Yellow Fever Virus (YFV)

Yellow Fever

• is a hemorrhagic fever ( like ebola multiple system organ problems) that affects significant portions of Centra America, South America, and other tropical environments

• also a hepatic virus (like HCV) meaning it targets, replicates & damages the liver

• spread by mosquito vector, Aedes egypti

  • first virus to be proven to transmit via mosquitoes

History of YFV

• first virus to be associated with mosquitoes

• likely originated in Africa where it is endemic among humans and primates

  • transmission likely originated from primate to human - zoonotic

• some immunity existed in native populations of Central and Northern Africa

• during colonization, colonials did not have immunity and large amount of people died

• carried to Europe and Americas as a reult of slave trade when shipping slaves

• first documented outbreak in Americas in 1647 on island of Barbados

Dr.John Mitchell

• 1805 documented an outbreak of disease in Virginia which caused widespread death, pain, discomfort, and yellow coloring of skin and eyes

• named it Yellow Fever

• looking at historical evidence he was misdiagnosing hepatitis but name stuck

Dr. Josiah Nott and Dr. Carlos Finlay

Josiah:

• noted outbreaks coincided with certain mosquitoes and moth population booms an thought they might play a role in transmission

Finlay:

• used epidemiology of the disease to establish that mosquitoes were the vector of YF not person-to-person transmission

Dr.Walter Reed

• 1890s: yellow fever outbreaks during Spanish-American war

• Dr and his team lead series of experiments on yellow fever control

  • resulted in the eradication of YF from Cuba and Panama through control of mosquito populations

• built of finlays findings and validated them

Dr.Max Theiler

• pioneered two vaccines in 1930s

• 17D vaccine

  • still used today

• nobel prize

Transmission of YFV

• vector: Aedes egypti

• Cycle:

  1. feed on infeccted humans

  2. virus infects hemocoel of mosquitoes and begins replication

  3. virus infects and replicates in salivary glands

  4. feed on infected human and repeat cycle

     • eggs will also be infected

The Urban Transmission Cycle

• populated areas

  1. Aedes egypti feeds on humans

  2. human is infected with YFV

  3. YFV replicates in Aedes egypti

  4. YFV transmitted in next feeding

  5. Aedes egypti lays eggs and eggs are infected wirh YFV

  6. repeats

The Sylvatic (Jungle or Forest) Transmission Cycle

• wild

• endemic to South America & Africa

  1. Aedes africanus feeds on primates

     • not humans unless they go to jungle

  2. primate is infected with YFV (asymptomatic)

     • leads to it becoming endemic

  3. YFV replicated in aedes africanus

  4. YFV transmitted in next feeding

  5. Aede africanus lays eggs , eggs are infected

  6. repeat

The Savannah Transmission Cycle

• endemic in Africa

• primary transmission path in Africa today

• combines the urban and sylvatic cycle

• overlap between the Aedes egypti and africanus

• makes it difficult to eradicate

YFV Pathogenesis

• circulates in the lymph nodes via the blood and infects lymph tissue

• replicates in dendritic cells

• can also infect macrophages and monocytes

• as infection progresses infected blood circulated to liver and infects the hepatocytes

• caused degradation and apoptosis of these cells

• apoptosis released cytokines

• once damage to liver is severe enough an effect called “cytokine storm”takes place

Cytokine Storm

• Hypercytokinemia: overwhelming of the immune response via inflammatory signals

• leads to multisystem organ failure and eventually death

Diagnosis

• typically diagnosed through a combination of lab diagnostics and travel history

• blood titer of YFV specific IgM and IgG conform YFV

• important to rule out other mosquito travel illnesses and hemorrhagic fevers as they have overlapping symptoms

  • malaria and ebola

YFV Viral Physiology

• enveloped

• +ssRNA virus

• 40-50nm

• Genus Flavivirus in Flaviviridae

  • like HCV

• Baltimore class IV Virus

• genome encode one single ORF for a long polyprotein and virus used host proteases to cleave into individual subunits

  • like HCV

• in the 3’ UTR region there is a know structure which stalls host exonucleases allowing subgenomic Flavivirus RNA (sfRNA) product to be translated

  • imp. for pathogenicity

Prevention of YFV

• centered around:

  1. vaccination

  2. control of mosquito vectors

Mosquito Control

1. used of personal insecticide to prevent biting

   • ex. DEET

2. treatment of all standing water in urban areas

   • limits replication

3. used of mosquito nets and screening in humans in affected areas