Viruses that cause haemorrhagic fever Flashcards
haemorrage is fluid leakage from what?
capillaries- thinner vessels, allows access to mosquitos
- single layer of endothelial cells, this barrier is maintained by PERICYTES
what is haemorrhage?
the escape of blood from any blood vessel in body
what does viral haemorrage cause?
- severe multi-system syndrome characterised by diffuse vascular leakage
- often bleeding (may/may not be life threatening)
give examples of viral haemorrage effects?
- bruises
- conjuctival inf (esp Dengue)
- epistaxis (nose bleed)
- petechie (nose bleed, esp Dengue)
- edema
give 2 examples of haemorrhagic blood borne viruses?
- Ebola
- Marburg
FILOVIRUSES
give an example of haemorrhagic airborne viruses?
Lassa virus
ARENAVIRUSES
give an example of haemorrhagic arthropod-borne viruses?
Dengue
FLAVIVIRUS
what is the family and genus of Ebola virus? what is the family and genus of Marburg virus?
Family Filoviridae
Genus Ebolavirus, Maburgvirus
what is the tropism of Ebola and Marburg?
immune cells (macrophages), hepatocytes, endothelia cells (then can cause haemorrhage)
what type of infection is caused by Ebola and Marburg? is there persistence?
- severe acute infection
- persistence can lead to future disease
what are the treatments/vaccines for Ebola/Marburg? Are there any?
no treatments/vaccines
how did Marburg end up in Germany?
where is Marburg virus found?
research using non human primates from Africa which carried Marburg virus found in Germany
- found normally in Angola, DRC recently in Uganda
where is Ebola found?
what is the most common Ebola?
Sudan, DRC
- most common is Zaire Ebola
Reston ebola is found where?
Philippines
why does the Ebola virus change from the original virus?
mutations cause evolution
what is the enzootic (wildlife) cycle for Ebola and MArburg?
animal reservoir in Pteropodiae
fruit BATS, megabats
what is the epizootic (wildlife) cycle for Ebola and MArburg?
how does this spillover to humans ?
infects non human primates (gorillas) and antelopes (Duikers)
at this point it can spillover into humans (go to forest for Bushmeat)
how is ebola transmitted?
how long is the incubation period?
- via body fluids (blood and others) (living and dead people) - sexual contact - contaminated surfaces INCUBATION PERIOD: 2-21 days
how does ebola progress and what symptoms does it cause?
day 7-9= headache, fatigue, muscle soreness
day 10= sudden high fever, vomiting blood, passive behaviour
day 11= bruising, brain damage, bleeding from nose, mouth anus
dau 12= FINAL STAGES
loss of consciousness, seizures, massive internal bleeding DEATH
what is the death rate for Ebola?
7 days after onset of symptoms =30% chance of surviving
3 weeks after symptoms= 90% chance of surviving
where can Ebola persist and what does this cause?
areas the immune system cannot reach TESTES- can enable sexual transmission EAR- hearing loss EYE- retro orbital pain, blurred vision BRAIN/CNS- meningitis UTERUS- transmission to fetus, stillbirth MUSCLE/JOINT- myalgia
how does Ebola cause haemorrage via cytokines?
immune distruption–> infects immune cells–> i.s responds by producing cytokines (POSITIVE FEEDBACK LOOP)—> HIGH levels of VASODILATORY cytokines—> allows opening up of vasculature to allow immune cells to enter tissues—> but the level of vasodilatory cytokines are too high O blood leakage—> haemorrhage
what are 2 other ways (other than cytokines) that ebola can cause haemorrhage?
1) direct infection of ENDOTHELIAL cells
2) infection of LIVER, this disrupts production of coagulase factors for clotting
3) infection of ADRENAL glands and KIDNEY, dirupts balance of blood pressure
in airborne viruses, do large or small droplets travel further?
small (>10m)
what is the family and genus of Lassa virus?
Arenaviridae Arenavirus
what is the tropism of Lassa virus?
broad, infects many organs and tissues
what kind of infection does LAssa virus cause?
acute, not persistent
around how many Lassa inf occur every year?
