iii. The Red Plague

Question 1

What causes The Red Plague?

Answer 1

Marburgvirus - haemorrhagic fever agent

Question 2

Marburgvirus - haemorrhagic fever agent

Family:
Genus:

Answer 2

• Family: Filoviridae (thread-like filament morphology, hence name); RNA virus - at least 4 genera, 2 = human infection
• Genus: Ebolavirus; 4 species confirmed to cause human disease: Zaire Ebolavirus (Zaire); Sudan Ebolavirus (Sudan); Budingbugyo Ebolavirus (Uganda); Tai Forest Ebolavirus (Ivory Coast)
• Genus: Marburgvirus: Species: Marburg Marburgvirus

Question 3

What are the strains of the Marburgvirus? (2)

Answer 3

2 strains: Marburg (MARV) - ancestral location ? Uganda; RAVN (RAAV) [Ravn name of Danish Pt whom 1st isolated] - ancestral location ? Kenya

Question 4

What was Marburgvirus originally called and where was its first outbreak?

Answer 4

Originally called ‘Green Monkey Fever’ - 1st outbreak in Marburg (Germany, 1967), Frankfurt, Belgrade. - Marburg Uni discovered from ‘Green’ monkeys from Uganda which had been exported to animal facilities in Europe. Lead to fatal haemorrhagic disease among monkeys, exposed lab workers & medical personnel. In SA in 1975 - 2 backpackers from Zim.

Question 5

Marburgvirus over time (1967-2021):

Answer 5

Question 6

Inc freq of recognised filovirus outbreaks in Africa since 1990
Possible reasons:
- better _______ and capability to rapidly diagnose and characterise filovirus
- Spread among non-human primates & other animals -> human _________ due to hunting, slaughtering, butchering and consumption of infected animal
- __________ and ecology is more complex that previously understood
- Animal-human spillover infections due to ________ on natural ecosystem
- Inc human exposure due to legal and illegal _______ incentives eg. Mining and tourism (Marburg)
- Proximity of outbreak to larger cities and human movement -> spread to other areas out of outbreak ________

Answer 6

surveillance
epidemic
Epidemiology
encroachment
financial
epicentre

Question 7

Isolation of genetically diverse Marburg virus in Egyptian fruit bats - PLOS (Aug, 2009):

(Bat _____ = common source of protein in W. Africa)

Answer 7

Question 8

Life-cycle of virus:

Answer 8

Reservoir: Bats
-> non-human primate/animal -> human in contact -> human

Enters via wounds/ mucous membranes Taken up by immune cells, inhibits interferon production -> dec immunity -> inc prolif of virus -> multi organ failure

Question 9

How is the Marburgvirus transmitted? (4)

Answer 9

• Typically, human infection starts with zoonotic exposure -> human-to-human contact spread (hunt/slaughtering, butchering, caregiving, burials, to & btwn healthcare workers)
• Contact with blood & bodily fluids/excretions during acute disease
• Persistence in breast milk and semen in convalescence -> sexual transmission
• No evidence of of casual skin contact with asymptomatic people

Question 10

Marburgvirus Disease (MVD):

• Incubation:
• Sudden onset:

Answer 10

3-9 days (2-21 days)

high fever, chills, severe headache & myalgia (sore muscles)

Question 11

Marburgvirus Disease (MVD):

Progressive & rapid severe ________, abdo pain & cramping, “Ghost-like” drawn features, deep set eyes, expressionless face. Rash on day 5.

Symptoms& Signs increasingly severe - +++ weight loss, ________ (day 5-7), delirium, multi-organ dysfunction, shock & death (Day 8-9), Fresh blood from nose, gums, vagina, ________ sites and blood in faeces

Answer 11

diarrhoea

haemorrhaging
venipuncture

Question 12

What is the fatality rate for Marburgvirus disease?

Answer 12

Fatality: 23-35% to > 80%

Question 13

What is the Strategy for controlling MVD outbreaks?

Answer 13

Question 14

Challenge:
MVD infections are rare and wide differential diagnosis

Bacterial:

Answer 14

Bacterial: meningococcal, streptococcal, staphylococcal, typhoid, other gram-negatives

Question 14

Challenge:
MVD infections are rare and wide differential diagnosis

Rickettsial:

Answer 14

eg. tick-bite fever

Question 15

Challenge:
MVD infections are rare and wide differential diagnosis

Spirochetal:

Answer 15

eg. Leptospirosis

Question 16

Challenge:
MVD infections are rare and wide differential diagnosis

Parasitic Infections:

Answer 16

Malaria

Question 17

Challenge:
MVD infections are rare and wide differential diagnosis

Viral infections:

Answer 17

HIV, fulminant hepatitis A & B, systemic herpes virus infection, haemorrhagic Varicella zoster, haemorrhagic measles etc.

Question 18

Challenge:
MVD infections are rare and wide differential diagnosis

Non-infective causes:

Answer 18

Non-infective causes: neoplasia, drug sensitivities, anticoagulants, snake-bite, glue sniffing, traditional medicines, agricultural and industrial chemicals

Question 19

How is this illness diagnosed? (3)

Answer 19

• Req high index of suspicion (knowledge or region where Marburgvirus outbreaks are occurring, Pt’s travel history, risk-assessment of exposures, exclusion of other common infection (above)
• Blood/Saliva RT-PCR for acute infections
• Serology (eg. ELISA antigen/antibody test) for current or past infections

Question 20

What is the prevention and treatment of this illness? (4)

Answer 20

1. No commercially available vaccines
2. Supportive care - rehydration with oral/intravenous fluids, treat specific symptoms -> improves survival
3. Monoclonal Antibodies (MABs) under dev and antivirals eg. Remdesivir and Favipiravir used in clinical studies for Ebola virus disease (EVD) could be tested/used for MVD under compassionate use/expanded access
4. Mvabea (MVA-Bn-Filo) vaccine against EVD: contain virus called Vaccinia Ankara Bavarian Nordic (MVA) modified or produce 4 proteins of Zaire Ebolavirus + 3 other viruses of same family (filoviridae); could potentially protect against MVD but efficacy no been proven in clinical trials