Document Detail

Rapid death of infant rhesus monkeys injected with Clostridium difficile toxins A and B: physiologic and pathologic basis.
MedLine Citation:
PMID:  6690674     Owner:  NLM     Status:  MEDLINE    
Clostridium botulinum can colonize and produce botulinal toxin in the human infant intestine, which the toxin then permeates to cause generalized flaccid paralysis, and occasionally, sudden death. This study was undertaken to test the hypothesis that toxins produced by other intestinal clostridia, e.g., C. difficile, might also cause systemic illness and sometimes death in infants (J Pediatr 100:568, 1982). Because this hypothesis could not be evaluated clinically until the systemic manifestations of C. difficile toxins in primates were known, infant rhesus monkeys were given 6 to 11 micrograms/kg of the recently purified C. difficile toxins A or B, either intravenously or intraperitoneally. The animals showed no abnormalities for several hours, but then developed lethargy, hypotonia, hypothermia, and, shortly before death, sudden elevation of serum concentrations of potassium, magnesium, and phosphorus and of enzymes that derived mainly from skeletal muscle, heart and brain. Five of six animals died quietly 3.5 to 8.0 hours after onset of symptoms. Death appeared to result from cessation of breathing, after which the sinus tachycardia then deteriorated to a flat ECG. Necropsy findings were insufficient to explain the cause of death. It appears that in infant monkeys microgram amounts of C. difficile toxins A and B can produce a rapid quiet death, the cause of which is undetectable at necropsy, a situation pathologically reminiscent of crib death in human infants, although the possible clinical identity of these two conditions has yet to be established.
S S Arnon; D C Mills; P A Day; R V Henrickson; N M Sullivan; T D Wilkins
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pediatrics     Volume:  104     ISSN:  0022-3476     ISO Abbreviation:  J. Pediatr.     Publication Date:  1984 Jan 
Date Detail:
Created Date:  1984-02-15     Completed Date:  1984-02-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375410     Medline TA:  J Pediatr     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  34-40     Citation Subset:  AIM; IM    
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MeSH Terms
Bacterial Proteins*
Bacterial Toxins / toxicity*
Cytotoxins / toxicity*
Disease Models, Animal
Enterotoxins / toxicity*
Macaca mulatta
Sudden Infant Death / etiology*,  pathology
Grant Support
Reg. No./Substance:
0/Bacterial Proteins; 0/Bacterial Toxins; 0/Cytotoxins; 0/Enterotoxins; 0/tcdA protein, Clostridium difficile; 0/toxB protein, Clostridium difficile

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