Viral haemorrhagic fever

Question 1

VHF - global distribution

Answer 1

Wide distribution

Total reported cases = 1,500,000
-36,000 cases per year

Question 2

VHF - transmission

Answer 2

Initial trigger almost always zoonotic:
-Spill-over to humans
-Unpredictable combination of factors = shedding patterns, land use change, social/economic conditions
-‘Human reservoirs’ - viable virus persists in survivors

Person-to-person:
-Direct contact with contaminated body fluids or objects through broken skin or mucous membranes

Question 3

VHF - at-risk population

Answer 3

People with contact with infected animals, rodents, animal excreta:
-Livestock owners, farmers, forest workers
-Households with infected rodents present

Household members and close contacts:
-Caring activities, symptomatic family members remaining in household
-Sexual partners

Nosocomial exposure:
-HCW, other patients

Question 4

VHF - proportion of asymptomatic infections

Answer 4

Ebola = 2.6-6.5%
CCHF = 70%
Lassa = 80%
Marbug = 0%

Difficulty of identifying due to non-specific common symptoms and case definition

Question 5

VHF - steps for outbreak control

Answer 5

Active case detection
Earlier and more rapid isolation and care
Triage and suspect managemenet
Faster, more frequent testing
IPC - healthcare, household and community
Contact tracing
Quarantine

Question 6

Ebola - organism

Answer 6

Ebola virus = filoviridiae virus

Species:
-BDBV = Bundibugyo virus
-EBOV = Ebola Zaire virus
-SUDV = Sudan virus
-TAFV = Tai Forest virus

No known human disease = Reston virus [RESTV] and Bombali virus [BOMV]

Question 7

Ebola - virus structure

Answer 7

Negative single strand RNA genome
-19 kilobases
-7 distinct genes = NP and GP targets for PCR diagnosis, treatment and vaccines

Lipid envelope easily destroyed by soap, chlorine and UV light

Question 8

Ebola - cycle of transmission

Answer 8

‘Single pass’ from animal to human
Amplification by person-to-person

Question 9

Ebola - largest outbreaks

Answer 9

West African 2013-2016:
-28,800 cases
-11,300 deaths

Question 10

Ebola - epidemiology

Answer 10

> 20 outbreaks since 1976

CFR [variable across species]:
-EBOV = 40-80%
-SUV = 40-55%
-BDBV = 35-40%
-TAFV = 0%

Question 11

Ebola - early clinical features

Answer 11

Early phase:
Day 0-1 = mild fever, headache

Day 2-3 = fever, headache
-Decreased appetite - nausea, onset of diarrhoea [2-3BM/day] - epigastric pain, hiccups

Question 12

Ebola - late phases

Answer 12

GI phase:
Day 4-9 = fever, HA, myalgia
-Increased diarrhoea/vomiting [upwards of 10L/day] - blood diarrhoea/emesis can be seen

Can be renal, encephalopathy and hypoglycaemia phenotypes

Terminal phase:
Day 10-12 = fever and GI symptoms subside
-Confusion and delirium worsen
-Comatose
-Oliguric/anuric

Question 13

Ebola - common lab findings

Answer 13

Elevated AST and ALT >1000
Low platelets
Elevated CRP
Leucocytosis, lymphopenia

Question 14

Ebola - management

Answer 14

Ebola treatment unit:
-Safe burial
-Trace, isolate and treat

Supportive:
-GI losses - IV fluid replacement
-Electrolyte monitoring and replacement
-Septic shock - fluids, prophylactic antibiotics

Experimental therapeutic trials:
-Remdesivir
Ebola Zaire specific:
-MAb114
-ZMAPP [composed of 3 MAbs]
-REGN-EB3 [Regeneron]

Question 15

Ebola - vaccine

Answer 15

rVSV-ZEBOV:
-Live attenuated recombinant vesiculovirus vaccine
-Ebola Zaire virus specific

Question 16

Ebola - incubation period

Answer 16

2-21 days

Question 17

Ebola - diagnosis

Answer 17

PCR - most commonly used
ELISA
Rapid antigen test [OraQuick]

