Marburg virus - Dr. S. Sivasankara Narayani

1. 17CY312 – MEDICAL
MICROBIOLOGY (UNIT –II)
Dr. S. SIVASANKARA NARAYANI
ASSISTANT PROFESSOR
DEPARTMENT OF MICROBIOLOGY
AYYA NADAR JANAKI AMMAL COLLEGE
SIVAKASI
02-09-2020Dr.SS
Marburg

2. INTRO
• Marburg virus disease - haemorrhagic fever, with a fatality ratio of up to 88%. I
• family as the virus that causes Ebola virus disease.
• Two large outbreaks - in Marburg and Frankfurt in Germany, and in Belgrade,
Serbia, in 1967,.
• The outbreak was associated with laboratory work using African green monkeys
(Cercopithecus aethiops) imported from Uganda.
• Subsequently, outbreaks - Angola, Democratic Republic of the Congo, Kenya,
South Africa (in a person with recent travel history to Zimbabwe) and Uganda.
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3. INTRO …
• In 2008, two independent cases were reported in travellers who visited a cave
inhabited by Rousettus bat colonies in Uganda.
• Human infection with Marburg virus disease initially results from prolonged
exposure to mines or caves inhabited by Rousettus bat colonies.
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4. TRANSMISSION
• Once an individual is infected with the virus, Marburg can spread through
human-to-human transmission via direct contact (through broken skin or mucous
membranes) with the blood, secretions, organs or other bodily fluids of infected
people, and with surfaces and materials (e.g. bedding, clothing) contaminated
with these fluid
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5. OUTBREAKS
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6. STRUCTURE
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7. GENOME
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8. FUNCTION
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9. LIFE CYCLE
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MARV initially attaches to target cells via interaction with cell surface molecules
(1).
Following endocytosis (2),
GP 1 is cleaved by endosomal proteases (3)
facilitating binding to NPC1, the entry receptor (4).
Fusion is mediated in a pH-dependent manner by GP 2. Following release of viral
nucleocapsid into the cytosol (5),
transcription of the viral genome takes place (6).
mRNA is subsequently translated by the host cell machinery (7).
Synthesis of GP takes place at the ER and undergoes multiple posttranslational
modifications on its way through the classical secretory pathway (8).
Positive sense antigenomes are synthesized from the incoming viral genomes (9).
These intermediate products then serve as templates to replicate new negative
sense genomes (10).
After cleavage in the Golgi, GP is transported to multivesicular bodies (MVB) and
to the cell membrane where budding takes place (11).
Nucleocapsids and VP24 are also recruited to sites of viral budding (12),
which is driven by VP40 (13).

10. SYMPTOMS
• high fever, - severe headache - severe malaise.
• Muscle aches.
• Severe watery diarrhoea - abdominal pain - cramping, nausea and vomiting can
begin on the third day.
• Diarrhoea can persist for a week.
• The appearance of patients at this phase has been described as showing “ghost-
like” drawn features, deep-set eyes, expressionless faces and extreme lethargy.
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11. CONT…
• A non-itchy rash has been noted between 2 and 7 days after the onset of
symptoms.
• Many patients develop severe haemorrhagic manifestations within 7 days
• fatal cases usually have bleeding, often from multiple areas.
• Fresh blood in vomitus and faeces is often accompanied by bleeding from the
nose, gums and vagina.
• Spontaneous bleeding at venepuncture sites (where intravenous access is
obtained to give fluids or obtain blood samples) can be particularly troublesome.
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12. SYMPTOMS
• During the severe phase of illness, patients have sustained high fevers.
• Involvement of the central nervous system can result in confusion, irritability and
aggression.
• Orchitis (inflammation of the testicles) has been reported occasionally in the late
phase (15 days).
In fatal cases, death usually occurs between 8 and 9 days after onset, usually
preceded by severe blood loss and shock
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13. COMPLICATION
• Retinitis (inflammation of the retinas of the eyes)
• Orchitis (inflammation of the testes)
• Hepatitis (liver inflammation)
• Uveitis (inflammation within he pigmented layer of the eye)
• Transverse myelitis (inflammation of a segment of the spinal cord)
• Encephalitis (brain inflammation)
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14. DIAGNOSIS
• It can be difficult to clinically distinguish Marburg virus disease (MVD) from other
infectious diseases such as malaria, typhoid fever, shigellosis, meningitis and
other viral haemorrhagic fevers. Confirmation that symptoms are caused by
Marburg virus infection are made using the following diagnostic methods:
• antibody enzyme-linked immunosorbent assay (ELISA);
• antigen detection tests;
• serum neutralization tests;
• reverse-transcriptase polymerase chain reaction (RT-PCR) assay; and
• virus isolation by cell culture.
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15. TREATMENT
• There is as yet no proven treatment available for Marburg virus disease.
• However, a range of potential treatments including blood products, immune
therapies and drug therapies are currently being evaluated.
• Supportive care – rehydration with oral or intravenous fluids – and treatment of
specific symptoms improves survival.
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16. TREATMENT
• Providing fluids
• Maintaining blood pressure
• Providing oxygen as needed
• Replacing lost blood
• Treating other infections that develop
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17. RECENT RESEARCH
• Sarepta Therapeutics has been developing the RNA-interfering drug termed
AVI-7288.
• This drug is targeted against the nucleocapsid protein of the virus, and the
company has reported infection protection in monkeys ranging from 83%-100%
when given four days after the monkeys were infected with Ebola.
• This drug is undergoing a phase 1 safety trial that began in May 2014.
• Another company, Tekmira Pharmaceuticals from British Columbia, has a lipid
nanoparticle that interferes with the RNA replication of this virus. It too has shown
protection against Marburg virus infection in monkeys. This drug is termed TKM-
Marburg (also termed NP-718m-LNP).
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18. CLARIFICATION
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sivasan91@gmail.com

19. QUESTIONS TO THINK
• Epidemiology of Marburg virus
• Diagnostic methods of Marburg viral disease
• Structure of Marburg virus
• mechanism of Marburg virus infection
• Name the genes involved in the Marburg infection?
• Treatment methods used for Marburg virus disease
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