2 million
are there any vaccines/treatment for Lassa virus?
no
how is Lassa virus transmitted?
rodents
what are the 2 branches of Arenaviruses? where are they found?
Old World- Africa
New World- Americas
where is Lassa virus found?
in West Africa
how is Lassa virus transmitted?
how is it transmitted from human-human?
- horizontal (between individuals) or vertical (from mother-> infant) transmission
- humans infected by INHALING AEROSOLISED FAECES also eating infected rodents
human-human (20%)
- sexual transmission
- contaminated medical equipment
what is the reservoir for Lassa infection?
rodents - Mastomys natalensis (multimammate rat)
what % of people have severe Lassa symptoms? what are the symptoms?
20%
Symptoms: general (fever, headache, sore throat, vom, diarrhoea)—> face swelling, low bp (due to blood leak from CVS), nose bleeds (CRITICAL)
how common is haemorrhage in Lassa? how severe is haemorrhage?
uncommon (~17%)
not severe enough to directly cause death
what causes haemorrhage in Lassa?
- dysfunction of PLATELETS and COAGULATION CASCADE
- virus replication in ENDOTHELIAL cells(doesn’t kill cells)
- NO CYTOKINE STORM
what is the primary cycle of transmission used by Dengue?
urban epidemic cycle
(human-mosquito-human)
- driven by: the mosquitos that cause Dengue are in close association with humans
what family and genus is Dengue virus? what are the serotypes of Dengue?
Flaviviridae Flavivirus
4 serotypes: DENV-1, DENV-2, DENV-3, DENV-4
what is the tropism of dengue?
immune cells (macrophages, dendritic cells) - can also infect hepatocytes and endothelial cells
what kind of infection does Dengue cause?
acute infection, no persistence
what transmits Dengue?
Ae. aegypti and Ae. albopictus mosquitoes
why is Dengue significant?
MOST SIGNIFICANT ARBOVIRUS INFECTING HUMANS
2.5 BILLION in high risk areas
what are the symptoms of Dengue?
- high persistant fever
- severe headache
- rash/mild bleeding (nose, gums, easy bruising)
- joint, muscle and bone pain
- severe pain BEHIND EYE
how does Dengue progress?
day -4 = day of mosquito bite
day -1 = VIRAEMIA develops and is DETECTABLE
day 0= day of fever
day 4= RISK OF SHOCK AND HAEMORRHAGE (12 hr period)
how many people does Dengue infect per year?
400 million
96 asymptomatic
1/2 million haemorrhagic (20% are fatal)
what is the biggest risk factor for Dengue Haemorrhagic Fever/ Dengue Shock Syndrome?
SEQUENTIAL INFECTION W/ DIFFERENT SEROTYPES
what happens if you only have primary dengue of 1 serotype?
low risk of haemorrhage
- life long immunity against the serotype you were infected with
- short term immunity against the other serotypes
what happens if you have primary dengue and then get reinfected with the same serotype as a secondary inf?
low risk of haemorrhage
what happens if you have primary dengue and then get reinfected with A DIFFERENT serotype as a secondary inf?
increased viral levels in patient blood
- high risk of haemorrhage
- life long immunity against all 4 serotypes
what is hyperendemicity?
multiple dengue virus serotypes co-circulating in the same location
how have vectors affected dengue circulation?
vector control methods can decrease the incidence of disease, eg Ae.aegypti
how is Dengue treated?
- no antiviral therapies
can treat with fluid replacement to prevent cirulatory collapse
is there a dengue vaccine? how effective is it? where is it used?
yes,
partially effective, but CAN ENHANCE DISEASE
- cont all 4 serotypes
- used in highly endemic countries Philippines, Mexico
who is given the dengue vaccine?
- children 9+
at this age children are usually already exposed to dengue O it provides lifelong immunity - mimics secondary inf w/ different serotype
how does dengue cause haemorrhage?
- cytokine storm(esp vasodilatory)
- pot inf of endothelial
- viral protein NS1 can DIRECTLY cause h
(can be used for diagnosis), causes endothelial cells to open up
