platelet aggregation.
     •  Serum enzyme levels are elevated;  AST is usually higher than ALT.
     •  Alkaline phosphatase and bilirubin levels are usually normal or only mildly elevated.

Marburg virus can be clearly diagnosed from specimens of deceased patients via immunohistochemistry, virus isolation, or PCR (polymerase chain reaction) of blood or tissue specimens.

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Mortality Rates.  The case fatality rate is approximately 25%.

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Treatment.   Supportive therapy (there is no specific treatment for Marburg hemorrhagic fever.  However, the virus itself is sensitive to lipid solvents, detergents, commercial hypochlorite disinfectants, and phenolic disinfectants.  The virus can also be destroyed by ultraviolet and gamma radiation.

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Outbreaks and History of Infection:
    .
Year Location Cases Status Dead

Mortality

Description
1967 Germany and Yogoslavia

25
6

primary
secondary

7
0

28%
0%

25 people contracted Marburg hemorrhagic fever after handing material from infected monkeys which were imported from Uganda.  An additional 6 people contracted the disease from the infected humans.
1975 South Africa

1
2

primary
secondary

1
0

100%
0%

An Australian contracted the disease while traveling through Zimbabwe and subsequently died after 12 days of illness. Two people who cared for him, his traveling companion and a nurse, contracted severe cases of the disease.  His companion contracted Marburg 7 days after the onset of his symptoms; the nurse contracted the disease 7 days after contact with the second patient.  Both companion and nurse survived.
1980 Kenya

1
1

primary
secondary

1
0

100%
0%

A French engineer contracted Marburg (and died); the physcian who attempted to resuscitate the engineer contracted the disease, but survived
1982 South Africa

1

primary

1

100%

A single occurrence; no secondary cases occurred.
1987 Kenya

1

primary

1

100%

A young Danish man who, while traveling in western Kenya, had visited the same park as the French engineer.  No secondary cases occurred.

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Vaccine.   None.   As with exposure to other filoviruses, exposure to Marburg does not confer subsequent immunity.  The antibody response in convalescent patients does not neutralize or protect against subsequent infection by Marburg virus.

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Odds 'n' Ends.  
     •  The attempt of epidemiologists to identify the Marburg reservoir (after the 1975 outbreak) resulted in the international recognition of Rift Valley hemorrhagic fever and Crimean-Congo hemorrhagic fever.

     •  Marburg and Ebola Zaire viruses have seven sequentially arranged genes contained in a single molecule.  This is the largest genome reported for members of the order Mononegavirales.

     •  In general, genes of rhabdoviruses and paramyxoviruses are separated by short, intergenic regions.  However, some genes of Marburg and Ebola actually overlap each other.  In the Marburg genome, there is one overlap; in Ebola, there are three overlaps.

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Links:
     •  Fact sheet - CDC Special Pathogens Branch  (includes electron microscope image of the virus)
     •  Genomic structure and molecular biology - Dept of Biology and Biotechnology, Worcester Polytechnic Institute


Copyright 2004 Tara K. Harper

All rights reserved.  It is illegal to reproduce or transmit in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, any part of this copyrighted file without permission in writing from Tara K. Harper.  Permission to download this file for personal use only is hereby granted by Tara K. Harper.


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