Experimental Cholera in the Chinchilla

Blachman, Uzy; Goss, S. J.; Pickett, M. J.

doi:10.1093/infdis/129.4.376

Cited by 16 publications

(9 citation statements)

References 12 publications

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“…The chinchilla model, however, requires 19 Mg (2) to give a positive response, and Ujiiye's use of the infant mouse requires at least 5 Mg (26).…”

Section: Discussionmentioning

confidence: 99%

“…Intact animal models used to study pathogenesis of cholera generally mimic the diarrheal symptomology. Net fluid secretion in response to oral or intraintestinal inoculation with viable organisms or enterotoxin has been demonstrated in several intact animals, including dogs (24,25), infant rabbits (10,11,14), chinchillas (2), and human volunteers (1,3). The commonly used closed model system of ligated lapine ileal loops also demonstrates net fluid secretion in response to viable organisms and enterotoxin (7,8).…”

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confidence: 99%

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Intestinal fluid accumulation induced by oral challenge with Vibrio cholerae or cholera toxin in infant mice

Baselski¹,

Briggs²,

Parker³

1977

Infect Immun

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The diarrheal response of orally inoculated infant mice to viable Vibrio cholerae and purified cholera toxin was quantitated by means of a fluid accumulation (FA) ratio. The FA ratio is defined as the gut weight/remaining body weight. FA ratios were determined in relation to time of exposure and dose. Onset of fluid accumulation with viable cells of strains CA401 and 569B occurred 8 h postinoculation and reached a near maximum at 16 h. A dose of 4 x 106 colony-forming units of strain CA401 was required for a positive response 16 to 18 h postinoculation. Several other classical cholera strains demonstrated a similar dose-related response. Strain 569B, however, required a 100-fold higher dose to give a positive response. Several mutant cholera strains with decreased virulence in other model systems elicited FA ratios decreased from wild-type values. Onset of fluid accumulation with cholera toxin occurred 6 to 8 h postinoculation and reached a maximum by 10 h. A dose of 0.5 Ag was required for a positive response 10 to 12 h postinoculation. The positive response to toxin could be inhibited by preincubation with specific antitoxin.

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“…The chinchilla model, however, requires 19 Mg (2) to give a positive response, and Ujiiye's use of the infant mouse requires at least 5 Mg (26).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Intestinal fluid accumulation induced by oral challenge with Vibrio cholerae or cholera toxin in infant mice

Baselski¹,

Briggs²,

Parker³

1977

Infect Immun

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“…The rabbit skin tests were essentially as described by Craig (24). Virulence, colonizing ability, and ability to stimulate immunity were evaluated in locally obtained chinchillas, 1-2 years old, by the techniques of Blachman et al (25,26). Assays for activation of adenylate cyclase in pigeon erythrocyte lysates (27) were performed on The publication costs of this article were defrayed in part by page charge payment.…”

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confidence: 99%

Selection and characteristics of a Vibrio cholerae mutant lacking the A (ADP-ribosylating) portion of the cholera enterotoxin.

Honda¹,

Finkelstein²

1979

Proc. Natl. Acad. Sci. U.S.A.

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After mutagenesis with nitrosoguanidine and selection by immuno-halo techniques, an avirulent mutant, designated Texas Star-SR, which produces no detectable A (active; ADP-ribosylating) region of the cholera enterotoxin (choleragen) but produces the B region (choleragenoid) in amounts similar to the hypertoxinogenic wild-type parent Vibrio cholerae (biotype El Tor serotype Ogawa), has been isolated. The mutant retains the colonizing ability, motility, prototrophy, and serologic characteristics of the parent. In relevant intestinal experimental models, it has been shown to be avirulent and to induce protection against challenge with virulent cholera vibrios. The mutant appears to be suitable for further evaluation in volunteers as a candidate living enteric vaccine against cholera and related enterotoxic enteropathies. Cholera is the prototype of an increasing number of newly recognized diarrheal diseases, enterotoxic enteropathies, which depend on soluble enterotoxins, some of which are related to the cholera enterotoxin (choleragen), both immunologically and by mode of action (1). Perhaps because of its intestinal locus, conventional cholera vaccines composed of killed bacteria, administered parenterally, are relatively ineffective in preventing cholera (2). However, the disease itself is an immunizing process (3). Further, a perorally administered hypotoxinogenic Vibrio cholerae mutant, M13 (4), was found to be avirulent for human beings and to induce substantial immunity against subsequent challenge with virulent cholera vibrios (5, 6). Because of its limited production of toxin antigen, M13 would offer little, if any, protection against other enterotoxic enteropathies. Because it also appeared to be unstable (5, 6), further evaluation of M13 as a vaccine was contra-indicated.Choleragen is a polymeric protein consisting of noncovalently associated subunits (7), of which the A region is responsible for activation of adenylate cyclase and the B region (choleragenoid), which has been shown to be highly immunogenic, is responsible for binding of the holotoxin to host cell membrane receptors, thereby facilitating entry of the A region (8-11). Thus an A-B+ V. cholerae mutant could be predicted to be avirulent and capable of stimulating local immunity against cholera and the immunologically related enterotoxins that share B-related antigens. The potential value of such a mutant was postulated earlier (12). The isolation and characterization of such an A-B+ mutant, which appears to be stable, is described in this report. METHODSV. cholerae Strains. Two hypertoxinogenic strains of V. cholerae were used. The first, V. cholerae 569B, a classical vibrio of the Inaba serotype, has been widely used by us and by others for production of choleragen and in genetic studies (4,(13)(14)(15)(16). The other was 3083, an El Tor biotype Ogawa serotype, isolated by one of us (R.A.F.) from a patient in Vietnam in 1964 (17), which has been shown to be highly adherent in infant rabbits (18). All strains and mutants were maintai...

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“…The pathogenesis of cholera and action of cholera enterotoxin have been studied in many animal models such as adult rabbits (9,14), infant rabbits (13), dogs (23), chinchillas (6), and infant mice (4,8). On the other hand, adult mice were resistant to challenge with live vibrio (17) although mice were susceptible to cholera enterotoxin (15).…”

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confidence: 99%