Dengue Virus Flashcards
What is dengue virus?
Tropical disease
Caused by dengue virus
Transmitted by Aedes aegypti mosquitos
How can dengue disease manifest?
Rash
Eye pain
Headache
Muscle pain
Bone pain
Nausea/vomiting
Joint pain
Describe the epidemiology of dengue
Mortality relatively low (<1%) but huge economic impact
Severe dengue has high mortality (>20%)
Endemic in over 100 countries
Affects 500 million people worldwide
0.5 million cases of severe dengue
Approximately 40,000 deaths
4th most significant infectious disease after TB, HIV and Malaria (before covid)
What type of virus is dengue?
RNA virus
What family does dengue virus belong to?
Flaviviridae, genus flavivirus
How are most flaviviruses transmitted?
By arthropods (mosquitos or ticks) - known as arboviruses
Name some other significant flaviviruses
Yellow fever virus
Chickungunya
Japanese encephalitis virus
West Nile virus
Zika virus
Describe how DENV replicates
Binds to receptor and enters into cell by endocytosis
Uncoating of virus and transport to ER
Viral RNA replication and protein translation
Immature virion assembly
Transport to golgi where virion matures
Exocytosis and virion release
What is the receptor that DENV binds to?
Not known but several candidates:
- heparin sulphate
- DC-SIGN
- mannose receptor
- HSPs
What cells does DENV infect?
Myeloid cells
Endothelial cells
Hepatocytes
Other cells
Describe the immune response to dengue
Tissue resident CD8 cells patrol skin for virus infected APCs
Killing of virus infected MHC-1-expressing cells by cytotoxic CD8
Killing of virus infected MHC-2-expressing cells by cytotoxic CD4
Promote/suppress inflammatory immune response depending on cytokines released
CD4 Tfh cells provides B cell help to produce high affinity antibodies
How many serotypes of dengue are there?
4
Less characterised serotype 5 recently reported
Describe infection with different serotypes
All serotypes can cause full spectrum disease
Infection with 1 serotype provides life-long protection against that serotype but only transient protection against others
Infection with 1 serotype can make infection with others worse
What is the typical incubation period of dengue?
4-7 days
What are the clinical symptoms of dengue infection?
Asymptomatic or mild fever (80%)
More severe illness (5%)
In small proportion it is life theratening - dengue haemorrhagic fever (DHF); bleeding, low levels of platelets, blood plasma leakage into tissues
Dengue shock syndrome (DSS) - dangerously low BP
What are warning signs of severe dengue disease?
Abdominal pains
Muscle, joint and bone pain
Frequent vomiting
Hepatomegaly
Mucosal bleeding
Lethargy
What are direct methods of dengue diagnosis?
Virus isolation
Genome detection
NS1 detection
These have high confidence but low accessibility
What are indirect methods of dengue diagnosis?
Serology IgM
Serology IgG
High accessibility but low confidence
What can be done in place of treatment of dengue?
No cure or specific treatment, can only relieve symptoms until infection has gone
e.g. taking paracetamol to relieve pain and fever, do not take aspirin or ibuprofen as can cause bleeding problems, drink plenty fluids to prevent dehydration, get plenty of rest
What are the issues with vaccine development of dengue virus?
Dengue virus infected cells are located in the mucosal tissue so need a mucosal vaccine
4 antigenically distinct serotypes of dengue virus so need a vaccine that protects against all
Dengue infection has antibody-dependent enhancement meaning ab will bind to pathogen but not prevent infection
Describe ADE of dengue
Abs against 1 serotype provide long term protection but subsequent infection with a different serotype means existing abs are not sufficiently neutralising
Instead, they form immune complexes with the virus which is still functional and these immune complexes are targeted to host Fc receptors and virus gains access to cell
Results in antibody-dependent enhancement of infection
What is the current status of a dengue vaccine?
1 licensed vaccine (CYD-TDV)
2 stage 3 vaccines - DENVax, TV003/TV005
A stage 2 vaccine - TDENV
A stage 1 vaccine - DEV-80E
Potential novel vaccine
What is the CYD-TDV vaccine?
Live attenuated tetravalent chimeric vaccine
What is denvaxia?
First dengue vaccine approved in more than 10 countries
Recommended for use in adults and children older than 9 pre-exposed to dengue
What is the TDV vaccine?
LATV chimeric dengue vaccine based on DENV-2
Recently approved by EMA
