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BIO 448B: Dengue and Yellow Fever


BIO 448B: Dengue and Yellow Fever Date: February 4th, 2008 Presented by: Ashley & Emma DENGUE: Transmission How does it occur: Dengue virus belongs to the family ... – PowerPoint PPT presentation

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Title: BIO 448B: Dengue and Yellow Fever

BIO 448B Dengue and Yellow Fever
  • Date February 4th, 2008
  • Presented by Ashley Emma

DENGUE Transmission
  • How does it occur
  • Dengue virus belongs to the family, Flaviridae
  • Included in this family are Yellow Fever Virus,
    Hepatitis C Virus, West Nile Virus and Japanese
    Encephalitis Virus
  • Single stranded, enveloped RNA virus that is 11
    000 bases in length
  • Dengue is transmitted from infected to
    susceptible humans by the day-biting female Aedes
    sp. mosquitoes
  • NOT through human to human contact
  • Prevention
  • Stagnant bodies of water serve as breeding sites
    for the mosquitoes therefore limiting their
    access to such environments is key to control of
    the disease through control of the vector

DENGUE Reservoir
  • Humans act as an amplifying host for the Dengue
  • Virus replicates in Aedes sp. mosquito midgut and
    other organs, infects and replicates in salivary
  • Vertical transmission to mosquito offspring, this
    can be repeated for a few generations without the
    adults feeding on an infected host.
  • The significance of a sylvatic reservoir in wild
    monkeys has not yet been established.

DENGUE Epidemiology
  • DF has caused infrequent epidemics since the 18th
  • DF has developed four serotypes (DEN-1, DEN-2,
    DEN-3, DEN-4)
  • WWII caused a change in the distribution of the
    disease leading to more frequent epidemics
  • Many of the Southeastern Asian countries were
    hyperendemic(ie. various serotypes of Dengue
    are present)
  • This led to DHF as there is epidemiological
    evidence that a second infection increases the
    risk of severe disease
  • Attempts to eradicate the mosquito population
    helped control the spread of the disease however
    in 1970 the programs ended and the vector
    population has resurged
  • Worldwide distribution in 2006
  • Blue countries have A.aegypti mosquitoes
  • Red countries have A.aegypti populations and
    dengue fever

DENGUE Transmission Cycle
DENGUE Clinical Features
  • Dengue Fever (DF)
  • Begins abruptly 3-15 days after bite
  • The break bone fever will resolve in a couple
    of days and then rebound (saddleback temperature
  • Accompanied by severe headaches, weakness,
    retro-orbital pain, intense muscle and joint pain
  • Heart rate may be lower then expected with the
    high temperature (relative bradycardia/Fagets
  • Transient flushing and pale pink rash is common
    and is normally seen on starting on the trunk
    and can be seen on the face
  • Bleeding is not uncommon with DF and this may be
    seen as gum bleeding, nose bleeding, GI bleeds
    and heavy menstrual bleeding
  • Dengue Fever is a disease typically seen in
    adults and older children
  • Self limiting, lasts 4-7 days, followed by
    complete recovery

DENGUE Clinical Features
  • Dengue Hemorrhagic Fever (DHF)
  • DHF show similar symptoms to the onset of DF more
    serious signs and symptoms appear as the
    infection progresses
  • In DHF there is an increased vascular
    permeability due to host immune factors such as
    cytokines and chemokines
  • Increased vascular permeability leads to a
    decrease in plasma volume this can be seen
    clinically with a high hematocrit (proportion of
    RBC compared with blood volume)
  • Thrombocytopenia (decreased platelets) as well as
    elevated Aspartate aminotransferase is common
  • Post mortem studies have shown extensive liver
    damage which can cause disruption in clotting
    mechanism and well as an increase in AST
  • Signs of problematic clotting and hemorrhage
    include skin hemorrhage (petechiae), nose bleeds,
    lower GI bleeding (blood in stool), hematuria and
    more severe bleeding may occur with fresh blood
    bleeds from upper GI track

