scholarly journals ETIOLOGY OF YELLOW FEVER

1919 ◽  
Vol 30 (1) ◽  
pp. 9-12 ◽  
Author(s):  
Hideyo Noguchi
Keyword(s):  
Yellow Fever ◽  
Experimental Infection ◽  
Guinea Pigs ◽  
Protective Property ◽  
Fatal Infection ◽  
Negative Results ◽  
Immunological Relationship

The serum from a number of persons recovering from yellow fever in Guayaquil was studied with a view to establishing its possible immunological relationship with a strain of Leptospira icteroides derived from one of the yellow fever patients. For this purpose the serum of convalescents was mixed either with an organ emulsion of a passage strain, or with a culture of the organism, and inoculated intraperitoneally into guinea pigs. The Pfeiffer reaction was first studied, and then the animals were allowed to live until the controls, inoculated with the same emulsion or culture of Leptospira icteroides but without the serum, or with serum from patients suffering from other diseases than yellow fever, had died of the experimental infection with typical symptoms A positive Pfeiffer phenomenon was observed in fifteen of the eighteen convalescent cases studied, or approximately 83 per cent. Sera from ten non-immune soldiers and from two malaria patients gave uniformly negative results. Protection from an ultimate fatal infection was afforded some of the guinea pigs which received the serum of yellow fever convalescents, while the control animals succumbed to the infection with typical symptoms. In one instance, in which the serum was tested on the 2nd and the 10th days of disease, a Pfeiffer reaction was demonstrated, as well as protective property against the infection, in the specimen from the 10th but not in that from the 2nd day. From the foregoing observations of immunity reactions it appears highly probable that Leptospira icteroides is etiologically related to yellow fever.

scholarly journals ETIOLOGY OF YELLOW FEVER

1919 ◽  
Vol 30 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Hideyo Noguchi
Keyword(s):  
Yellow Fever ◽  
Experimental Infection ◽  
Guinea Pigs ◽  
The Other ◽  
Febrile Reaction ◽  
Infection Experiment ◽  
Fatal Infection ◽  
Other Hand ◽  
Immunity Reaction ◽  
Highly Virulent

The majority of guinea pigs inoculated with the blood of yellow fever patients escaped a fatal infection. There were a number of instances in which the inoculation of yellow fever blood induced in these animals a temporary febrile reaction on the 4th or 5th day, followed in some cases by slight jaundice, but with a rapid return to normal. Most of these guinea pigs when later inoculated with an organ emulsion of a passage strain of Leptospira icteroides resisted the infection. On the other hand, the animals which had previously been inoculated with the blood of malaria patients or normal guinea pigs died of the typical experimental infection after being inoculated with the infectious organ emulsion. It appears from the results just described that a number of nonfatal, mild, or abortive infections follow the inoculation of blood of yellow fever patients into guinea pigs. The fact that such animals manifested refractoriness to a subsequent attempt to infect with a highly virulent passage strain of Leptospira icteroides is an indication, judging from the reciprocal immunity reaction, that they actually passed through an infection with the same organism, or a strain closely related to it, as that which was used for the second infection experiment

scholarly journals ETIOLOGY OF YELLOW FEVER

1920 ◽  
Vol 31 (2) ◽  
pp. 159-168 ◽  
Author(s):  
Hideyo Noguchi
Keyword(s):  
Guinea Pig ◽  
Beneficial Effect ◽  
Yellow Fever ◽  
Experimental Infection ◽  
Guinea Pigs ◽  
Fatal Outcome ◽  
Clinical Manifestations ◽  
Immune Serum ◽  
Definite Advantage ◽  
Fever Patient

