YELLOW FEVER

Yellow Fever

Yellow fever is a viral hemorrhagic disease caused by the yellow fever virus, a flavivirus transmitted primarily by Aedes mosquitoes. It is endemic in tropical regions of Africa and South America. The disease is characterized by a sudden onset of fever, chills, headache, back pain, and muscle aches, with a risk of severe complications including jaundice, bleeding, and organ failure. Yellow fever is named for the jaundice that affects some patients, turning their skin and eyes yellow.

Morphology

• Family: Flaviviridae , a member of togavirus family causes yellow fever

• Structure: Enveloped, icosahedral capsid.

• Genome: Positive-sense, single-stranded RNA.

• Size: Approximately 40-50 nm in diameter.

• Distinctive Features: The virus has a lipid envelope derived from the host cell membrane, with surface proteins (E and M proteins) that facilitate viral entry into host cells.

Microscopic Appearance

Electron Microscopy: The yellow fever virus appears as spherical particles with a smooth surface due to the lipid envelope. The nucleocapsid is visible inside the envelope.

Mode of Transmission

• Mosquito Bites: The primary mode of transmission is through the bite of infected female Aedes mosquitoes, particularly Aedes aegypti. The mosquitoes become infected when they bite a person or primate with yellow fever and can then transmit the virus to other humans.

• Urban Cycle: Involves human-to-mosquito-to-human transmission, typically in urban areas.

• Sylvatic (Jungle) Cycle: Involves monkey-to-mosquito-to-human transmission in forested areas, where the virus circulates among non-human primates.

Virulence Factors

• E Protein (Envelope Glycoprotein): Facilitates viral attachment and entry into host cells, crucial for initiating infection.

• NS Proteins: Non-structural proteins (e.g., NS1, NS3) involved in viral replication, immune evasion, and modulation of the host response.

• Cytokine Storm: The virus can induce an excessive immune response, leading to severe inflammation and tissue damage.

Pathogenesis

After the virus enters the bloodstream through a mosquito bite, it infects and replicates in the lymph nodes and other tissues, leading to viremia. The liver is a primary target, where the virus infects hepatocytes, leading to cell death and inflammation. This results in jaundice, one of the hallmark features of the disease. The virus can also affect the kidneys, heart, and spleen, leading to widespread organ damage. In severe cases, a cytokine storm can exacerbate tissue damage, leading to hemorrhagic symptoms, shock, and multi-organ failure.

Clinical Manifestations

• Acute Phase: Sudden onset of fever, chills, severe headache, back pain, muscle pain, nausea, vomiting, fatigue, and weakness.

• Toxic Phase: Occurs in approximately 15% of patients, characterized by high fever, jaundice, abdominal pain, vomiting, bleeding (from the mouth, nose, eyes, or stomach), and renal dysfunction. This phase can be fatal.

• Jaundice: Yellowing of the skin and eyes due to liver damage.

• Hemorrhagic Symptoms: Bleeding can occur from various sites, including gastrointestinal bleeding, leading to "black vomit" (vomitus with blood).

• Organ Failure: In severe cases, the liver and kidneys may fail, leading to death.

Lab Diagnosis

• Serology: Detection of specific IgM and IgG antibodies against yellow fever virus using enzyme-linked immunosorbent assay (ELISA).

• RT-PCR: Reverse transcription polymerase chain reaction can detect viral RNA in blood or tissue samples, providing a definitive diagnosis, especially in the early stages of infection.

• Viral Isolation: The virus can be isolated from blood during the acute phase of infection, typically using cell culture techniques.

• Culture Conditions:

  • Temperature: Yellow fever virus is typically cultured at 37°C.

  • Medium: The virus can be cultured in various cell lines, including Vero cells.

  • Time: Cytopathic effects (CPE) may take several days to develop.

Treatment

• Supportive Care: There is no specific antiviral treatment for yellow fever. Management focuses on supportive care, including hydration, pain relief, and treatment of complications such as bleeding and organ failure.

• Hospitalization: Severe cases may require intensive care, particularly to manage bleeding, jaundice, and renal failure.

• Avoidance of Aspirin and NSAIDs: These medications can increase the risk of bleeding and are generally avoided in yellow fever patients.

Prevention

• Vaccination: The yellow fever vaccine is highly effective and provides long-lasting immunity. It is recommended for people living in or traveling to endemic areas. The vaccine is typically given as a single dose and provides lifelong protection in most individuals.

• Mosquito Control: Reducing mosquito populations through insecticide spraying, elimination of breeding sites (standing water), and using bed nets can help prevent the spread of yellow fever.

• Travel Precautions: Travelers to endemic areas should be vaccinated and take precautions to avoid mosquito bites, such as using insect repellent and wearing protective clothing.