Marburg Virus-Dr Winnie

MARBURG VIRUS
Dr. WINNIE EZEKIEL

MWAMTOBE
REG NO:2021-04-03292
INTERNAL MEDICINE
SUPERVISOR: Dr EILU
Emmanuel
02/05/2024 Marburg virus 1

MORPHOLOGY

MORPHOLOGY
 Family: Filoviridae
 Order Mononegavirales
 Genus :Marburgvirus includes a

single species, Marburg
marburgvirus,

MORPHOLOGY
 2 members: Marburg virus

(MARV) and Ravn virus (RAVV)
 Pleomorphic , appearing as
filaments, circles, or a “number 6”
formation.
 Filamentous virons :892 nm long

and have a diameter of 91 nm

MORPHOLOGY
 Glycoprotein (GP) is a transmembrane surface protein that is

responsible for binding to host cellular receptors and viral/host
membrane fusion.
 Viral protein (VP)40 is a matrix protein involved in

transferring nucleocapsids to the plasma membrane and
budding of the virus from the host cell.
 VP24 is involved in nucleocapsid formation and assembly.

MORPHOLOGY
 Nucleoprotein (NP), VP35 (polymerase cofactor), VP30

(transcription activator), and L (RNA-dependent RNA
polymerase) are proteins that make up the nucleocapsid
 Nonsegmented
 Negative-sense, Single-stranded RNA viruses. (19kb)

EPIDEMIOLOGY
Centers for Disease Control and Prevention CDC,2021

EPIDEMIOLOGY

EPIDEMIOLOGY

EPIDEMIOLOGY

EPIDEMIOLOGY

EPIDEMIOLOGY

Nyakarahuka L et al, 2017 :Emerging Infectious Diseases
Nyakarahuka L et al,2020
Nyakarahuka L et al,2017

Viral reservoirs
 Egyptian fruit bats (Rousettus

aegyptiacus) captured in a mine in
Uganda where numerous infections
had occurred in workers over a 10-
year period (WHO ,2021)
 It shed virus in oral and vaginal

fluids without becoming ill, and that
increased shedding occurs when
female bats give birth
 The wide geographic dispersion of

outbreaks of Marburg virus disease
suggests the virus is present among
chronically infected bats across all of
central Africa
Transmission

Transmission
 In addition, one man who survived infection transmitted the virus to his
wife, apparently through sexual intercourse.
 Infection during patient care or washing of a cadaver may result from the
inadvertent transfer of virus on contaminated hands to the mouth or eyes.
 When appropriate precautions have been used, secondary spread has been
limited
 In contrast, hospitals that do not employ adequate infection control

measures may enhance the spread of virus. As an example, Marburg virus
appears to have been transmitted through the use of improperly sterilized
injection equipment during the 2004 outbreak in Angola
Pathogenesis
DIC: Disseminated intravascular coagulation; GP: Glycoprotein; TF: Tissue

factor; TRAIL: TNF-related apoptosis-inducing ligand.
Pathogenesis
 After the virus enters the body via mucous membrane or skin penetration,
macrophages and dendritic cells are the first cells to be infected.
 Filoviruses replicate readily within these ubiquitous "sentinel" cells,

causing their necrosis and releasing large numbers of new viral particles
into extracellular fluid
 The spread of virus via lymphatic channels to regional lymph nodes results
in further rounds of replication, followed by bloodstream dissemination to
dendritic cells and to fixed and mobile macrophages in the liver, spleen,
and other lymphoid tissues.

