Abstract
In our studies with the pathogenic bacteriumClostridium perfringens type A and its cytotoxic-enterotoxins (CTEs), we have obtained results that imply an involvement of this organism in the sudden infant death syndrome (SIDS). In fecal samples obtained from SIDS infants (n=164) and non-SIDS infants (n=57),C. perfringens type A was present in high numbers in >80% of SIDS and <2% of control non-SIDS cases respectively. Fecal samples from SIDS infants analyzed by ELISA forC. perfringens type A CTEs showed a very strong positive correlation with the presence of the organism. Histopathological examination of ileal tissue from SIDS infants showed remarkable similarity to tissue from animal models affected byC. perfringens type A CTEs, where the patterns of damage were positively correlated with the age of the animal. We propose that systemic distribution of the CTEs acts parasympathomimetically to trigger a biochemical cascade that alters cardiorespiratory control. Death may subsequently ensue in an immunologically vulnerable infant.
Similar content being viewed by others
Literature Cited
Aboud M, Michalski-Stern T, Nitzan Y, Salzberg S (1980) Enhancement of cellular protein synthesis sensitivity to diphtheria toxin by interferon. Infect Immun 28:11–16
Althoff H (1980) Sudden infant death syndrome. Stuttgart: Gustav Fischer Verlag
Arnon SS (1989) Infant botulism. In: Finegold SM, George WL (eds) Anaerobic infections in humans. New York: Academic Press, pp 601–609
Arnon SS, Midura TF, Damus K, Wood RM, Chin J (1978) Intestinal infection and toxin production byClostridium botulinum as one cause of sudden infant death syndrome. Lancet i:1273–1277
Arnon SS, Mills DC, Day PA, Henrickson RV, Sullivan NM, Wilkins TD (1984) Rapid death of infant rhesus monkeys injected withClostridium difficile toxins A and B: physiologic and pathologic basis. J Pediatr 104: 34–40
Bacon C, Scott D, Jones P (1979) Heatstroke in well wrapped infants. Lancet i:422–425
Beckwith JB (1973) The sudden infant death syndrome. Curr Probl Pediatr 3:1–36
Beckwith JB (1988) Intrathoracic petechial hemorrhages: a clue to the mechanism of death in sudden infant death syndrome? Ann N Y Acad Sci 533:37–47
Benno Y, Sawada K, Mitsuoka T (1984) The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants. Microbiol Immunol 28:975–986
Bettelheim LA, Goldwater PN, Dwyer BW, Bourne AJ, Smith DL (1990) ToxigenicEscherichia coli associated with sudden infant death syndrome. Scand J Infect Dis 22:467–476
Bruce K, Becker LE (1992) Quantitation of medullary astrogliosis in sudden infant death syndrome. Pediatr Neurosurg 17:74–79
Cairns SR, Thomson M, Lawson AM, Madigan MJ, Variend S, Peters TJ (1983) Biochemical and histological assessment of hepatic lipid in sudden infant death syndrome. J Clin Pathol 36:1188–1192
Cato EP, George WL, Finegold SM (1986) The genusClostridium. In: Holt JG (ed-in-chief), Bergey's manual of systematic bacteriology. Baltimore: Williams and Wilkins, vol. 2, pp 1141–1200
Chonmaitree T, Baron S (1991) Bacteria and viruses induce production of interferon in the cerebrospinal fluid of children with acute meningitis: a study of 57 cases and review. Rev Infect Dis 13:1061–1065
Cooperstock MS, Steffen E, Yolken R, Onderdonk A (1982)Clostridium difficile in normal infants and sudden infant death syndrome: an association with infant formula feeding. Pediatrics 70:91–95
Damas E, Siarakas S, Murrell WG (1992) Absorption of bacterial toxins from the intestinal tract of the rabbit (a cot death model) and the effect of the toxins on their catecholamine levels and behavior. Abstracts of the 2nd International SIDS Conference, Sydney, Australia 1992:112
Donta S, Myers M (1982)Clostridium difficile in asymptomatic neonates. J Pediatr 100:431–434
Garcia-Alvarado JS, Labbe RG, Rodriguez MA (1992) Sporulation and enterotoxin production byClostridium perfringens type A at 37 and 43°C. Appl Environ Microbiol 58:1411–1414
Gordis L (1982) Should dead cases be matched to dead controls. Am J Epidemiol 115:1–5
Gurwith MJ, Langston C, Citron D (1981) Toxin-producing bacteria in infants: lack of an association with sudden infant death syndrome. Am J Dis Child 135:1104–1106
Harmon SM, Duncan CL (1984)Clostridium perfringens. In: Speck ML (ed) Compendium for the microbiological examination of foods. Washington American Public Health Association, pp 483–495
Hauschild AH, Niilo L, Dorward WJ (1967) Experimental enteritis with food poisoning and classical strains ofClostridium perfringens type A in lambs. J Infect Dis 117:379–386
Heredia NL, Labbe RG, Rodriguez MA, Garcia-Alvarado JS (1991) Growth, sporulation and enterotoxin production byClostridium perfringens type A in the presence of human bile salts. FEMS Microbiol Lett 84:15–22
Jakeman KJ, Rushton DI, Smith H (1990) Exacerbation of bacterial toxicity to infant ferrets by influenza virus: possible role in sudden infant death syndrome. J Infect Dis 163:35–40
