Lecture 8 - Yellow Fever

What virus causes Yellow Fever?

Yellow Fever Virus (YFV), a positive-sense, single-stranded RNA virus of the family Flaviviridae.

Who discovered that Yellow Fever was transmitted by mosquitoes?

Dr. Walter Reed around 1900.

What group of diseases does Yellow Fever belong to?

Hemorrhagic fevers.

Which cells does the Yellow Fever virus infect?

Monocytes, macrophages, Schwann cells, and dendritic cells.

Which cells do other flaviviruses infect: West Nile, Dengue, and Zika?

West Nile: neurons; Dengue: skin cells; Zika: neural progenitor cells.

What are the main vectors of Yellow Fever?

Aedes aegypti, Aedes africanus, semi-domestic Aedes spp., Haemagogus spp., and Sabethes spp.

Which regions are Haemagogus and Sabethes mosquitoes found in?

Central and South America (forest canopy/jungle areas).

What are the primary hosts of Yellow Fever?

Humans and non-human primates.

What are the three transmission cycles of Yellow Fever in Africa?

Sylvatic (jungle), Intermediate (savanna), and Urban cycles.

What are the two transmission cycles of Yellow Fever in South America?

Sylvatic (jungle) and Urban cycles.

Describe the Sylvatic (jungle) cycle of Yellow Fever.

Virus circulates between non-human primates and forest mosquitoes (e.g., Haemagogus, Sabethes, or Aedes africanus); humans get infected when entering forests.

Describe the Intermediate (savanna) cycle of Yellow Fever.

Virus transmitted between monkeys and humans via semi-domestic Aedes spp. in rural/savanna areas; small outbreaks occur.

Describe the Urban cycle of Yellow Fever.

Aedes aegypti transmits the virus human-to-human, causing large urban epidemics.

How is Yellow Fever transmitted to humans?

Through the bite of an infected Aedes mosquito; humans are infectious to mosquitoes from 1 day before to 5 days after fever onset.

What is the incubation period for Yellow Fever?

3–6 days.

What are the early symptoms of Yellow Fever?

Sudden fever, chills, severe headache, back pain, muscle pain, nausea, vomiting, weakness, and fatigue.

What is the remission phase in Yellow Fever?

A temporary improvement lasting a few hours to one day before severe symptoms return.

What are the severe or toxic phase symptoms of Yellow Fever?

High fever, jaundice (yellow skin/eyes), bleeding, shock, and organ failure.

What percentage of infected people develop severe Yellow Fever?

About 15%.

What is the fatality rate among severe Yellow Fever cases?

30–60%.

Once recovered from Yellow Fever, what type of immunity develops?

Lifelong immunity.

How is Yellow Fever diagnosed early in infection?

RT-PCR or virus isolation from serum during the first 3–4 days of illness.

How is Yellow Fever diagnosed later in infection?

By detecting virus-specific IgM and neutralizing antibodies in serum.

What tests are used to detect Yellow Fever antibodies?

ELISA (IgM-capture), Microsphere Immunoassay (MIA), and IgG ELISA.

Why must Yellow Fever serology be confirmed?

Because of cross-reactivity with other flaviviruses (e.g., Dengue, West Nile).

What confirmatory test is used for Yellow Fever?

Plaque Reduction Neutralization Test (PRNT).

Is there a specific antiviral treatment for Yellow Fever?

No; only supportive care is available.

What supportive treatments are used for Yellow Fever?

Rest, fluids, fever control; avoid NSAIDs or aspirin to prevent bleeding.

Why should Yellow Fever patients avoid mosquito bites after symptoms begin?

To prevent infecting uninfected mosquitoes that can spread the virus to others.

What type of vaccine prevents Yellow Fever?

A live-attenuated 17D vaccine.

How long does one dose of the Yellow Fever vaccine protect you?

Lifelong protection for most people.

Who should receive the Yellow Fever vaccine?