DENGUE WHO grading of DHF
  • I Positive tourniquet test and/or easy bruising
  • II Spontaneous bleeding
  • III Early signs of circulatory failure
  • IV Profound shock

DENGUE Clinical Features
  • Dengue Shock Syndrome (DSS)
  • DSS is characterized as impending circulatory
  • Circulatory failure is due to the decrease
    intravascular blood volume due to the increased
    vascular permeability
  • Decreased volume leads to poor blood pressure and
    therefore cell starvation because of the
    inability of the heart to pump the oxygen and
    nutrients throughout the body
  • Signs and symptoms include decreased blood
    pressure, cold extremities and a rapid pulse

DENGUE Diagnosis
  • Diagnosis of Dengue is done through serological
    tests that are unavailable in many of the areas
    that the disease is prevalent
  • Bedside test reporting IgM and IgG are being
    developed however the accuracy of the tests are
  • Bedside tests are being improved upon to make
    surveillance easier thereby aiding in proper
    diagnosis and tracking of the disease
  • PCR genome amplification is also an option but
    also requires sophisticated equipment

DENGUE Management
  • Treatment is supportive gt no antivirals for
  • Patient with DF
  • Avoid being bitten until fever has subsided
  • Bedrest
  • Avoidance of Asprin due to its potential to
    worsen the bleeding other analgesics maybe used
    for muscle pain
  • Patients with DHF or DSS
  • Management of vascular permeability through the
    use of IV fluids and plasma expansion (Albumin
    and Blood products may be given if available)
  • Corticosteriods have been used for their anti
    immune effects thereby decreasing vascular
    permeability however they are shown to have no
    significant effect

DENGUE Prevention Control
  • The emphasis of prevention is controlling the
  • In the past large group efforts have eradicated
    the mosquito population with the use of DDT
    however once the effort stopped the population
    returned as did Dengue
  • Larval habitats can be treated with insecticide.
    Insecticidal space sprays, using vehicle-mounted
    or portable machines, are used for emergency
  • Community approach of education and ridding
    domestic areas of stagnant water has shown to be
    effective and sustainable but slow
  • A top down bottom up approach has been
    discussed allowing for fast and sustainable
    eradication of the vector population

DENGUE Vaccine
  • No vaccine for Dengue yet.
  • WHO designated the development of a vaccine that
    would encompass all four strains a priority
  • Live attenuated vaccine is in clinical trials in
  • Molecular technology has been incorporated in
    hopes of finding a vaccine against Dengue
  • DNA vaccine have shown most promise, however the
    risks associated with DNA vaccines are unknown

DENGUE Discussion
  • What are some of the challenges that might have
    come up when trying to create a vaccine for
    Dengue Fever?
  • In the Gubler paper it talks about the
    epidemiology for Dengue being only tracked as
    DHF. A foreseeable problem with this is that
    even though this is a more severe form of the
    disease it underestimates numbers of
    infected/affected individuals with dengue fever.
    As well, DHF is more prevalent in children and
    since children may have less of an impact on
    economic productivity,"DALY"s, and therefore
    morbidity there may be an underreporting that
    costs the education and eradication efforts

YELLOW FEVER Transmission
  • Yellow fever is a single serotype enveloped, RNA
    virus of the flavivirus family
  • The vector of this arbovirus is the Aedes aegypti
  • No human to human transmission
  • The virus affects humans and monkeys
  • Jungle Yellow fever occurs when humans are in the
    jungle where the virus is normally transmitted
    from vector to monkey
  • Urban Yellow fever occurs when mosquitos breed
    near plastic container in urban centres virus is
    transmitted human to human via the mosquito

YELLOW FEVER Transmission Contd
YELLOW FEVER Epidemiology
  • Yellow fever is common in Africa and South
    America gt WHO estimates 200,000 cases/year
  • There are five genotypes (two are S. American and
    the other three African)
  • Yellow fever is the first vector-borne viral
    disease discovered and the original viral
    hemorrhagic fever
  • There is evidence that it has been around for
    3000 years.
  • Most of the fatalities associated with Yellow
    fever occur in Africa and are due to poor vector
    control and in people without access to vaccines
  • Deaths are associated in unvaccinated travellers