Kariks J (1985) Is shock the mode of death in SIDS? Med Hypotheses 18:331–349
Kautter DA, Lynt RK (1984)Clostridium botulinum. In: Speck ML (ed) Compendium for the microbiological examination of foods. Washington: American Public Health Association, pp 468–482
Kinney HC, Filiano JJ, Harper RM (1992) The neuropathology of the sudden infant death syndrome: a review. J Neuropathol Exp Neurol 51:115–126
Lindsay JA, Dennison JD (1986a) A scanning electron microscope study of the effect of an enterotoxin fromClostridium perfringens 8–6 on mice of different ages. J Gen Microbiol 132:2893–2898
Lindsay JA, Dennison JD (1986b) Histopathological effect ofClostridium perfringens 8–6 enterotoxin on rabbit intestine. Curr Microbiol 13:61–66
Lindsay JA, Mach AS (1992)Clostridium perfringens cytotoxic-enterotoxins as triggers for death in the sudden infant death syndrome: alterations in the actionin vitro andin vivo by an activator molecule from brush border membranes. Submitted
Lyerly DM, Saum KE, McDonald DK, Wilkins TD (1985) Effects ofClostridium difficile toxins given intragastrically to animals. Infect Immum 47:349–352
Malam JE, Carrick GF, Telford DR, Morris JA (1992) Staphylococcal toxins and sudden infant death syndrome. J Clin Pathol 45:716–721
Martin LM (1991) Cloning of theClostridium perfringens type A (8–6) enterotoxin gene intoEscherichia coli Chi 1776. M.S. Thesis, University of Florida, Gainesville
McClane BA, Wnek AP, Whitaker-Dowling P (1987) Interferon pretreatment enhances the sensitivity of Vero toClostridium perfringens type A enterotoxin. Microb Pathogen 3:195–206
McDonel JL (1980)Clostridium perfringens toxins. Pharmacol Ther 10:617–655
McKendrick N, Drucker DB, Morris JA, Telford DR, Barson AJ, Oppenheim BA, Crawley BA, Gibbs A (1992) Bacterial toxins: a possible cause of cot death. J Clin Pathol 45:49–53
Mills DC, Midura TF, Arnon SS (1985) Improved selective medium for the isolation of lipase-positiveClostridium botulinum from feces of human infants. J Clin Microbiol 21:947–950
Morris JA (1987) Hypothesis: common bacterial toxins are a possible cause of the sudden infant death syndrome. Med Hypotheses 22:211–222
Murrell TG, Ingham BG, Moss JR, Taylor WB (1987) A hypothesis concerningClostridium perfringens type A enterotoxin (CPE) and sudden infant death syndrome (SIDS). Med Hypotheses 22:401–413
Murrell WG, Stewart B, O'Neill C, Siarakas S, Kariks S (1992) The role of enterotoxigenic bacteria in SIDS. Abstracts of the 2nd International SIDS Conference, Sydney, Australia 1992:52
Niilo L (1973) Effect on calves of the intravenous injection of the enterotoxin ofClostridium perfringens type A. J Comp Pathol 83:265–269
Risse M, Weiler G (1989) Differential diagnosis SIDS/non-SIDS on the basis of histological findings of petechial thymus hemorrhages. Forensic Sci Int 43:1–7
Ryan T, Ostfeld B, Buckalew P, Hegyi T (1992) Sudden infant death syndrome in New Jersey: 1991. New Jersey Med 89:670–673
Seto DS, Carver DH (1978) Circulating interferon in sudden infant death syndrome. Proc Soc Exp Biol Med 157:378–380
Sivan Y, She G, Schonfeld T, Nitzan M, Nutman J (1992) Sudden infant death syndrome in the Tel Aviv and Petah Tikva districts. Isr J Med Sci 28:430–435
Stanton AN, Scott DJ, Downham MA (1980) Is overheating a factor in some unexpected infant deaths. Lancet i:1054–1057
Stark PL, Lee A (1982) The microbial ecology of the large bowel of breast-fed and formula-fed infants during the first year of life. J Med Microbiol 15:189–203
Stubbings DP (1990)Clostridium perfringens enterotoxemia in two young horses. Vet Rec 127:431
Telford DR, Morris JA, Hughes P, Conway AR, Lee S, Barson AJ, Drucker DB (1989) The nasopharyngeal bacterial flora in the sudden infant death syndrome. J Infect 18:125–130
Valdes-Dapena M (1980) Sudden infant death syndrome: a review of the medical literature 1974–79. Pediatrics 66:597–614
Variend S, Sunderland R (1984) Small intestinal mucosal abnormalities in post-perinatal deaths. J Clin Pathol 37:283–287
Wilkinson MA (1992) The sudden infant death syndrome in Florida: an epidemiological, pathological and microbiological study. M.S. Thesis, University of Florida, Gainesville
Willinger M (1989) SIDS: a challenge. J NIH Res 1:73–80
Wilson KH, Kennedy MJ, Fekety FR (1982) Use of sodium taurocholate to enhance spore recovery on a medium selective forClostridium difficile. J Clin Microbiol 15:443–446
Author information
Authors and Affiliations
Additional information
Florida Agricultural Experiment Station Journal Series No. R-02419.
Rights and permissions
About this article
Cite this article
Lindsay, J.A., Mach, A.S., Wilkinson, M.A. et al. Clostridium perfringens type A cytotoxic-enterotoxin(s) as triggers for death in the sudden infant death syndrome: Development of a toxico-infection hypothesis. Current Microbiology 27, 51–59 (1993). https://doi.org/10.1007/BF01576834
Issue Date:
DOI: https://doi.org/10.1007/BF01576834