Nonimmune Persons Research Articles

II. EFFECT OF TRANSFUSED BLOOD AND OF STREPTOCOCCIC ANTISERUM ON THE CONCENTRATIONS OF ANTIFIBRINOLYSIN AND ANTISTREPTOLYSIN IN THE BLOOD OF THE RECIPIENTS

Blood transfusions are employed almost universally in the treatment of patients with severe hemolytic streptococcic infections. For this purpose, blood of three different types has come into general use, i. e., blood from nonimmune persons, from convalescents and from donors prepared by vaccination. Numerous clinical reports justify the use of blood from nonimmune donors, especially when the patient is anemic or suffering from a prolonged illness. Of particular interest in relation to the present study are the investigations of erysipelas in childhood by Schaffer and Rothman¹and the review of the therapeutic value of transfusions in scarlet fever by Look.²These authors support the generally accepted opinion that blood from normal, healthy donors is of value in these infections. The literature of the past forty years contains a large number of reports on the use of blood from convalescent patients in the treatment of patients with scarlet fever.

ETIOLOGY OF YELLOW FEVER

Analysis of the records of instances in which non-immune persons contracted yellow fever notwithstanding vaccination shows that the onset of disease occurs soon after vaccination, the longest period being 13 days. Since the average incubation period in yellow fever is 6 days, it seems that infection must have taken place in some instances during the period while protection was developing. These instances led to a study of the possibility of immediate protection by means of the anti-icteroides serum. It had already been shown that the immune serum protects at once against experimental Leptospira icteroides infection, but it remained to determine how long the protection would last. Guinea pigs were given different quantities of the immune serum and subsequently injected, at various intervals, with a virulent strain of Leptospira icteroides. Complete protection enduring 5 days was obtained with as minute a quantity of serum as 0.002 cc. per 1,000 gm. of body weight. After 5 days, however, the immune substance rapidly diminished, and to keep the animal protected for as long as 10 days it was necessary to give 100 times as much, or 0.2 cc. For a man weighing 80 kilos, 0.16 cc. (0.002 x 80) would theoretically be sufficient to protect for at least 5 days, 1.6 cc. for 7 days, and 16 cc. for 10 days. This temporary protection may be a valuable antecedent to that furnished by vaccination, since the final effect of the latter cannot be expected until at least 9 to 10 days have passed.

ETIOLOGY OF YELLOW FEVER

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 degrees C. The optimum temperature, at which it remains viable for many months, is 26 degrees . The climate in most of the tropical countries offers optimum conditions both for Leptospira icteroides and for the mosquito which carries and nourishes it.

SANITATION OF THE CIAL REFERENCE YELLOW TROPICS WITH SPETO MALARIA AND FEVER

If we go back to the year 1898 and consider the point of view of Europeans and their American descendants about to enter the tropics, yellow fever to them was by far the most dangerous disease with which they were likely to come in contact. I am referring now principally to the American tropics, as yellow fever affected principally this region. And this was particularly the case when it was intended to send large bodies of nonimmune persons, such as our army of occupation in Cuba. Yellow fever had caused more disaster to military expeditions going to these tropics than had all the other tropical diseases put together, and it had been equally fatal to non-immune individuals in civil life. Our military surgeons, therefore, in their sanitary recommendations considered more particularly this disease. Yellow fever frequently affected the southern portions of the United States, and military surgeons were very confident

The Transmission of Yellow Fever.

New York City, Aug. 11, 1903. To the Editor: —On my arrival from Cuba I perused with great interest the article of Dr. James Carroll on Transmission of Yellow Fever, published inThe Journal, May 23, 1903, the replies made to it by Drs. Carlos I. Finlay and Aristides Agramonte, both of Havana, Cuba, and Dr. Carroll's last rejoinder. I wish briefly to state a few facts on the matter discussed by pointing out the principal differences between the experiments of Drs. Finlay and Delgado, on one side, and the Army Yellow Fever Commission on the other. The contrast is truly remarkable, and fully explains the point in question. Finlay and Delgado were trying to find in theculexmosquito a prophylactic agent by means of which they could make non-immune persons immune to yellow fever, very much as it happens with the vaccine virus against smallpox; and the