Flaviviruses

Question 1

What are flaviviruses?

Answer 1

Viruses of the family Flaviviridae are important arthropod-borne viruses in both human and veterinary medicine

• Maintained in a transmission cycle in nature (mosquitoes and ticks)
• Widely distributed throughout the world (excluding polar regions)
• Nearly 60 different viruses identified

Question 2

What are the properties of Flaviviruses?

Answer 2

• ssRNA enveloped viruses, 40-65 nm in diameter
• (+) sense RNA genome, ~10,000 bp
• Single ORF (polyprotein)
• 3 structure proteins
  
  • Capsid (C), envelope (Env), and small membrane (prM) proteins
• 8 non-structural proteins
  
  • NS1, NS2A, NS2B, NS3, NS4A, 2K, NS4B and NS5Q
  • NS3 and NS5 add 5’-m7G cap structure to genomic RNA

Question 3

Describe the West Nile Virus.

Answer 3

• ~80% of people who are infected show no symptoms at all
• People typically develop symptoms between 3 and 14 days after they are bitten by the infected mosquito
• Mild: West Nile Fever; fever, headache, body aches, nausea, vomiting, and occasionally swollen lymph glands or a skin rash
• Severe (> 1%): Neuroinvasive disease; high fever, headache, neck stiffness, stupor, disorientation, coma, tremors, convulsions, muscle weakness, vision loss, numbness and paralysis
• People over 50 at higher risk to get severe illness

Question 4

What is West Nile Virus history?

Answer 4

• Likely emerged 1,000 years ago
• Possible cause of Alexander the Great’s early death
• WNV was first isolated from a feverish woman in Uganda; subsequently spread throughout Africa and Asia
• 1st appearance of WNV in Western Hemisphere in NY in 1999

Question 5

What is the epidemiology of WNV?

Answer 5

Centers for Disease Control (CDC) is:

• Coordinating a nation-wide electronic database where states share information about WNV
• Helping states develop and carry out improved mosquito prevention and control programs
• Developing better, faster tests to detect and diagnose WNV
• Creating new education tools and programs for the media, the public, and health professionals
• Opening new testing laboratories for WNV
• Working with partners on the development of vaccines

Question 6

How are Birds and WNV related?

Answer 6

• Birds are a reservoir for WNV
• Birds sustain viremia 1-4 days post-exposure
• Symptoms unlike humans
• Drowsy, unable to fly or walk
• Encephalitis
• WNV detected in dead birds of at least 326 species
• Crows and jays
• Dead crows were 1st clue that WNV has spread across US

Question 7

How is WNV prevented?

Answer 7

Reduce the number of mosquito bites you get. Make a habit of using insect repellent with DEET when outdoors. Spray repellent on exposed skin and clothing. Get the details about safe repellent use.
Prime mosquito-biting hours are usually dusk to dawn. Pay special attention to protection during these hours, or avoid being outdoors.
You can reduce the number of mosquitoes around your home. Mosquitoes breed in standing water, so check your yard once a week: get rid of containers that aren’t being used, empty water from flower pots, change water in bird baths and maintain clean gutters.
Make sure window and door screens are in good condition. Have an older neighbor or family member? See if they need help installing or repairing screens.

Question 8

What is Dengue Fever?

Answer 8

• Also known as “breakbone fever”
• Caused by dengue virus
• Most infected individuals are asymptomatic (80%)
• Symptoms: fever, headache, muscle, and joint pains, and a rash similar to measles
• Small proportion develop dengue hemorrhagic fever
• Bleeding, low platelet #’s, plasma leakage, and dangerously low blood pressure (dengue shock syndrome)

Question 9

What is dengue fever?

Answer 9

• Also known as “breakbone fever”
• Caused by dengue virus
• Most infected individuals are asymptomatic (80%)
• S_ymptoms:_ fever, headache, muscle, and joint pains, and a rash similar to measles
• Small proportion develop dengue hemorrhagic fever
• Bleeding, low platelet #’s, plasma leakage, and dangerously low blood pressure (dengue shock syndrome)

Question 10

What was the impact of dengue fever?

