Yellow Fever

Some result of experiment says that their findings bear directly on ideas which are developed in this communication. Thus in their now classic studies with human volunteers, which proved the correctness of the theory that yellow fever was transmitted by the bite of an Aedes mosquito, they made the following observations. Mosquitos become infective when they had the disease. Mosquitos did not become infective when they bit early in the incubation period or late in the disease. Mosquitos were not infective soon after they had bitten and become so only after a period of 12 days of more. They then remained infective for life. These findings, so puzzling at the time, are now fully understood. Each can be explained on the basis of modern knowledge of virus reproduction and the result thereof.

Yellow fever is still one of the most classic of the virus diseases of man, and it may be rewarding to review its pathogenesis briefly. When an infected mosquito bites, a very small amount of yellow fever virus is introduced into the blood. This small amount of virus then promptly dissapears. The virus does not reappear in the peripheral blood until just before the disease develops. Therefore, normal mosquitos biting during the four-day incubation period do not take in virus. However, during the incubation period, the virus is undergoing reproduction in cells, of the liver and other organs. When the number of cells damaged by the reproductive process becomes large enough, symptoms and signs of yellow fever rapidly appear. At about this time large numbers of newly formed virus particles are released from the infected tissues into the blood. Now, if a mosquito bites, it will take in virus.

As the disease progresses, still higher concentrations of virus develop in the liver, lyph nodes, and kidneys. This is the result of continued virus reproduction. In parallel, the concentration of virus in the blood increases rapidly and may reach a level of 10 particles per ml. If a mosquito bites at this time. It will take in considerable amount of virus. After about fourth day of disease, neutralizing antibodies begin to appear, and as they increase in concentration, the number of infective virus particles in the body rapidly decrease, and the disease a biting mosquito fails to take in any infective virus and so cannot transmit to agent.