YELLOW FEVER Epidemiology Contd
YELLOW FEVER Epidemiology Contd
YELLOW FEVER Epidemiology Contd
  • Countries requiring proof of yellow fever
    vaccination from all travellers
  • Benin
  • Burkina Faso
  • Cameroon
  • Central African Republic
  • Congo
  • Côte d'Ivoire
  • Democratic Republic of the Congo (formerly
  • French Guiana
  • Gabon
  • Ghana
  • Liberia
  • Mali
  • Niger
  • Rwanda
  • Sao Tome and Principe
  • Togo
  • Source International Travel and Health, 2000,
    World Health Organization

YELLOW FEVER Pathogenesis
  • Mosquito bite leading to the inoculation of the
    virus in the host
  • Virus will move to the lymph nodes and
    disseminate towards the target organs
  • Liver is shown in monkey model to be infected 24
    hours post inoculation gt midzonal liver cells
    undergo apoptosis leading to death without
  • Kidney cell will also undergo tissue changes that
    will eventually lead to disruption of the
    Bowmanns capsule gtlead to proteins being
    excreted through the patients urine
  • Cytokines will cause hypotension and shock
  • Hypotension will lead to further kidney damage
    due to a decreased perfusion of the renal tubules
    and this will lead to renal failure with
    associated decrease urine output

YELLOW FEVER Clinical Features
  • The extent of Yellow fever varies from non
    specific illness to liver and kidney failure
  • First signs and symptoms are fever, chills,
    malaise, muscle and back pain
  • Patients will have relative bradycardia for their
    elevated temperature (Fagets Sign)
  • There may be a brief remission followed by more
    severe symptoms of vomiting, abdominal pain,
    dehydration, jaundice, decreased urine output,
    hypotension and haemtemesis (vomiting of blood)

  • Yellow fever is difficult to recognize,
    especially during the early stages
  • It can easily be confused with malaria, typhoid,
    rickettsial diseases, haemorrhagic viral fevers
    (e.g. Lassa, Ebola, Crimean Congo), arboviral
    infections (e.g. Dengue), leptospirosis, viral
    hepatitis and poisoning (e.g. carbon
  • A laboratory analysis is required to confirm a
    suspect case.
  • Blood tests (serology assays such as ELISA) can
    detect yellow fever antibodies that are produced
    in response to the infection.
  • Several other techniques such as PCR and antigen
    assays are used to identify the virus itself in
    blood specimens or liver tissue collected after
  • These tests require highly trained laboratory
    staff using specialized equipment and materials.

  • Supportive therapy is given to a patient
    diagnosed with Yellow Fever
  • Aggressive fluid management and electrolyte
    balance is key as the patients kidneys may not
    be functioning optimally
  • Patients that are hemorrhaging may require blood
    or blood products to help with anemia and
    decreased blood volume
  • Dialysis will be required for patients in renal

  • The single-dose 'live attenuated' vaccine for
    yellow fever is safe and effective
  • Passaged through eggs to attenuate, vaccine is
    produced in eggs
  • It is recommended for individuals 9 months of age
    and older.
  • The vaccine becomes protective after 10 days,
    and provides immunity to a vaccinated individual
    for 10 years or more.
  • For individuals who are pregnant,
    immuno-suppressed or allergic to eggs, the yellow
    fever vaccination may not be recommended.

  • It has been shown that mosquitoes can pass the
    Yellow Fever virus vertically to their offspring.
    Why do you think that this is important and what
    sort of implications might this have for your
    control measures?
  • Do you think that viruses with mosquito vectors
    should pool some funding to increase education
    and safe domestic areas for the inhabitants of
    mosquito areas? Malaria research get 17 times
    the funding that dengue gets.
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