The use ot a polyvalent immune serum ot nign potency in tne treatment of an experimental infection of guinea pigs with Leptospira icteroides was found to be of definite advantage in checking the progress of the infection. When administered during the period of incubation the serum was found capable of completely preventing the development of the disease, although on subsequent examination hemorrhagic lesions of greater or less number and extent were found in the lungs of the guinea pigs which survived. Moreover, the serum modified the course of the disease and when used in the early stages of infection prevented a fatal outcome. Employed at a later stage, however, when jaundice and nephritis had been present for several days and the animal was near collapse, the serum had no perceptible beneficial effect. This was, of course, to be expected in view of the incidence of various pathological phases of this disease—nephritis, hepatitis, and other toxic symptoms in succession. In man the clinical manifestations are more gradual and distinct than in the guinea pig, yet the yellow fever patient whose temperature is sub-normal, and who has reached the stage of hemorrhages from the gums, nose, stomach, and intestines, and of uremia and cholemia, would seem to have little or no chance of deriving benefit from the use of a specific immune serum. This latter assumption would probably hold irrespective of the relation which Leptospira icteroides proves to have to the etiology of yellow fever.

scholarly journals ETIOLOGY OF YELLOW FEVER

1919 ◽  
Vol 29 (6) ◽  
pp. 565-584 ◽  
Author(s):  
Hideyo Noguchi
Keyword(s):  
Yellow Fever ◽  
Causative Agent ◽  
Guinea Pigs ◽  
Gastrointestinal Mucosa ◽  
Marked Rise ◽  
Negative Results ◽  
Early Appearance ◽  
Gingival Mucosa

By injecting into guinea pigs the blood of yellow fever cases occurring in Guayaquil a group of symptoms and lesions closely resembling those observed in human yellow fever were induced in a limited number of instances. Of 74 guinea pigs inoculated with specimens of blood from 27 cases of yellow fever, 8, representing 6 cases, came down with the symptoms; namely, a marked rise of temperature after a period of incubation averaging 3 to 6 days, with simultaneous suffusion of the capillaries, particularly of the conjunctivæs and soles, then preliminary hyperleucocytosis followed by progressive leucopenia, the early appearance of albumin and casts in the urine, which gradually diminishes in volume as the disease progresses. The fever lasts only a few days, rapidly dropping first to the normal and then usually to subnormal. At this period jaundice manifests itself in varying degrees of intensity, first in the scleras, then in the skin and the urine. Hemorrhages from the nasal or gingival mucosa or anus have been observed to occur during this period. Autopsies reveal deep jaundice throughout the entire tissue. The liver is fatty and yellow, the kidney hyperemic, and often swollen and hemorrhagic. Hemorrhagic spots were almost always found in the lungs and gastrointestinal mucosa. Guinea pigs are usually rather sensitive to the infection, though many appeared to be somewhat resistant and some even refractory. The injection of the yellow fever blood into ringtail monkeys, rabbits, cats, guatusas, weasels, and sloths among the mammalians, and pigeons, ground-doves, bluebirds, mantas, blackbirds, parrakeets, reedbirds, blancos, and toucans among the birds, gave negative results. In the blood, liver, and kidneys of the guinea pigs experimentally infected with the blood of yellow fever patients a minute organism was demonstrated which closely resembles in morphology the causative agent of infectious jaundice (Leptospira icterohamorrhagiæ). The leptospira transmitted from yellow fever cases to guinea pigs was found to induce similar symptoms and lesions upon further passage into normal guinea pigs. The leptospira obtained from cases of yellow fever has been givern the provisional name of Leptospira icteroides.

scholarly journals ETIOLOGY OF YELLOW FEVER

1919 ◽  
Vol 29 (6) ◽  
pp. 585-596 ◽  
Author(s):  
Hideyo Noguchi
Keyword(s):  
Gastrointestinal Tract ◽  
Guinea Pig ◽  
Yellow Fever ◽  
Experimental Infection ◽  
Guinea Pigs ◽  
Febrile Reaction ◽  
Hemorrhagic Diathesis ◽  
Bile Pigments ◽  
Pathological Changes ◽  
Subcutaneous Inoculation

