Flavivirus

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Togaviruses and Flaviviruses
Unique features of Togaviruses &
Flaviviruses
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Enveloped
Positive sense
ssRNA
Togaviruses replicate in the cytoplasm and
bud at the plasma membranes
Flaviviruses replicate in the cytoplasm and
bud at internal membranes
Togaviruses and Flaviviruses
Virus group
Togaviruses
Alphavirus
Rubivirus
Arterivirus
Flaviviruses
Flaviviridae
Hepaciviridae
Pestivirus
Human pathogens
Arboviruses
Rubella virus
None
Arboviruses
Hepatitis C virus
None
Togaviruses and Flaviviruses
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Alphavirus and Flavivirus are discussed
together because of similarities in the
diseases that they cause, as well as in
epidemiology.
Most are transmitted by arthropods and are
therefore arboviruses (arthropod-borne
viruses).
They differ in size, morphology, gene
sequence, and replication.
Togaviruses and Flaviviruses
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The alphaviruses and flaviviruses:
These viruses have a very broad host
range, including vertebrates (e.g., mammals,
birds, amphibians, reptiles) and invertebrates
(e.g., mosquitoes, ticks). Diseases spread by
animals or with an animal reservoir are called
zoonoses.
Togaviruses
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Alphavirus, Rubivirus, and Arterivirus.
No known arteriviruses cause disease in
humans, so this genus is not discussed
further.
Rubella virus is the only member of the
Rubivirus group; it is discussed separately,
because its disease manifestation (German
measles) and its means of spread differ from
those of the alphaviruses.
Togaviruses and Flaviviruses
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The Flaviviridae include the flaviviruses,
pestiviruses, and hepaciviruses (hepatitis C
and G viruses).
Hepatitis C and G are discussed inhepatitis
viruses.
Arboviruses
Disease
Vector
Host
Distribution
disease
Aedes & other
mosquitos
Aedes & other
mosquitos
Birds
Africa,Austral
ia,India
East and west
Africa
Subclinic
al
Subclinic
al
Venezuelan
equine
enceph.
Aedes, Culex
Rodents
,horses
North,South,&C
entral America
Eastern
equine encep.
Aedes,
Culiseta
Birds
North&South
America,
Caribbean
Mild
systemic,
severe
encephal.
Mild
systemic,
encephal.
Western
equine encep.
Culex,
Culiseta
Birds
North & South
America
Alphaviruses
Sindbis
Semliki
forest
Birds
Mild
systemic,
encephal.
Arboviruses
Disease
Vector
Host
Distribution
disease
Aedes
Humans,
Monkeys
Africa, Asia
Fever,
Arthralgi
a,
arthritis
Alphaviruses
Chikungunya
Arboviruses
Disease
Vector Host
Distribution
disease
Dengue
Aedes
Humans,
Monkeys
Worldwide,esp.
Tropics
Yellow fever
Aedes
Humans,
monkeys
Africa, South
America
Mild
systemic;
break-bone
fever,
dengue
hemorrhagic
fever, and
dengue shock
syndrome
Hepatitis,
hemorrhagic
fever
Flaviviruses
Arboviruses
Disease
Vector Host
Distribution
disease
Japanese
encephalitis
Culex
Pigs, birds
Asia
Encephalitis
West Nile
encephalitis
Culex
Birds
Afr.,Eur.,Cent
ralAsia,N.Amer
St. Louis
encephallitis
Culex
Birds
N. America
Fever,
encep.,
hepatitis
Encephalitis
Ixodes &
dermocen
tor
ticks
Birds
Russia
Small
mammals
N. America
Flaviviruses
Russian
spring-summer
encephalitis
Powassan
encephalitis
Ixodes
ticks
Encephalitis
Encephalitis
Togaviruses & Flaviviruses/Clinical
syndromes
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Alphavirus disease is usually characterized
as low-grade disease
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Can progress to encephalitis in humans
Flavivirus infections are relatively benign
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Serious aseptic meningitis, encephalitis,
hemorrhagic disesase can occur
Togaviruses & Flaviviruses/Clinical
syndromes
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Hemorrhagic disesases
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Dengue
Yellow fever viruses
Togaviruses & Flaviviruses/Clinical
syndromes
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Hemorrhagic disesases
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Dengue virus
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Major worldwide problem
100 million cases of dengue fever/year
250 000 cases of dengue hemorrhagic fever/y
Dengue shock syndrome
Togaviruses & Flaviviruses/Clinical
syndromes
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Hemorrhagic disesases
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Yellow fever viruses
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Severe systemic disease
Degeneration of the liver, kidney, heart +
hemorrhages
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“JAUNDICE”
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Mortality rate: ~ 50% during epidemics
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Togaviruses & Flaviviruses/Laboratory
diagnosis
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Cell culture
cell lines
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IF, hemadsorbtion
RT-PCR
Serology
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ELISA
HI
LA
vertebrate and mosquito
difficult
Togaviruses & Flaviviruses/Treatment,
Prevention, and Control
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No treatment!
“The easiest means of preventing the spread
of any arbovirus is elimination of its vector
and breeding grounds”
Vaccines
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Yellow fever
live vaccine (17D strain)
EEE, WEE, Japanese, Russian SSE
killed vaccines
Rubella virus
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Same structural properties and mode of
replication as the other toga’s
Rubella is a respiratory virus
Does not cause readily detectable
cytopathologic effects
Rubella
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One of the 5 classic childhood
exantems
 Measles
 Roseola
 Fifth disease
 Chickenpox
Rubella
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Rubella: “little red” in Latin
“German measles”
Infects URT
local lymphe nodes
viremia
Shedding
respiratory droplets
Only one serotype
Natural infection
lifelong protective
immunity
Congenital Rubella
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“Serious congenital abnormalities in the
child”
If the mother does not have antibody
The virus can replicate in most tissues
of the fetus
The normal growth, mitosis, and
chromosomal structure of the fetus’s
cells can be altered by the infection
Congenital Rubella
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The normal growth, mitosis, and
chromosomal structure of the fetus’s
cells can be altered by the infection
Improper development of the fetus,
small size of the infected baby, and the
teratogenic effects
Congenital Rubella
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1.
2.
The nature of the disorder is
determined by
The tissue affected
The stage of development disrupted
Congenital Rubella
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~20% of women of childbearing age
escape infection during childhood and
are susceptible to infection unless
vaccinated
Rubella/Clinical syndromes
Rubella disease
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Normally benign
3 day of maculopapular or macular rash
and swollen glands
More severe in adults
Rubella/Clinical syndromes
Congenital disease
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The fetus is at major risk until the 20th
week of pregnancy
Most common manifestations:
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Cataracts
Mental retardation
deafness
Rubella/Laboratory diagnosis
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Anti-Rubella IgM by ELISA
Avidity test: Low avidity
4x increase in IgG
Antibodies to rubella are assayed early
in pregnancy to determine the immune
status of the woman
Rubella/Treatment, Prevention, and
Control
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No treatment
Vaccination (live)
MMR vaccine
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