ETIOLOGY OF YELLOW FEVER
Authors: Noguchi Hideyo 
Published: June 2004

The foregoing experiments show that symptoms and lesions closely resembling those of yellow fever in man may be induced in guinea pigs by the bite of female stegomyias that have previously sucked the blood of a yellow fever patient or of an animal experimentally infected with Leptospira icteroides. With mosquitoes infected directly from a yellow fever patient the infectivity seems to become manifest after a longer period of incubation than with those infected with the animal blood. In the former, at least 12 days are said to be necessary before they become infectious, and this hypothesis seems to be borne out by the present experiment. On the other hand, the mosquitoes which were engorged with the infected blood of the guinea pig were found to be capable of transmitting the disease within 8 days after the feeding. This discrepancy may be explained by the fact that the number of leptospira existing in experimentally infected guinea pigs is far greater than that in human blood.
The frequency with which positive transmission by the stegomyia was obtained in both instances was very small indeed, in view of the number of mosquitoes employed. It appears that even under natural circumstances the percentage of mosquitoes that eventually become infected with the yellow fever microbe by sucking the blood may be very small. It has already been shown by previous investigators that to transmit yellow fever from a patient to a non-immune person requires from 0.1 to 2 cc. of blood at the height of disease. According to my estimate a female stegomyia may take up 0.01 cc. or even less. Apparently a mosquito occasionally becomes infectious by taking up the one or two organisms which happen to be circulating in the peripheral blood of man, and it is these occasionally infected few which carry the disease. It is not difficult to realize the extent of ever increasing danger from a constant supply of the microbic virus which an endemic center or an epidemic of yellow fever can provide. One infected mosquito may mean many patients, and the life of such a mosquito is usually longer than that of the persons whom it fatally infects.
Finally, it is of interest to note that the development and maintenance of Leptospira icteroides are indispensably associated with the blood constituent, the serum, and this is amply supplied by the bloodsucking insect. The organism is one of the most fragile of all the pathogenic parasites and cannot survive the concurrence of other less fastidious organisms such as bacteria. The comparatively aseptic body cavity of the stegomyia furnishes a secure shelter for the parasite, which undoubtedly penetrates the zone of safety as soon as it is taken into the stomach of the insect. Unlike many other parasites this organism is capable of penetrating the intact skin or a bacteriaproof filter, and hence it is probably an easy matter for it to pierce the tissue of the visceral organs of the mosquito. Whether or not Leptospira icteroides can survive and multiply only in the body of Stegomyia calopus and not in other varieties or genera is yet to be determined.
Another interesting fact with regard to the extrinsic life of this organism is that it can multiply steadily at a temperature from 18–37°C. The optimum temperature, at which it remains viable for many months, is 26°. The climate in most of the tropical countries offers optimum conditions both for Leptospira icteroides and for the mosquito which carries and nourishes it.