Skip to main content
Log in

Clostridium perfringens type A cytotoxic-enterotoxin(s) as triggers for death in the sudden infant death syndrome: Development of a toxico-infection hypothesis

  • Published:
Current Microbiology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Literature Cited

  1. 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

    Google Scholar 

  2. Althoff H (1980) Sudden infant death syndrome. Stuttgart: Gustav Fischer Verlag

    Google Scholar 

  3. Arnon SS (1989) Infant botulism. In: Finegold SM, George WL (eds) Anaerobic infections in humans. New York: Academic Press, pp 601–609

    Google Scholar 

  4. 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

    Google Scholar 

  5. 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

    Google Scholar 

  6. Bacon C, Scott D, Jones P (1979) Heatstroke in well wrapped infants. Lancet i:422–425

    Google Scholar 

  7. Beckwith JB (1973) The sudden infant death syndrome. Curr Probl Pediatr 3:1–36

    Google Scholar 

  8. 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

    Google Scholar 

  9. 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

    Google Scholar 

  10. 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

    Google Scholar 

  11. Bruce K, Becker LE (1992) Quantitation of medullary astrogliosis in sudden infant death syndrome. Pediatr Neurosurg 17:74–79

    Google Scholar 

  12. 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

    Google Scholar 

  13. 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

    Google Scholar 

  14. 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

    Google Scholar 

  15. 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

    Google Scholar 

  16. 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

  17. Donta S, Myers M (1982)Clostridium difficile in asymptomatic neonates. J Pediatr 100:431–434

    Google Scholar 

  18. 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

    Google Scholar 

  19. Gordis L (1982) Should dead cases be matched to dead controls. Am J Epidemiol 115:1–5

    Google Scholar 

  20. 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

    Google Scholar 

  21. 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

    Google Scholar 

  22. 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

    Google Scholar 

  23. 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

    Google Scholar 

  24. 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

    Google Scholar 

  25. Kariks J (1985) Is shock the mode of death in SIDS? Med Hypotheses 18:331–349

    Google Scholar 

  26. 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

    Google Scholar 

  27. Kinney HC, Filiano JJ, Harper RM (1992) The neuropathology of the sudden infant death syndrome: a review. J Neuropathol Exp Neurol 51:115–126

    Google Scholar 

  28. 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

    Google Scholar 

  29. Lindsay JA, Dennison JD (1986b) Histopathological effect ofClostridium perfringens 8–6 enterotoxin on rabbit intestine. Curr Microbiol 13:61–66

    Google Scholar 

  30. 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

  31. Lyerly DM, Saum KE, McDonald DK, Wilkins TD (1985) Effects ofClostridium difficile toxins given intragastrically to animals. Infect Immum 47:349–352

    Google Scholar 

  32. Malam JE, Carrick GF, Telford DR, Morris JA (1992) Staphylococcal toxins and sudden infant death syndrome. J Clin Pathol 45:716–721

    Google Scholar 

  33. Martin LM (1991) Cloning of theClostridium perfringens type A (8–6) enterotoxin gene intoEscherichia coli Chi 1776. M.S. Thesis, University of Florida, Gainesville

    Google Scholar 

  34. 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

    Google Scholar 

  35. McDonel JL (1980)Clostridium perfringens toxins. Pharmacol Ther 10:617–655

    Google Scholar 

  36. 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

    Google Scholar 

  37. 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

    Google Scholar 

  38. Morris JA (1987) Hypothesis: common bacterial toxins are a possible cause of the sudden infant death syndrome. Med Hypotheses 22:211–222

    Google Scholar 

  39. 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

    Google Scholar 

  40. 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

  41. Niilo L (1973) Effect on calves of the intravenous injection of the enterotoxin ofClostridium perfringens type A. J Comp Pathol 83:265–269

    Google Scholar 

  42. 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

    Google Scholar 

  43. Ryan T, Ostfeld B, Buckalew P, Hegyi T (1992) Sudden infant death syndrome in New Jersey: 1991. New Jersey Med 89:670–673

    Google Scholar 

  44. Seto DS, Carver DH (1978) Circulating interferon in sudden infant death syndrome. Proc Soc Exp Biol Med 157:378–380

    Google Scholar 

  45. 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

    Google Scholar 

  46. Stanton AN, Scott DJ, Downham MA (1980) Is overheating a factor in some unexpected infant deaths. Lancet i:1054–1057

    Google Scholar 

  47. 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

    Google Scholar 

  48. Stubbings DP (1990)Clostridium perfringens enterotoxemia in two young horses. Vet Rec 127:431

    Google Scholar 

  49. 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

    Google Scholar 

  50. Valdes-Dapena M (1980) Sudden infant death syndrome: a review of the medical literature 1974–79. Pediatrics 66:597–614

    Google Scholar 

  51. Variend S, Sunderland R (1984) Small intestinal mucosal abnormalities in post-perinatal deaths. J Clin Pathol 37:283–287

    Google Scholar 

  52. Wilkinson MA (1992) The sudden infant death syndrome in Florida: an epidemiological, pathological and microbiological study. M.S. Thesis, University of Florida, Gainesville

    Google Scholar 

  53. Willinger M (1989) SIDS: a challenge. J NIH Res 1:73–80

    Google Scholar 

  54. 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

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Florida Agricultural Experiment Station Journal Series No. R-02419.

Rights and permissions

Reprints 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

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01576834

Keywords

Navigation