Experimental cholera in humans.

Benyajati, C.

doi:10.1136/bmj.1.5480.140

Cited by 39 publications

(9 citation statements)

References 10 publications

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“…Southwestern Medical School, Dallas, Texas 75235) (Received for publication 10 March 1969) Earlier reports (1-5) have described the partial purification and some of the properties of choleragen, an antigenic, diarrheagenic protein enterotoxin elaborated by certain strains of cholera vibrios. Although the biological activity of choleragen in promoting fluid loss via the intestinal tract is usually demonstrated in experimental animal systems, such as the infant rabbit or the ligated intestinal loop of the adult rabbit, a choleragen-containing culture filtrate has been reported to produce eholeraic manifestations in human subjects (6) thus confirming its activity and pertinence to the human disease. In addition, similar biologic activities have been found in filtrates of the liquid stool of cholera patients (7,8).…”

Section: (From the Departments Of Microbiology And Biochemistry The mentioning

confidence: 99%

Pathogenesis of Experimental Cholera

Finkelstein

LoSpalluto

1969

The Journal of Experimental Medicine

286

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Choleragen, a diarrheagenic protein enterotoxin elaborated by Vibrio cholerae, has been isolated from the supernate of fermenter cultures by steps involving ammonium sulfate precipitation, DEAE cellulose, Sephadex G-75, and Agarose A-5m chromatography. The resulting product appears to be pure according to immunoelectrophoretic, disc electrophoretic, ultracentrifugal, and immunologic criteria. Sephadex gel filtration and membrane filtration studies suggest a molecular size of 61,000. The isolated product is highly active in inducing experimental cholera in infant and adult rabbit models. It also elicits, in small dosage, an increased vascular permeability in skin. These observations indicate that choleragenicity and increased vascular permeability are intimately associated phenomena and may be manifestations of the same basic mechanism. An additional, antigenically identical, protein has also been isolated by the same procedures. The latter substance, termed "choleragenoid", lacks the permeability effect and choleragenicity of the choleragen moiety. Its size (estimated from Sephadex gel filtration at 42,000) is smaller than that of choleragen and it also differs in charge. Choleragenoid may prove useful as a nontoxic immunogen to protect against pathologic effects of V. cholerae infection.

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Section: (From the Departments Of Microbiology And Biochemistry The mentioning

confidence: 99%

Pathogenesis of Experimental Cholera

Finkelstein

LoSpalluto

1969

The Journal of Experimental Medicine

286

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“…The exotoxin produced by Vibrio cholerae in culture filtrates has been shown to mimic the clinical symptoms of cholera in test animals (7)(8)(9)11) and humans (2). After colonization of the small intestine by cholera vibrios, the disease is initiated by attachment of toxin to receptors on intestinal mucosal cells (4,21,27).…”

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confidence: 99%

Radioimmunoassay for the Antigenic Determinants of Cholera Toxin and Its Components

et al. 1977

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A radioimmunoassay procedure is described for the detection of cholera toxin and its component polypeptide chains. Cholera toxin, A subunit, B subunit, a chain, and y chain were iodinated by the chloramine T procedure. Radiolabeling did not significantly alter the polyacrylamide electrophoretic migration patterns of the toxin or its components. Moreover, radiolabeled toxin, B subunit, and a chain preparations retained substantial ability to bind to intestinal mucosal homogenates. The minimal amount of antitoxin detectable with radiolabeled toxin was 0.04 antitoxin units/ml. Substitution of radiolabeled B subunit, A subunit, and a chain for radiolabeled toxin decreased the sensitivity of the test. Radiolabeled y chain did not bind to the antitoxin preparation. Competitive inhibition studies, with titrated anti-choleragen serum and radiolabeled toxin or components, indicated that the minimum concentration of toxin detectable was the reaction between antitoxin with the toxin and/or its component polypeptide chains. Preliminary reports of immunological studies assumed the A and B subunits were antigenically 621 on July 31, 2020 by guest http://iai.asm.org/ Downloaded from

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“…The production of experimental cholera in a human volunteer was described in 1966 after Syncase cholerigen, a sterile filtrate of broth culture of V. cholerae classical Inaba strain 569 B, was directly introduced into the volunteer’s small intestine. 5 This observation showed that diarrhea could be produced in the absence of viable cholera vibrios and suggested that a cholerigenic factor was responsible for clinical disease. Experimental cholera was later demonstrated in a dose–response fashion after purified cholera toxin was administered orally to volunteers.…”

Section: Lessons In Pathogenicitymentioning

confidence: 96%

“…Challenge studies involving cholera date from 1892, with the first recorded intentional infection in humans with V. cholerae an attempt to fulfill Koch’s postulates. 5 Over the past 40 years, challenge studies have served as a unique research tool with many useful applications in the development of cholera vaccines.…”

Section: Challenge Studiesmentioning

confidence: 99%

The utility of human challenge studies in vaccine development: lessons learned from cholera

Shirley¹,

McArthur²

2011

VDT

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Experiments in which virulent infectious organisms are administered to healthy adult volunteers with the intent to deliberately induce infection have been practiced for centuries. Many useful applications have developed from these experiments such as the provision of evidence of microbial pathogenicity and the identification of key virulence factors. Challenge studies have also played an important role in the evaluation of preliminary efficacy of potential vaccine candidates. Over the past 40 years, these experimental human challenge studies have found particular utility with regards to the development of both living and nonliving attenuated cholera vaccines. This review highlights some of the important contributions made by these challenge studies to cholera vaccine research.

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Experimental cholera in humans.

Cited by 39 publications

References 10 publications

Pathogenesis of Experimental Cholera

Pathogenesis of Experimental Cholera

Radioimmunoassay for the Antigenic Determinants of Cholera Toxin and Its Components

The utility of human challenge studies in vaccine development: lessons learned from cholera

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