YELLOW FEVER

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YELLOW FEVER

• Sean Scheler
• December 2, 2004
• Microbiology Dr. Boyle

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Overview

• History
• Characteristics
• Transmission
• Symptoms
• Structure
• Prevention
• Vaccine

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History

• Carlos Finlay
• Cuban physician and scientist.
• Pioneered the early research on YF.
• Hypothesized that YF was spread by mosquitoes.
• Walter Reed
• Appointed by the government to head the Yellow
  Fever Commission.

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Characteristics of Yellow Fever

• Part of the Flavivirus Family
• Dengue Fever, St. Louis Encephalitis, Japanese
  Encephalitis, and Hepatitis C
• Transmitted by mosquitoes
• Aedes aegypti
• Spherical viruses
• Capsid, membrane protein, and envelope protein
• Class IV
• Positive single strained RNA

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Transmission of Yellow Fever

• Three types of transmission to humans
• Sylatic or jungle YF
• Intermediate YF
• Urban YF
• Vertical and Horizontal Transmission
• Vertical transmission is mosquito to mosquito.
• Horizontal transmission is when an infected
  mosquito bites a non-infected human or monkey.

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Early symptoms of Yellow Fever

• Acute phase
• Fever
• Muscle pains (prominent backaches)
• Headaches
• Shivers
• Nausea
• These symptoms are also closely related to the
  flu and common cold.
• Usually recover in 3-4 days

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Deadly symptoms of Yellow Fever

• Toxic phase
• Fever
• Jaundice
• Yellowish color develops in the patients face
  and eyes
• This gives Yellow fever its name
• Complains of abdominal pain with vomiting.
• Bleeding can occur from the mouth, nose, eyes
  and/or stomach.
• Once this happens, blood appears in the vomit and
  faeces.
• Kidney function deteriorates this can range from
  abnormal protein levels in the urine
  (albuminuria) to complete kidney failure with no
  urine production (anuria).
• Half of the patients in the "toxic phase" die
  within 10-14 days. The remainder recover without
  significant organ damage.

From The WHO website, http//www.who.int/mediacent
re/factsheets/fs100/en/print.html
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Structure of the Yellow Fever Virus

• Spherical viruses
• Capsid, Membrane protein, and Envelope protein
• Capsid (C protein)
• Structural Protein
• Houses the RNA and the viral RNA polymerase
• Membrane protein (prM/M)
• Helps the capsid pass through the cell membrane.
• Nonstructural proteins (NS)
• Nonstructural protein 1 (NS1) is a glycosylated
  protein found on an infected cells surface and
  is involved in viral assembly and release. This
  protein induces protective antibodies.
• Nonstructural protein 5 is a viral RNA
  polymerase.

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Envelope Protein (E protein)

• E protein
• Helps bind the YFV to the host cell.
• Domains I and II have cellular specific receptors
  that allow the virus to bind to the cell.
• Plays a role in determining out breaks between
  wild YF and YF17D.
• There is differences between Wild YF an YF17D is
  in the genotype, prM/M and E protein

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Prevention

• Mosquito control
• In the late 19th century and early 20th there was
  no effective pest control.
• After World War II there was extensive use DDT.
• DDT was harmful to the environment, so safer
  pesticides were developed
• DEET
• Better living conditions
• Vaccine?
• Yes, there is a very affective vaccine.

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Vaccine

• YF17D
• Is given attenuated to the patient.
• Once given to the patient there is approximately
  95 immunity from YF for about ten years.
• Risks
• There are not have not been many problems related
  with the YF17D vaccine
• People who are at risk are
• Infants under 12 months
• Immunocompromised
• However

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Recent Outbreaks

• Brazil
• An outbreak of YF occurred in Minas Gerais.
• The problem was YF17D vaccine and the wild YF
  could not be identified.
• The only way that they could identified which was
  which was by the genotypes either of the prM or
  the E protein.
• Abidjan, Ivory Coast
• Here there was an outbreak of urban YF, which led
  to a city wide immunization campaign.
• The fear here was that with this massive project,
  officials were afraid of Adverse event following
  immunization (AEFI).
• There were only 86 AEFI reported all of which
  recovered.

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References

• Bispo de Filippis, Ana Maria, et al. Isolation
  and characterization of wild type yellow fever
  virus in case temporally associated with 17DD
  vaccination during an outbreak of yellow fever in
  Brazil. Vaccine. 22 (2004) 1073-1078.
• Bonaldo, Myrna C., et al. Surface expression
  of an Immunodominant Malaria Protein B Cell by
  Yellow Fever. Journal of Molecular Biology.
  315 (2002) 873-885.
• Charlier, Nathalie, Pieter Leyssen, Erik De
  Clereq, and Johan Neyts. Rodent models for the
  study of therapy against flavivirus infections.
  Review. Antiviral Research. 63 (2004) 67-77.
• Dunster, Lee M., et al. Molecular and
  Biological Changes Associated with HeLa Cell
  Attenuation of Wild-Type Yellow Fever Virus.
  Virology. 261 (1999) 309-318.
• eMedeicine, comp. Yellow Fever. G. David
  Reeder, Theodore Englar Woodward, Thomas Herchine
  (Ed.), Francisco Talavera (Ed.), Richard B. Brown
  (Ed.), Eleftherios Mylonakis (Ed.), and Burke A.
  Cunha (Ed.). Home Page. 25 Feb 2002.
  eMedicine. 28 Nov 2004. (lthttp//www.emedicine.co
  m/med/topic2432.htmgt).
• Fitzner, Julia, et al. Safety of the yellow
  fever vaccine during the September 2001 mass
  vaccination campaign in Abidjan, Ivory Coast.
  Vaccine 23 (2004) 156-162.
• Gubler, D.J. The changing epidemiology of
  yellow fever and dengue, 1900 to 2003 full
  cycle? Comparative Immunology infectous
  diseases. 27 (2004) 319-330.
• McCullough, David. The Path Between the Seas The
  Creation of the Panama Canal 1870-1914. New
  York Simon and Schuster, 1977.
• Lederberg, Joshua (ed.). Encyclopedia of
  microbiology. 2 ed. Vol 1 of 4. New York
  Academic Press, 1982.
• Ruiz-Linares, Andes, et al. Processing of
  Yellow Fever Polyprotein  Role of cellular
  Protease in Maturation of the structural
  proteins. Journal of Virology. Oct. 1989
  4199-4209.
• University of Virginia Health Science library,
  comp. Philip S. Hench Walter Reed Yellow Fever
  collection. Joan Echtenkamp Klein , comp. Home
  Page. 31 Aug 2004. University of Virginia. 28
  Nov 2004. (lthttp//etext.lib.virginia.edu/healths
  ci/reed/finlay.htmlgt).
• van der Most, Robbert, et al. Yellow Fever
  Virus 17D Envelope and NS3 Proteins are Major
  Targets of Antiviral T cell Response in Mice.
  Virology. 296 (2002) 117-124.
• World Health Organization, comp. Yellow Fever
  Fact Sheet. The World Health Organization,
  comp. Home page. Dec 2001. The World Health
  Organization. 26 Nov 2004. (lthttp//www.who.int/
  mediacentre/factsheet/fs100/en/print.htmlgt).

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Questions?