Question 18

Lassa fever - organism

Answer 18

Lassa virus
Single-stranded RNA virus - family arenaviridae
7 lineages

Question 19

Lassa fever - animal reservoir

Answer 19

Zoonotic infection transmitted from rodent to humans

Mastomys natalensis [multimammate rat]

Question 20

Lassa fever - transmission

Answer 20

Rodent to human:
-Ingestion of food contaminated with faeces, urine or blood
-Handling, killing and ingesting rodents

Human to human:
-Healthcare settings
-Sexual transmission possible
-Vertical transmission

Most infections are rat-to-human
[unlike Ebola which is mainly human to human]

Question 21

Lassa fever - epidemiology

Answer 21

80% asymptomatic
only 20% of those become symptomatic
CFR 15% among severe presentation
All age groups affected
M=F

Question 22

Lassa fever - geographical distribution

Answer 22

Endemic in many West African countries

Largest burden in Nigeria and Sierra Leone

Question 23

Lassa fever - seasonal pattern

Answer 23

Can occur all year around
Peaks during dry season [December to April]

Although two peaks in both dry and rainy season [June - August] in Sierra Leone

Question 24

Lassa fever - contagious period

Answer 24

2-21 days

Question 25

Lassa fever - initial symptoms

Answer 25

Vague symptoms: -Fever -Generalised weakness -Malaise -Headache -Sore throat = common presentation -Chest pain -Myalgia -N+V -Diarrhoea -Pain in back and abdomen [serositis]

Question 26

Lassa fever - severe symptoms

Answer 26

20% severe symptoms Facial oedema ARDS Hepatitis Renal failure Seizures, reduced GCS Bleeding from orifices

Question 27

Lassa fever - complications

Answer 27

Bleeding from orifices DIC Pleural or pericardial effusion Renal failure Multi-organ failure CNS: -Encephalitis -Encephalopathy -Sensorineural hearing loss

Question 28

Lassa fever - sensorineural hearing loss

Answer 28

Bilateral or unilateral deafness affecting the 8th cranial nerve 1/3rd infections result in different levels of deafness No correlation between severity of disease and occurrence

Question 29

Lassa fever - lab diagnosis

Answer 29

Cell culture IFA Complement fixation tests ELISA for LASV antigens and IgM antibodies PCR Lateral flow assays

Question 30

Lassa fever - management

Answer 30

Supportive care Specific antiviral therapy: -Ribavirin = more effective during early stages

Question 31

Lassa fever - future therapeutics

Answer 31

Favipiravir Zidampidine Stampidine AG1478

Question 32

Crimean-Congo haemorrhagic fever [CCHF] - organism

Answer 32

Tick-borne virus [Nairovirus] in family Bunyaviridae

Question 33

CCHF - transmission

Answer 33

Tick exposure = Ixodid [hard] ticks -Genus hyalomma Contact with blood/tissue of infected animals/person Occupational disease: -Famers, HCW, slaughtermen, hunters

Question 34

CCHF - epidemiology

Answer 34

Geographic distribution - Africa, Central and South Asia Overall mortality = 20-30%

Question 35

CCHF - incubation period

Answer 35

IP 1-14 days Shorter IP with tick transmission

Question 36

CCHF - clinical manifestations

Answer 36

Acute fever, myalgia, headache Bleeding from day 3-5 Progressive multisystem involvement [end of 1st week] in 5-30%: -Thrombocytopenia -Leucopenia -Renal failure -Elevated AST/ALT

Question 37

CCHF - differential diagnosis

Answer 37

-Tick-bite fever [Rickettsia africae] = associated with petechial rash and eschar, treatment doxycycline or ciprofloxacin -Bacterial septicaemia -Leptospirosis, Q fever, plague -Malaria, trypanosomiasis -Viral hepatitis

Question 38

CCHF - diagnosis

Answer 38

PCR - negative by day 13, highest in 1st week Serology = IgM and IgG [detectable from day 4]

Question 39

CCHF - management

Answer 39

Early recognition and infection control Manage high risk exposures Contact monitoring Supportive care Ribavirin