Studies are reported on the type of disease induced in guinea pigs, dogs, and monkeys by inoculating them (1) with the blood or organ emulsions of guinea pigs or other susceptible animals experimentally infected with Leptospira icteroides, and (2) with a pure culture of the organism. Particular attention has been given in these experiments to the clinical features of the experimental infection in the various animals and to the pathological changes resulting from the infection. The symptoms and pathological lesions induced in guinea pigs are much more pronounced than those observed in dogs or marmosets. The period of incubation is nearly the same in all three species, 72 to 96 hours with intraperitoneal or subcutaneous inoculation, and a day or more longer when the infection is induced percutaneously or per os. The febrile reaction in the guinea pig and marmoset is about the same; in the dog there is less fever. The amount of albumin, casts, and bile pigments in the urine is more abundant in the guinea pig and marmoset than in the dog, and these animals also appear on the whole to become more intensely icteric. The black or bilious vomit, however, though occurring frequently in dogs during life, is observed in the guinea pig and marmoset at autopsy. The hemorrhagic diathesis is most pronounced in guinea pigs, less so in marmosets, and least in dogs. In dogs) for example, subcutaneous hemorrhages almost never occur, and the lungs usually show only a few minute ecchymoses. The pleurse, pericardium, and other serous surfaces of the thorax and abdomen remain free from ecchymoses, which, however, with hyperemia, are very marked along the gastrointestinal tract. The symptoms and lesions observed in animals experimentally infected with Leptospira icteroides closely parallel those of human yellow fever. The pathological changes occurring in human cases of yellow fever are similar to those induced by inoculation in guinea pigs and marmosets and in respect to their intensity stand intermediate between those arising in the two animals mentioned.

scholarly journals ETIOLOGY OF YELLOW FEVER

1921 ◽  
Vol 33 (6) ◽  
pp. 683-692 ◽  
Author(s):  
Alfred E. Cohn ◽  
Hideyo Noguchi
Keyword(s):  
Yellow Fever ◽  
Experimental Infection ◽  
Guinea Pigs ◽  
Heart Block ◽  
Similar Reaction ◽  
Whole Heart

1. Slowing of the heart occurred in monkeys and guinea pigs during the febrile period of the experimental infection due to Leptospira icteroides. A similar reaction took place in animals inoculated with Leptospira icterohœmorrhagiœ. 2. The mechanism of slowing was usually due to slowing of the whole heart. 3. Once incomplete heart block was seen. Changes in the ventricular complex occurred four times.

scholarly journals ETIOLOGY OF YELLOW FEVER

1919 ◽  
Vol 30 (2) ◽  
pp. 87-93 ◽  
Author(s):  
Hideyo Noguchi
Keyword(s):  
Yellow Fever ◽  
Experimental Infection ◽  
Guinea Pigs ◽  
Dark Field ◽  
Blood Film ◽  
Fresh Blood ◽  
The Third ◽  
Fresh State ◽  
Liver And Kidney ◽  
Made In

