scholarly journals ETIOLOGY OF YELLOW FEVER

1919 ◽  
Vol 29 (6) ◽  
pp. 565-584 ◽  
Author(s):  
Hideyo Noguchi

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.

1919 ◽  
Vol 30 (1) ◽  
pp. 9-12 ◽  
Author(s):  
Hideyo Noguchi

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.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1141
Author(s):  
Noha M. Elhosseiny ◽  
Tamer M. Samir ◽  
Aliaa A. Ali ◽  
Amani A. El-Kholy ◽  
Ahmed S. Attia

Neonatal sepsis is a leading cause of death among newborns and infants, especially in the developing world. The problem is compounded by the delays in pinpointing the causative agent of the infection. This is reflected in increasing mortality associated with these cases and the spread of multi-drug-resistant bacteria. In this work, we deployed bioinformatics and proteomics analyses to determine a promising target that could be used for the identification of a major neonatal sepsis causative agent, Klebsiella pneumoniae. A 19 amino acid peptide from a hypothetical outer membrane was found to be very specific to the species, well conserved among its strains, surface exposed, and expressed in conditions simulating infection. Antibodies against the selected peptide were conjugated to gold nanoparticles and incorporated into an immunochromatographic strip. The developed strip was able to detect as low as 105 CFU/mL of K. pneumoniae. Regarding specificity, it showed negative results with both Escherichia coli and Enterobacter cloacae. More importantly, in a pilot study using neonatal sepsis cases blood specimens, the developed strip selectively gave positive results within 20 min with those infected with K. pneumoniae without prior sample processing. However, it gave negative results in cases infected with other bacterial species.


1920 ◽  
Vol 32 (5) ◽  
pp. 601-625 ◽  
Author(s):  
Hideyo Noguchi ◽  
I. J. Kligler

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


Author(s):  
Б. В. Борисевич ◽  
В. Г. Скибіцький ◽  
Г. В. Козловська ◽  
А. В. Козловська

Викладено результати дослідження гістоморфо-логічних змін органів і тканин мурчаків, інфікованихентеротоксигенними штамами Y. enterocoliticа. Зок-рема встановлено, що найбільше уражається тонкакишка, де виявляють поверхневий некротичний енте-рит. Токсини збудника хвороби, потрапляючи в кров,спричиняють дистрофічні зміни в печінці та підшлун-ковій залозі, спричиняють екстракапілярний серознийгломерулонефрит та дистрофічні зміни епітеліюканальців нирок, а також серозний міокардит. Інфі-кування мурчаків призводить до значної активаціївсіх імунокомпетентних органів організму – тимусу,селезінки, соматичних і вісцеральних лімфовузлів. The results of the study of histomorphological changes in organs and tissues of guinea pigs infected with enterotoxigenic strains of Y. enterocolitica were presented. We established, in particular, the most affected in small intestine, where superficial necrotic enteritis was determined. Toxins are causative agent, getting into the bloodstream cause degenerative changes in the liver and pancreas. And also serous ecstracapillary glomerulonephritis and degenerated changes of epithelial tubules of the kidneys and serous myocarditis were caused. The infecting of guinea pigs leads significant activation of immune organs: thymus, spleen, somatic and visceral lymph nodes.


1919 ◽  
Vol 29 (2) ◽  
pp. 199-213 ◽  
Author(s):  
Yutaka Ido ◽  
Hiroshi Ito ◽  
Hidetsune Wani

1. Spirochata hebdomadis is always present in seven day fever and can be confirmed by animal experiments with guinea pigs of light weight. 2. The causative agent of this disease can also be found in film preparations of the blood of patients, though it is not present in large numbers. 3. Spirochæta hebdomadis is discharged in the urine of patients having seven day fever. The number of spirochetes in the urine is great during convalescence. 4. Seven day fever is a disease found not only in the Prefecture of Fukuoka, but in many other districts of Japan as well.


1920 ◽  
Vol 31 (2) ◽  
pp. 159-168 ◽  
Author(s):  
Hideyo Noguchi

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.


1935 ◽  
Vol 35 (1) ◽  
pp. 1-22 ◽  
Author(s):  
J. Isgaer Roberts

1. Earlier attempts to trace the vector of tropical typhus in Kenya failed. The only references to the subject in the available literature consist of mere suggestions that a mite would most likely prove to be the transmitter.2. An investigation made in an area whence most Nairobi cases of tropical typhus were reported, suggested that a tick (R. pulchellus) would be the most likely vector.3. Transmission experiments made in the belief that one of the unclassed fevers of man was conveyed by R. pulchellus have so far yielded negative results. There is, however, sufficient circumstantial evidence available pointing to this tick as vector of a form of mild typhus to man—this demands further investigation.4. At Mombasa and Nairobi, houses reported to be heavily infested with ticks, or houses investigated after the occurrence of the tropical typhus in them, have yielded only R. sanguineus.5. R. sanguineus (3 ♀), taken from a dog in a house where the last typhus case had occurred 8 months previously, gave a typical typhus syndrome when emulsified and inoculated into a male guinea-pig. R. sanguineus (1 ♀, 12 ⊙), taken in a house where a child had recently contracted typhus, also gave a positive result with guinea-pigs and the virus was further transmitted by passage through other guinea-pigs.6. The infestation of houses by R. sanguineus and the incidence of tropical typhus among human beings appear to be influenced by unfavourable weather conditions, causing the ticks to seek relatively dry and warm places for purposes of oviposition or metamorphosis, thus invading houses. In the absence of dogs, its usual hosts, the tick attacks man.