Pathogenesis
 Two virus-encoded proteins, VP24 and VP35, facilitate rapid

systemic dissemination by blocking the production of type I
interferon by infected cells and inhibiting the response to
exogenous interferon
 Further spread of virus to hepatocytes, adrenal cortical, and

other parenchymal cells results in extensive tissue necrosis

Pathogenesis
 Systemic inflammatory response

 Vascular dysfunction, shock, and death from Marburg virus disease.
 Infected macrophages and other target cells produce large quantities of

proinflammatory cytokines and chemokines, while the release of nitric
oxide, prostacyclin, and other vasoactive substances produces a general
increase in vascular permeability
 In addition to the effects of circulating proinflammatory mediators, the

production of tissue factor on the surface of virus-infected cells triggers
coagulation cascades, leading to disseminated intravascular coagulation

Pathogenesis
 Impairment of adaptive immunity
 Failure to show an antibody response to the virus ; this
impairment reflects both direct and indirect attacks on immune
function.
 Dendritic cells, fail to be activated by filoviral infection and are

destroyed through necrosis
 Adaptive immunity is also impaired by a massive loss of

lymphocytes. These cells are not infected by filoviruses, but
undergo "bystander" apoptosis, presumably induced by
inflammatory mediators and/or the loss of support signals from
dendritic cells
02/05/2024 Marburg
Marzi A et al,2019: Virology virus
Journal 26
CLINICAL PRESENTATION

Clinical manifestations
 "Marburg virus disease”
 Incubation period -one week (2-10) 2-21 days (route of
infection ,infective dose) (Hume A et al,2012) (Marzi A et
al,2019)
 Abrupt onset of fever, chills, and general malaise
 Signs and symptoms :weakness, anorexia, severe headache,

vomiting, diarrhea, and pain in the muscles of the trunk and
lower back.
 Petechial hemorrhages of mucous membranes, ecchymoses,
and continued oozing from venipuncture sites.(Late disease)

Clinical manifestations
 Severe bleeding from the gastrointestinal tract or other

sites :terminal phase of fatal infections.
 Additional clinical findings :a diffuse maculopapular rash,

hiccups, chest pain, shortness of breath, headache, confusion,
seizures, obtundation, and coma.

Investigations
 DIAGNOSIS
 Reverse-transcription polymerase chain reaction (RT-PCR) -
the detection of specific RNA sequences
 Enzyme-linked immunosorbent assay (ELISA)-Viral antigens
 Enzyme-linked immunosorbent assay (ELISA )-antibody
capture
 Serum neutralization test
 Electron microscopy
 Virus isolation by cell culture.

Investigations
 Complete blood count-Leukopenia, Thrombocytopenia,
 Liver function test -Elevations in serum transaminase

(aspartate aminotransferase [AST] and alanine
aminotransferase [ALT]) levels
 Renal function test-Increases in serum blood urea nitrogen

(BUN) and creatinine, and abnormal coagulation indices

TREATMENT
 Currently there are no vaccines or antiviral treatments

approved for MVD.
 Supportive care – rehydration with oral or intravenous fluids

– and treatment of specific symptoms, improves survival.
 Prevent the development of shock while the patient's immune

system mobilizes the responses needed to eliminate the virus.

Treatment and Vaccine MVD
 Experimental treatments. As examples:
 Monoclonal antibodies were found to be protective in mice
 A phosphorodiamidate morpholino oligomer, and a lipid-

encapsulated siRNA, both targeting messenger RNA
encoding the viral nucleoprotein, also protected macaques.

Treatment and Vaccine MVD
 One small-molecule drug under development is the

nucleoside analogue BCX4430, which prevented the death
of macaques when treatment began two days after the
Marburg virus challenge . (Uptodate , 2018)
 Vaccine — In one study, the Vesicular Stomatitis Virus (VSV)

vaccine protected macaques from death when administered 24
or 48 hours after an otherwise lethal Marburg virus challenge.
Research continuing…

Prevention and control
 Reducing the risk of bat-to-human
transmission
 Wear gloves and other appropriate

protective clothing (including masks),
(mines and caves)
 During outbreaks all animal products

(blood and meat) should be thoroughly
cooked before consumption.

 Reducing the risk of human-to-human transmission in the

community .
 Close physical contact with Marburg patients should be
avoided.
 Gloves and appropriate personal protective equipment should

be worn when taking care of ill patients at home.
 Regular hand washing should be performed after visiting sick

relatives in hospital, as well as after taking care of ill patients
at home.

Communities affected by Marburg

 Population -informed, both about the nature of
the disease itself and about necessary outbreak
containment measures.

