Flaviviridae

Virus properties

Spherical, 4060 nm in diameter.

Genome: positive sense, single-stranded RNA,
11 kb in size, infectious
Envelope: 3 structural polypeptides, 2
glycosylated
Replication: cytoplasm
Assembly: within ER
All viruses are serologically related.
Inactivatedby acid pH, heat, lipid solvents,
detergents, bleach, phenol, 70% alcohol and
formaldehyde

Flavivirus life cycle

Pathogenesis

Primary viral multiplication occurs in myeloid,

and lymphoid cells or in vascular endothelium
Multiplication in the CNS depends on the
ability of virus to pass the blood-brain barrier
and to infect nerve cells
In natural infection of birds and mammals,
inapparent infection is usual.
(initial step) For several days there is viremia
and arthropod vectors acquire the virus by
sucking blood during this period

In experimental animals,
Subcutaneous inoculation
Viral replication in the lymph nodes
Virus enters bloodstream
* different tissues support further viral replication, incl.
monocyte-macrophages, endothelial cells, lung, liver, and
muscles.
Virus crosses the blood-brain barrier via unknown
mechanisms
Widespread neuronal degeneration occurs in all arbovirusinduced encephalitides.

Invasion depends on many factors incl.

Level of
viremia
*agedependent
susceptibilit
y in
humans
The
virulence of
the virus
strain

Genetic
background
of the host

Host innate
and
adaptive
immune
responses

Clinical Findings

Incubation: 4-21days
Inapparent infections are common.
Some- mild flu-like illness; othersencephalitides
Sudden onset with severe headache, chills
and fever, nausea and vomiting, generalized
pains and malaise
Within 24-48hrs, marked drowsiness develops
and may become stuporous.
Mortality rate varies.
Sequelae may be mild to severe.

TRANSMISSION
(causing Encephalitis)

Members

Arthropod borne (mosquitoes, ticks)

Dengue

Japanese B encephalitis
St. Louis encephalitis
Tick-borne encephalitis
Yellow fever viruses
West Nile fever
Kyasanur Forest disease
Louping ill
Murray Valley encephalitis
Omsk hemorrhagic fever
Brazilian encephalitis (Rocio virus)
**Hepa C virus

Japanese B Encephalitis

Leading cause of viral encephalitis in Asia

Mortality can exceed 30%
Up to 50% of survivors are left with neurologic
and psychiatric sequelae
1st and 2nd trimesters infections
fetal
death
Seroprevalence studies indicate nearly
universal exposure by adulthood (300:1)
NO treatment
Several effective vaccines are available in
Asia

West Nile Fever

caused by a member of the Japanese B encephalitis

antigenic complex
occurs in Europe, Middle East, Africa, former Soviet Union,
SW Asia, and, more recently, the US
about 80% are asymptomatic, about 20% causing West
Nile fever, <1% causing neuroinvasive disease
Fatal encephalitis is more common in older people.
produces viremia and an acute, mild febrile disease with
lymph adenopathy and rash.
Only one antigenic type of virus exists, and immunity is
presumably permanent.
Prevention depends on mosquito control and protection
against mosquito bites

Tick-Borne Encephalitis

important cause of encephalitis in Europe,

Russia, and northern China
occurs chiefly in the early summer
no specific treatment
Personal protective measures, such as
wearing appropriate clothing, can help reduce
the risk of exposure.

TICK-BORNE FLAVIS.

Yellow Fever Virus

Mosquito-borne (A aegypti)
Tropics and subtropics of Africa and S.
America
Yellow fever has not invaded Asia even though
the vector, A aegypti, is widely distributed
there.
7 genotypes, 1 serotype

Clinical findings

3-6days incubation period

At abrupt onset, the patient has fever, chills,
headache, dizziness, myalgia, and backache
followed by nausea, vomiting, and
bradycardia.
Recovery or Severity.
Severe cases: with liver and renal dysfunction
and hemorrhage, with high mortality rate esp.
in young children and elderly adults.
No sequelae.
Permanent immunity develops in patients.

Laboratory Diagnosis

Detection or Isolation:
immunohistochemistry, ELISA antigen capture
or PCR tests
Serologic tests using ELISA capture, HI test

Treatment, Prevention, and Control

no antiviral drug therapy

vaccination is the most effective preventive
measure
Vigorous mosquito abatement programs in
South America; however, vector control is
impractical in many parts of Africa.
Proper mosquito control on airplanes and
vaccination of all persons at least 10 days
before arrival in or from an endemic zone

DENGUE

Clinical disease begins 47 days (range, 314

days) after an infective mosquito bite.
characterized by fever, severe headache,
muscle and joint pain, nausea and vomiting,
eye pain, and rash.
Severe forms of the disease, dengue
hemorrhagic fever and dengue shock
syndrome, principally affect children.

Dengue Hemorrhagic fever / Dengue Shock

syndrome

may occur in individuals (usu. children) with

passively acquired or preexisting nonneutralizing heterologous dengue antibody
caused by a previous infection with a different
serotype of virus.
key pathological feature is increased vascular
permeability with plasma leakage into the
interstitial spaces associated with increased
levels of vasoactive cytokines.

Laboratory Diagnosis

Reverse transcriptase PCR (RT-PCR)-based

methods
Serologic diagnosis: envelope/membrane
viral protein-specific capture IgM or IgG ELISA
and the HI test

Immunity

4 serotypes of the virus exist

Infection confers lifelong protection against
that serotype, but cross protection between
serotypes is of short duration.
Reinfection with a virus of a different serotype
after the primary attack is more apt to result
in severe disease.

Epidemiology

distributed worldwide in tropical regions,

endemic in areas where Aedes vectors exist
In 2008 dengue was the most important
mosquito-borne viral disease affecting
humans.
An estimated 50M or more cases annually
worldwide, with 400,000 cases of dengue
hemorrhagic fever.
Dengue hemorrhagic fever is a leading cause
of childhood death in several Asian countries.

Epidemiology

In urban communities, dengue epidemics are

explosive and involve appreciable portions of
the population; Often start during the rainy
season.
In the tropics, mosquito breeding throughout
the year maintains the disease.
W WII spread dengue from SE Asia throughout
the Pacific
Aedes albopictus (Asia in origin, discovered in
Texas) can overwinter farther north, increasing
the risk of epidemic dengue in the US.

Treatment and Control

no antiviral drug therapy

Dengue hemorrhagic fever can be treated by
fluid replacement therapy
no vaccine yet
Control depends on antimosquito measures