More than 100 different members of the Flaviviridae are known, and are subdivided into 3 genera:
I. Flavivirus (including dengue, yellow fever, and West Nile viruses)
II. Pestivirus
III. Hepacivirus (hepatitis C viruses)
These genera have diverse biological properties and cause distinct diseases. However, they have similar genome organization and replication mechanisms.
Virion Properties
Morphology
- Virions consist of an envelope and a nucleocapsid
- Virus capsid is enveloped
- Virions are spherical to pleomorphic measuring 40-60 nm in diameter
- Surface projections are small spikes surrounded by a prominent fringe
- Capsid/nucleocapsid is round and exhibits polyhedral symmetry. The core is isometric and has a diameter of 25-30 nm
Genome
- Monopartite, linear, ssRNA(+) genome of about 10-12 kb
- Virion RNA is infectious, serves as both the genome and the viral messenger RNA
- Has 5' end encodes structural proteins which has a stem and loop structure
- Non-structural proteins (protease, helicase, polymerase) encoded at the 3' end
Examples of Flavivirus
Dengue Virus
Dengue virus causes dengue and dengue hemorrhagic fever. It is an arbovirus. It has four serotypes, known as DEN-1, 2, 3, and 4. Most common caused by Aedes aegypti Mosquito.
Aedes aegypti can be identified by the white bands or scale patterns on its legs and thorax.
Two electron images of mature Dengue-2 virus particles replicating in five-day-old tissue culture cells:
Dengue Fever (Primary Infection)
Dengue fever is an acute viral illness characterized by:
- Fever
- Headache
- Muscle and joint pain
- Nausea/vomiting
- Rash
- Hemorrhagic manifestations
Some cases may present with or develop encephalitic signs and symptoms, such as:
- Decreased level of consciousness—including lethargy, confusion, and coma
- Seizures
- Nuchal rigidity
- Paresis
- Dengue Haemorrahgic Fever / Dengue Shock Syndrome (Secondary Infection)
Four Grades of DHF
- Grade 1
Fever and nonspecific constitutional symptoms
Positive tourniquet test is only hemorrhagic manifestation - Grade 2
Grade 1 manifestations + spontaneous bleeding - Grade 3
Signs of circulatory failure (rapid/weak pulse, narrow pulse pressure, hypotension, cold/clammy skin) - Grade 4
Profound shock (undetectable pulse and BP)
Symptoms
Antibody Response
Infection will result in lifelong immunity to that serotype, but only temporary immunity to other serotypes.
Primary Infection
- IgM antibodies appear approximately 5 days after onset of symptoms and rise for the next 1-3 weeks
- IgM antibodies detectable for up to 6 months
- IgG are detectable at approximately 14 days after onset of symptoms and are maintained for life
Secondary Infection
- Approximately 5% patients do not produce detectable levels of specific IgM
- IgM titre can be slower to rise in secondary infection
- IgG appears approximately 2 days after symptoms appear
- IgG titre significantly higher in secondary infection
Treatment
- No specific treatment for dengue fever.
- Intravenous fluid replacement and use of plasma expanders oxygen therapy blood transfusions in cases of severe bleeding heparin for severe haemorrhage.
Prevention
Vaccination???
Presently no vaccine for prevention.
Vaccine development for dengue and DHF is difficult because any of four different viruses may cause disease, and because protection against only one or two dengue viruses could actually increase the risk of more serious disease.
Vector Control:
Chemical Control
- Insecticide
- Mosquitoes screen
Biological and Environmental Control
- Place fish in containers to eat larvae
- Elimination of larval habitats
Yellow Fever Virus
Yellow fever is transmitted by the bite of an infected mosquito. Infants and children are at higher risk. There are two cycles of infection: one carried by monkeys and one by humans.
Jungle yellow fever
- Mainly a disease of monkeys in the tropical rain forest
- People get it when they are bitten by mosquitoes that have been infected by monkeys
- Is rare and occurs mainly in persons who work in tropical rain forests
Urban yellow fever
- A disease of humans
- Spread by mosquitoes that have been infected by other people
- Cause of most yellow fever outbreaks and epidemics
Symptoms
Yellow fever's incubation period (the amount of time between the introduction of the virus into the host and the development of symptoms) is three to six days. During this time, there are generally no symptoms identifiable to the host.
Period of invasion
-lasts two to five days
-begins with an abrupt onset of symptoms
- Fever and chills
- Intense headache
- Muscle aches
- Nausea
- Strawberry tongue
Period of intoxication
-last 3 to 9 days
-represents the most severe and potentially fatal phase of the illness)
- Jaundice
- Black vomit
- Hypotension
- Shock
- Cardiac arrhythmia
- Confusion
Treatment
No specific treatment for yellow fever.
Dehydration and fever can be corrected with oral rehydration salts and paracetamol. Any superimposed bacterial infection should be treated with an appropriate antibiotic.
Prevention
Vaccination???
A very safe, very effective yellow fever vaccine exists. About 95% of vaccine recipients acquire long-term immunity to the yellow fever virus.
Vector Control:
· Insecticide
West Nile Virus
West Nile fever is a disease caused by West Nile Virus. West Nile Virus has an extremely broad host range. It replicates in humans, horses, and several species of birds. Most infected individuals show few signs of illness, but some develop severe neurological illness which can be fatal.
Symptoms
Most cases are mild and flu-like symptoms:
- Fever
- Muscular aches and pains
- Rash
- Swollen lymph glands
In more severe cases:
- Encephalitis
- Meningitis
- Confusion
- Severe muscle weakness
Typically those patients who develop a more severe form of the disease are likely to be people with a weakened immune system which includes the older person or those with certain chronic illnesses.
Treatment
No specific treatment, other than supportive care, is available.
Prevention
Vaccination???
No vaccine is available.
Vector Control:
Insect repellents