Yellow Fever

Yellow fever is transmitted through infected Aedes or Haemagogus mosquitoes. When a mosquito bites, the virus enters the skin and infects local immune cells such as dendritic cells and macrophages. These infected cells then migrate to nearby lymph nodes, where viral replication increases before the virus enters the bloodstream in a process called viremia.

The virus infects hepatocytes, causing both apoptosis and necrosis. Kupffer cells, the liver's specialized macrophages, release proinflammatory cytokines that intensify hepatocellular damage. This destruction disrupts bilirubin metabolism, causing hyperbilirubinemia and leading to jaundice, the characteristic yellowing of skin and eyes, similar to complications seen in viral meningitis and other severe viral infections.

Yellow fever progresses through three distinct stages. The febrile phase includes fever, myalgia, and headache. This may be followed by a brief remission where symptoms temporarily improve. In severe cases, the toxic phase develops, characterized by hemorrhage, jaundice, renal dysfunction, and potentially multi-organ failure.

Jaundice results from hepatocyte destruction that disrupts bilirubin metabolism. When the liver cannot process bilirubin normally, it accumulates in the blood and tissues, causing the characteristic yellowing of skin and eyes. This buildup occurs because viral infection and immune-mediated damage prevent proper hepatic function.

Kupffer cells, the liver's resident macrophages, worsen hepatocellular damage by releasing proinflammatory cytokines during infection. This immune-mediated injury intensifies tissue destruction beyond direct viral effects. The inflammatory response, while attempting to control the virus, paradoxically causes significant organ damage during severe yellow fever.

After the virus infects local immune cells in the skin, these cells migrate to nearby lymph nodes where viral replication significantly increases. This amplification in lymph nodes leads to viremia, allowing the virus to enter the bloodstream and spread systemically to vital organs including the liver.

A single dose of the live-attenuated yellow fever vaccine provides long-lasting immunity and is the cornerstone of prevention. The vaccine triggers strong neutralizing antibody responses that protect against future infections. Broad vaccination coverage combined with vector control represents the essential public health strategy for reducing transmission in endemic regions.