Answer 10

• During the 19th century, dengue was considered a sporadic disease (limited travel)
• Today, dengue ranks as the most important mosquito-borne viral disease in the world
• 2.5 billion people live in over 100 endemic countries
• 50 million infections occur annually
• 500,00 cases of DHF
• 22,000 deaths annually (mainly children)
• Incidence has increased 30-fold in last 50 yrs
• Prior to 1970, only 9 countries had experienced cases of DHF
• Number has increased more than 4-fold

Question 11

What is the gengue virus?

Answer 11

• Mosquito-borne Flavivirus
• Typical Flavivirus genome size and organization
• E/Env protein: attachment
• prM: virion maturation
• NS3/NS5: RNA cap
• At least 4 genotypes based on Env protein (DENV-1 to DENV-4)
• Widespread distribution of these 4 viruses
• Recent prevalance of DENV-1

Question 12

What is gengue virus transmission?

Answer 12

• Aedes aegypti mosquito is the primary vector of dengue
  
  • Daytime feeder (early morning, before dusk)
  • Females bite multiple people during each feeding period
• A. albopictus mosquito is secondary vector
  
  • North America and Europe (temp. tolerant)
• Virus transmitted to humans through the bites of infected female mosquitoes
• Infected humans are the main carriers and multipliers of the virus
  
  • Source of virus for uninfected mosquitoes
  • Transmission 4-5 days after symptoms 1st appear

Question 13

What is the treatment for DHF?

Answer 13

No specific treatment exists for Dengue fever

• Proper medical care
• Maintenance of patients body fluid volume is critical to severe dengue care (mortality reduced from 20% to > 1%)

No vaccine currently exists to protect against Dengue

• Focus of global research efforts

Question 14

What is antibody-dependent enhancement?

Answer 14

Happens when a person who has been previously infected with dengue gets infected moths or years later with a different serotype.

• More severe clinical course of disease
• Higher viremia

Infection produces both neutralizing IgG antibodies (some cross-protective) as well as antibodies that neutralize virus partially or not at all

• These antibodies bind virus paradoxically leading to enhanced viral entry and uptake

Question 15

What is Dengue Prevention & Control?

Answer 15

Only method to control/prevent disease transmission is to combat the vector:

• Environmental management to prevent access to egg-laying habitats
• Proper disposal of solid waste
• Covering, emptying, cleaning domestic water storage containers
• Use of insecticides (“bait”, space spraying)
• Personal protection (window screens, long-sleeved clothes, repellants)
• Surveillance

Question 16

What is the World Health Organization (WHO)?

Answer 16

• Epidemiology/surveillance
• Network of global labs
• Provide guidance to countries for effective mangement of dengue outbreaks
• Provide training on clinical management, diagnosis, and vector control
• Development of new tools and therapies

Question 17

What are the factors favoring spread of Dengue and DHF?

Answer 17

• Rapid population growth in endemic areas
• Increased larval habitats
• Unreliable water supplies lead to storage of water in containers at home
• Increased solid waste (plastic containers, used tires, etc.)
• Geographic expansion of mosquito aided by international commercial trade and increased air travel
• Breakdown of vector control measures (Aedes aegytpi)

Question 18

What is Yellow Fever?

Answer 18

• Caused by yellow fever virus
• Transmitted by bite of a female A. aegypti mosquito
• Incubation period of 3-6 days
• Most cases are mild (lasting 3-4 days)
• Fever, headache, chills, muscle pain, nausea
• 15% of cases enter “toxic phase”
• Jaundice, abdominal pain, bleeding, black vomit
• 20% fatality rate (over fatality rate of 3%)
• Urban cycle: mosquitoes → humans
• Forest/jungle cycle: mosquitoes → non-human primates
• Vaccine available

Question 19

What is the history of yellow fever?

Answer 19

• 25 major outbreaks during Colonial period
• Decimation of English and French troops stationed in the West Indies
• 27,000 of Napolean’s troops
• Philadelphia (1793): outbreak killed several thousand people and forced President Washington to flee the city

Question 20

What is the epidemiology of Yellow fever?

Answer 20

• 600 million people living in endemic areas (South American and Africa)
• 200,000 cases of disease and 30,000 deaths annually
• 90% of infections occur on Africa continent