People aged 9 months and older traveling to or living in endemic areas of Africa or South America.

What are possible risks of the Yellow Fever vaccine?

Rare viscerotropic disease (3–12 per million doses, higher in people over 60).

Why can the Yellow Fever vaccine be dangerous for immunocompromised people?

It is a live virus vaccine.

Where is Yellow Fever endemic?

In tropical and subtropical regions of Africa and South America.

What is the global burden of Yellow Fever?

About 200,000 cases and 30,000 deaths per year (90% in Africa).

What percentage of severe Yellow Fever cases result in death?

20–50%.

Who is at risk of Yellow Fever infection?

Anyone exposed to mosquitoes in endemic countries, including unvaccinated travelers.

How do Yellow Fever outbreaks affect countries?

They strain healthcare systems and cause economic disruption in densely populated areas.

Compare Yellow Fever with Dengue, Zika, and West Nile viruses.

All are flaviviruses spread by mosquitoes; Yellow Fever has a vaccine, the others do not.

Compare Yellow Fever’s severe symptoms to Dengue’s.

Yellow Fever causes jaundice, bleeding, and organ failure; Dengue causes hemorrhagic fever and shock.

Compare Yellow Fever’s vectors in Africa and South America.

Africa: Aedes africanus, A. aegypti, semi-domestic Aedes spp.; South America: Haemagogus spp., Sabethes spp., A. aegypti.

Which mosquito transmits Yellow Fever in urban outbreaks?

Aedes aegypti.

What is the main prevention strategy for Yellow Fever?

Vaccination and mosquito control (eliminate standing water, use repellents, screens).

How does the Yellow Fever transmission cycle differ between continents?

Africa has a third “intermediate” cycle involving both monkeys and humans; South America has only jungle and urban cycles.

What is the incubation period for Yellow Fever virus?

Typically 3–6 days.

Describe the appearance of Yellow Fever’s toxic phase.

Patients show jaundice, bleeding, and organ failure after a short remission.

What type of immunity develops after natural Yellow Fever infection?

Lifelong protection against reinfection.

What is the life cycle of an Anopheles mosquito?

Adult → Egg → Larva → Pupa → Adult (complete in 7–14 days depending on conditions).

Where do female Anopheles mosquitoes lay their eggs?

Directly on the surface of water.

How do Anopheles larvae rest in water?

Parallel to the surface; they do not have breathing tubes.

How do Aedes and Culex larvae differ from Anopheles larvae?

They rest at an angle to the water surface and have breathing tubes.

How can you distinguish an adult Anopheles mosquito from Aedes or Culex?

Anopheles holds its proboscis and body in a straight line; Aedes and Culex rest at an angle.

What is the most lethal malaria species infecting humans?

Plasmodium falciparum.

How many Plasmodium species regularly infect humans?

Five: P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi.

What type of organism causes malaria?

A protozoan parasite in the phylum Apicomplexa.

What type of transmission does malaria undergo?

Cyclopropagative transmission (parasite develops and multiplies in the mosquito).

Describe the malaria life cycle in humans.

Sporozoites infect liver cells → schizonts form → release merozoites → infect red blood cells → form trophozoites → schizonts → more merozoites → some become gametocytes.

What is the dormant stage in the liver of some malaria species?

Hypnozoites (seen in P. vivax and P. ovale).

Which malaria stage is transmitted to mosquitoes?

Gametocytes (sexual stages in human blood).

Where do malaria parasites undergo sexual reproduction?

In the mosquito midgut (forming zygotes, ookinetes, and oocysts).

What stage of the malaria parasite is injected into humans by the mosquito?

Sporozoites.

What is the significance of the malaria sporozoite stage?

It is the infectious stage introduced into the human host during a mosquito bite.

What U.S. program eliminated malaria as a major public health problem?

The 1947–1949 National Malaria Eradication Program using DDT, drainage, and breeding site control.