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28 Cards in this Set

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What are 4 examples of Faviviruses?
yellow fever virus, west nile subgroup, tick-borne encephalitis subgroup and dengue virus subgroup.
Dengue Virus characteristics:
There are four serologically related viruses, 1, 2, 3 and 4. They are single-stranded positive sense RNA. Spherical with a lipid envelope and a icosehedral nucleocapsid core.
How are the DV's proteins produced?
As a single polypeptide, post translational cleavage by viral and host proteinases.
Has DV adapted to humans, or another animal?
Completely to humans, they are no longer dependent on animal reservoirs. They are maintained in large urban areas in human-mosquito-human transmission cycles.
Dengue is transmitted by?
Aedes aegypti, a day biting mosquito.
Classical dengue fever (DF) characterised by:
fever, headache, severe pains in muscles, joints.. recovery generally complete. This is the type most people get.
Dengue haemorrhagic fever (DHF) is characterised by:
Initial fever leads to suddel collapse, sometimes associated with severe shock (DSS), it is more common in infants and children and evidence of prior infection is important.
Trends in global incidence?
It is variable and depends onepidemic activity. 50-100 million cases of DF and 500,000 of DHF per year causing a total of 20,000 deaths.
What contributes to increased spread?
Tropics, poplation growth and uncontrolled urbanization. The lack of effective mosquito control and increased air travel as well as a decay in public health infrastructure.
Clinical and pathological features.
fever, severe headache, myalgias, minor haemorrhagic manifestations. Occasionally produce shock and haemorrhage leading to death.
How long does DF last?
2-7 days
Feature of DHF/DSS?
Leaky capillaries with no injury toblood vessels or endothelial cells.
Liver involvement is..
common with an accompanied minor elevation of serum transaminase. In severe infections, the liver enlarges and may even fail.
Treatement includes:
Bed rest, antipyretic drugs, analgesics along with fluid/electrolyte replacement for DHS/DSS.
Risk factors:
There is no cross immunity between each serotype and so 4 serotypes leads to a potential of 4 infections. Age (younger), immune status and genetic disposition also contribute.
Basis of DHF?
Both viral and host factors effect the severity of the disease. Evidence that DHF is determined by host immune factors, primed by previous exposure to different serotype (second infection), or the presence of maternal Ab.
Likely cause of DHF?
Immunopathogenesis - rather than protecting the host, the immune response destroys or changes the function of organs.
Immune response to DHF..
Abs contribute to the prevention or recovery via neutralisation of dengue viruses, complement mediated cytolysis and antibody-dependent cell mediated cytolysis.
Antibody-dependent enhacement (ADE)
Abs may increase dengue infection of monocytes/macrophages. Virus antibody complex attaches to Fc receptor.
Chemical mediators and DHF
Cytokines and chemical mediators released during immune response may be basis of DHF. Includes ADE, activation of complement and serotype-cross-reactive cyt T lymphocytes. Some can induce plasma leakage and shock, therefore changes in endothelial cells leads to permeability.
Ab complexes with virus and leads to..
enhanced infection of monocytes/macrophages
An increased number of infected monocytes leads to
an increase in T cell activation
Levels of what are increased from T cells?
Cytokines.
The final result of the immune response leads to
vascular leak syndrome
ADE and immunopathology of DHF
1. Dengue specific Ab binds to Fc receptor on monocyte and enhances virus uptake.
2. Increased vascular permeability.
3. Bleeding.
4. Disseminated intravascular coagulation due to circulating Ag-Ab complexes.
Diagnosis:
Serology: hemagglutination, IgG ELISA can distinguish primary and secondary infection.
Virus isolation
RT-PCR
Animal models are used for:
research purposes, to dissect what is going on. But it does not mimic disease we see in humans as the fever is adept to humans.
Summary..
Ab dependent enhancement, monocytes/macrophages targets.
Cytokine, T-cell and complement induction.
Promotes vascular permeability.