Examinations of fresh blood from yellow fever patients by means of the dark-field microscope, made in more than twenty-seven cases, revealed in three cases the presence of Leptospira icteroides. In no instance was a large number of organisms found, a long search being required before one was encountered. The injection of the blood into guinea pigs from two of the three positive cases induced in the animals a fatal infection, while the blood from the third positive case failed to infect the guinea pigs fatally. Careful but by no means exhaustive dark-field searches for the leptospira with fresh specimens of blood from the remaining cases of yellow fever ended without positive findings, although four of the specimens, when injected into guinea pigs, caused a fatal leptospira infection. Stained blood film preparations from the corresponding cases were also examined, but the percentage showing the leptospira in the blood was no greater than that found by examination in the fresh state with the dark-field microscope. In fact, owing to the defective stains that were available at the time of the investigation a great many slides did not take the proper coloration with Giemsa's or Wright's stain and could not be relied upon. Regarding the presence of Leptospira icteroides in various organs both dark-field and stained films were examined. In only one instance so far a few organisms were detected in the emulsion of liver taken shortly after death from a case dying on the 4th day of yellow fever. This part of the work will be reported later upon completion. Examinations of the urine from different cases of yellow fever were made both by dark-field microscope and by inoculation into guinea pigs. The results were totally negative in thirteen cases, including many convalescents, but in one case one of the guinea pigs inoculated with 10 cc. of the urine came down on the 15th day with suggestive symptoms (suspicion of jaundice, and some hemorrhagic and parenchymatous lesions of the lungs and kidneys). This specimen showed no leptospira by dark-field examination. In experimental infection of guinea pigs with Leptospira icteroides the blood became infective in many instances 48 hours after inoculation, and was always infective after 72 hours. The liver and kidney become infective simultaneously with the blood. Detection of the organism by means of the dark-field microscope has seldom been accomplished before the 5th day. The organisms are most abundant on the 6th to the 7th day, but become fewer or completely disappear before death. In the meanwhile the number of organisms increases in the liver and kidney, from which they disappear as the jaundice and other symptoms become aggravated. When death occurs these organs seem to have lost most of the leptospira) and positive transfer by means of them is less certain. At the later stage of the disease the blood is often free from the organisms and ceases to be infective. Positive transmission with blood obtained from moribund animals is not impossible, however, even when no leptospira can be detected under the dark-field microscope.

scholarly journals EXPERIMENTAL STUDIES ON YELLOW FEVER OCCURRING IN MERIDA, YUCATAN

1920 ◽  
Vol 32 (5) ◽  
pp. 601-625 ◽  
Author(s):  
Hideyo Noguchi ◽  
I. J. Kligler
Keyword(s):  
Guinea Pig ◽  
Yellow Fever ◽  
Guinea Pigs ◽  
Secondary Infection ◽  
Fatal Case ◽  
Primary Cultures ◽  
Experimental Studies ◽  
Dark Field ◽  
Liver And Kidney ◽  
Positive Direct

Injections into guinea pigs of the blood and the emulsions of liver and kidney obtained at autopsy from a fatal case of yellow fever in Merida induced in some of these animals, after a period of several days incubation, a rise of temperature which lasted 1, 2, or more days. When killed for examination at this febrile stage the animals invariably showed hemorrhagic areas of various size, sometimes few and sometimes numerous, in the lungs, and also, though less constantly, in the gastrointestinal mucosa, together with general hyperemia of the liver and kidneys. In a guinea pig (No. 6) inoculated with the liver emulsion of Case 1 there was a trace of jaundice on the 9th day. Injections of the blood or liver and kidney emulsions from such animals into normal guinea pigs reproduced the febrile reactions and the visceral lesions. The majority of the animals which were allowed to live and complete the course of the infection rapidly returned to normal (within several days). Examinations of these surviving guinea pigs after 2 weeks revealed the presence of rather old hemorrhagic foci in the lungs. In the course of further attempts to transfer the passage strain, a secondary infection by a bacillus of the paratyphoid group caused many deaths among the guinea pigs and resulted finally in the loss of the strain from Case 1. Most of the cultures made with the heart's blood taken at autopsy from Case 1 proved to be contaminated with a bacillus of the coli group. The contents of the apparently uncontaminated tubes were inoculated into guinea pigs, but the results were for the most part negative or vitiated by a secondary infection. Dark-field search for the leptospira with the autopsy materials was negative, although prolonged and thorough examination was not practicable at the time of these experiments. Our efforts were concentrated on obtaining positive animal transmission rather than on the time-consuming demonstration of the leptospira, which when unsuccessful does not necessarily exclude the presence of the organism in small numbers. Likewise, the dark-field work with the material from guinea pigs was confined to a brief examination and was omitted in many instances. Under these circumstances no leptospira was encountered in any of the material from Case 1. On the other hand, the results obtained with the specimens of blood from Case 2 were definitely positive, not only in the transmission of the disease directly, or indirectly by means of cultures, into guinea pigs, but also in the demonstration of the leptospira in the primary cultures and in the blood and organ emulsions of guinea pigs experimentally infected with such cultures. Definite positive direct transmissions were obtained with the specimens of blood drawn on the 2nd and 3rd days. No blood was taken on the 4th or 6th days. There were indications of abortive or mild leptospira infection in the guinea pigs inoculated with the blood taken on the 5th day. Regarding the inoculation of cultures from Case 2, it may be stated that only the cultures (leptospira +) made with the blood drawn on the 2nd day caused a definite fatal infection in guinea pigs. From this series a continuous passage in the guinea pig has been successfully accomplished. One of the guinea pigs (No. 48) inoculated with the culture 5 days old (leptospira +) made from the blood taken on the 3rd day presented typical symptoms, and a positive transfer from this to another animal (No. 98) was also made. Cultures of the blood drawn on the 5th and 7th days gave unsatisfactory results, owing to a secondary contamination. Leptospiras were detected in some of the culture tubes containing 2nd and 3rd day specimens of blood from Case 2; they were few in number and for the most part immotile, owing perhaps to some unfavorable cultural condition such as a fungus contamination. Charts 17, 18, and 19 give a summary of the experiments. See PDF for Structure