Outbreak containment measures

 Prompt , safe and dignified burial of the deceased
 Identifying people who may have been in contact with someone

infected with Marburg and monitoring their health for 21 days
 Separating the healthy from the sick to prevent further spread
 Providing care to confirmed patient and maintaining good

hygiene and a clean environment need to be observed.

Controlling infection in healthcare
settings
 Basic hand hygiene,
 Respiratory hygiene,
 Use of personal protective equipment

(to block splashes or other contact
with infected materials),
 Safe injection practices and
 Safe and dignified burial practices.

 Controlling infection in healthcare
settings
When in close contact (within 1 metre)

 face protection (a face shield or a medical
mask and goggles),
 A clean, non-sterile long-sleeved gown, and

gloves (sterile gloves for some procedures).
 Laboratory workers - handling infected

samples by trained staff and processed in
suitably equipped laboratories

Marburg viral persistence in in people recovering from Marburg

virus disease
 Immune-privileged sites in some people who have recovered from

Marburg virus disease-testicles and the inside of the eye.
 In women who have been infected while pregnant, the virus persists in
the placenta, amniotic fluid and foetus AND if infected while
breastfeeding, the virus may persist in breast milk.
 Marburg virus transmission via infected semen has been documented

up to seven weeks after clinical recovery.
 (WHO,2021)
 Male Marburg survivors should be enrolled in

semen testing programmes when discharged
(starting with counselling) and offered semen
testing when mentally and physically ready,
within three months of disease onset.

 Marburg survivors and their sexual partners should either:

 abstain from all sexual practices, or
 observe safer sexual practices through correct and

consistent condom use until their semen has twice tested
undetected (negative) for Marburg virus.

 Having tested undetected (negative), survivors can safely

resume normal sexual practices with minimized risk of
Marburg virus transmission.
 Male survivors of Marburg virus disease should practice safer

sexual practices and hygiene for 12 months from onset of
symptoms or until their semen twice tests undetected
(negative) for Marburg virus.

 Until such time as their semen has twice tested

undetected (negative) for Marburg, survivors should
practice good hand and personal hygiene by
immediately and thoroughly washing with soap and
water after any physical contact with semen,
including after masturbation.
 During this period used condoms should be handled

safely, and safely disposed of, so as to prevent
contact with seminal fluids.
References
• MG, K., K, D., ES, S., & TJ, C. (2020). Marburg virus disease: A summary
for clinicians. International Journal of Infectious Diseases : IJID : Official
Publication of the International Society for Infectious Diseases, 99, 233–242.
https://doi.org/10.1016/J.IJID.2020.07.042
• KM, C., J, L., TK, W., CD, B., KA, K., DK, N., JJ, B., CW, S., CJ, R., JM,
W., SR, R., JM, B., AP, C., JM, D., G, P., MG, S., JH, K., S, B., & X, Z.
(2018). Persistent Marburg Virus Infection in the Testes of Nonhuman
Primate Survivors. Cell Host & Microbe, 24(3), 405-416.e3.
https://doi.org/10.1016/J.CHOM.2018.08.003
• Selvaraj, S. A., Lee, K. E., Harrell, M., Ivanov, I., & Allegranzi, B. (2018).
Infection Rates and Risk Factors for Infection Among Health Workers During
Ebola and Marburg Virus Outbreaks: A Systematic Review. The Journal of
Infectious Diseases, 218(suppl_5), S679–S689.
https://doi.org/10.1093/INFDIS/JIY435
References
• Marburg virus disease. (n.d.). Retrieved October 24, 2021, from https://www.who.int/news-
room/fact-sheets/detail/marburg-virus-disease
• L, N., J, O., A, T., S, B., S, W., S, K., S, K., M, W., I, M., M, D., J, B., J, L., U, S., PE, R., ST,
N., & TR, S. (2017). Isolated Case of Marburg Virus Disease, Kampala, Uganda, 2014.
Emerging Infectious Diseases, 23(6), 1001–1004. https://doi.org/10.3201/EID2306.170047
• L, N., IJ, S., S, B., S, M., A, T., J, K., B, K., J, L., P, R., S, N., & T, S. (2020). A retrospective
cohort investigation of seroprevalence of Marburg virus and ebolaviruses in two different
ecological zones in Uganda. BMC Infectious Diseases, 20(1). https://doi.org/10.1186/S12879-
020-05187-0
• Nyakarahuka, L., Shoemaker, T. R., Balinandi, S., Chemos, G., Kwesiga, B., Mulei, S.,
Kyondo, J., Tumusiime, A., Kofman, A., Masiira, B., Whitmer, S., Brown, S., Cannon, D.,
Chiang, C.-F., Graziano, J., Morales-Betoulle, M., Patel, K., Zufan, S., Komakech, I., …
Lutwama, J. J. (2019). Marburg virus disease outbreak in Kween District Uganda, 2017:
Epidemiological and laboratory findings. PLOS Neglected Tropical Diseases, 13(3), e0007257.
https://doi.org/10.1371/JOURNAL.PNTD.0007257

