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ETIOLOGY OF YELLOW FEVER : II. TRANSMISSION EXPERIMENTS ON YELLOW FEVER
1Laboratories of The Rockefeller Institute for Medical Research.
Abstract:
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 conjunctivaes 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 icterohamorrhagiae). 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.
Insights
Researchers induced yellow fever symptoms in guinea pigs using infected blood. A novel bacterium, Leptospira icteroides, was identified as the likely cause of yellow fever in these animal models.
Area of Science:
- * Infectious Diseases
- * Microbiology
- * Veterinary Pathology
Background:
- * Yellow fever is a severe viral hemorrhagic disease transmitted by mosquitoes.
- * Previous research has focused on viral etiologies, with limited success in establishing animal models that fully replicate human disease.
- * Understanding the causative agent and developing reliable experimental models are crucial for developing effective treatments and prevention strategies.
Purpose of the Study:
- * To investigate the potential for inducing yellow fever-like symptoms in laboratory animals by inoculating them with blood from human yellow fever cases.
- * To identify any microorganisms present in infected animals that could be responsible for the induced pathology.
- * To characterize the morphology and pathogenicity of any identified microorganisms.
Main Methods:
- * Inoculation of guinea pigs with blood from confirmed yellow fever cases in Guayaquil.
- * Observation and documentation of clinical signs, including fever, jaundice, and hemorrhage.
- * Microscopic examination of blood, liver, and kidney samples from infected guinea pigs to identify potential causative agents.
- * Experimental transmission of the identified microorganism to naive guinea pigs to confirm pathogenicity.
Main Results:
- * A subset of inoculated guinea pigs (8 out of 74) developed symptoms mimicking human yellow fever, including fever, jaundice, albuminuria, and hemorrhagic lesions.
- * A minute, spiral-shaped organism, provisionally named *Leptospira icteroides*, was consistently found in the blood, liver, and kidneys of infected guinea pigs.
- * This organism, when passaged to other guinea pigs, induced similar symptoms and lesions, confirming its role in the experimental disease.
- * Inoculation attempts in other mammals and birds yielded negative results.
Conclusions:
- * *Leptospira icteroides* is identified as a potential causative agent of yellow fever, capable of inducing disease in guinea pigs.
- * The study establishes a new animal model for yellow fever research using *Leptospira icteroides*.
- * Further research is warranted to elucidate the precise relationship between *Leptospira icteroides* and human yellow fever and its epidemiological significance.