scholarly journals FATAL INFECTION OF IRRADIATED WHITE MICE WITH EUROPEAN TYPHUS BY THE INTRA-ABDOMINAL ROUTE

1941 ◽  
Vol 73 (5) ◽  
pp. 669-680
Author(s):  
P. Y. Liu ◽  
John C. Snyder ◽  
John F. Enders
Keyword(s):  
Guinea Pigs ◽  
Brain Lesions ◽  
Rickettsial Infection ◽  
X Ray ◽  
Fatal Infection ◽  
Adult Mice ◽  
Abdominal Route ◽  
Peritoneal Washings ◽  
Cross Immunity ◽  
Observation Period

A fatal infection of irradiated white mice with the Breinl strain of European typhus has been established and passed serially for 22 passages by the intra-abdominal route. Rickettsiae were abundant and easily demonstrable in the moribund or dead mice. The mortality of irradiated mice infected with passage material (peritoneal washings or blood) was nearly 100 per cent as contrasted to no mortality in the control mice given the same dose of x-ray (450 R) and the same volume of fluid intra-abdominally. (The observation period of control mice was arbitrarily limited to 14 days.) After eighteen passages in irradiated mice no increase in virulence for non-irradiated adult mice was detected. After passage in guinea pigs, the rickettsial infection deriving from the mouse passage material was identical with the Breinl strain as judged by fever, cross immunity tests, and brain lesions in sections.

Iron as a replacement for mucin in the establishment of meningococcal infection in mice

1976 ◽  
Vol 22 (6) ◽  
pp. 832-838 ◽  
Author(s):  
G. A. Calver ◽  
C. P. Kenny ◽  
G. Lavergne
Keyword(s):  
Neisseria Meningitidis ◽  
Experimental Infection ◽  
Ferrous Sulphate ◽  
Gastric Mucin ◽  
Meningococcal Infection ◽  
Iron Dextran ◽  
Iron Compounds ◽  
Fatal Infection ◽  
Lethal Doses

Experimental infection of mice with Neisseria meningitidis was established by the injection of the bacteria suspended in solutions of various iron compounds. The progressive and fatal infection caused by otherwise non-lethal doses of organisms was produced in these mice after prior injection with ferrous sulphate or concomitant injection with iron sorbitol citrate or iron dextran. Reduction in LD50 to levels at least comparable to those obtained in the mucin challenge system was achieved; in some serogroups of N. meningitidis the LD50 was decreased more than a million fold. The results suggest that iron, which is a component of hog gastric mucin, is a factor involved in the establishment of meningococcal infection in mice. Use of iron compounds as injection medium offers a more advantageous system than mucin, since controlled administration of chemically defined substances occurs.

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