1918 ◽  
Vol 28 (4) ◽  
pp. 435-448 ◽  
Author(s):  
Yutaka Ido ◽  
Hiroshi Ito ◽  
Hidetsune Wani

A new species of spirochete which we have called Spirochæta hebdomadis has been described as the specific etiological agent of seven day fever, a disease prevailing in the autumn in Fukuoka and other parts of Japan. This spirochete is distinguishable from Spirochæta icterohæmorrhagiæ to which it presents certain similarities. Young guinea pigs are susceptible to inoculation with the blood of patients and to pure cultures of the spirochete, and those developing infection exhibit definite symptoms suggestive of those of seven day fever in man. The blood serum of convalescents from seven day fever contains specific immune bodies acting spirochetolytically and spirocheticidally against the specific spirochetes, but not against Spirochæta icterohæmorrhagiæ. The field mouse (Microtus montebelli) is the normal host of the spirochetes, which have been detected in the kidneys and urine of 3.3 per cent of the animals examined. The endemic area of prevalence of seven day fever corresponds with the region in which field mice abound.


1921 ◽  
Vol 33 (2) ◽  
pp. 253-260 ◽  
Author(s):  
Hideyo Noguchi ◽  
I. J. Kligler

Serum from yellow fever convalescents from Payta, Piura, and Morropon gave a positive Pfeiffer reaction with the strains of Leptospira icteroides isolated in Guayaquil and Merida. The serum also protected the guinea pigs from these strains in the majority of instances. The Pfeiffer reaction was complete with all recent convalescents (7 to 36 days) but slight or partial in some instances with serum derived from individuals who had had the attack of yellow fever 10 months previously. The virulence of the Morropon strains was found to be approximately the same as that of the Guayaquil or Merida strains. With one strain the minimum lethal dose for the guinea pig was less than 0.00001 cc. of a kidney emulsion from an infected guinea pig. Suitable quantities of the anti-icteroides serum administered to guinea pigs inoculated with 2,000 to 20,000 minimum lethal doses of infective material prevented the development of the infection, or a fatal outcome, according as the serum was given during the incubation period or after fever had appeared. The earlier the administration of the serum the smaller was the quantity needed; during the incubation period 0.0001 to 0.001 cc. was sufficient, during the febrile period 0.01 to 0.1 cc. was required to check the progress of the disease, and even at the time when jaundice had already appeared, the injection of 0.1 to 1 cc. saved three out of four animals inoculated with Strain 3 and one out of three inoculated with Strain 1. The native guinea pigs secured in Payta proved to be unusually refractory to infection with Leptospira icteroides as compared with normal guinea pigs recently imported from New York. Fresh rabbit serum is recommended for culture work with Leptospira icteroides.


2021 ◽  
Vol 2 (3) ◽  
pp. 70-74
Author(s):  
S. E. Haramain ◽  
S. O. Yagoub

Vegetables can be vehicles for transmission of E. coli O157:H7 to humans, therefore, this study carried out in order to investigate the presence of Enterohemorrhagic E. coli in ten different types of leafy green vegetables, determined their susceptibility to thirteen antibiotics and detected the presence of some virulence genes. Method: Five-hundred samples of green leafy vegetables namely (Lettuce, Spanish, Rocket, Parsley, Mallow, Coriander, Portulaca, Lettuce, Dill, Basil and Chard) were examined for presence of E. coli O157:H7, by using standard microbiological tests (CHROMagarTM O157:H7), further detection of E. coli O157:H7 was done by Multiplex PCR (mPCR) for the detection of virulence genes (stx1, stx2, intmin and hlyA) These genes are causative factors of settlement, adhesion, and attack of STEC bacteria to gastrointestinal mucosa. Results: E. coli O157:H7 was isolated from eight (80%) out of ten types of green leafy vegetable as 12 (2.40%) in which the highest percentage of isolation was shown in Dill and Chards samples as (4.2%), Coriander and Mallow showed percentage of isolation as (3.33% and 3.03%) respectively, Parsley, Portulaca and Lettuce showed percentages of isolation as 2.43%, 1.92%, respectively, the least percentage of isolation was shown in Rocket (1.7%), No E. coli O157:H7, was detected in Spinach and Basil. Makkah collected samples showed isolation of 7 isolates out of 12 (58.33%). All isolates were resistant to Methicillin (5µg), Metronidazole (5 µg) and Ampicillin (10 µg). Stx2 (110 bp), Stx1 (349 bp), hly A (165 bp) genes were detected. All isolates showed negative results for presence of intimin gene (890 bp). This study concluded that there is a high risk for occurrence of E. coli O157:H7 outbreaks due to consumption of the green leafy vegetables sold in Jeddah Central Market. 


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