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MARBURG VIRUS

Dr. WINNIE EZEKIEL

02/05/2024 Marburg virus 1

02/05/2024 Marburg virus 2

 Genus :Marburgvirus includes a

02/05/2024 Marburg virus 3

 2 members: Marburg virus

 Filamentous virons :892 nm long

02/05/2024 Marburg virus 4

 Glycoprotein (GP) is a transmembrane surface protein that is

 Viral protein (VP)40 is a matrix protein involved in

 VP24 is involved in nucleocapsid formation and assembly.

02/05/2024 Marburg virus 5

 Nucleoprotein (NP), VP35 (polymerase cofactor), VP30

 Negative-sense, Single-stranded RNA viruses. (19kb)

02/05/2024 Marburg virus 6

Centers for Disease Control and Prevention CDC,2021

02/05/2024 Marburg virus 7

Centers for Disease Control and Prevention CDC,2021

02/05/2024 Marburg virus 8

Centers for Disease Control and Prevention CDC,2021

02/05/2024 Marburg virus 9

Centers for Disease Control and Prevention CDC,2021

02/05/2024 Marburg virus 10

Centers for Disease Control and Prevention CDC,2021

Centers for Disease Control and Prevention CDC,2021

02/05/2024 Marburg virus 16

 Egyptian fruit bats (Rousettus

 It shed virus in oral and vaginal

 The wide geographic dispersion of

02/05/2024 Marburg virus 18

 In contrast, hospitals that do not employ adequate infection control

DIC: Disseminated intravascular coagulation; GP: Glycoprotein; TF: Tissue

 Filoviruses replicate readily within these ubiquitous "sentinel" cells,

02/05/2024 Marburg virus 22

 Two virus-encoded proteins, VP24 and VP35, facilitate rapid

 Further spread of virus to hepatocytes, adrenal cortical, and

02/05/2024 Marburg virus 23

 Systemic inflammatory response

 Infected macrophages and other target cells produce large quantities of

 In addition to the effects of circulating proinflammatory mediators, the

02/05/2024 Marburg virus 24

 Dendritic cells, fail to be activated by filoviral infection and are

 Adaptive immunity is also impaired by a massive loss of

02/05/2024 Marburg virus 27

 Abrupt onset of fever, chills, and general malaise

 Signs and symptoms :weakness, anorexia, severe headache,

02/05/2024 Marburg virus 28

 Severe bleeding from the gastrointestinal tract or other

 Additional clinical findings :a diffuse maculopapular rash,

02/05/2024 Marburg virus 29

02/05/2024 Marburg virus 31

 Complete blood count-Leukopenia, Thrombocytopenia,

 Liver function test -Elevations in serum transaminase

 Renal function test-Increases in serum blood urea nitrogen

02/05/2024 Marburg virus 32

 Currently there are no vaccines or antiviral treatments

 Supportive care – rehydration with oral or intravenous fluids

 Prevent the development of shock while the patient's immune

02/05/2024 Marburg virus 33

 Experimental treatments. As examples:

 Monoclonal antibodies were found to be protective in mice